Modular Synthesis of Highly Substituted 3-Azapyrroles by Rh(II)-Catalyzed N–H Bond Insertion and Cyclodehydration

Matthew B Williams; Alistair Boyer

doi:10.1021/acs.joc.2c00434

. 2022 May 3;87(24):16139–16156. doi: 10.1021/acs.joc.2c00434

Modular Synthesis of Highly Substituted 3-Azapyrroles by Rh(II)-Catalyzed N–H Bond Insertion and Cyclodehydration

Matthew B Williams ¹, Alistair Boyer ^1,^*

PMCID: PMC9764362 PMID: 35503987

Abstract

graphic file with name jo2c00434_0012.jpg

A modular synthesis of highly substituted 3-azapyrroles has been developed using a three-step sequence comprising copper-catalyzed alkyne–azide cycloaddition (CuAAC), N–H bond insertion, and cyclodehydration. 1-Sulfonyl-1,2,3-triazoles (1-STs) can be accessed from common alkyne and sulfonyl azide building blocks by CuAAC using CuTC. Rhodium(II)-acetate-promoted 1-ST denitrogenation results in highly electrophilic rhodium azavinyl carbenes that, here, underwent insertion into the N–H bond of secondary α-aminoketones to form 1,2-aminoalkenes. These products were cyclized and dehydrated using BF₃·OEt₂ into highly substituted 3-azapyrroles. The three steps (CuAAC, N–H bond insertion, and cyclodehydration) could be telescoped into a one-pot process. The method proved to be highly efficient and tolerated a wide range of substituents.

Introduction

Pyrroles are ubiquitous five-membered nitrogen-containing heteroaromatic compounds that display valuable properties, making them key fragments in a wide variety of natural products,¹ pharmaceuticals,² and functional materials.³ Several valuable pyrroles have 3-aza substitution, including the DNA minor groove binders netropsin⁴1 and distamycin A⁵2 as well as other natural products such as geranylpyrrol 3 (Figure 1).⁶

Selected biologically active 3-azapyrroles.

The value of pyrroles has inspired many synthetic approaches spanning the whole history of organic chemistry.⁷ However, these established methods are not always easily adapted to the synthesis of 3-azapyrroles.⁸ Therefore, development of novel synthetic strategies toward this privileged heterocycle is necessary. Ideally, newly developed methods should begin from cheap and readily available starting materials and be straightforward to carry out practically, highly atom efficient, modular, and tolerant of a wide range of functional groups.

The reactivity of 1-sulfonyl-1,2,3-triazoles 4 (1-STs) has been developed such that they can be considered readily accessed building blocks⁹ for the facile synthesis of a wide range of value-added products.¹⁰ The sulfonyl group provides an ideal balance to the triazole heterocycle, bringing stability but also allowing on demand reactivity when an appropriate catalyst system is deployed. The majority of examples of this strategy involve triazoles and rhodium(II) carboxylate catalysts, although, recently, palladium(0) catalysts have shown analogous reactivity with 1-trifluoromethanesulfonylbenzotriazoles 5.¹¹

The key reactivity of 1-STs arises from the catalyst promoting Dimroth equilibration and denitrogenation of the nitrogen-rich heterocycle to give a highly reactive organometallic intermediate 6 (Scheme 1). In terms of reactivity, the organometallic species 6 can be considered as a three-atom ylidic synthon 7 with its positive component on the carbon and negative component on the nitrogen atom. Therefore, reaction with a suitable two-carbon π component results in the formation of a new five-membered nitrogen heterocycle 8, i.e., a pyrrole, indole, or reduced version thereof. This reactivity has been developed across a wide spectrum of substrates: alkenes,^11b,11d,12 alkynes,¹³ enol ethers,¹⁴ furans,¹⁵ indoles,¹⁶ and even arene moieties.¹⁷ There have also been some unique approaches to pyrroles and indoles from unsaturated carbonyl species,¹⁸ alcoholic unsaturated carbonyl species,¹⁹ unsaturated 1-STs,²⁰ and vinyl anilines.²¹ The versatility of 1-ST reactivity means that many reactions are possible that result in heterocycle formation by the inclusion of a nitrogen-containing tether^22,23 or by providing valuable access to substrates that can be converted into five-membered azaheterocycles in short order.^24,25 In the majority of these examples, the mechanism dictates that the nitrogen atom remaining following denitrogenation of the triazole becomes the heteroatom component of the heterocycle that is generated. However, in reactions of 1-STs with certain nitrogen-containing substrates, the triazole nitrogen can become a 3-aza substituent of the pyrrole (Scheme 2).

Upon treatment with a Rh(II) carboxylate, 1-STs formed an electron-deficient metallocarbene 6 that reacted with the nitrogen lone pair of isoxazoles 10. Ring opening of the isoxazole 11 was followed by cyclization to form a pyrrole 12 with a 3-azasulfonyl substituent.²⁶ In a similar fashion but with azirenes, the azirene 13 lone pair reacted with the highly electron-deficient rhodium carbene 6 followed by collapse of the intermediate to form a pyrrole 15, again with a 3-azasulfonyl substituent.²⁷

The insertion of metallocarbenes into X–H bonds has been developed into a valuable reaction,²⁸ and this formation of C–N bonds from N–H bonds is another class of transformation that has been demonstrated with 1-STs.^21,29 Here, we recognized that α-aminoketones are the hydrated equivalent of azirenes. Therefore, bringing together an α-aminoketone 16 and a 1-ST through N–H bond insertion (17) and then performing cyclodehydration would result in a strategically complementary approach to valuable 3-azapyrroles 18.

Results

The substrates for this study, namely, α-aminoketones and 1-STs are both readily accessed from readily available materials (Scheme 3). The α-aminoketones 16 were formed by simple S_N2 displacement of commercial α-haloketones 20 by anilines 19. Additional substitution could be introduced to the α-position of the ketone owing to its acidic nature (16g). The 1-STs 4 were formed in excellent yield by copper-catalyzed azide–alkyne cycloaddition (CuAAC), and the modular nature of 1-ST synthesis is a key strength to this methodology. It is noteworthy that the use of copper(I) thiophene-2-carboxylate (CuTC) has been specifically developed for 1-ST synthesis.⁹

Next, the focus was establishing the optimum conditions for insertion of the metallocarbene derived from the 1-ST into the N–H bond of an appropriate aniline to bring together all the requisite atoms for the planned pyrrole synthesis (Table 1). A 4-tolyl-1-tosyltriazole 4a was treated with a slight excess of α-aminoketone 16a and 5 mol % of Rh₂(OAc)₄ in toluene at 80 °C with 4 Å molecular sieves.³⁰ These conditions resulted in the formation of the N–H insertion product 17a in high yield (81%, entry 1).³¹ Commonly employed Rh₂(octanoate)₄ and Rh₂(esp)₂³² also promoted the N–H bond insertion but with lower efficiency, whereas no reaction occurred with bulky catalysts Rh₂(triphenylacetate)₄ and Rh₂(S-tPTTL)₄³³ (entries 4 and 5). The choice of solvent had a minor effect on the reaction outcome, but the yield was improved to 93% when using toluene (entries 6–8). Increasing the temperature from 60 to 80 °C provided a small increase in yield (entry 9), but increasing the temperature further caused the yield to decrease (entries 10 and 11); no reaction occurred below 60 °C (entry 12). These findings were congruous with previous work that showed Rh₂(OAc)₄ and Rh₂(octanoate)₄ to be the most effective for related N–H bond insertions of α-amino esters, carbamates, and carbazoles.^21,29 However, this process was more tolerant to solvent compared with other processes, specifically with toluene being generally incompatible in the other examples.

Table 1. Optimization of N–H Insertion^a.

entry	catalyst	solvent	T (°C)	yield (%)
1	Rh₂(OAc)₄	CHCl₃	60	81
2	Rh₂(esp)₂	CHCl₃	60	70
3	Rh₂(octanoate)₄	CHCl₃	60	38
4	Rh₂(TPA)₄	CHCl₃	60	no reaction
5	Rh₂(S-tPTTL)₄	CHCl₃	60	no reaction
6	Rh₂(OAc)₄	(CH₂Cl)₂	60	87
7	Rh₂(OAc)₄	CH₂Cl₂	60	91
8	Rh₂(OAc)₄	PhMe	60	93
9	Rh₂(OAc)₄	PhMe	80	94
10	Rh₂(OAc)₄	PhMe	100	85
11	Rh₂(OAc)₄	PhMe	120	58
12	Rh₂(OAc)₄	PhMe	40	no reaction

Open in a new tab

0.2 mmol 4a, 1.1 equiv of 16a, 0.03 M, sealed vial, yield by internal standard ¹H NMR.

It was anticipated that the Lewis acidic nature of the Rh(II) carboxylate might also promote cyclodehydration of the 1,2-diaminoalkene to form the corresponding pyrrole, but this transformation was not detected. Therefore, the heterocycle forming process was evaluated in a separate^23d,26b,34 operation (Table 2).

Table 2. Optimization of Cyclodehydration^a.

entry	reagent (equiv)	solvent	T (°C)	yield (%)
1	BF₃·OEt₂ (0.5)	CH₂Cl₂	80	49
2	BF₃·OEt₂ (1.0)	CH₂Cl₂	80	66
3	BF₃·OEt₂ (3.0)	CH₂Cl₂	80	72
4	BF₃·OEt₂ (3.0)	(CH₂Cl)₂	80	65
5	BF₃·OEt₂ (3.0)	PhMe	80	19
6	BF₃·OEt₂ (3.0)	MeCN	80	38
7	BF₃·OEt₂ (3.0)	CH₂Cl₂	60	32
8	BF₃·OEt₂ (3.0)	CH₂Cl₂	40	32

Open in a new tab

0.2 mmol 17a, 0.03 M, sealed vial, yield by internal standard ¹H NMR.

Treatment of the 1,2-diaminoalkene 17a with a selection of dehydrating/acidic reagents; including p-toluene sulfonic acid, trimethylsilyl triflate, acetic acid, and phosphorus oxychloride resulted in the decomposition of substrate with only a minimal amount of the desired pyrrole 18a. Gratifyingly, using BF₃·OEt₂³⁵ (0.5 equiv) in dichloromethane at 80 °C gave a modest 49% yield of pyrrole 18a (Table 2, entry 1) with a cleaner reaction profile (¹H NMR). Increasing the amount of Lewis acid from 0.5 to 3.0 equiv was accompanied by an increase in yield to 72% (entries 2 and 3). 1,2-Dichloroethane, toluene, and acetonitrile were considered as alternative solvents, but the yields were lower than those of dichloromethane, giving complex mixtures (entries 4–6). Reducing the temperature to less than 80 °C resulted in a more sluggish reaction (entries 7 and 8).

With the reaction conditions for a pyrrole synthesis sequence established, the generality of this process was explored (Scheme 4). Upon varying the N-aryl substituent, the Rh(II)-catalyzed N–H insertion and BF₃·OEt₂ promoted cyclodehydration were found to be highly tolerant with good to excellent yields obtained for both reactions (17a–d and 18a–d). Surprisingly, when a mesityl group or naphthyl group was used, the Rh(II)-catalyzed reaction led to the pyrroles 18e,f in good yield directly, and no 1,2-diamine product 17e,f was observed. This difference in reactivity was attributed to promotion of the cyclization by raising the energy of unreactive conformations through steric interactions, placing the reacting centers in close proximity. Aliphatic amines were challenging substrates for the Rh(II)-catalyzed reaction and so were not compatible with this process, presumably owing to their increased basicity.

Variation of the ketone substituent was also studied, allowing control of the 4- and 5-positions of the resulting pyrrole (Scheme 5). Having an additional α-substituent in the substrate aminoketone was evaluated, and this proved to be compatible with the optimized conditions, giving a fully substituted pyrrole product 18g in high yield over the two operations.

When more conjugated or electron-rich ketone substituents were studied, these also gave good yields for the two operations (18h,i). Interestingly, using more electron-withdrawing substituents NO₂, CN, and Cl gave the expected N–H insertion products 17j–l alongside the corresponding pyrroles 18j–l, giving almost quantitative combined yields of the products. The two products were readily separated by column chromatography, and the 1,2-diaminoalkenes 17j–l could be transformed into their corresponding pyrroles 18j–l in good yield. Extending the reaction time in the presence of rhodium catalyst to 16 h led to formation of only the pyrrole products in high yield (87% of 18j, 81% of 18k, and 65% of 18l). It is suggested that direct formation of pyrroles proceeded in these cases via the same products of N–H insertion, but that the more electron-withdrawing substituents activated the ketone toward nucleophilic attack, allowing cyclodehydration to occur with the more mildly Lewis acidic Rh(II) catalyst. This is consistent with the more electron-withdrawing NO₂ and CN groups giving more pyrrole product than the Cl substituent.

Different substituents at the 4-position of 1-ST 4 were also studied (Scheme 6). Heteroaromatic, electron-rich aromatic, and alkenyl 1-ST 4-substituents gave excellent yields for N–H insertion (17m–o). Interestingly, the alkene substrate completed N–H insertion (17o), despite the known intramolecular rearrangement of alkenyl 1-STs to a different class of pyrrole.²⁰ Pyrroles 18m,n were formed from these products using BF₃·OEt₂, again all with good to excellent yield. Variation of the sulfonyl group was also examined. Use of an electron-donating p-MeOC₆H₄SO₂ group gave an excellent yield for N–H insertion (17p) but a moderate yield for cyclization to pyrrole 18p. On the other hand, the electron-withdrawing p-NO₂C₆H₄SO₂ group and the small mesyl group gave a moderate yield for N–H insertion for 17q,r but an excellent yield for cyclodehydration to the pyrrole 18q,r.

The key contributors to inefficiency in synthesis often come not from the reactions themselves but in the purification of intermediates, so combining or telescoping multiple operations in one pot or domino sequences is an excellent way to boost efficiency.³⁶ CuAAC is highly versatile and has been incorporated in one-pot sequences with rhodium(II) reactions of 1-STs since the earliest work in the field,^18c,20,37 so this was also investigated here (Scheme 7). Although, each of the sequential operations (CuAAC, N–H insertion, and cyclodehydration) had reagents and catalysts that should be tolerant to the previous conditions in the sequence, their solvent varied. Dichloromethane was selected for the one-pot process because it was significantly better than other solvents in the cyclodehydration step and worked well with the other steps, and the amount was selected to match the concentration of the most sensitive Rh(II)-catalyzed step. Treatment of p-tolylacetylene with tosyl azide in the presence of CuTC in CH₂Cl₂ gave complete conversion to the corresponding 1-ST 4a. Without isolation, α-aminoketone 16a and Rh₂(OAc)₄ were added to the mixture, and the vial was sealed and heated for 3 h at 80 °C. Then BF₃·OEt₂ (3.0 equiv) was added, and the reaction mixture was stirred for a further 15 min at 80 °C. Standard aqueous workup (NaHCO₃) and filtration through silica gel afforded the pyrrole 18a in 90% yield. This represented a marked improvement over the three separate steps (90 vs 58%) as well as making the overall process much more time- and material-efficient. Furthermore, the amount of copper and rhodium catalysts used was decreased to 5 and 1 mol %, respectively, without any deleterious effect. The one-pot process was applied to a range of terminal alkynes 21, sulfonyl azides 22, and amines 16, all of which gave excellent yields of the corresponding pyrroles 18 with considerable improvement over the stepwise equivalent. The one-pot procedure was also completed on a larger scale (4.61 mmol), using (CH₂Cl)₂ in place of CH₂Cl₂ and under reflux instead of in a sealed vial, and the protocol delivered the product 18h in excellent 76% yield.

Scheme 7 — Isolated yield.

On 4.6 mmol scale, using (CH₂Cl)₂ in place of CH₂Cl₂, isolated yield.

Finally, the cleavage of the N-sulfonyl bond was demonstrated (eq 1). The N-tosyl pyrrole 18a was treated with triflic acid at 90 °C, followed by workup with ethylene diamine,³⁸ to reveal the pyrrole with a NH₂ group 23a in 77% yield.

graphic file with name jo2c00434_0001.jpg

Conclusion

A procedure has been developed that allows rapid assembly of 3-azapyrroles from readily available starting materials. The 1-ST and secondary amine starting materials were accessed in high yield from readily available building blocks. Rhodium(II) acetate was the optimum catalyst to promote 1-ST denitrogenation and insertion into the N–H bond of a range of α-aminoketones to form 1,2-aminoalkenes in high yields. For bulky arylamines and electron-deficient ketones, the 1,2-aminoalkenes cyclized into the corresponding 3-azapyrroles under rhodium catalysis, but for most examples, this was not the case and BF₃·OEt₂ proved to be a reliable Lewis acid for promoting the transformation into the heterocyclic products. These steps could be conducted individually or telescoped into a one-pot process beginning from sulfonyl azides, alkynes, and ketones, exploiting the orthogonal reactivity in the sequence. The availability of individual substrates means that this method represents a highly modular approach to pyrroles, allowing each of the five substituents to be customized through judicious choice of starting materials.

Experimental Details

CAUTION: Nitrogen-rich compounds, such as azides and triazoles, can decompose violently with the loss of nitrogen gas. Although no problems were encountered in this study, appropriate precautions should be taken.

General Information and Methods

NMR spectra were recorded on 400 and 500 MHz Bruker spectrometers. Chemical shifts are given in parts per million, and the spectra are calibrated to the residual ¹H and ¹³C signals of the solvents. ¹³C NMR spectra were collected with complete proton decoupling, and assignments were made using COSY, HSQC, HMBC, and NOESY experiments. Samples were melted directly from the procedures described. High-resolution mass spectra were obtained on Agilent 6546 LC/Q-TOF and Bruker microTOFq instruments by Analytical Services at the University of Glasgow School of Chemistry. IR spectra were recorded using spectrometers fitted with an ATR device. CH₂Cl₂ and toluene were purified on a PureSolv PM500, and other reagents were used as received. Reactions were monitored by thin layer chromatography (TLC) using Merck TLC silica gel 60 F254 aluminum-foil baked plates. Compounds were visualized by UV light at nanometer resolution or by staining with potassium permanganate. Column chromatography was performed using a Teledyne ISCO Combiflash Rf+ system using Redisep Rf silica cartridges.

General Procedure 1: CuAAC to Form 1STs

Copper(I) thiophene-2-carboxylate (10 mol %) and alkyne 21 (1.1 equiv) were dissolved in PhMe (0.1 M) and cooled to 0 °C (ice bath). After 10 min, sulfonyl azide 22 (1.0 equiv) was added in one portion and the reaction mixture was allowed to reach ambient temperature. When the reaction was complete (TLC, 1–3 h), the mixture was diluted with saturated aqueous NH₄Cl and extracted with ethyl acetate (3 × 10 mL mmol^–1). The combined organic layers were washed with brine, dried (MgSO₄), filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (SiO₂, rapid gradient of 10–30% ethyl acetate in petroleum ether) to give the 1-ST 4.

4-(4-Tolyl)-1-tosyl-1,2,3-triazole (4a)

4-Ethynyltoluene (547 μL, 4.3 mmol, 1.1 equiv) and 4-toluenesulfonyl azide (809 mg, 4.1 mmol, 1.0 equiv) were treated with CuTC (69 mg, 0.36 mmol, 9 mol %) in PhMe (40 mL) according to General Procedure 1 to give the title compound 4a (1.17 g, 91%) as a white solid: mp 127 °C dec (lit. 158–159 °C);³⁹ ν_max (film) 3150, 2940, 1593, 1497, 1392, 1194, and 1179 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 8.26 (1 H, s, triazole CH), 8.02 (2 H, d, J = 8.4 Hz, Ar), 7.71 (2 H, d, J = 8.4 Hz, Ar), 7.39 (2 H, d, J = 7.8 Hz, Ar), 7.23 (2 H, d, J = 7.8 Hz, Ar), 2.45 (3 H, s, CH₃) and 2.38 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 147.4 (Ar), 147.3 (triazole C4), 139.1 (Ar), 133.2 (Ar), 130.4 (2 × ArH), 129.7 (2 × ArH), 128.7 (2 × ArH), 126.0 (Ar), 126.0 (2 × ArH), 118.5 (triazole C5), 21.8 (CH₃) and 21.3 (CH₃); HRMS (ESI-TOF) m/z [M + Na]⁺ calcd for C₁₆H₁₅N₃NaO₂S⁺ 336.0777; found 336.0767. Recorded data are consistent with previous values.³⁹

4-(Thiophen-2-yl)-1-tosyl-1,2,3-triazole (4m)

2-Ethynylthiophene (438 μL, 4.6 mmol, 1.1 equiv) and 4-toluenesulfonyl azide (828 mg, 4.2 mmol, 1.0 equiv) were treated with CuTC (80 mg, 0.42 mmol, 10 mol %) in PhMe (42 mL) according to General Procedure 1 to give the title compound 4m (1.24 g, 97%) as a white solid: mp 87 °C dec (lit. 140–141 °C);^18f ν_max (film) 3136, 2924, 1593, 1393, 1346, 1196, 1177, and 1092 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 8.20 (1 H, s, triazole CH), 8.02 (2 H, d, J = 8.5 Hz, Ar), 7.44 (1 H, dd, J = 3.6, 1.2 Hz, thiophene CH), 7.39 (2 H, d, J = 8.5 Hz, Ar), 7.34 (1 H, dd, J = 5.1, 1.2 Hz, thiophene CH), 7.08 (1 H, dd, J = 5.1, 3.6 Hz, thiophene CH) and 2.45 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 147.4 (triazole C4), 142.5 (thiophene C2), 133.0 (Ar), 130.8 (Ar), 130.5 (2 × ArH), 128.7 (2 × ArH), 127.8 (thiophene CH), 126.3 (thiophene CH), 125.6 (thiophene CH), 118.1 (triazole C5) and 21.8 (CH₃); HRMS (ESI-TOF) m/z [M + Na]⁺ calcd for C₁₃H₁₁N₃NaO₂S₂⁺ 328.0185; found 328.0184. Recorded data are consistent with previous values.^18f

4-(4-Methoxyphenyl)-1-tosyl-1,2,3-triazole (4n)

1-Ethynyl-4-methoxybenzene (535 μL, 4.1 mmol, 1.1 equiv) and 4-toluenesulfonyl azide (740 mg, 3.8 mmol, 1.0 equiv) were treated with CuTC (71 mg, 0.37 mmol, 10 mol %) in PhMe (40 mL) according to General Procedure 1 to give the title compound 4n (1.05 g, 85%) as a white solid: mp 96 °C dec (lit. 100–101 °C);⁴⁰ ν_max (film) 3144, 2932, 2839, 1616, 1497, 1393, 1331, 1250, 1177, and 1088 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 8.22 (1 H, s, triazole CH), 8.01 (2 H, d, J = 8.5 Hz, Ar), 7.74 (2 H, d, J = 8.9 Hz, Ar), 7.37 (2 H, d, J = 8.5 Hz, Ar), 6.95 (2 H, d, J = 8.9 Hz, Ar), 3.83 (3 H, s, OCH₃) and 2.43 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 160.2 (Ar), 147.3 (Ar), 147.2 (triazole C4), 133.1 (Ar), 130.4 (2 × ArH), 128.6 (2 × ArH), 127.4 (2 × ArH), 121.4 (Ar), 117.9 (triazole C5), 114.4 (2 × ArH), 55.3 (OCH₃) and 21.8 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₁₆H₁₆N₃O₃S⁺ 330.0907; found 330.0909. Recorded data are consistent with previous values.⁴⁰

4-(Cyclohexen-1-yl)-1-tosyl-1,2,3-triazole (4o)

1-Ethynylcyclohex-1-ene (485 μL, 4.1 mmol, 1.1 equiv) and 4-toluenesulfonyl azide (740 mg, 3.8 mmol, 1.0 equiv) were treated with CuTC (71 mg, 0.37 mmol, 10 mol %) in PhMe (40 mL) according to General Procedure 1 to give the title compound 4o (950 mg, 83%) as a white solid: mp 100 °C dec (lit. 102–103 °C);³⁹ ν_max (film) 3148, 2928, 2859, 1593, 1389, 1177, and 1092 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.97 (2 H, d, J = 8.5 Hz, Ar), 7.88 (1 H, s, triazole CH), 7.36 (2 H, d, J = 8.5 Hz, Ar), 6.66 (1 H, tt, J = 3.9, 1.8 Hz, =CH), 2.43 (3 H, s, CH₃), 2.34–2.27 (2 H, m, CH₂), 2.22–2.15 (2 H, m, CH₂), 1.78–1.71 (2 H, m, CH₂) and 1.70–1.61 (2 H, m, CH₂); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 148.9 (triazole C4), 147.0 (Ar), 133.3 (Ar), 130.3 (2 × ArH), 128.5 (2 × ArH), 127.7 (=CH), 125.8 (=C), 117.3 (triazole C5), 26.2 (CH₂), 25.3 (CH₂), 22.2 (CH₂), 22.0 (CH₂) and 21.8 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₁₅H₁₈N₃O₂S⁺ 304.1114; found 304.1113. Recorded data are consistent with previous values.³⁹

1-Methanesulfonyl-4-(4-tolyl)-1,2,3-triazole (4p)

4-Ethynyltoluene (558 μL, 4.4 mmol, 1.1 equiv) and methanesulfonyl azide (484 mg, 4.0 mmol, 1.0 equiv) were treated with CuTC (76 mg, 0.40 mmol, 10 mol %) in PhMe (40 mL) according to General Procedure 1 to give the title compound 4p (898 mg, 95%) as a white solid: mp 95 °C dec (lit. 120–122 °C dec.);⁴¹ ν_max (film) 3140, 3028, 2924, 1381, 1231, 1184, 1161, and 1038 cm^–1; ¹H NMR (500 MHz, 25.0 °C, CDCl₃) δ 8.26 (1 H, s, triazole CH), 7.76 (2 H, d, J = 8.0 Hz, Ar), 7.28 (2 H, d, J = 8.0 Hz, Ar), 3.56 (3 H, s, CH₃) and 2.41 (3 H, s, CH₃); ¹³C{¹H} NMR (126 MHz, 25.0 °C, CDCl₃) δ 147.6 (triazole C4), 139.4 (Ar), 129.8 (2 × ArH), 126.1 (2 × ArH), 125.8 (Ar), 118.4 (triazole C5), 42.7 (CH₃) and 21.4 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₁₀H₁₂N₃O₂S⁺ 238.0645; found 238.0646. Recorded data are consistent with previous values.⁴¹

1-(4-Nitrobenzenesulfonyl)-4-(4-tolyl)-1,2,3-triazole (4q)

4-Ethynyltoluene (533 μL, 4.2 mmol, 1.1 equiv) and 4-nitrobenzenesulfonyl azide (913 mg, 4.0 mmol, 1.0 equiv) were treated with CuTC (76 mg, 0.40 mmol, 10 mol %) in PhMe (40 mL) according to General Procedure 1 to give the title compound 4q (1.20 g, 87%) as a white solid: mp 106 °C dec; ν_max (film) 3140, 3109, 1532, 1408, 1397, 1346, and 1188 cm^–1; ¹H NMR (500 MHz, 25.0 °C, CDCl₃) δ 8.44 (2 H, d, J = 9.0 Hz, Ar), 8.36 (2 H, d, J = 9.0 Hz, Ar), 8.30 (1 H, s, triazole CH), 7.71 (2 H, d, J = 8.2 Hz, Ar), 7.25 (2 H, d, J = 8.2 Hz, Ar) and 2.39 (3 H, s, CH₃); ¹³C{¹H} NMR (126 MHz, 25.0 °C, CDCl₃) δ 151.6 (Ar), 148.0 (triazole C4), 141.6 (Ar), 139.6 (Ar), 130.1 (2 × ArH), 129.8 (2 × ArH), 126.1 (2 × ArH), 125.4 (Ar), 125.0 (2 × ArH), 118.6 (triazole C5) and 21.4 (CH₃); HRMS (ESI-TOF) m/z [M(hydrolyzed triazole) + H]⁺ calcd for C₉H₁₀N₃⁺ 160.0869; found 160.0875.

1-(4-Methoxylphenylsulfonyl)-4-(4-tolyl)-1,2,3-triazole (4r)

4-Ethynyltoluene (279 μL, 2.2 mmol, 1.1 equiv) and 4-methoxybenzenesulfonyl azide (426 mg, 2.0 mmol, 1.0 equiv) were treated with CuTC (38 mg, 0.20 mmol, 10 mol %) in PhMe (20 mL) according to General Procedure 1 to give the title compound 4r (372 mg, 56%) as a white solid: mp 102 °C dec; ν_max (film) 2940, 2923, 1593, 1577, 1497, 1391, 1233, and 1168 cm^–1; ¹H NMR (500 MHz, 25.0 °C, CDCl₃) δ 8.26 (1 H, s, triazole CH), 8.08 (2 H, d, J = 9.1 Hz, Ar), 7.71 (2 H, d, J = 8.1 Hz, Ar), 7.24 (2 H, d, J = 8.1 Hz, Ar), 7.03 (2 H, d, J = 9.1 Hz, Ar), 3.89 (3 H, s, OCH₃) and 2.38 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 12707.0 (Ar), 165.3 (Ar), 147.4 (triazole C4), 139.1 (Ar), 131.2 (2 × ArH), 129.7 (2 × ArH), 127.9 (Ar), 126.0 (2 × ArH), 118.4 (triazole C5), 115.1 (2 × ArH), 55.9 (OCH₃) and 21.3 (CH₃); HRMS (ESI-TOF) m/z [M + Na]⁺ calcd for C₁₆H₁₅N₃NaO₃S⁺ 352.0726; found 352.0719. Recorded data are consistent with previous values.⁴²

General Procedure 2: Formation of α-Aminoketones

Amine 19 (1.0 equiv) was dissolved in a 1:1 mixture of water and ethanol (0.2 M). NaHCO₃ (1.0 equiv) was added followed by the α-bromoketone 20 (1.0 equiv), and the reaction mixture was stirred until completion (TLC, 2–24 h). The reaction mixture was diluted with ethyl acetate, and the aqueous phase was extracted with ethyl acetate (3 × 5 mL mmol^–1). The combined organic layers were washed with brine, dried (MgSO₄), and concentrated in vacuo. This product was either purified by recrystallization from CHCl₃/pentane or by column chromatography (SiO₂, gradient of 10–30% EtOAc in petroleum ether).

1-(4-Tolyl)-2-(4-tolylamino)ethan-1-one (16a)

p-Toluidine (1.00 g, 9.4 mmol, 1.0 equiv) and 2-bromo-4′-methylacetophenone (2.00 g, 9.4 mmol, 1.0 equiv) were treated with sodium hydrogen carbonate (789 mg, 9.4 mmol, 1.0 equiv) in ethanol (30 mL) and water (30 mL) according to General Procedure 2 for 16 h, and then the crude product was purified by recrystallization (CHCl₃/pentane) to give the title compound 16a (1.93 g, 86%) as a yellow solid: mp 130–138 °C (lit. 130–133 °C);⁴³ ν_max (film) 3405, 3029, 1682, 1612, 1527, and 1356 cm^–1; ¹H NMR (500 MHz, 22.2 °C, CDCl₃) δ 7.92 (2 H, d, J = 8.5 Hz, Ar), 7.31 (2 H, d, J = 7.8 Hz, Ar), 7.04 (2 H, d, J = 7.8 Hz, Ar), 6.65 (2 H, d, J = 8.5 Hz, Ar), 4.85 (1 H, br s, NH), 4.58 (2 H, s, CH₂), 2.44 (3 H, s, CH₃) and 2.26 (3 H, s, CH₃); ¹³C{¹H} NMR (126 MHz, 22.6 °C, CDCl₃) δ 194.9 (C=O), 144.9 (Ar), 144.8 (Ar), 132.5 (Ar), 129.8 (2 × ArH), 129.5 (2 × ArH), 127.8 (2 × ArH), 127.0 (Ar), 113.2 (2 × ArH), 50.6 (CH₂), 21.8 (CH₃) and 20.4 (CH₃); HRMS (ESI-TOF) m/z [M + Na]⁺ calcd for C₁₆H₁₇NNaO⁺ 262.1202; found 262.1204.

2-(4-Chlorophenylamino)-1-(4-tolyl)ethan-1-one (16b)

4-Chloroaniline (255 mg, 2.0 mmol, 1.0 equiv) and 2-bromo-4′-methylacetophenone (426 mg, 2.0 mmol, 1.0 equiv) were treated with sodium hydrogen carbonate (168 mg, 2.0 mmol, 1.0 equiv) in ethanol (5 mL) and water (5 mL) according to General Procedure 2 for 24 h, and then the crude product was purified by recrystallization (CHCl₃/pentane) to give the title compound 16b (438 mg, 84%) as a white solid: mp 125 °C dec (lit. 167–169 °C);⁴⁴ ν_max (film) 3393, 3030, 1675, 1603, 1499, 1353, 1188, and 1092 cm^–1; ¹H NMR (400 MHz, 22.4 °C, CDCl₃) δ 7.90 (2 H, d, J = 8.2 Hz, Ar), 7.31 (2 H, d, J = 8.2 Hz, Ar), 7.16 (2 H, d, J = 8.8 Hz, Ar), 6.64 (2 H, d, J = 8.8 Hz, Ar), 4.54 (2 H, s, CH₂) and 2.44 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 22.8 °C, CDCl₃) δ 194.2 (C=O), 145.6 (Ar), 145.0 (Ar), 132.2 (Ar), 129.6 (2 × ArH), 129.2 (2 × ArH), 127.8 (2 × ArH), 122.4 (Ar), 114.1 (2 × ArH), 50.1 (CH₂) and 21.7 (CH₃); HRMS (ESI-TOF) m/z [M + Na]⁺ calcd for C₁₅H₁₄ClNNaO⁺ 282.0656; found 282.0655.

1-(4-Tolyl)-2-(3-trifluoromethylphenylamino)ethan-1-one (16c)

3-Trifluoromethylaniline (323 mg, 2.0 mmol, 1.0 equiv) and 2-bromo-4′-methylacetophenone (426 mg, 2.0 mmol, 1.0 equiv) were treated with sodium hydrogen carbonate (168 mg, 2.0 mmol, 1.0 equiv) in ethanol (5 mL) and water (5 mL) according to General Procedure 2 for 16 h, and then the crude product was purified by recrystallization (CHCl₃/pentane) to give the title compound 16c (343 mg, 58%) as a white solid: mp 133–135 °C; ν_max (film) 3402, 2928, 1678, 1605, 1501, 1362, 1339, 1254, 1161, and 1115 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.94 (2 H, d, J = 8.2 Hz, Ar), 7.33 (2 H, d, J = 8.2 Hz, Ar), 7.32–7.29 (1 H, m, Ar), 7.01–6.96 (1 H, m, Ar), 6.90–6.84 (2 H, m, Ar), 5.22 (1 H, br s, NH), 4.60 (2 H, s, CH₂) and 2.45 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 193.9 (C=O), 147.2 (Ar), 145.1 (Ar), 132.2 (Ar), 131.7 (q, J = 31.9 Hz, ArH), 129.7 (ArH), 129.6 (2 × ArH), 127.9 (2 × ArH), 124.3 (q, J = 272.3 Hz, CF₃), 116.3 (ArH), 114.1 (q, J = 4.1 Hz, ArH), 108.7 (q, J = 4.0 Hz, ArH), 49.7 (CH₂) and 21.8 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₁₆H₁₅F₃NO⁺ 294.1100; found 294.1110.

2-(4-Methoxyphenylamino)-1-(4-tolyl)ethan-1-one (16d)

p-Anisidine (246 mg, 2.0 mmol, 1.0 equiv) and 2-bromo-4′-methylacetophenone (426 mg, 2.0 mmol, 1.0 equiv) were treated with sodium hydrogen carbonate (168 mg, 2.0 mmol, 1.0 equiv) in ethanol (5 mL) and water (5 mL) according to General Procedure 2 for 24 h, and then the crude product was purified by recrystallization (CHCl₃/pentane) to give the title compound 16d (454 mg, 89%) as a yellow solid: mp 97–100 °C (lit. 102–103 °C);⁴³ ν_max (film) 3395, 3007, 2930, 2832, 1675, 1607, 1515, 1236, 1182, and 1037 cm^–1; ¹H NMR (400 MHz, 22.4 °C, CDCl₃) δ 7.91 (2 H, d, J = 8.2 Hz, Ar), 7.31 (2 H, d, J = 8.2 Hz, Ar), 6.83 (2 H, d, J = 8.9 Hz, Ar), 6.68 (2 H, d, J = 8.9 Hz, Ar), 4.55 (2 H, s, CH₂), 3.76 (3 H, s, OCH₃) and 2.44 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 23.0 °C, CDCl₃) δ 195.0 (C=O), 152.3 (Ar), 144.7 (Ar), 141.6 (Ar), 132.5 (Ar), 129.5 (2 × ArH), 127.8 (2 × ArH), 115.0 (2 × ArH), 114.2 (2 × ArH), 55.8 (OCH₃), 51.1 (CH₂) and 21.7 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₁₆H₁₈NO₂⁺ 256.1332; found 256.1330.

1-(4-Tolyl)-2-(2,4,6-trimethylphenylamino)ethan-1-one (16e)

2,4,6-Trimethylaniline (271 mg, 2.0 mmol, 1.0 equiv) and 2-bromo-4′-methylacetophenone (426 mg, 2.0 mmol, 1.0 equiv) were treated with sodium hydrogen carbonate (168 mg, 2.0 mmol, 1.0 equiv) in ethanol (5 mL) and water (5 mL) according to General Procedure 2 for 16 h, and then the crude product was purified by recrystallization (CHCl₃/pentane) to give the title compound 16e (397 mg, 74%) as an off white solid: mp 123 °C dec; ν_max (film) 3028, 2974, 2924, 2870, 1686, 1609, and 1069 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.84 (2 H, d, J = 7.8 Hz, Ar), 7.27 (2 H, d, J = 7.8 Hz, Ar), 6.84 (2 H, s, Ar), 4.54 (1 H, br s, NH), 4.48 (2 H, s, CH₂), 2.42 (3 H, s, CH₃), 2.35 (6 H, s, 2 × CH₃) and 2.24 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 196.4 (C=O), 144.6 (Ar), 143.9 (Ar), 132.5 (Ar), 131.1 (Ar), 129.5 (2 × ArH), 129.4 (2 × ArH), 129.0 (2 × Ar), 127.7 (2 × ArH), 55.3 (CH₂), 21.7 (CH₃), 20.5 (CH₃) and 18.7 (2 × CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₁₈H₂₂NO⁺ 268.1696; found 268.1696.

2-(Naphth-2-ylamino)-1-(4-tolyl)ethan-1-one (16f)

2-Naphthylamine (285 mg, 2.0 mmol, 1.0 equiv) and 2-bromo-4′-methylacetophenone (426 mg, 2.0 mmol, 1.0 equiv) were treated with sodium hydrogen carbonate (202 mg, 2.4 mmol, 1.2 equiv) in ethanol (5 mL) and water (5 mL) according to General Procedure 2 for 16 h, and then the crude product was purified by recrystallization (CHCl₃/pentane) to give the title compound 16f (422 mg, 77%) as a gray solid: mp 120–125 °C; ν_max (film) 3418, 3051, 2920, 1686, 1582, 1523, 1408, and 1235 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 8.09–8.04 (1 H, m, naphthyl CH), 7.99 (2 H, d, J = 8.1 Hz, Ar), 7.84–7.79 (1 H, m, naphthyl CH), 7.54–7.46 (2 H, m, naphthyl CH), 7.38 (1 H, dd, J = 8.2, 7.5 Hz, naphthyl CH), 7.34 (2 H, d, J = 8.1 Hz, Ar), 7.29–7.26 (1 H, m, naphthyl CH), 6.61 (1 H, dd, J = 7.5, 1.1 Hz, naphthyl CH), 5.83 (1 H, br s, NH), 4.73 (2 H, s, CH₂) and 2.46 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 194.6 (C=O), 145.0 (naphthyl C), 142.4 (Ar), 134.4 (naphthyl C), 132.5 (naphthyl C), 129.7 (2 × ArH), 128.6 (naphthyl CH), 128.0 (2 × ArH), 126.5 (naphthyl CH), 126.0 (naphthyl CH), 124.9 (naphthyl CH), 123.4 (Ar), 120.3 (naphthyl CH), 117.7 (naphthyl CH), 104.4 (naphthyl CH), 50.2 (CH₂) and 21.8 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₁₉H₁₈NO⁺ 276.1383; found 276.1389.

1-(4-Tolyl)-2-(4-tolylamino)propan-1-one (16g)

NaH (60% suspension in mineral oil, 50 mg, 1.25 mmol, 1.1 equiv) was suspended in DMF (10 mL) and cooled to 0 °C (ice bath), and 1-(4-tolyl)-2-(4-tolylamino)ethan-1-one 16a (338 mg, 1.14 mmol, 1.0 equiv) was added in three portions. The reaction was stirred for 30 min and then MeI (92 μL, 1.48 mmol, 1.3 equiv) was added, and the reaction stirred for a further 3 h. Water was added, and the aqueous phase was extracted with Et₂O (3 × 15 mL). The combined organic layers were washed with water, brine, dried over MgSO₄, filtered, and concentrated in vacuo. Purification by flash column chromatography (SiO₂, gradient of 5–20% EtOAc in petroleum ether) gave the title compound as an orange oil (250 mg, 87%). Recorded data are consistent with previous values:⁴⁵ ν_max (film) 3387, 2982, 2920, 1682, 1609, and 1520 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.92 (2 H, d, J = 8.3 Hz, Ar), 7.30 (2 H, d, J = 7.9 Hz, Ar), 6.98 (2 H, d, J = 7.9 Hz, Ar), 6.60 (2 H, d, J = 8.3 Hz, Ar), 5.08 (1 H, q, J = 6.9 Hz, CH), 2.43 (3 H, s, CH₃), 2.23 (3 H, s, CH₃) and 1.46 (3 H, d, J = 6.9 Hz, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 200.5 (C=O), 144.5 (Ar), 144.3 (Ar), 132.2 (Ar), 129.8 (2 × ArH), 129.5 (2 × ArH), 128.6 (2 × ArH), 127.1 (Ar), 113.7 (2 × ArH), 53.6 (CH), 21.7 (CH₃), 20.4 (CH₃) and 19.7 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₁₇H₂₀NO⁺ 254.1539; found 254.1542.

1-(Naphth-2-yl)-2-(4-tolylamino)ethan-1-one (16h)

p-Toluidine (429 mg, 4.0 mmol, 1.0 equiv) and 2-bromo-1-(naphthalen-2-yl)ethan-1-one (996 mg, 4.0 mmol, 1.0 equiv) were treated with sodium hydrogen carbonate (336 mg, 4.0 mmol, 1.0 equiv) in ethanol (10 mL) and water (10 mL) according to General Procedure 2 for 2 h, and then the crude product was purified by recrystallization (CHCl₃/pentane) to give the title compound 16h (980 mg, 89%) as a yellow solid: mp 130 °C dec; ν_max (film) 3395, 2970, 2924, 2862, 1682, 1620, 1528, 1057, and 1015 cm^–1; ¹H NMR (400 MHz, 22.0 °C, CDCl₃) δ 8.55 (1 H, s, naphthyl CH), 8.07 (1 H, dd, J = 8.6, 1.8 Hz, naphthyl CH), 8.01 (1 H, dd, J = 8.0, 1.3 Hz, naphthyl CH), 7.95 (1 H, d, J = 8.6 Hz, naphthyl CH), 7.91 (1 H, d, J = 8.4 Hz, naphthyl CH), 7.64 (1 H, ddd, J = 8.2, 6.9, 1.5 Hz, naphthyl CH), 7.59 (1 H, ddd, J = 8.2, 6.9, 1.5 Hz, naphthyl CH), 7.07 (2 H, d, J = 8.6 Hz, Ar), 6.72 (2 H, d, J = 8.4 Hz, Ar), 5.05 (1 H, br s, NH), 4.76 (2 H, s, CH₂) and 2.27 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 22.7 °C, CDCl₃) δ 195.2 (C=O), 144.8 (naphthyl C), 135.9 (Ar), 132.5 (naphthyl C), 132.3 (naphthyl C), 129.9 (2 × ArH), 129.6 (naphthyl CH), 129.4 (naphthyl CH), 128.8 (naphthyl CH), 128.8 (naphthyl CH), 127.9 (naphthyl CH), 127.2 (Ar), 127.1 (naphthyl CH), 123.4 (naphthyl CH), 113.3 (2 × ArH), 50.9 (CH₂) and 20.4 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₁₉H₁₈NO⁺ 276.1383; found 276.1391.

1-(4-Methoxyphenyl)-2-(4-tolylamino)ethan-1-one (16i)

p-Toluidine (429 mg, 4.0 mmol, 1.0 equiv) and 2-bromo-4′-methoxyacetophenone (916 mg, 4.0 mmol, 1.0 equiv) were treated with sodium hydrogen carbonate (336 mg, 4.0 mmol, 1.0 equiv) in ethanol (10 mL) and water (10 mL) according to General Procedure 2 for 2 h to give the title compound 16i (888 mg, 87%) as a brown solid: mp 111–114 °C; ν_max (film) 3402, 3001, 2920, 2843, 1674, 1601, 1512, 1258, 1177, and 1034 cm^–1; ¹H NMR (400 MHz, 22.3 °C, CDCl₃) δ 8.00 (2 H, d, J = 8.9 Hz, Ar), 7.04 (2 H, d, J = 8.3 Hz, Ar), 6.98 (2 H, d, J = 8.9 Hz, Ar), 6.66 (2 H, d, J = 8.3 Hz, Ar), 5.00 (1 H, br s, NH), 4.56 (2 H, s, CH₂), 3.90 (3 H, s, OCH₃) and 2.26 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 23.0 °C, CDCl₃) δ 193.6 (C=O), 164.0 (Ar), 144.9 (Ar), 130.1 (2 × ArH), 129.9 (2 × ArH), 128.0 (Ar), 127.1 (Ar), 114.0 (2 × ArH), 113.3 (2 × ArH), 55.5 (OCH₃), 50.4 (CH₂) and 20.4 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₁₆H₁₈NO₂⁺ 256.1332; found 256.1333.

1-(4-Nitrophenyl)-2-(4-tolylamino)ethan-1-one (16j)

p-Toluidine (429 mg, 4.0 mmol, 1.0 equiv) and 2-bromo-4′-nitroacetophenone (976 mg, 4.0 mmol, 1.0 equiv) were treated with sodium hydrogen carbonate (336 mg, 4.0 mmol, 1.0 equiv) in ethanol (10 mL) and water (10 mL) according to General Procedure 2 for 2 h, and then the crude product was purified by recrystallization (CHCl₃/pentane) to give the title compound 16j (971 mg, 90%) as a red solid: mp 127 °C dec (lit. 147–150 °C);⁴⁶ ν_max (film) 3032, 2924, 2866, 1678, 1601, 1524, and 1346 cm^–1; ¹H NMR (400 MHz, 22.2 °C, CDCl₃) δ 8.37 (2 H, d, J = 8.8 Hz, Ar), 8.18 (2 H, d, J = 8.8 Hz, Ar), 7.05 (2 H, d, J = 8.4 Hz, Ar), 6.65 (2 H, d, J = 8.4 Hz, Ar), 4.74 (1 H, br s, NH), 4.66 (2 H, s, CH₂) and 2.26 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 23.0 °C, CDCl₃) δ 194.1 (C=O), 150.7 (Ar), 144.4 (Ar), 139.4 (Ar), 130.0 (2 × ArH), 128.9 (2 × ArH), 127.6 (Ar), 124.1 (2 × ArH), 113.2 (2 × ArH), 51.4 (CH₂) and 20.4 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₁₅H₁₅N₂O₃⁺ 271.1077; found 271.1084.

1-(4-Cyanophenyl)-2-(4-tolylamino)ethan-1-one (16k)

p-Toluidine (429 mg, 4.0 mmol, 1.0 equiv) and 2-bromo-4′-cyanoacetophenone (896 mg, 4.0 mmol, 1.0 equiv) were treated with sodium hydrogen carbonate (336 mg, 4.0 mmol, 1.0 equiv) in ethanol (10 mL) and water (10 mL) according to General Procedure 2 for 2 h to give the title compound 16k (921 mg, 92%) as an orange solid: mp 126 °C dec; ν_max (film) 3322, 2924, 2866, 2230, 1678, 1605, 1516, 1404, and 1277 cm^–1; ¹H NMR (400 MHz, 22.1 °C, CDCl₃) δ 8.11 (2 H, d, J = 8.5 Hz, Ar), 7.83 (2 H, d, J = 8.5 Hz, Ar), 7.04 (2 H, d, J = 8.4 Hz, Ar), 6.64 (2 H, d, J = 8.4 Hz, Ar), 4.62 (2 H, s, CH₂) and 2.26 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 23.0 °C, CDCl₃) δ 194.3 (C=O), 144.4 (Ar), 137.9 (Ar), 132.7 (2 × ArH), 129.9 (2 × ArH), 128.2 (2 × ArH), 127.5 (Ar), 117.7 (Ar), 117.1 (C≡N), 113.2 (2 × ArH), 51.2 (CH₂) and 20.4 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₁₆H₁₅N₂O⁺ 251.1179; found 251.1178.

1-(4-Chlorophenyl)-2-(4-tolylamino)ethan-1-one (16l)

p-Toluidine (429 mg, 4.0 mmol, 1.0 equiv) and 2-bromo-4′-chloroacetophenone (934 mg, 4.0 mmol, 1.0 equiv) were treated with sodium hydrogen carbonate (336 mg, 4.0 mmol, 1.0 equiv) in ethanol (10 mL) and water (10 mL) according to General Procedure 2 for 2 h, and then the crude product was purified by recrystallization (CHCl₃/pentane) to give the title compound 16l (866 mg, 83%) as a yellow solid: mp 127–130 °C (lit. 150–152 °C);⁴⁴ ν_max (film) 3391, 2916, 2859, 1682, 1589, and 1524 cm^–1; ¹H NMR (400 MHz, 22.4 °C, CDCl₃) δ 7.96 (2 H, d, J = 8.6 Hz, Ar), 7.49 (2 H, d, J = 8.6 Hz, Ar), 7.04 (2 H, d, J = 8.4 Hz, Ar), 6.64 (2 H, d, J = 8.4 Hz, Ar), 4.76 (1 H, br s, NH), 4.58 (2 H, s, CH₂) and 2.26 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 22.8 °C, CDCl₃) δ 194.2 (C=O), 144.7 (Ar), 140.3 (Ar), 133.3 (Ar), 129.9 (2 × ArH), 129.2 (2 × ArH), 129.2 (2 × ArH), 127.2 (Ar), 113.2 (2 × ArH), 50.7 (CH₂) and 20.4 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₁₅H₁₅ClNO⁺ 260.0837; found 260.0834.

1-Cyclopropyl-2-(4-tolylamino)ethan-1-one (16u)

p-Toluidine (429 mg, 4.0 mmol, 1.0 equiv) and 2-bromo-1-cyclopropylethanone (652 mg, 4.0 mmol, 1.0 equiv) were treated with sodium hydrogen carbonate (336 mg, 4.0 mmol, 1.0 equiv) in ethanol (10 mL) and water (10 mL) according to General Procedure 2 for 16 h to give the title compound 16u (562 mg, 74%) as a brown solid: mp 75–78 °C; ν_max (film) 3395, 3013, 2920, 2859, 1694, 1616, 1524, 1393, and 1069 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.01 (2 H, d, J = 8.5 Hz, Ar), 6.54 (2 H, d, J = 8.5 Hz, Ar), 4.52 (1 H, br s, NH), 4.15 (2 H, s, CH₂), 2.24 (3 H, s, CH₃), 2.01 (1 H, tt, J = 7.8, 4.6 Hz, cyclopropane CH), 1.16–1.12 (2 H, m, cyclopropane CH₂) and 1.01–0.95 (2 H, m, cyclopropane CH₂); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 206.5 (C=O), 144.8 (Ar), 129.8 (2 × ArH), 126.9 (Ar), 113.0 (2 × ArH), 54.5 (CH₂), 20.4 (CH₃), 18.8 (cyclopropane CH) and 11.3 (2 × cyclopropane CH₂); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₁₂H₁₆NO⁺ 190.1226; found 190.1230.

1-(2-Tolyl)-2-(4-tolylamino)ethan-1-one (16v)

p-Toluidine (429 mg, 4.0 mmol, 1.0 equiv) and 2-bromo-2′-methylacetophenone (852 mg, 4.0 mmol, 1.0 equiv) were treated with sodium hydrogen carbonate (336 mg, 4.0 mmol, 1.0 equiv) in ethanol (10 mL) and water (10 mL) according to General Procedure 2 for 16 h, and then the crude product was purified by recrystallization (CHCl₃/pentane) to give the title compound 16v (421 mg, 44%) as an orange solid: mp 124–127 °C; ν_max (film) 3387, 2924, 2851, 1690, 1620, and 1524 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.74–7.71 (1 H, m, Ar), 7.46–7.42 (1 H, m, Ar), 7.34–7.29 (2 H, m, Ar), 7.03 (2 H, d, J = 8.3 Hz, Ar), 6.62 (2 H, d, J = 8.3 Hz, Ar), 4.48 (2 H, s, CH₂), 2.55 (3 H, s, CH₃) and 2.25 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 198.8 (C=O), 144.9 (Ar), 138.9 (Ar), 135.4 (Ar), 132.3 (ArH), 132.1 (ArH), 129.9 (2 × ArH), 128.1 (ArH), 127.0 (Ar), 125.9 (ArH), 113.2 (2 × ArH), 52.6 (CH₂), 21.4 (CH₃) and 20.4 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₁₆H₁₈NO⁺ 240.1383; found 240.1388.

General Procedure 3: Rh(II)-Catalyzed N–H Bond Insertion

Under argon, Rh₂(OAc)₄ (5 mol %) was added to a solution of α-aminoketone 16 (1.1 equiv) and triazole 4 (1.0 equiv) in toluene (0.03 M) in a flame-dried vial with freshly dried 4 Å molecular sieves. The vial was sealed with a Teflon cap and stirred at 80 °C (heating block) until complete (TLC, 2–4 h). The reaction mixture was concentrated in vacuo and purified by flash column chromatography (SiO₂, gradient from 10–30% EtOAc in petroleum ether) to give the 1,2-diamine product 17.

1-[(2-Oxo-2-(4-tolyl)ethyl)(4-tolyl)amino]-1-(4-tolyl)-2-(tosylamino)ethene (17a)

Triazole 4a (94 mg, 0.30 mmol, 1.0 equiv) and α-aminoketone 16a (79 mg, 0.33 mmol, 1.1 equiv) were treated with Rh₂(OAc)₄ (7 mg, 0.02 mmol, 5 mol %) in PhMe (10 mL) according to General Procedure 3 to give the title compound 17a (139 mg, 88%) as a yellow solid: mp 61–69 °C; ν_max (film) 3250, 3032, 2924, 1690, 1609, 1512, and 1161 cm^–1; ¹H NMR (400 MHz, 22.4 °C, CDCl₃) δ 9.36 (1 H, d, J = 10.6 Hz, NH), 7.87 (2 H, d, J = 8.3 Hz, Ar), 7.65 (2 H, d, J = 8.3 Hz, Ar), 7.30 (2 H, d, J = 8.0 Hz, Ar), 7.17 (2 H, d, J = 8.3 Hz, Ar), 7.12 (2 H, d, J = 8.3 Hz, Ar), 7.10 (2 H, d, J = 8.3 Hz, Ar), 6.92 (1 H, d, J = 10.6 Hz, =CH), 6.75 (2 H, d, J = 8.6 Hz, Ar), 6.30 (2 H, d, J = 8.6 Hz, Ar), 4.66 (2 H, br s, CH₂), 2.45 (3 H, s, CH₃), 2.34 (3 H, s, CH₃), 2.33 (3 H, s, CH₃) and 2.20 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 23.2 °C, CDCl₃) δ 197.2 (C=O), 145.3 (Ar), 143.3 (Ar), 143.0 (Ar), 137.9 (Ar), 137.4 (Ar), 132.7 (Ar), 131.8 (Ar), 129.7 (2 × ArH), 129.6 (2 × ArH), 129.5 (2 × ArH), 129.4 (2 × ArH), 128.3 (2 × ArH), 127.1 (Ar), 126.6 (2 × ArH), 125.9 (=C), 124.9 (2 × ArH), 121.8 (=CH), 112.2 (2 × ArH), 56.5 (CH₂), 21.8 (CH₃), 21.4 (CH₃), 21.1 (CH₃) and 20.3 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₂H₃₃N₂O₃S⁺ 525.2206; found 525.2204.

1-[(4-Chlorophenyl)(2-oxo-2-(4-tolyl)ethyl)amino]-1-(4-tolyl)-2-(tosylamino)ethene (17b)

Triazole 4a (94 mg, 0.30 mmol, 1.0 equiv) and α-aminoketone 16b (86 mg, 0.33 mmol, 1.1 equiv) were treated with Rh₂(OAc)₄ (7 mg, 0.02 mmol, 5 mol %) in PhMe (10 mL) according to General Procedure 3 to give the title compound 17b (147 mg, 90%) as a yellow solid: mp 72 °C dec; ν_max (film) 3264, 3063, 2924, 1686, 1605, 1493, 1339, 1289, 1161, and 1092 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 9.40 (1 H, d, J = 10.6 Hz, NH), 7.89 (2 H, d, J = 8.2 Hz, COTol), 7.64 (2 H, d, J = 8.3 Hz, SO₂Tol), 7.32 (2 H, d, J = 7.9 Hz, Tol), 7.18–7.12 (6 H, m, Ar), 6.94 (1 H, d, J = 10.6 Hz, =CH), 6.84 (2 H, d, J = 9.1 Hz, NTol), 6.30 (2 H, d, J = 9.1 Hz, NTol), 4.68 (2 H, br s, CH₂), 2.47 (3 H, s, CH₃), 2.40 (3 H, s, CH₃) and 2.36 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 196.8 (C=O), 145.7 (Ar), 144.5 (Ar), 143.4 (Ar), 138.1 (Ar), 137.8 (Ar), 132.2 (Ar), 131.6 (Ar), 129.7 (2 × ArH), 129.6 (2 × ArH), 129.5 (2 × ArH), 128.9 (2 × ArH), 128.4 (2 × ArH), 126.5 (2 × ArH), 125.5 (=C), 124.8 (2 × ArH), 123.0 (Ar), 122.1 (=CH), 113.5 (2 × ArH), 56.4 (OCH₃), 21.8 (CH₃), 21.5 (CH₃) and 21.1 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₁H₃₀ClN₂O₃S⁺ 545.1660; found 545.1655.

1-[(2-Oxo-2-(4-tolyl)ethyl)(3-trifluoromethylphenyl)amino]-1-(4-tolyl)-2-(tosylamino)ethene (17c)

Triazole 4a (94 mg, 0.30 mmol, 1.0 equiv) and α-aminoketone 16c (97 mg, 0.33 mmol, 1.1 equiv) were treated with Rh₂(OAc)₄ (7 mg, 0.02 mmol, 5 mol %) in PhMe (10 mL) according to General Procedure 3 to give the title compound 17c (142 mg, 82%) as a white solid: mp 110 °C dec; ν_max (film) 3136, 3032, 2928, 1678, 1609, 1335, and 1165 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 9.40 (1 H, d, J = 10.6 Hz, NH), 7.86 (2 H, d, J = 8.3 Hz, Ar), 7.65 (2 H, d, J = 8.3 Hz, Ar), 7.31 (2 H, d, J = 7.9 Hz, Ar), 7.15–7.10 (6 H, m, Ar), 7.06 (1 H, dd, J = 8.1, 7.9 Hz, Ar), 6.97 (1 H, d, J = 10.6 Hz, =CH), 6.94 (1 H, d, J = 7.9 Hz, Ar), 6.64–6.60 (1 H, m, Ar), 6.57 (1 H, dd, J = 8.1, 2.6 Hz, Ar), 4.71 (2 H, br s, CH₂), 2.45 (3 H, s, CH₃), 2.34 (3 H, s, CH₃) and 2.32 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 196.6 (C=O), 146.2 (Ar), 145.8 (Ar), 143.4 (Ar), 137.8 (Ar), 137.7 (Ar), 131.8 (Ar), 131.8 (q, J = 33.3 Hz, Ar), 131.5 (Ar), 129.8 (ArH), 129.8 (2 × ArH), 129.7 (2 × ArH), 129.6 (2 × ArH), 128.4 (2 × ArH), 126.6 (2 × ArH), 124.7 (2 × ArH), 124.5 (=C), 122.5 (=CH), 115.5 (ArH), 114.9 (q, J = 4.1 Hz, ArH), 108.5 (q, J = 2.4 Hz, ArH), 56.5 (CH₂), 21.9 (CH₃), 21.4 (CH₃) and 21.1 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₂H₃₀F₃N₂O₃S⁺ 579.1924; found 579.1928.

1-[(4-Methoxyphenyl)(2-oxo-2-(4-tolyl)ethyl)amino]-1-(4-tolyl)-2-(tosylamino)ethene (17d)

Triazole 4a (94 mg, 0.30 mmol, 1.0 equiv) and α-aminoketone 16d (84 mg, 0.33 mmol, 1.1 equiv) were treated with Rh₂(OAc)₄ (7 mg, 0.02 mmol, 5 mol %) in PhMe (10 mL) according to General Procedure 3 to give the title compound 17d (144 mg, 89%) as a yellow solid: mp 45–50 °C; ν_max (film) 3252, 2924, 2855, 1690, 1609, 1512, 1250, 1161, and 1034 cm^–1; ¹H NMR (500 MHz, 25.1 °C, CDCl₃) δ 9.32 (1 H, d, J = 10.6 Hz, NH), 7.86 (2 H, d, J = 8.3 Hz, COTol), 7.63 (2 H, d, J = 8.3 Hz, SO₂Tol), 7.28 (2 H, d, J = 8.0 Hz, COTol), 7.16 (2 H, d, J = 8.3 Hz, Tol), 7.11 (2 H, d, J = 8.3 Hz, SO₂Tol), 7.10 (2 H, d, J = 8.0 Hz, Tol), 6.88 (1 H, d, J = 10.6 Hz, =CH), 6.53 (2 H, d, J = 9.1 Hz, NC₆H₄OMe), 6.32 (2 H, d, J = 9.1 Hz, NC₆H₄OMe), 4.63 (2 H, br s, CH₂), 3.70 (3 H, s, OCH₃), 2.44 (3 H, s, COTol), 2.33 (3 H, s, CH₃) and 2.33 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 197.4 (C=O), 152.4 (Ar), 145.4 (Ar), 143.1 (Ar), 139.9 (Ar), 138.0 (Ar), 137.5 (Ar), 132.8 (Ar), 131.9 (Ar), 129.6 (2 × ArH), 129.6 (2 × ArH), 129.5 (2 × ArH), 128.3 (2 × ArH), 126.7 (2 × ArH), 126.2 (=C), 124.9 (2 × ArH), 121.8 (=CH), 114.7 (2 × ArH), 113.3 (2 × ArH), 56.8 (CH₂), 55.6 (OCH₃), 21.8 (CH₃), 21.5 (CH₃) and 21.1 (CH₃); HRMS (ESI-TOF) m/z [M – H]⁻ calcd for C₃₂H₃₁N₂O₄S^– 539.2010; found 539.2017.

1-[(1-Oxo-1-(4-tolyl)prop-2-yl)(4-tolyl)amino]-1-(4-tolyl)-2-(tosylamino)ethene (17g)

Triazole 4a (94 mg, 0.30 mmol, 1.0 equiv) and α-aminoketone 16g (84 mg, 0.33 mmol, 1.1 equiv) were treated with Rh₂(OAc)₄ (7 mg, 0.02 mmol, 5 mol %) in PhMe (10 mL) according to General Procedure 3 to give the title compound 17g (142 mg, 88%) as a yellow solid: mp 65 °C dec; ν_max (film) 3094, 3028, 2924, 1674, 1605, 1512, 1343, 1289, 1235, and 1157 cm^–1; ¹H NMR (500 MHz, 25.0 °C, CDCl₃) δ 10.51 (1 H, d, J = 10.8 Hz, NH), 8.09 (2 H, d, J = 8.2 Hz, COTol), 7.72 (2 H, d, J = 8.3 Hz, SO₂Tol), 7.37 (2 H, d, J = 8.2 Hz, COTol), 7.31 (1 H, d, J = 10.8 Hz, =CH), 7.15 (2 H, d, J = 8.3 Hz, SO₂Tol), 7.11 (2 H, d, J = 8.1 Hz, Tol), 7.04 (2 H, d, J = 8.1 Hz, Tol), 6.70 (2 H, d, J = 8.7 Hz, NTol), 6.25 (2 H, d, J = 8.7 Hz, NTol), 5.48 (1 H, q, J = 7.4 Hz, CH), 2.49 (3 H, s, COTol), 2.35 (3 H, s, SO₂Tol), 2.28 (3 H, s, Tol), 2.13 (3 H, s, NTol) and 1.11 (3 H, d, J = 7.4 Hz, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 203.3 (C=O), 145.5 (Ar), 143.2 (Ar), 143.0 (Ar), 138.1 (Ar), 136.6 (Ar), 134.6 (Ar), 131.4 (Ar), 129.9 (2 × ArH), 129.7 (2 × ArH), 129.5 (2 × ArH), 129.5 (2 × ArH), 128.7 (2 × ArH), 126.9 (Ar), 126.7 (2 × ArH), 125.5 (=CH), 123.9 (2 × ArH), 121.2 (=C), 112.3 (2 × ArH), 57.7 (CH), 21.8 (CH₃), 21.5 (CH₃), 21.0 (CH₃), 20.2 (CH₃) and 16.0 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₃H₃₅N₂O₃S⁺ 539.2363; found 539.2368.

1-[(2-(Naphth-2-yl)-2-oxoethyl)(4-tolyl)amino]-1-(4-tolyl)-2-(tosylamino)ethene (17h)

Triazole 4a (94 mg, 0.30 mmol, 1.0 equiv) and α-aminoketone 16h (91 mg, 0.33 mmol, 1.1 equiv) were treated with Rh₂(OAc)₄ (7 mg, 0.02 mmol, 5 mol %) in PhMe (10 mL) according to General Procedure 3 to give the title compound 17h (159 mg, 95%) as a yellow solid: mp 58 °C dec; ν_max (film) 3240, 3032, 2920, 2862, 1678, 1512, 1161, and 1092 cm^–1; ¹H NMR (400 MHz, 25.4 °C, CDCl₃) δ 9.31 (1 H, d, J = 10.7 Hz, NH), 8.46 (1 H, s, naphthyl CH), 8.02 (1 H, dd, J = 8.6, 1.7 Hz, naphthyl CH), 7.95 (1 H, d, J = 7.5 Hz, naphthyl CH), 7.94 (1 H, d, J = 8.7 Hz, naphthyl CH), 7.91 (1 H, d, J = 8.0 Hz, naphthyl CH), 7.66 (2 H, d, J = 8.3 Hz, Ar), 7.65–7.63 (1 H, m, naphthyl CH), 7.59 (1 H, ddd, J = 8.1, 6.9, 1.3 Hz, naphthyl CH), 7.21 (2 H, d, J = 8.3 Hz, Ar), 7.13 (2 H, d, J = 8.1 Hz, Ar), 7.08 (2 H, d, J = 8.1 Hz, Ar), 6.94 (1 H, d, J = 10.7 Hz, =CH), 6.77 (2 H, d, J = 7.9 Hz, Ar), 6.34 (2 H, d, J = 8.7 Hz, Ar), 4.81 (2 H, br s, CH₂), 2.34 (3 H, s, CH₃), 2.26 (3 H, s, CH₃) and 2.20 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 24.8 °C, CDCl₃) δ 197.6 (C=O), 143.3 (Ar), 143.1 (naphthyl C), 138.0 (Ar), 137.5 (naphthyl C), 136.1 (naphthyl C), 132.8 (Ar), 132.3 (Ar), 131.7 (Ar), 130.0 (naphthyl CH), 129.7 (2 × ArH), 129.6 (2 × ArH), 129.6 (naphthyl CH), 129.4 (2 × ArH), 129.1 (naphthyl CH), 128.8 (naphthyl CH), 127.9 (naphthyl CH), 127.3 (Ar), 127.2 (naphthyl CH), 126.7 (2 × ArH), 125.9 (=C), 125.0 (2 × ArH), 123.6 (naphthyl CH), 122.0 (=CH), 112.3 (2 × ArH), 56.8 (CH₂), 21.4 (CH₃), 21.1 (CH₃) and 20.3 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₅H₃₃N₂O₃S⁺ 561.2206; found 561.2208.

1-[(2-(4-Methoxyphenyl)-2-oxoethyl)(4-tolyl)amino]-1-(4-tolyl)-2-(tosylamino)ethene (17i)

Triazole 4a (94 mg, 0.30 mmol, 1.0 equiv) and α-aminoketone 16i (84 mg, 0.33 mmol, 1.1 equiv) were treated with Rh₂(OAc)₄ (7 mg, 0.02 mmol, 5 mol %) in PhMe (10 mL) according to General Procedure 3 to give the title compound 17i (123 mg, 76%) as a brown solid: mp 69–74 °C; ν_max (film) 3225, 3028, 2920, 2859, 1674, 1597, 1512, 1339, 1265, 1234, 1161, and 1092 cm^–1; ¹H NMR (400 MHz, 25.4 °C, CDCl₃) δ 9.45 (1 H, d, J = 10.6 Hz, NH), 7.95 (2 H, d, J = 8.9 Hz, Ar), 7.63 (2 H, d, J = 8.3 Hz, Ar), 7.16 (2 H, d, J = 8.3 Hz, Ar), 7.12 (2 H, d, J = 8.0 Hz, Ar), 7.10 (2 H, d, J = 8.6 Hz, Ar), 6.95 (2 H, d, J = 8.9 Hz, Ar), 6.90 (1 H, d, J = 10.6 Hz, =CH), 6.74 (2 H, d, J = 8.0 Hz, Ar), 6.29 (2 H, d, J = 8.6 Hz, Ar), 4.62 (2 H, br s, CH₂), 3.89 (3 H, s, OCH₃), 2.34 (3 H, s, CH₃), 2.32 (3 H, s, CH₃) and 2.19 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.1 °C, CDCl₃) δ 196.0 (C=O), 164.4 (Ar), 143.4 (Ar), 143.0 (Ar), 138.1 (Ar), 137.4 (Ar), 132.8 (Ar), 130.6 (2 × ArH), 129.7 (2 × ArH), 129.6 (2 × ArH), 129.4 (2 × ArH), 127.4 (Ar), 127.1 (Ar), 126.7 (2 × ArH), 125.9 (=C), 124.9 (2 × ArH), 121.9 (=CH), 114.0 (2 × ArH), 112.2 (2 × ArH), 56.3 (CH₂), 55.6 (OCH₃), 21.5 (CH₃), 21.1 (CH₃) and 20.3 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₂H₃₃N₂O₄S⁺ 541.2156; found 541.2158.

1-[(2-(4-Nitrophenyl)-2-oxoethyl)(4-tolyl)amino]-1-(4-tolyl)-2-(tosylamino)ethene (17j)

Triazole 4a (94 mg, 0.30 mmol, 1.0 equiv) and α-aminoketone 16j (89 mg, 0.33 mmol, 1.1 equiv) were treated with Rh₂(OAc)₄ (7 mg, 0.02 mmol, 5 mol %) in PhMe (10 mL) according to General Procedure 3 to give the title compound 17j (70 mg, 42%) as a pink solid. Under the reaction conditions, there was also some cyclodehydration to the corresponding pyrrole 18j (80 mg, 50%): mp 115 °C dec; ν_max (film) 3183, 2924, 2856, 1694, 1516, 1343, 1215, 1161, and 1092 cm^–1; ¹H NMR (400 MHz, 24.9 °C, CDCl₃) δ 8.78 (1 H, d, J = 10.8 Hz, NH), 8.34 (2 H, d, J = 8.8 Hz, Ar), 8.11 (2 H, d, J = 8.8 Hz, Ar), 7.64 (2 H, d, J = 8.4 Hz, Ar), 7.17 (2 H, d, J = 8.4 Hz, Ar), 7.15 (2 H, d, J = 8.0 Hz, Ar), 7.11 (2 H, d, J = 8.6 Hz, Ar), 6.88 (1 H, d, J = 10.8 Hz, =CH), 6.76 (2 H, d, J = 8.0 Hz, Ar), 6.28 (2 H, d, J = 8.6 Hz, Ar), 4.71 (2 H, s, CH₂), 2.37 (3 H, s, CH₃), 2.33 (3 H, s, CH₃) and 2.21 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 196.5 (C=O), 150.9 (Ar), 143.3 (Ar), 143.0 (Ar), 138.7 (Ar), 137.9 (Ar), 137.8 (Ar), 132.4 (Ar), 129.8 (2 × ArH), 129.7 (2 × ArH), 129.5 (2 × ArH), 129.3 (2 × ArH), 127.8 (Ar), 126.7 (2 × ArH), 125.4 (=C), 125.0 (2 × ArH), 124.1 (2 × ArH), 121.6 (=CH), 112.3 (2 × ArH), 57.0 (CH₂), 21.5 (CH₃), 21.1 (CH₃) and 20.3 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₁H₃₀N₃O₅S⁺ 556.1901; found 556.1883.

1-[(2-(4-Cyanophenyl)-2-oxoethyl)(4-tolyl)amino]-1-(4-tolyl)-2-(tosylamino)ethene (17k)

Triazole 4a (94 mg, 0.30 mmol, 1.0 equiv) and α-aminoketone 16k (83 mg, 0.33 mmol, 1.1 equiv) were treated with Rh₂(OAc)₄ (7 mg, 0.02 mmol, 5 mol %) in PhMe (10 mL) according to General Procedure 3 to give the title compound 17k (65 mg, 40%) as a yellow solid. Under the reaction conditions, there was also some cyclodehydration to the corresponding pyrrole 18k (78 mg, 50%): mp 113 °C dec; ν_max (film) 3245, 3028, 2924, 2856, 2230, 1690, 1512, 1161, and 1092 cm^–1; ¹H NMR (500 MHz, 25.0 °C, CDCl₃) δ 8.81 (1 H, d, J = 10.8 Hz, NH), 8.04 (2 H, d, J = 8.8 Hz, Ar), 7.80 (2 H, d, J = 8.8 Hz, Ar), 7.64 (2 H, d, J = 8.3 Hz, Ar), 7.16 (2 H, d, J = 7.9 Hz, Ar), 7.14 (2 H, d, J = 8.7 Hz, Ar), 7.11 (2 H, d, J = 8.3 Hz, Ar), 6.88 (1 H, d, J = 10.8 Hz, =CH), 6.75 (2 H, d, J = 7.9 Hz, Ar), 6.27 (2 H, d, J = 8.7 Hz, Ar), 4.68 (2 H, s, CH₂), 2.37 (3 H, s, CH₃), 2.33 (3 H, s, CH₃) and 2.20 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 26.0 °C, CDCl₃) δ 196.7 (C=O), 143.2 (Ar), 143.0 (Ar), 137.9 (Ar), 137.7 (Ar), 137.2 (Ar), 132.7 (2 × ArH), 132.4 (Ar), 129.8 (2 × ArH), 129.7 (2 × ArH), 129.5 (2 × ArH), 128.6 (2 × ArH), 127.8 (Ar), 126.7 (2 × ArH), 125.4 (=C), 125.0 (2 × ArH), 121.6 (=CH), 117.6 (Ar), 117.5 (C≡N), 112.3 (2 × ArH), 56.9 (CH₂), 21.5 (CH₃), 21.1 (CH₃) and 20.3 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₂H₃₀N₃O₃S⁺ 536.2002; found 536.2005.

1-[(2-(4-Chlorophenyl)-2-oxoethyl)(4-tolyl)amino]-1-(4-tolyl)-2-(tosylamino)ethene (17l)

Triazole 4a (94 mg, 0.30 mmol, 1.0 equiv) and α-aminoketone 16l (86 mg, 0.33 mmol, 1.1 equiv) were treated with Rh₂(OAc)₄ (7 mg, 0.02 mmol, 5 mol %) in PhMe (10 mL) according to General Procedure 3 to give the title compound 17l (109 mg, 67%) as a yellow solid. Under the reaction conditions, there was also some cyclodehydration to the corresponding pyrrole 18l (50 mg, 32%): mp 63 °C dec; ν_max (film) 3175, 3028, 2920, 1686, 1589, 1512, 1339, 1223, 1161, and 1092 cm^–1; ¹H NMR (400 MHz, 26.0 °C, CDCl₃) δ 9.09 (1 H, d, J = 10.7 Hz, NH), 7.89 (2 H, d, J = 8.6 Hz, Ar), 7.63 (2 H, d, J = 8.3 Hz, Ar), 7.47 (2 H, d, J = 8.6 Hz, Ar), 7.15 (2 H, d, J = 8.3 Hz, Ar), 7.12 (2 H, d, J = 8.6 Hz, Ar), 7.10 (2 H, d, J = 8.6 Hz, Ar), 6.90 (1 H, d, J = 10.7 Hz, =CH), 6.75 (2 H, d, J = 8.7 Hz, Ar), 6.28 (2 H, d, J = 8.7 Hz, Ar), 4.64 (2 H, br s, CH₂), 2.35 (3 H, s, CH₃), 2.33 (3 H, s, CH₃) and 2.20 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 26.0 °C, CDCl₃) δ 196.6 (C=O), 143.2 (Ar), 143.1 (Ar), 140.9 (Ar), 137.9 (Ar), 137.6 (Ar), 132.6 (Ar), 132.6 (Ar), 129.7 (2 × ArH), 129.6 (2 × ArH), 129.6 (2 × ArH), 129.4 (2 × ArH), 129.2 (2 × ArH), 127.5 (Ar), 126.7 (2 × ArH), 125.7 (=C), 124.9 (2 × ArH), 121.8 (=C), 112.2 (2 × ArH), 56.6 (CH₂), 21.5 (CH₃), 21.1 (CH₃) and 20.3 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₁H₃₀ClN₂O₃S⁺ 545.1660; found 545.1659.

1-[(2-Oxo-2-(4-tolyl)ethyl)(4-tolyl)amino]-1-(thiophen-2-yl)-2-(tosylamino)ethene (17m)

Triazole 4m (92 mg, 0.30 mmol, 1.0 equiv) and α-aminoketone 16a (79 mg, 0.33 mmol, 1.1 equiv) were treated with Rh₂(OAc)₄ (7 mg, 0.02 mmol, 5 mol %) in PhMe (10 mL) according to General Procedure 3 to give the title compound 17m (124 mg, 80%) as an orange solid: mp 126 °C dec; ν_max (film) 3148, 3032, 2920, 1678, 1609, 1516, 1339, 1231, 1161, and 1092 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 9.39 (1 H, d, J = 10.7 Hz, NH), 7.88 (2 H, d, J = 8.3 Hz, Ar), 7.64 (2 H, d, J = 8.3 Hz, Ar), 7.31 (2 H, d, J = 8.3 Hz, Ar), 7.12 (1 H, dd, J = 5.1, 1.2 Hz, thiophene CH), 7.10 (2 H, d, J = 8.3 Hz, Ar), 6.92 (1 H, dd, J = 5.1, 3.6 Hz, thiophene CH), 6.90 (1 H, d, J = 10.7 Hz, =CH), 6.84 (1 H, dd, J = 3.6, 1.2 Hz, thiophene CH), 6.77 (2 H, d, J = 8.3 Hz, Ar), 6.31 (2 H, d, J = 8.3 Hz, Ar), 4.71 (2 H, br s, CH₂), 2.45 (3 H, s, CH₃), 2.33 (3 H, s, CH₃) and 2.19 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 197.2 (C=O), 145.5 (Ar), 143.1 (Ar), 142.6 (thiophene C2), 141.0 (Ar), 137.8 (Ar), 131.8 (Ar), 129.7 (2 × ArH), 129.6 (2 × ArH), 129.4 (2 × ArH), 128.3 (2 × ArH), 127.7 (thiophene CH), 127.5 (Ar), 126.7 (2 × ArH), 123.8 (thiophene CH), 122.9 (thiophene CH), 122.0 (=CH), 121.7 (=C), 112.4 (2 × ArH), 56.5 (CH₂), 21.8 (CH₃), 21.5 (CH₃) and 20.3 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₂₉H₂₉N₂O₃S₂⁺ 517.1614; found 517.1617.

1-(4-Methoxyphenyl)-1-[(2-oxo-2-(4-tolyl)ethyl)(4-tolyl)amino]-2-(tosylamino)ethene (17n)

Triazole 4n (99 mg, 0.30 mmol, 1.0 equiv) and α-aminoketone 16a (79 mg, 0.33 mmol, 1.1 equiv) were treated with Rh₂(OAc)₄ (7 mg, 0.02 mmol, 5 mol %) in PhMe (10 mL) according to General Procedure 3 to give the title compound 17n (152 mg, 94%) as an orange solid: mp 66–70 °C; ν_max (film) 3275, 3032, 2924, 1682, 1601, 1512, 1339, 1250, and 1161 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 9.27 (1 H, d, J = 10.6 Hz, NH), 7.86 (2 H, d, J = 8.3 Hz, Ar), 7.64 (2 H, d, J = 8.3 Hz, Ar), 7.28 (2 H, d, J = 8.3 Hz, Ar), 7.19 (2 H, d, J = 8.8 Hz, Ar), 7.11 (2 H, d, J = 8.3 Hz, Ar), 6.82 (2 H, d, J = 8.8 Hz, Ar), 6.81 (1 H, d, J = 10.6 Hz, =CH), 6.74 (2 H, d, J = 8.6 Hz, Ar), 6.29 (2 H, d, J = 8.6 Hz, Ar), 4.63 (2 H, br s, CH₂), 3.79 (3 H, s, CH₃), 2.44 (3 H, s, CH₃), 2.34 (3 H, s, CH₃) and 2.19 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 197.2 (C=O), 159.3 (Ar), 145.3 (Ar), 143.3 (Ar), 143.0 (Ar), 138.0 (Ar), 131.9 (Ar), 129.7 (2 × ArH), 129.5 (2 × ArH), 129.4 (2 × ArH), 128.3 (2 × ArH), 128.1 (Ar), 127.2 (Ar), 126.7 (2 × ArH), 126.3 (2 × ArH), 125.8 (=C), 120.8 (=CH), 114.3 (2 × ArH), 112.3 (2 × ArH), 56.4 (CH₂), 55.4 (OCH₃), 21.8 (CH₃), 21.5 (CH₃) and 20.3 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₂H₃₃N₂O₄S⁺ 541.2156; found 541.2148.

1-(Cyclohexen-1-yl)-1-[(2-oxo-2-(4-tolyl)ethyl)(4-tolyl)amino]-2-(tosylamino)ethene (17o)

Triazole 4o (91 mg, 0.30 mmol, 1.0 equiv) and α-aminoketone 16a (79 mg, 0.33 mmol, 1.1 equiv) were treated with Rh₂(OAc)₄ (7 mg, 0.02 mmol, 5 mol %) in PhMe (10 mL) according to General Procedure 3 to give the title compound 17o (126 mg, 82%) as a yellow solid: mp 140 °C dec; ν_max (film) 3152, 3032, 2924, 1678, 1609, 1516, 1343, and 1161 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 9.41 (1 H, d, J = 10.7 Hz, NH), 7.90 (2 H, d, J = 8.2 Hz, Ar), 7.64 (2 H, d, J = 8.3 Hz, Ar), 7.32 (2 H, d, J = 8.2 Hz, Ar), 7.09 (2 H, d, J = 8.3 Hz, Ar), 6.79 (2 H, d, J = 8.6 Hz, Ar), 6.51 (1 H, d, J = 10.7 Hz, =CH), 6.18 (2 H, d, J = 8.6 Hz, Ar), 5.46 (1 H, t, J = 4.2 Hz, =CH), 4.62 (2 H, br s, CH₂), 2.46 (3 H, s, CH₃), 2.31 (3 H, s, CH₃), 2.19 (3 H, s, CH₃), 2.15–2.08 (2 H, m, CH₂), 2.07–2.00 (2 H, m, CH₂), 1.72–1.64 (2 H, m, CH₂) and 1.62–1.52 (2 H, m, CH₂); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 197.6 (C=O), 145.3 (Ar), 143.3 (Ar), 142.9 (Ar), 137.8 (Ar), 132.0 (Ar), 129.9 (=C), 129.6 (2 × ArH), 129.5 (2 × ArH), 129.3 (2 × ArH), 128.4 (=C), 128.3 (2 × ArH), 126.6 (2 × ArH), 126.5 (Ar), 123.5 (=CH), 121.3 (=CH), 111.7 (2 × ArH), 57.2 (CH₂), 25.5 (CH₂), 24.9 (CH₂), 22.5 (CH₂), 22.2 (CH₂), 21.8 (CH₃), 21.4 (CH₃) and 20.3 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₁H₃₅N₂O₃S⁺ 515.2363; found 515.2355.

2-(4-Methoxybenzenesulfonylamino)-1-[(2-oxo-2-(4-tolyl)ethyl)(4-tolyl)amino]-1-(4-tolyl)ethene (17p)

Triazole 4r (99 mg, 0.30 mmol, 1.0 equiv) and α-aminoketone 16a (79 mg, 0.33 mmol, 1.1 equiv) were treated with Rh₂(OAc)₄ (7 mg, 0.02 mmol, 5 mol %) in PhMe (10 mL) according to General Procedure 3 to give the title compound 17p (142 mg, 87%) as a yellow solid: mp 60–66 °C; ν_max (film) 3148, 3028, 2920, 1678, 1597, 1516, 1339, 1304, 1258, 1157, and 1092 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 9.31 (1 H, d, J = 10.7 Hz, NH), 7.86 (2 H, d, J = 8.3 Hz, Ar), 7.69 (2 H, d, J = 9.0 Hz, Ar), 7.28 (2 H, d, J = 7.8 Hz, Ar), 7.16 (2 H, d, J = 8.3 Hz, Ar), 7.10 (2 H, d, J = 7.8 Hz, Ar), 6.90 (1 H, d, J = 10.7 Hz, =CH), 6.77 (2 H, d, J = 9.0 Hz, Ar), 6.76 (2 H, d, J = 8.4 Hz, Ar), 6.30 (2 H, d, J = 8.4 Hz, Ar), 4.65 (2 H, br s, CH₂), 3.79 (3 H, s, OCH₃), 2.44 (3 H, s, CH₃), 2.32 (3 H, s, CH₃) and 2.19 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 197.2 (C=O), 162.6 (Ar), 145.3 (Ar), 143.4 (Ar), 137.4 (Ar), 132.8 (Ar), 132.7 (Ar), 131.9 (Ar), 129.7 (2 × ArH), 129.6 (2 × ArH), 129.5 (2 × ArH), 128.8 (2 × ArH), 128.3 (2 × ArH), 127.2 (Ar), 125.8 (=C), 124.9 (2 × ArH), 122.0 (=CH), 113.9 (2 × ArH), 112.2 (2 × ArH), 56.5 (OCH₃), 55.4 (CH₃), 21.8 (CH₃), 21.1 (CH₃) and 20.3 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₂H₃₃N₂O₄S⁺ 541.2156; found 541.2158.

2-(4-Nitrobenzenesulfonylamino)-1-[(2-oxo-2-(4-tolyl)ethyl)(4-tolyl)amino]-1-(4-tolyl)ethene (17q)

Triazole 4q (103 mg, 0.30 mmol, 1.0 equiv) and α-aminoketone 16a (79 mg, 0.33 mmol, 1.1 equiv) were treated with Rh₂(OAc)₄ (7 mg, 0.02 mmol, 5 mol %) in PhMe (10 mL) according to General Procedure 3 to give the title compound 17q (66 mg, 40%) as a yellow solid: mp 143 °C dec; ν_max (film) 3102, 3032, 2920, 1678, 1605, 1516, 1346, 1231, and 1165 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 9.77 (1 H, d, J = 10.2 Hz, NH), 8.12 (2 H, d, J = 9.0 Hz, Ar), 7.88 (2 H, d, J = 9.0 Hz, Ar), 7.85 (2 H, d, J = 8.3 Hz, Ar), 7.29 (2 H, d, J = 8.6 Hz, Ar), 7.18 (2 H, d, J = 8.3 Hz, Ar), 7.12 (2 H, d, J = 7.9 Hz, Ar), 6.88 (1 H, d, J = 10.2 Hz, =CH), 6.68 (2 H, d, J = 7.9 Hz, Ar), 6.26 (2 H, d, J = 8.6 Hz, Ar), 4.65 (2 H, br s, CH₂), 2.44 (3 H, s, CH₃), 2.34 (3 H, s, CH₃) and 2.16 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 197.9 (C=O), 149.7 (Ar), 146.6 (Ar), 145.9 (Ar), 143.7 (Ar), 138.2 (Ar), 132.1 (Ar), 131.5 (Ar), 129.7 (2 × ArH), 129.7 (2 × ArH), 129.6 (2 × ArH), 128.3 (2 × ArH), 128.0 (Ar), 127.9 (=C), 127.7 (2 × ArH), 125.2 (2 × ArH), 124.0 (2 × ArH), 120.6 (=CH), 112.5 (2 × ArH), 56.6 (CH₂), 21.8 (CH₃), 21.1 (CH₃) and 20.1 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₁H₃₀N₃O₅S⁺ 556.1901; found 556.1903.

2-(Mesylamino)-1-[(2-oxo-2-(4-tolyl)ethyl)(4-tolyl)amino]-1-(4-tolyl)ethene (17r)

Triazole 4p (71 mg, 0.30 mmol, 1.0 equiv) and α-aminoketone 16a (79 mg, 0.33 mmol, 1.1 equiv) were treated with Rh₂(OAc)₄ (7 mg, 0.02 mmol, 5 mol %) in PhMe (10 mL) according to General Procedure 3 to give the title compound 17r (65 mg, 48%) as a yellow solid: mp 111–116 °C; ν_max (film) 2924, 1682, 1609, 1516, 1331, 1231, and 1150 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 9.18 (1 H, d, J = 10.4 Hz, NH), 7.91 (2 H, d, J = 8.2 Hz, Ar), 7.29 (2 H, d, J = 7.9 Hz, Ar), 7.24 (2 H, d, J = 8.2 Hz, Ar), 7.14 (2 H, d, J = 7.9 Hz, Ar), 6.98 (2 H, d, J = 8.5 Hz, Ar), 6.85 (1 H, d, J = 10.4 Hz, =CH), 6.54 (2 H, d, J = 8.5 Hz, Ar), 4.76 (2 H, br s, CH₂), 2.90 (3 H, s, CH₃), 2.43 (3 H, s, CH₃), 2.35 (3 H, s, CH₃) and 2.23 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 197.5 (C=O), 145.5 (Ar), 143.7 (Ar), 137.7 (Ar), 132.6 (Ar), 131.8 (Ar), 130.0 (2 × ArH), 129.7 (2 × ArH), 129.6 (2 × ArH), 128.3 (2 × ArH), 127.8 (Ar), 125.7 (=C), 125.0 (2 × ArH), 121.4 (=CH), 112.6 (2 × ArH), 56.4 (CH₂), 42.0 (CH₃), 21.8 (CH₃), 21.1 (CH₃) and 20.3 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₂₆H₂₉N₂O₃S⁺ 449.1893; found 449.1901.

General Procedure 4: Cyclodehydration

Under argon, boron trifluoride diethyl etherate (3.0 equiv) was added in one portion to a solution of 1,2-diamine 17 (1.0 equiv) in CH₂Cl₂ (0.03 M) in a flame-dried vial. The vial was sealed with a Teflon cap and heated at 80 °C (heating block) for 15 min. The reaction mixture was cooled to ambient temperature; saturated aqueous NaHCO₃ was added, and the aqueous phase was extracted with CH₂Cl₂ (3 × 30 mL mmol^–1). The combined organic layers were washed with brine, dried (MgSO₄), and concentrated in vacuo. Purification by column chromatography (SiO₂, gradient of 10–30% EtOAc in petroleum ether) gave the pyrrole 18.

General Procedure 5: One-Pot Pyrrole Synthesis

Under argon, copper(I) thiophene-2-carboxylate (5 mol %) was added to a solution of alkyne 21 (1.1 equiv) in CH₂Cl₂ (0.03 M) in a flame-dried vial with freshly dried 4 Å molecular sieves. The mixture was cooled to 0 °C (ice bath) and stirred for 10 min. Then sulfonyl azide 22 (1.1 equiv) was added, and the reaction mixture was allowed to reach ambient temperature. When the CuAAC reaction was complete (TLC, 6–16 h), amine 16 (1.0 equiv) was added, followed by Rh₂(OAc)₄ (1 mol %), and the vial was sealed with a Teflon cap and heated to 80 °C (heating block) for 3 h. The reaction mixture was cooled to ambient temperature and boron trifluoride diethyl etherate (3.0 equiv) was added in one portion. The vial was sealed and heated to 80 °C (heating block) for 15 min. After being cooled to ambient temperature, the reaction was quenched by addition of saturated aqueous NaHCO₃, and the aqueous phase was extracted with CH₂Cl₂ (3 × 30 mL mmol^–1). The combined organic layers were washed with brine, dried (MgSO₄), filtered through a short pad of silica (eluting with CH₂Cl₂), and concentrated in vacuo to deliver the pyrrole 18.

3-Tosylamino-1,2,4-tri(4-tolyl)pyrrole (18a)

1,2-Diaminoalkene 17a (105 mg, 0.20 mmol, 1.0 equiv) was treated with BF₃·OEt₂ (74 μL, 0.60 mmol, 3.0 equiv) in CH₂Cl₂ (6.7 mL) according to General Procedure 4 to give the title compound 18a (74 mg, 73%) as an orange solid. 4-Ethynyltoluene (64 μL, 0.55 mmol, 1.1 equiv) and 4-toluenesulfonyl azide (108 mg, 0.55 mmol, 1.1 equiv) were treated with CuTC (5 mg, 26 μmol, 5 mol %) in CH₂Cl₂ (17 mL), followed by α-aminoketone 16a (120 mg, 0.50 mmol, 1.0 equiv) and Rh₂(OAc)₄ (2 mg, 4.5 μmol, 1 mol %), and finally BF₃·OEt₂ (185 μL, 1.5 mmol, 3.0 equiv) according to General Procedure 5 to give the title compound 18a (228 mg, 90%): mp 170 °C dec; ν_max (film) 3268, 3028, 1516, 1389, 1327, and 1157 cm^–1; ¹H NMR (500 MHz, 25.0 °C, CDCl₃) δ 7.35 (2 H, d, J = 8.1 Hz, Ar), 7.25 (2 H, d, J = 8.0 Hz, Ar), 7.09 (2 H, d, J = 8.1 Hz, Ar), 7.07 (2 H, d, J = 8.4 Hz, Ar), 6.97 (2 H, d, J = 8.4 Hz, Ar), 6.94 (2 H, d, J = 8.1 Hz, Ar), 6.88 (1 H, s, pyrrole CH), 6.87 (2 H, d, J = 8.1 Hz, Ar), 6.82 (2 H, d, J = 8.0 Hz, Ar), 6.24 (1 H, s, NH), 2.37 (3 H, s, CH₃), 2.33 (3 H, s, CH₃), 2.32 (3 H, s, CH₃) and 2.30 (3 H, s, CH₃); ¹³C{¹H} NMR (126 MHz, 25.0 °C, CDCl₃) δ 142.3 (Ar), 137.4 (Ar), 137.0 (Ar), 136.7 (Ar), 136.4 (Ar), 135.5 (Ar), 131.9 (Ar), 131.0 (Ar), 129.8 (2 × ArH), 129.5 (2 × ArH), 129.0 (2 × ArH), 128.7 (2 × ArH), 128.6 (2 × ArH), 127.4 (2 × ArH), 127.2 (pyrrole), 127.0 (2 × ArH), 125.2 (2 × ArH), 123.6 (pyrrole), 119.3 (pyrrole CH), 115.3 (pyrrole), 21.3 (CH₃), 21.3 (CH₃), 21.2 (CH₃) and 21.2 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₂H₃₁N₂O₂S⁺ 507.2101; found 507.2100.

1-(4-Chlorophenyl)-2,4-di(4-tolyl)-3-tosylaminopyrrole (18b)

1,2-Diaminoalkene 17b (109 mg, 0.20 mmol, 1.0 equiv) was treated with BF₃·OEt₂ (74 μL, 0.60 mmol, 3.0 equiv) in CH₂Cl₂ (6.7 mL) according to General Procedure 4 to give the title compound 18b (86 mg, 82%) as a yellow solid. 4-Ethynyltoluene (38 μL, 0.33 mmol, 1.1 equiv) and 4-toluenesulfonyl azide (66 mg, 0.33 mmol, 1.1 equiv) were treated with CuTC (3 mg, 16 μmol, 5 mol %) in CH₂Cl₂ (10 mL), followed by α-aminoketone 16b (78 mg, 0.30 mmol, 1.0 equiv) and Rh₂(OAc)₄ (1 mg, 2.3 μmol, 1 mol %), and finally BF₃·OEt₂ (111 μL, 0.90 mmol, 3.0 equiv) according to General Procedure 5 to give the title compound 18b (101 mg, 64%): mp 170 °C dec; ν_max (film) 3268, 3020, 2920, 1497, 1385, 1327, 1157, and 1092 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.31 (2 H, d, J = 8.0 Hz, Ar), 7.22 (2 H, d, J = 8.0 Hz, Ar), 7.21 (2 H, d, J = 8.7 Hz, Ar), 7.07 (2 H, d, J = 8.0 Hz, Ar), 6.99 (2 H, d, J = 8.7 Hz, Ar), 6.94 (2 H, d, J = 7.9 Hz, Ar), 6.85 (1 H, s, pyrrole CH), 6.84 (2 H, d, J = 7.9 Hz, Ar), 6.81 (2 H, d, J = 8.0 Hz, Ar), 6.19 (1 H, s, NH), 2.35 (3 H, s, CH₃), 2.31 (3 H, s, CH₃) and 2.28 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 23.0 °C, CDCl₃) δ 142.4 (Ar), 138.4 (Ar), 137.1 (Ar), 137.0 (Ar), 135.8 (Ar), 132.3 (Ar), 130.7 (Ar), 129.9 (2 × ArH), 129.3 (Ar), 129.1 (2 × ArH), 129.0 (2 × ArH), 128.9 (2 × ArH), 128.7 (2 × ArH), 127.4 (2 × ArH), 127.0 (2 × ArH), 126.8 (pyrrole), 126.5 (2 × ArH), 124.2 (pyrrole), 119.1 (pyrrole CH), 115.9 (pyrrole), 21.4 (CH₃), 21.3 (CH₃) and 21.2 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₁H₂₈ClN₂O₂S⁺ 527.1555; found 527.1562.

2,4-Di(4-tolyl)-3-tosyl-1-(3-trifluoromethylphenyl)aminopyrrole (18c)

1,2-Diaminoalkene 17c (58 mg, 0.10 mmol, 1.0 equiv) was treated with BF₃·OEt₂ (37 μL, 0.30 mmol, 3.0 equiv) in CH₂Cl₂ (3.3 mL) according to General Procedure 4 to give the title compound 18c (36 mg, 64%) as a yellow solid. 4-Ethynyltoluene (38 μL, 0.33 mmol, 1.1 equiv) and 4-toluenesulfonyl azide (66 mg, 0.33 mmol, 1.1 equiv) were treated with CuTC (3 mg, 16 μmol, 5 mol %) in CH₂Cl₂ (10 mL), followed by α-aminoketone 16c (88 mg, 0.30 mmol, 1.0 equiv) and Rh₂(OAc)₄ (1 mg, 2.3 μmol, 1 mol %), and finally BF₃·OEt₂ (111 μL, 0.90 mmol, 3.0 equiv) according to General Procedure 5 to give the title compound 18c (131 mg, 78%): mp 145 °C dec; ν_max (film) 3256, 2924, 1497, 1458, 1385, 1327, 1161, 1130, 1096, and 1072 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.48–7.43 (1 H, m, Ar), 7.40–7.37 (1 H, m, Ar), 7.35 (1 H, d, J = 7.8 Hz, Ar), 7.31 (2 H, d, J = 7.9 Hz, Ar), 7.23 (2 H, d, J = 8.2 Hz, Ar), 7.17–7.13 (1 H, m, Ar), 7.07 (2 H, d, J = 7.9 Hz, Ar), 6.95 (2 H, d, J = 8.0 Hz, Ar), 6.91 (1 H, s, pyrrole CH), 6.84 (2 H, d, J = 8.0 Hz, Ar), 6.82 (2 H, d, J = 8.2 Hz, Ar), 6.20 (1 H, s, NH), 2.35 (3 H, s, CH₃), 2.30 (3 H, s, CH₃) and 2.28 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 142.5 (Ar), 140.3 (Ar), 137.4 (Ar), 136.9 (Ar), 135.9 (Ar), 132.1 (Ar), 131.5 (q, J = 32.9 Hz, Ar), 130.5 (Ar), 129.9 (2 × ArH), 129.4 (ArH), 129.0 (2 × ArH), 129.0 (2 × ArH), 128.7 (2 × ArH), 128.6 (ArH), 127.5 (2 × ArH), 127.0 (2 × ArH), 126.6 (pyrrole), 124.6 (pyrrole), 123.5 (q, J = 272.4 Hz, CF₃), 123.2 (q, J = 3.8 Hz, ArH), 121.9 (q, J = 3.5 Hz, ArH), 118.9 (pyrrole CH), 116.4 (pyrrole), 21.4 (CH₃), 21.3 (CH₃) and 21.2 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₂H₂₈F₃N₂O₂S⁺ 561.1818; found 561.1826.

2,4-Di(4-tolyl)-1-(4-methoxyphenyl)-3-tosylaminopyrrole (18d)

1,2-Diaminoalkene 17d (108 mg, 0.20 mmol, 1.0 equiv) was treated with BF₃·OEt₂ (74 μL, 0.60 mmol, 3.0 equiv) in CH₂Cl₂ (6.7 mL) according to General Procedure 4 to give the title compound 18d (69 mg, 66%) as a yellow solid: mp 158 °C dec; ν_max (film) 3271, 2920, 2859, 1512, 1323, 1250, 1157, 1092, and 1034 cm^–1; ¹H NMR (400 MHz, 22.1 °C, CDCl₃) δ 7.33 (2 H, d, J = 8.0 Hz, Ar), 7.23 (2 H, d, J = 8.2 Hz, Ar), 7.06 (2 H, d, J = 8.0 Hz, Ar), 6.99 (2 H, d, J = 9.0 Hz, Ar), 6.91 (2 H, d, J = 7.8 Hz, Ar), 6.84 (2 H, d, J = 7.8 Hz, Ar), 6.83 (1 H, s, pyrrole CH), 6.80 (2 H, d, J = 8.2 Hz, Ar), 6.77 (2 H, d, J = 9.0 Hz, Ar), 6.23 (1 H, s, NH), 3.77 (3 H, s, OCH₃), 2.34 (3 H, s, CH₃), 2.29 (3 H, s, CH₃) and 2.27 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 22.9 °C, CDCl₃) δ 158.1 (Ar), 142.3 (Ar), 137.0 (Ar), 136.7 (Ar), 135.5 (Ar), 133.0 (Ar), 132.1 (Ar), 131.1 (Ar), 129.9 (2 × ArH), 128.9 (2 × ArH), 128.7 (2 × ArH), 128.6 (2 × ArH), 127.4 (2 × ArH), 127.2 (pyrrole), 127.0 (2 × ArH), 126.7 (2 × ArH), 123.4 (pyrrole), 119.5 (pyrrole CH), 115.0 (pyrrole), 114.0 (2 × ArH), 55.4 (OCH₃), 21.4 (CH₃), 21.3 (CH₃) and 21.2 (CH₃); HRMS (ESI-TOF) m/z [M + Na]⁺ calcd for C₃₂H₃₀N₂NaO₃S⁺ 545.1869; found 545.1858.

2,4-Di(4-tolyl)-3-tosyl-1-(2,4,6-trimethylphenyl)aminopyrrole (18e)

Triazole 4a (94 mg, 0.30 mmol, 1.0 equiv) and α-aminoketone 16e (88 mg, 0.33 mmol, 1.1 equiv) were treated with Rh₂(OAc)₄ (7 mg, 0.02 mmol, 5 mol %) in PhMe (10 mL) according to General Procedure 3. During the N–H insertion, spontaneous cyclodehydration occurred to give the title compound 18e (111 mg, 69%) as a yellow wax: ν_max (film) 3264, 3024, 2920, 2866, 1493, 1381, 1327, and 1161 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.35 (2 H, d, J = 8.0 Hz, Ar), 7.19 (2 H, d, J = 8.3 Hz, Ar), 7.09 (2 H, d, J = 8.0 Hz, Ar), 6.84 (2 H, d, J = 8.0 Hz, Ar), 6.81 (2 H, s, Ar), 6.80 (2 H, d, J = 8.3 Hz, Ar), 6.69 (2 H, d, J = 8.0 Hz, Ar), 6.57 (1 H, s, pyrrole CH), 6.27 (1 H, s, NH), 2.35 (3 H, s, CH₃), 2.28 (3 H, s, CH₃), 2.25 (3 H, s, CH₃), 2.24 (3 H, s, CH₃) and 1.92 (6 H, s, 2 × CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 142.5 (Ar), 137.9 (Ar), 136.5 (Ar), 136.0 (Ar), 135.7 (2 × Ar), 135.6 (Ar), 135.4 (Ar), 132.0 (Ar), 131.3 (Ar), 128.9 (2 × ArH), 128.7 (2 × ArH), 128.6 (2 × ArH), 128.5 (4 × ArH), 127.3 (pyrrole), 127.3 (2 × ArH), 127.2 (2 × ArH), 123.4 (pyrrole), 118.6 (pyrrole CH), 113.7 (pyrrole), 21.5 (CH₃), 21.2 (CH₃), 21.2 (CH₃), 21.0 (CH₃) and 17.7 (2 × CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₄H₃₅N₂O₂S⁺ 535.2414; found 535.2423.

2,4-Di(4-tolyl)-1-naphth-2-yl-3-tosylaminopyrrole (18f)

Triazole 4a (94 mg, 0.30 mmol, 1.0 equiv) and α-aminoketone 16f (91 mg, 0.33 mmol, 1.1 equiv) were treated with Rh₂(OAc)₄ (7 mg, 0.02 mmol, 5 mol %) in PhMe (10 mL) according to General Procedure 3. During the N–H insertion, spontaneous cyclodehydration occurred to give the title compound 18f (117 mg, 72%) as a yellow solid: mp 150 °C dec; ν_max (film) 3268, 3048, 2920, 2866, 1412, 1323, 1157, and 1092 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.88–7.83 (1 H, m, naphthyl CH), 7.79 (1 H, d, J = 8.4 Hz, naphthyl CH), 7.62–7.58 (1 H, m, naphthyl CH), 7.55–7.45 (2 H, m, naphthyl CH), 7.40 (2 H, d, J = 8.1 Hz, Ar), 7.34 (1 H, dd, J = 8.3, 7.3 Hz, naphthyl CH), 7.28 (2 H, d, J = 8.4 Hz, Ar), 7.21 (1 H, dd, J = 7.3, 1.2 Hz, naphthyl CH), 7.10 (2 H, d, J = 7.6 Hz, Ar), 6.89 (1 H, s, pyrrole CH), 6.83 (2 H, d, J = 7.6 Hz, Ar), 6.73 (4 H, app s, Ar), 6.29 (1 H, s, NH), 2.36 (3 H, s, CH₃), 2.27 (3 H, s, CH₃) and 2.16 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 142.5 (naphthyl C), 136.7 (Ar), 136.6 (Ar), 136.4 (Ar), 135.6 (Ar), 134.0 (naphthyl C), 133.8 (pyrrole), 131.0 (Ar), 130.8 (naphthyl C), 129.2 (2 × ArH), 129.0 (2 × ArH), 128.7 (2 × ArH), 128.5 (2 × ArH), 128.4 (naphthyl CH), 128.1 (naphthyl CH), 127.4 (2 × ArH), 127.2 (2 × ArH), 127.1 (Ar), 127.0 (naphthyl CH), 126.5 (naphthyl CH), 125.7 (naphthyl CH), 125.0 (naphthyl CH), 123.3 (pyrrole), 123.1 (naphthyl CH), 121.1 (pyrrole CH), 114.6 (pyrrole), 21.4 (CH₃), 21.2 (CH₃) and 21.1 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₅H₃₁N₂O₂S⁺ 543.2101; found 543.2109.

5-Methyl-3-tosylamino-1,2,4-tri(4-tolyl)pyrrole (18g)

1,2-Diaminoalkene 17g (54 mg, 0.10 mmol, 1.0 equiv) was treated with BF₃·OEt₂ (37 μL, 0.30 mmol, 3.0 equiv) in CH₂Cl₂ (3.3 mL) according to General Procedure 4 to give the title compound 18g (38 mg, 73%) as a yellow solid. 4-Ethynyltoluene (38 μL, 0.33 mmol, 1.1 equiv) and 4-toluenesulfonyl azide (66 mg, 0.33 mmol, 1.1 equiv) were treated with CuTC (3 mg, 16 μmol, 5 mol %) in CH₂Cl₂ (10 mL), followed by α-aminoketone 16g (76 mg, 0.30 mmol, 1.0 equiv) and Rh₂(OAc)₄ (1 mg, 2.3 μmol, 1 mol %), and finally BF₃·OEt₂ (111 μL, 0.90 mmol, 3.0 equiv) according to General Procedure 5 to give the title compound 18g (106 mg, 68%): mp 154 °C dec; ν_max (film) 3271, 3028, 2920, 2866, 1512, 1381, 1323, 1157, and 1092 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.19 (2 H, d, J = 8.3 Hz, Ar), 7.14–7.06 (6 H, m, Ar), 6.98 (2 H, d, J = 8.3 Hz, Ar), 6.86–6.84 (4 H, m, Ar), 6.81 (2 H, d, J = 7.9 Hz, Ar), 6.18 (1 H, s, NH), 2.37 (3 H, s, CH₃), 2.32 (3 H, s, CH₃), 2.29 (3 H, s, CH₃), 2.25 (3 H, s, CH₃) and 2.01 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 142.0 (Ar), 137.2 (Ar), 137.2 (Ar), 136.0 (Ar), 135.9 (Ar), 135.2 (Ar), 131.4 (Ar), 131.0 (Ar), 129.8 (2 × ArH), 129.6 (2 × ArH), 129.4 (2 × ArH), 128.8 (2 × ArH), 128.6 (2 × ArH), 128.4 (2 × ArH), 128.3 (2 × ArH), 127.9 (pyrrole), 126.9 (2 × ArH), 125.9 (pyrrole), 120.6 (pyrrole), 114.6 (pyrrole), 21.4 (CH₃), 21.2 (CH₃), 21.2 (CH₃), 21.1 (CH₃) and 12.0 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₃H₃₃N₂O₂S⁺ 521.2257; found 521.2256.

1,2-Di(4-tolyl)-4-(naphth-2-yl)-3-tosylaminopyrrole (18h)

1,2-Diaminoalkene 17h (56 mg, 0.10 mmol, 1.0 equiv) was treated with BF₃·OEt₂ (37 μL, 0.30 mmol, 3.0 equiv) in CH₂Cl₂ (3.3 mL) according to General Procedure 4 to give the title compound 18h (36 mg, 66%) as an orange solid. 4-Ethynyltoluene (38 μL, 0.33 mmol, 1.3 equiv) and 4-toluenesulfonyl azide (66 mg, 0.33 mmol, 1.3 equiv) were treated with CuTC (3 mg, 16 μmol, 6 mol %) in CH₂Cl₂ (10 mL), followed by α-aminoketone 16h (72 mg, 0.26 mmol, 1.0 equiv) and Rh₂(OAc)₄ (1 mg, 2.3 μmol, 1 mol %), and finally BF₃·OEt₂ (111 μL, 0.90 mmol, 3.4 equiv) according to General Procedure 5 to give the title compound 18h (142 mg, > 98%). On a larger scale, 4-ethynyltoluene (590 μL, 5.1 mmol, 1.1 equiv) and 4-toluenesulfonyl azide (1.29 g, 6.5 mmol, 1.4 equiv) were treated with CuTC (44 mg, 0.23 mmol, 5 mol %) in CH₂Cl₂ (170 mL), followed by α-aminoketone 16h (1.27 g, 4.6 mmol, 1.0 equiv) and Rh₂(OAc)₄ (20 mg, 45 μmol, 1 mol %), and finally BF₃·OEt₂ (1.71 mL, 14 mmol, 3.0 equiv) according to General Procedure 5 to give the title compound (1.89 g, 76%) as an orange solid: mp 160 °C dec; ν_max (film) 3264, 3036, 2924, 1516, 1377, 1327, 1157, and 1092 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.79–7.76 (2 H, m, Ar), 7.73–7.69 (1 H, m, Ar), 7.67 (1 H, d, J = 8.5 Hz, Ar), 7.52 (1 H, dd, J = 8.4, 1.7 Hz, Ar), 7.47–7.39 (2 H, m, Ar), 7.21 (2 H, d, J = 8.3 Hz, Ar), 7.08 (2 H, d, J = 7.9 Hz, Ar), 7.02–6.98 (6 H, m, Ar), 7.00 (1 H, s, pyrrole CH), 6.57 (2 H, d, J = 7.8 Hz, Ar), 6.27 (1 H, s, NH), 2.33 (3 H, s, CH₃), 2.32 (3 H, s, CH₃) and 1.98 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 142.5 (Ar), 137.4 (Ar), 137.0 (Ar), 136.9 (Ar), 136.6 (Ar), 133.6 (naphthyl C), 132.7 (Ar), 132.0 (naphthyl C), 131.5 (naphthyl C), 130.0 (2 × ArH), 129.5 (2 × ArH), 128.8 (2 × ArH), 128.6 (2 × ArH), 127.9 (naphthyl CH), 127.7 (naphthyl CH), 127.5 (naphthyl CH), 127.2 (naphthyl CH), 126.9 (2 × ArH), 126.3 (naphthyl CH), 125.7 (pyrrole), 125.6 (naphthyl CH), 125.3 (2 × ArH), 125.2 (naphthyl CH), 123.4 (pyrrole), 119.9 (pyrrole CH), 115.5 (pyrrole), 21.3 (CH₃), 21.1 (CH₃) and 21.0 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₅H₃₁N₂O₂S⁺ 543.2101; found 543.2109.

1,2-Di(4-tolyl)-4-(4-methoxyphenyl)-3-tosylaminopyrrole (18i)

1,2-Diaminoalkene 17i (54 mg, 0.10 mmol, 1.0 equiv) was treated with BF₃·OEt₂ (37 μL, 0.30 mmol, 3.0 equiv) in CH₂Cl₂ (3.3 mL) according to General Procedure 4 to give the title compound 18i (32 mg, 61%) as a yellow solid: mp 160 °C dec; ν_max (film) 3264, 3036, 2920, 2859, 1505, 1389, 1323, 1242, 1157, and 1092 cm^–1; ¹H NMR (400 MHz, 26.0 °C, CDCl₃) δ 7.36 (2 H, d, J = 8.8 Hz, Ar), 7.24 (2 H, d, J = 8.4 Hz, Ar), 7.04 (2 H, d, J = 7.9 Hz, Ar), 6.94 (2 H, d, J = 8.2 Hz, Ar), 6.91 (2 H, d, J = 8.2 Hz, Ar), 6.84 (2 H, d, J = 7.9 Hz, Ar), 6.83 (1 H, s, pyrrole CH), 6.82 (2 H, d, J = 8.4 Hz, Ar), 6.80 (2 H, d, J = 8.8 Hz, Ar), 6.17 (1 H, s, NH), 3.82 (3 H, s, OCH₃), 2.30 (3 H, s, CH₃), 2.29 (3 H, s, CH₃) and 2.28 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 26.0 °C, CDCl₃) δ 158.1 (Ar), 142.4 (Ar), 137.4 (Ar), 137.1 (Ar), 136.8 (Ar), 136.4 (Ar), 131.8 (Ar), 129.9 (2 × ArH), 129.5 (2 × ArH), 128.7 (2 × ArH), 128.7 (2 × ArH), 128.6 (2 × ArH), 127.3 (Ar), 127.1 (2 × ArH), 126.6 (pyrrole), 125.2 (2 × ArH), 123.3 (pyrrole), 119.1 (pyrrole CH), 115.3 (pyrrole), 113.7 (2 × ArH), 55.2 (OCH₃), 21.4 (CH₃), 21.3 (CH₃) and 20.9 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₂H₃₁N₂O₃S⁺ 523.2050; found 523.2059.

1,2-Di(4-tolyl)-4-(4-nitrophenyl)-3-tosylaminopyrrole (18j)

1,2-Diaminoalkene 17j (56 mg, 0.10 mmol, 1.0 equiv) was treated with BF₃·OEt₂ (37 μL, 0.30 mmol, 3.0 equiv) in CH₂Cl₂ (3.3 mL) according to General Procedure 4 to give the title compound 18j (42 mg, 78%) as an orange solid. 4-Ethynyltoluene (38 μL, 0.33 mmol, 1.1 equiv) and 4-toluenesulfonyl azide (66 mg, 0.33 mmol, 1.1 equiv) were treated with CuTC (3 mg, 16 μmol, 5 mol %) in CH₂Cl₂ (10 mL), followed by α-aminoketone 16j (81 mg, 0.30 mmol, 1.0 equiv) and Rh₂(OAc)₄ (1 mg, 2.3 μmol, 1 mol %), and finally BF₃·OEt₂ (111 μL, 0.90 mmol, 3.0 equiv) according to General Procedure 5 to give the title compound 18j (120 mg, 74%): mp 175 °C dec; ν_max (film) 3264, 3036, 2924, 1597, 1393, 1335, 1161, and 1151 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 8.11 (2 H, d, J = 8.9 Hz, Ar), 7.71 (2 H, d, J = 8.9 Hz, Ar), 7.23 (2 H, d, J = 8.3 Hz, Ar), 7.07 (2 H, d, J = 8.1 Hz, Ar), 7.04 (1 H, s, pyrrole CH), 6.96–6.90 (4 H, m, Ar), 6.83 (2 H, d, J = 8.3 Hz, Ar), 6.74 (2 H, d, J = 8.1 Hz, Ar), 6.32 (1 H, s, NH), 2.31 (3 H, s, CH₃), 2.30 (3 H, s, CH₃) and 2.25 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 145.6 (Ar), 143.1 (Ar), 141.4 (Ar), 137.4 (Ar), 137.2 (Ar), 136.8 (Ar), 136.5 (Ar), 132.9 (Ar), 129.7 (2 × ArH), 129.6 (2 × ArH), 128.9 (2 × ArH), 128.9 (2 × ArH), 127.4 (2 × ArH), 127.1 (2 × ArH), 126.3 (pyrrole), 125.1 (2 × ArH), 123.7 (2 × ArH), 121.3 (pyrrole), 120.8 (pyrrole CH), 115.4 (pyrrole), 21.3 (CH₃), 21.3 (CH₃) and 21.0 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₁H₂₈N₃O₄S⁺ 538.1795; found 538.1803.

4-(4-Cyanophenyl)-1,2-di(4-tolyl)-3-tosylaminopyrrole (18k)

1,2-Diaminoalkene 17k (54 mg, 0.10 mmol, 1.0 equiv) was treated with BF₃·OEt₂ (37 μL, 0.30 mmol, 3.0 equiv) in CH₂Cl₂ (3.3 mL) according to General Procedure 4 to give the title compound 18k (37 mg, 71%) as a yellow solid: mp 165 °C dec; ν_max (film) 3275, 3036, 2924, 2226, 1605, 1543, 1516, 1393, 1327, and 1161 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.65 (2 H, d, J = 8.7 Hz, Ar), 7.52 (2 H, d, J = 8.7 Hz, Ar), 7.22 (2 H, d, J = 8.1 Hz, Ar), 7.06 (2 H, d, J = 7.9 Hz, Ar), 6.99 (1 H, s, pyrrole CH), 6.95–6.90 (4 H, m, Ar), 6.84 (2 H, d, J = 8.1 Hz, Ar), 6.74 (2 H, d, J = 8.1 Hz, Ar), 6.27 (1 H, s, NH), 2.31 (3 H, s, CH₃), 2.30 (3 H, s, CH₃) and 2.30 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 143.0 (Ar), 139.2 (Ar), 137.3 (Ar), 137.1 (Ar), 136.9 (Ar), 136.5 (Ar), 132.8 (Ar), 132.0 (2 × ArH), 129.7 (2 × ArH), 129.6 (2 × ArH), 128.9 (2 × ArH), 128.9 (2 × ArH), 127.5 (2 × ArH), 127.0 (2 × ArH), 126.4 (pyrrole), 125.1 (2 × ArH), 121.7 (pyrrole), 120.5 (pyrrole CH), 119.4 (pyrrole), 115.3 (C≡N), 109.0 (Ar), 21.4 (CH₃), 21.3 (CH₃) and 21.0 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₂H₂₈N₃O₂S⁺ 518.1897; found 518.1904.

4-(4-Chlorophenyl)-1,2-di(4-tolyl)-3-tosylaminopyrrole (18l)

1,2-Diaminoalkene 17l (55 mg, 0.10 mmol, 1.0 equiv) was treated with BF₃·OEt₂ (37 μL, 0.30 mmol, 3.0 equiv) in CH₂Cl₂ (3.3 mL) according to General Procedure 4 to give the title compound 18l (41 mg, 77%) as a yellow solid: mp 160 °C dec; ν_max (film) 3268, 2924, 1501, 1389, 1157, and 1092 cm^–1; ¹H NMR (400 MHz, 26.0 °C, CDCl₃) δ 7.36 (2 H, d, J = 8.5 Hz, Ar), 7.24 (2 H, d, J = 8.3 Hz, Ar), 7.18 (2 H, d, J = 8.5 Hz, Ar), 7.05 (2 H, d, J = 8.0 Hz, Ar), 6.95 (2 H, d, J = 8.1 Hz, Ar), 6.93 (2 H, d, J = 8.3 Hz, Ar), 6.88 (1 H, s, pyrrole CH), 6.85 (2 H, d, J = 8.1 Hz, Ar), 6.84 (2 H, d, J = 8.0 Hz, Ar), 6.18 (1 H, s, NH), 2.31 (6 H, s, 2 × CH₃) and 2.30 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 26.0 °C, CDCl₃) δ 142.8 (Ar), 137.2 (Ar), 137.1 (Ar), 136.9 (Ar), 136.7 (Ar), 132.6 (Ar), 132.4 (Ar), 131.8 (Ar), 129.9 (2 × ArH), 129.5 (2 × ArH), 128.8 (2 × ArH), 128.8 (2 × ArH), 128.6 (2 × ArH), 128.3 (2 × ArH), 127.0 (2 × ArH), 126.9 (pyrrole), 125.2 (2 × ArH), 122.4 (pyrrole), 119.6 (pyrrole CH), 115.2 (pyrrole), 21.5 (CH₃), 21.3 (CH₃) and 21.0 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₁H₂₈ClN₂O₂S⁺ 527.1555; found 527.1559.

1,4-Di(4-tolyl)-2-(thiophen-2-yl)-3-tosylaminopyrrole (18m)

1,2-Diaminoalkene 17m (52 mg, 0.10 mmol, 1.0 equiv) was treated with BF₃·OEt₂ (37 μL, 0.30 mmol, 3.0 equiv) in CH₂Cl₂ (3.3 mL) according to General Procedure 4 to give the title compound 18m (38 mg, 76%) as a yellow solid: mp 187 °C dec; ν_max (film) 3268, 2920, 1516, 1397, 1327, 1161, and 1092 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.32 (2 H, d, J = 8.3 Hz, Ar), 7.24 (2 H, d, J = 8.1 Hz, Ar), 7.18 (1 H, dd, J = 5.1, 1.2 Hz, thiophene CH), 7.12 (2 H, d, J = 8.2 Hz, Ar), 7.05 (2 H, d, J = 8.2 Hz, Ar), 7.03 (2 H, d, J = 8.1 Hz, Ar), 6.86 (2 H, d, J = 8.3 Hz, Ar), 6.85 (1 H, s, pyrrole CH), 6.82 (1 H, dd, J = 5.1, 3.6 Hz, thiophene CH), 6.66 (1 H, dd, J = 3.6, 1.2 Hz, thiophene CH), 6.32 (1 H, s, NH), 2.35 (3 H, s, CH₃), 2.34 (3 H, s, CH₃) and 2.28 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 142.5 (Ar), 137.3 (Ar), 137.1 (Ar), 136.9 (Ar), 135.6 (Ar), 130.7 (Ar), 130.7 (thiophene C2), 129.5 (2 × ArH), 128.9 (2 × ArH), 128.8 (2 × ArH), 128.4 (thiophene CH), 127.3 (2 × ArH), 127.1 (2 × ArH), 126.7 (thiophene CH), 126.4 (thiophene CH), 125.7 (2 × ArH), 125.6 (pyrrole), 123.6 (pyrrole), 120.4 (pyrrole CH), 116.5 (pyrrole), 21.4 (CH₃), 21.2 (CH₃) and 21.0 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₂₉H₂₇N₂O₂S₂⁺ 499.1508; found 499.1517.

1,4-Di(4-tolyl)-2-(4-methoxyphenyl)-3-tosylaminopyrrole (18n)

1,2-Diaminoalkene 17n (54 mg, 0.10 mmol, 1.0 equiv) was treated with BF₃·OEt₂ (37 μL, 0.30 mmol, 3.0 equiv) in CH₂Cl₂ (3.3 mL) according to General Procedure 4 to give the title compound 18n (44 mg, 84%) as a yellow solid: mp 75 °C dec; ν_max (film) 3275, 2924, 1516, 1393, 1323, 1250, 1157, and 1092 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.31 (2 H, d, J = 8.1 Hz, Ar), 7.24 (2 H, d, J = 8.3 Hz, Ar), 7.06 (2 H, d, J = 8.1 Hz, Ar), 7.05 (2 H, d, J = 8.3 Hz, Ar), 6.94 (2 H, d, J = 8.4 Hz, Ar), 6.90 (2 H, d, J = 8.8 Hz, Ar), 6.85 (1 H, s, pyrrole CH), 6.82 (2 H, d, J = 8.4 Hz, Ar), 6.65 (2 H, d, J = 8.8 Hz, Ar), 6.15 (1 H, s, NH), 3.78 (3 H, s, OCH₃), 2.34 (3 H, s, CH₃), 2.31 (3 H, s, CH₃) and 2.27 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 158.7 (Ar), 142.4 (Ar), 137.4 (Ar), 137.1 (Ar), 136.5 (Ar), 135.5 (Ar), 131.8 (Ar), 131.3 (2 × ArH), 131.1 (Ar), 129.5 (2 × ArH), 129.0 (2 × ArH), 128.7 (2 × ArH), 127.4 (2 × ArH), 127.1 (2 × ArH), 125.3 (2 × ArH), 123.5 (pyrrole), 122.7 (pyrrole), 119.2 (pyrrole CH), 115.2 (pyrrole), 113.5 (2 × ArH), 55.1 (OCH₃), 21.4 (CH₃), 21.2 (CH₃) and 21.0 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₂H₃₁N₂O₃S⁺ 523.2050; found 523.2057.

1,4-Di(4-tolyl)-2-(cyclohexen-1-yl)-3-tosylaminopyrrole (18o)

1,2-Diaminoalkene 17o (51 mg, 0.10 mmol, 1.0 equiv) was treated with BF₃·OEt₂ (37 μL, 0.30 mmol, 3.0 equiv) in CH₂Cl₂ (3.3 mL) according to General Procedure 4 to give the title compound 18o (28 mg, 57%) as a brown solid: mp 80 °C dec; ν_max (film) 3271, 3036, 2928, 1709, 1593, 1516, 1492, 1393, 1246, 1157, and 1092 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.41 (2 H, d, J = 8.3 Hz, Ar), 7.22 (2 H, d, J = 8.5 Hz, Ar), 7.19 (2 H, d, J = 8.5 Hz, Ar), 7.17 (2 H, d, J = 8.3 Hz, Ar), 7.00 (2 H, d, J = 7.9 Hz, Ar), 6.97 (2 H, d, J = 7.9 Hz, Ar), 6.69 (1 H, s, pyrrole CH), 6.15 (1 H, s, NH), 5.80–5.76 (1 H, m, =CH), 2.37 (3 H, s, CH₃), 2.32 (3 H, s, CH₃), 2.30 (3 H, s, CH₃), 2.10–2.03 (2 H, m, CH₂), 1.57–1.52 (2 H, m, CH₂), 1.48–1.42 (2 H, m, CH₂) and 1.39–1.32 (2 H, m, CH₂); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 142.6 (Ar), 138.1 (Ar), 137.2 (Ar), 136.5 (Ar), 135.2 (Ar), 134.5 (pyrrole), 131.5 (=CH), 131.2 (Ar), 129.6 (2 × ArH), 128.9 (2 × ArH), 128.8 (2 × ArH), 128.7 (=C), 127.4 (2 × ArH), 127.2 (2 × ArH), 124.0 (2 × ArH), 123.0 (pyrrole), 118.1 (pyrrole CH), 114.4 (pyrrole), 28.2 (CH₂), 25.7 (CH₂), 22.4 (CH₂), 21.5 (CH₂), 21.4 (CH₃), 21.1 (CH₃) and 21.0 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₁H₃₃N₂O₂S⁺ 497.2257; found 497.2265.

3-(4-Methoxybenzenesulfonylamino)-1,2,4-tri(4-tolyl)pyrrole (18p)

1,2-Diaminoalkene 17p (54 mg, 0.10 mmol, 1.0 equiv) was treated with BF₃·OEt₂ (37 μL, 0.30 mmol, 3.0 equiv) in CH₂Cl₂ (3.3 mL) according to General Procedure 4 to give the title compound 18p (26 mg, 50%) as a yellow solid. 4-Ethynyltoluene (38 μL, 0.33 mmol, 1.1 equiv) and 4-methoxybenzenesulfonyl azide (70 mg, 0.33 mmol, 1.1 equiv) were treated with CuTC (3 mg, 16 μmol, 5 mol %) in CH₂Cl₂ (10 mL), followed by α-aminoketone 16a (72 mg, 0.30 mmol, 1.0 equiv) and Rh₂(OAc)₄ (1 mg, 2.3 μmol, 1 mol %), and finally BF₃·OEt₂ (111 μL, 0.90 mmol, 3.0 equiv) according to General Procedure 5 to give the title compound 18p (88 mg, 56%): mp 150 °C dec; ν_max (film) 3271, 3020, 2920, 1593, 1501, 1389, 1323, 1258, 1153, and 1096 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.33 (2 H, d, J = 8.2 Hz, Ar), 7.27 (2 H, d, J = 8.9 Hz, Ar), 7.06 (2 H, d, J = 7.7 Hz, Ar), 7.05 (2 H, d, J = 7.7 Hz, Ar), 6.95 (2 H, d, J = 8.9 Hz, Ar), 6.93 (2 H, d, J = 8.2 Hz, Ar), 6.87 (2 H, d, J = 9.1 Hz, Ar), 6.86 (1 H, s, pyrrole CH), 6.47 (2 H, d, J = 9.1 Hz, Ar), 6.17 (1 H, s, NH), 3.76 (3 H, s, OCH₃), 2.34 (3 H, s, CH₃), 2.31 (3 H, s, CH₃) and 2.29 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 162.3 (Ar), 137.4 (Ar), 136.7 (Ar), 136.5 (Ar), 135.5 (Ar), 131.9 (Ar), 131.6 (Ar), 131.1 (Ar), 129.9 (2 × ArH), 129.5 (2 × ArH), 129.1 (2 × ArH), 129.0 (2 × ArH), 128.8 (2 × ArH), 127.4 (2 × ArH), 127.3 (pyrrole), 125.2 (2 × ArH), 123.5 (pyrrole), 119.4 (pyrrole CH), 115.4 (pyrrole), 113.2 (2 × ArH), 55.3 (OCH₃), 21.2 (CH₃), 21.1 (CH₃) and 21.0 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₂H₃₁N₂O₃S⁺ 523.2050; found 523.2058.

3-(4-Nitrobenzenesulfonylamino)-1,2,4-tri(4-tolyl)pyrrole (18q)

1,2-Diaminoalkene 17q (56 mg, 0.10 mmol, 1.0 equiv) was treated with BF₃·OEt₂ (37 μL, 0.30 mmol, 3.0 equiv) in CH₂Cl₂ (3.3 mL) according to General Procedure 4 to give the title compound 18q (45 mg, 83%) as an orange solid: mp 180 °C dec; ν_max (film) 3271, 3036, 2920, 2862, 1516, 1404, 1389, 1346, 1161, and 1092 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.80 (2 H, d, J = 8.8 Hz, Ar), 7.53 (2 H, d, J = 8.8 Hz, Ar), 7.26 (2 H, d, J = 8.1 Hz, Ar), 7.06 (2 H, d, J = 7.6 Hz, Ar), 7.05 (2 H, d, J = 7.6 Hz, Ar), 6.94 (2 H, d, J = 8.3 Hz, Ar), 6.93 (2 H, d, J = 7.8 Hz, Ar), 6.88 (2 H, d, J = 8.3 Hz, Ar), 6.87 (1 H, s, pyrrole CH), 6.53 (1 H, s, NH), 2.32 (3 H, s, CH₃), 2.31 (3 H, s, CH₃) and 2.29 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 149.3 (Ar), 145.7 (Ar), 137.4 (Ar), 137.1 (Ar), 136.8 (Ar), 136.2 (Ar), 132.6 (Ar), 130.7 (Ar), 129.9 (2 × ArH), 129.6 (2 × ArH), 129.1 (2 × ArH), 128.9 (2 × ArH), 128.2 (2 × ArH), 127.4 (2 × ArH), 127.0 (pyrrole), 125.2 (2 × ArH), 123.7 (pyrrole), 123.2 (2 × ArH), 119.7 (pyrrole CH), 114.0 (pyrrole), 21.2 (CH₃), 21.0 (CH₃) and 21.0 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₁H₂₈N₃O₄S⁺ 538.1795; found 538.1805.

3-Mesylamino-1,2,4-tri(4-tolyl)pyrrole (18r)

1,2-Diaminoalkene 17r (45 mg, 0.10 mmol, 1.0 equiv) was treated with BF₃·OEt₂ (37 μL, 0.30 mmol, 3.0 equiv) in CH₂Cl₂ (3.3 mL) according to General Procedure 4 to give the title compound 18r (30 mg, 69%) as an orange solid: mp 93–94 °C; ν_max (film) 3268, 2924, 1516, 1393, 1319, and 1153 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.51 (2 H, d, J = 8.1 Hz, Ar), 7.22 (2 H, d, J = 7.8 Hz, Ar), 7.15 (2 H, d, J = 8.4 Hz, Ar), 7.10 (2 H, d, J = 8.1 Hz, Ar), 7.09 (2 H, d, J = 8.1 Hz, Ar), 7.02 (2 H, d, J = 8.4 Hz, Ar), 6.96 (1 H, s, pyrrole CH), 5.92 (1 H, s, NH), 2.37 (3 H, s, CH₃), 2.33 (3 H, s, CH₃), 2.32 (3 H, s, CH₃) and 2.29 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 137.5 (Ar), 137.4 (Ar), 136.7 (Ar), 136.3 (Ar), 132.1 (Ar), 131.0 (Ar), 130.2 (2 × ArH), 129.6 (2 × ArH), 129.5 (2 × ArH), 129.2 (2 × ArH), 127.9 (2 × ArH), 127.5 (pyrrole), 125.3 (2 × ArH), 123.7 (pyrrole), 119.5 (pyrrole CH), 115.3 (pyrrole), 40.7 (Ms), 21.3 (CH₃), 21.2 (CH₃) and 21.0 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₂₆H₂₇N₂O₂S⁺ 431.1788; found 431.1797.

4-(4-Cyanophenyl)-2-(4-methoxyphenyl)-1-(4-tolyl)-3-tosylaminopyrrole (18s)

1-Ethynyl-4-methoxybenzene (43 μL, 0.32 mmol, 1.2 equiv) and 4-toluenesulfonyl azide (66 mg, 0.33 mmol, 1.2 equiv) were treated with CuTC (3 mg, 16 μmol, 6 mol %) in CH₂Cl₂ (10 mL), followed by α-aminoketone 16e (75 mg, 0.28 mmol, 1.0 equiv) and Rh₂(OAc)₄ (1 mg, 2.3 μmol, 1 mol %), and finally BF₃·OEt₂ (111 μL, 0.90 mmol, 3.2 equiv) according to General Procedure 5 to give the title compound 18s (127 mg, 85%) as an orange solid: mp 140 °C dec; ν_max (film) 3268, 2924, 2226, 1609, 1566, 1516, 1327, 1292, 1250, 1161, 1092, and 1034 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.64 (2 H, d, J = 8.7 Hz, Ar), 7.52 (2 H, d, J = 8.7 Hz, Ar), 7.25 (2 H, d, J = 8.2 Hz, Ar), 7.06 (2 H, d, J = 7.9 Hz, Ar), 6.98 (1 H, s, pyrrole CH), 6.93 (2 H, d, J = 8.2 Hz, Ar), 6.86 (2 H, d, J = 7.9 Hz, Ar), 6.80 (2 H, d, J = 8.8 Hz, Ar), 6.65 (2 H, d, J = 8.8 Hz, Ar), 6.25 (1 H, s, NH), 3.78 (3 H, s, CH₃), 2.31 (3 H, s, CH₃) and 2.31 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 159.0 (Ar), 143.0 (Ar), 139.2 (Ar), 137.1 (Ar), 136.9 (Ar), 136.7 (Ar), 132.7 (Ar), 132.0 (2 × ArH), 131.1 (2 × ArH), 129.7 (2 × ArH), 128.9 (2 × ArH), 127.5 (2 × ArH), 127.1 (2 × ArH), 125.2 (2 × ArH), 121.7 (pyrrole), 121.6 (pyrrole), 120.2 (pyrrole CH), 119.4 (pyrrole), 115.1 (C≡N), 113.7 (2 × ArH), 109.0 (Ar), 55.1 (OCH₃), 21.4 (CH₃) and 21.0 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₂H₂₈N₃O₃S⁺ 534.1846; found 534.1851.

1,4-Di(4-tolyl)-2-(4-methoxyphenyl)-5-methyl-3-tosylaminopyrrole (18t)

1-Ethynyl-4-methoxybenzene (43 μL, 0.32 mmol, 1.1 equiv) and 4-toluenesulfonyl azide (66 mg, 0.33 mmol, 1.1 equiv) were treated with CuTC (3 mg, 16 μmol, 5 mol %) in CH₂Cl₂ (10 mL), followed by α-aminoketone 16g (76 mg, 0.30 mmol, 1.0 equiv) and Rh₂(OAc)₄ (1 mg, 2.3 μmol, 1 mol %), and finally BF₃·OEt₂ (111 μL, 0.90 mmol, 3.0 equiv) according to General Procedure 5 to give the title compound 18t (118 mg, 73%) as an orange solid: mp 70 °C dec; ν_max (film) 3275, 2920, 2851, 1512, 1462, 1381, 1323, 1246, 1157, 1092, and 1030 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.20 (2 H, d, J = 7.4 Hz, Ar), 7.13–7.05 (6 H, m, Ar), 6.96 (2 H, d, J = 8.1 Hz, Ar), 6.88 (2 H, d, J = 8.6 Hz, Ar), 6.82 (2 H, d, J = 8.1 Hz, Ar), 6.59 (2 H, d, J = 8.6 Hz, Ar), 6.03 (1 H, s, NH), 3.74 (3 H, s, OCH₃), 2.36 (3 H, s, CH₃), 2.32 (3 H, s, CH₃), 2.29 (3 H, s, CH₃) and 2.01 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 158.2 (Ar), 142.1 (Ar), 137.3 (Ar), 137.2 (Ar), 135.9 (Ar), 135.3 (Ar), 131.4 (Ar), 131.2 (2 × ArH), 130.8 (Ar), 129.5 (2 × ArH), 129.4 (2 × ArH), 128.8 (2 × ArH), 128.6 (2 × ArH), 128.3 (2 × ArH), 127.0 (2 × ArH), 125.7 (pyrrole), 123.4 (pyrrole), 120.4 (pyrrole), 114.5 (pyrrole), 113.2 (2 × ArH), 55.0 (CH₃), 21.4 (CH₃), 21.2 (CH₃), 21.1 (CH₃) and 11.9 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₃H₃₃N₂O₃S⁺ 537.2206; found 537.2207.

4-Cyclopropyl-1,2-di(4-tolyl)-3-tosylaminopyrrole (18u)

4-Ethynyltoluene (43 μL, 0.37 mmol, 1.2 equiv) and 4-toluenesulfonyl azide (66 mg, 0.33 mmol, 1.1 equiv) were treated with CuTC (3 mg, 16 μmol, 5 mol %) in CH₂Cl₂ (10 mL), followed by α-aminoketone 16u (57 mg, 0.30 mmol, 1.0 equiv) and Rh₂(OAc)₄ (1 mg, 2.3 μmol, 1 mol %), and finally BF₃·OEt₂ (111 μL, 0.90 mmol, 3.0 equiv) according to General Procedure 5 to give the title compound 18u (70 mg, 51%) as a yellow solid: mp 66 °C dec; ν_max (film) 3271, 3005, 2924, 2862, 1516, 1323, and 1161 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.37 (2 H, d, J = 8.3 Hz, Ar), 6.98 (2 H, d, J = 7.8 Hz, Ar), 6.91 (2 H, d, J = 8.3 Hz, Ar), 6.82 (2 H, d, J = 8.1 Hz, Ar), 6.81 (2 H, d, J = 7.8 Hz, Ar), 6.59 (2 H, d, J = 8.1 Hz, Ar), 6.39 (1 H, d, J = 0.8 Hz, pyrrole CH), 6.14 (1 H, s, NH), 2.30 (3 H, s, CH₃), 2.27 (3 H, s, CH₃), 2.26 (3 H, s, CH₃), 1.85 (1 H, ttd, J = 8.3, 5.2, 0.8 Hz, cyclopropane CH), 0.82 (2 H, ddd, J = 8.3, 6.1, 4.0 Hz, 2 × cyclopropane CH) and 0.51 (2 H, ddd, J = 6.1, 5.2, 4.0 Hz, 2 × cyclopropane CH); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 142.5 (Ar), 137.6 (Ar), 136.8 (Ar), 136.4 (Ar), 136.0 (Ar), 130.2 (Ar), 129.5 (2 × ArH), 129.3 (2 × ArH), 128.8 (2 × ArH), 128.5 (2 × ArH), 127.3 (pyrrole), 127.2 (2 × ArH), 126.3 (pyrrole), 125.1 (2 × ArH), 117.6 (pyrrole), 116.9 (pyrrole CH), 21.5 (CH₃), 21.2 (CH₃), 20.9 (CH₃), 7.6 (2 × cyclopropane CH₂) and 5.7 (cyclopropane); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₂₈H₂₉N₂O₂S⁺ 457.1944; found 457.1943.

1,2-Di(4-tolyl)-4-(2-tolyl)-3-tosylaminopyrrole (18v)

4-Ethynyltoluene (43 μL, 0.37 mmol, 1.2 equiv) and 4-toluenesulfonyl azide (66 mg, 0.33 mmol, 1.1 equiv) were treated with CuTC (3 mg, 16 μmol, 5 mol %) in CH₂Cl₂ (10 mL), followed by α-aminoketone 16v (72 mg, 0.30 mmol, 1.0 equiv) and Rh₂(OAc)₄ (1 mg, 2.3 μmol, 1 mol %), and finally BF₃·OEt₂ (111 μL, 0.90 mmol, 3.0 equiv) according to General Procedure 5 to give the title compound 18v (82 mg, 54%) as a yellow solid: mp 80 °C dec; ν_max (film) 3271, 3063, 2924, 1516, 1389, 1327, and 1161 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.19 (2 H, d, J = 8.3 Hz, Ar), 7.15–7.04 (6 H, m, Ar), 7.01–6.98 (4 H, m, Ar), 6.97 (2 H, d, J = 8.3 Hz, Ar), 6.82 (2 H, d, J = 7.8 Hz, Ar), 6.69 (1 H, s, pyrrole CH), 6.08 (1 H, s, NH), 2.31 (6 H, s, 2 × CH₃), 2.29 (3 H, s, CH₃) and 2.23 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 142.2 (Ar), 137.5 (2 × Ar), 136.8 (Ar), 136.4 (Ar), 136.2 (Ar), 133.3 (Ar), 131.0 (pyrrole), 130.5 (ArH), 130.1 (2 × ArH), 129.9 (ArH), 129.5 (2 × ArH), 128.8 (2 × ArH), 128.8 (2 × ArH), 127.4 (Ar), 126.8 (2 × ArH), 126.5 (ArH), 125.4 (ArH), 125.2 (2 × ArH), 122.6 (pyrrole), 120.3 (pyrrole CH), 116.3 (pyrrole), 21.4 (CH₃), 21.3 (CH₃), 20.9 (CH₃) and 20.7 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₂H₃₁N₂O₂S⁺ 507.2101; found 507.2111.

1,4-Di(4-tolyl)-2-(4-fluorophenyl)-3-tosylaminopyrrole (18w)

1-Ethynyl-4-fluorobenzene (40 mg, 0.33 mmol, 1.1 equiv) and 4-toluenesulfonyl azide (66 mg, 0.33 mmol, 1.1 equiv) were treated with CuTC (3 mg, 16 μmol, 5 mol %) in CH₂Cl₂ (10 mL), followed by α-aminoketone 16a (72 mg, 0.30 mmol, 1.0 equiv) and Rh₂(OAc)₄ (1 mg, 2.3 μmol, 1 mol %), and finally BF₃·OEt₂ (111 μL, 0.90 mmol, 3.0 equiv) according to General Procedure 5 to give the title compound 18w (134 mg, 87%) as a yellow solid: mp 90 °C dec; ν_max (film) 3275, 3024, 2920, 2866, 1510, 1505, 1412, 1389, 1323, 1223, 1157, and 1092 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.29–7.23 (4 H, m, ArH), 7.08–7.04 (2 H, m, ArH), 7.06 (2 H, d, J = 7.9 Hz, ArH), 6.99 (2 H, dd, J = 8.8, 5.4 Hz, C₆H₄F), 6.93 (2 H, d, J = 8.3 Hz, Ar), 6.86 (1 H, s, pyrrole CH), 6.83 (2 H, d, J = 7.9 Hz, ArH), 6.81 (2 H, dd, J = 8.8, 8.8 Hz, C₆H₄F), 6.21 (1 H, app d, J = 8.5 Hz, NH), 2.35 (3 H, s, CH₃), 2.32 (3 H, s, CH₃) and 2.28 (3 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 161.9 (d, J = 247.2 Hz, C₆H₄F), 142.6 (Ar), 137.1 (Ar), 137.1 (Ar), 136.8 (Ar), 135.7 (Ar), 131.9 (d, J = 8.2 Hz, 2 × C₆H₄F), 131.0 (pyrrole), 130.8 (Ar), 129.6 (2 × ArH), 129.0 (2 × ArH), 128.8 (2 × ArH), 127.4 (2 × ArH), 127.0 (2 × ArH), 126.4 (d, J = 3.4 Hz, C₆H₄F), 125.3 (2 × ArH), 123.7 (pyrrole), 119.6 (pyrrole CH), 115.6 (pyrrole), 115.0 (d, J = 21.6 Hz, 2 × C₆H₄F), 21.4 (CH₃), 21.2 (CH₃) and 20.9 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₃₁H₂₈FN₂O₂S⁺ 511.1850; found 511.1856.

3-Amino-1,2,4-tri(4-tolyl)pyrrole (23a)

Triflic acid (16 μL, 0.18 mmol, 3.0 equiv) was added to a solution of pyrrole 18a (30 mg, 0.059 mmol, 1.0 equiv) in 1,2-dichloroethane (2.0 mL) at 0 °C (ice bath). The mixture was heated at 90 °C (heating block) in a sealed vial for 2.5 h. The reaction mixture was cooled to ambient temperature, and the reaction was quenched by the addition of ethylenediamine (2 drops) followed by 1 M aqueous NaOH (2.0 mL). The aqueous phase was extracted with dichloromethane (3 × 2.0 mL), and the combined organic layers were washed with brine, dried (MgSO₄), and concentrated in vacuo. Purification by flash column chromatography (SiO₂, 5% hexane in ethyl acetate) gave the title compound 23a (16 mg, 77%) as a yellow oil: ν_max (film) 3402, 3322, 3028, 2920, 2859, 1516, and 1389 cm^–1; ¹H NMR (400 MHz, 25.0 °C, CDCl₃) δ 7.52 (2 H, d, J = 8.1 Hz, Ar), 7.23 (2 H, d, J = 7.7 Hz, Ar), 7.12–7.00 (8 H, m, Ar), 6.85 (1 H, s, pyrrole CH), 3.35 (2 H, br s, NH), 2.38 (3 H, s, 2 × CH₃) and 2.32 (6 H, s, CH₃); ¹³C{¹H} NMR (101 MHz, 25.0 °C, CDCl₃) δ 138.1 (Ar), 135.4 (Ar), 135.4 (Ar), 135.3 (Ar), 131.9 (pyrrole), 129.5 (2 × ArH), 129.5 (2 × ArH), 129.2 (3 × ArH and Ar), 128.9 (2 × ArH), 128.6 (pyrrole), 127.1 (2 × ArH), 124.5 (2 × ArH), 119.2 (pyrrole CH), 117.9 (Ar), 116.9 (pyrrole), 21.2 (CH₃), 21.1 (CH₃) and 20.9 (CH₃); HRMS (ESI-TOF) m/z [M + H]⁺ calcd for C₂₅H₂₅N₂⁺ 353.2012; found 353.2014.

Acknowledgments

A.B. thanks the Royal Society and TATA for a University Research Fellowship. M.B.W. thanks the Royal Society for a PhD studentship.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.joc.2c00434.

High-resolution ¹H and ¹³C NMR spectra of all products and selected NOESY spectra (PDF)

Author Contributions

The manuscript was written through contributions of all authors.

The authors declare no competing financial interest.

Supplementary Material

jo2c00434_si_001.pdf^{(10.1MB, pdf)}

References

a Singh N.; Singh S.; Kohli S.; Singh A.; Asiki H.; Rathee G.; Chandra R.; Anderson E. A. Recent Progress in the Total Synthesis of Pyrrole-Containing Natural Products (2011–2020). Org. Chem. Front. 2021, 8, 5550–5573. 10.1039/D0QO01574A. [DOI] [Google Scholar]; b Young I. S.; Thornton P. D.; Thompson A. Synthesis of Natural Products Containing the Pyrrolic Ring. Nat. Prod. Rep. 2010, 27, 1801–1839. 10.1039/c0np00014k. [DOI] [PubMed] [Google Scholar]; c Fürstner A. Chemistry and Biology of Roseophilin and the Prodigiosin Alkaloids: A Survey of the Last 2500 Years. Angew. Chem., Int. Ed. 2003, 42, 3582–3603. 10.1002/anie.200300582. [DOI] [PubMed] [Google Scholar]
a Bhardwaj V.; Gumber D.; Abbot V.; Dhiman S.; Sharma P. Pyrrole: A Resourceful Small Molecule in Key Medicinal Hetero-Aromatics. RSC Adv. 2015, 5, 15233–15266. 10.1039/C4RA15710A. [DOI] [Google Scholar]; b Li Petri G.; Spanò V.; Spatola R.; Holl R.; Raimondi M. V.; Barraja P.; Montalbano A. Bioactive Pyrrole-Based Compounds with Target Selectivity. Eur. J. Med. Chem. 2020, 208, 112783. 10.1016/j.ejmech.2020.112783. [DOI] [PMC free article] [PubMed] [Google Scholar]
a Curran D.; Grimshaw J.; Perera S. D. Poly(Pyrrole) as a Support for Electrocatalytic Materials. Chem. Soc. Rev. 1991, 20, 391–404. 10.1039/cs9912000391. [DOI] [Google Scholar]; b Maeda H. Supramolecular Chemistry of Pyrrole-Based Π-Conjugated Molecules. Bull. Chem. Soc. Jpn. 2013, 86, 1359–1399. 10.1246/bcsj.20130219. [DOI] [Google Scholar]; c Loudet A.; Burgess K. Bodipy Dyes and Their Derivatives: Syntheses and Spectroscopic Properties. Chem. Rev. 2007, 107, 4891–4932. 10.1021/cr078381n. [DOI] [PubMed] [Google Scholar]
a Finlay A. C.; Hochstein F. A.; Sobin B. A.; Murphy F. X. Netropsin, a New Antibiotic Produced by a Streptomyces. J. Am. Chem. Soc. 1951, 73, 341–343. 10.1021/ja01145a113. [DOI] [Google Scholar]; b Nguyen G. T. H.; Leung W. Y.; Tran T. N.; Wang H.; Murray V.; Donald W. A. Mechanism for the Binding of Netropsin to Hairpin DNA Revealed Using Nanoscale Ion Emitters in Native Mass Spectrometry. Anal. Chem. 2020, 92, 1130–1137. 10.1021/acs.analchem.9b04209. [DOI] [PubMed] [Google Scholar]; c Lewis E. A.; Munde M.; Wang S.; Rettig M.; Le V.; Machha V.; Wilson W. D. Complexity in the Binding of Minor Groove Agents: Netropsin Has Two Thermodynamically Different DNA Binding Modes at a Single Site. Nucleic Acids Res. 2011, 39, 9649–9658. 10.1093/nar/gkr699. [DOI] [PMC free article] [PubMed] [Google Scholar]
a Arcamone F.; Penco S.; Orezzi P.; Nicolella V.; Pirelli A. Structure and Synthesis of Distamycin A. Nature 1964, 203, 1064–1065. 10.1038/2031064a0. [DOI] [PubMed] [Google Scholar]; b Zimmer C.Effects of the Antibiotics Netropsin and Distamycin a on the Structure and Function of Nucleic Acids. In Progress in Nucleic Acid Research and Molecular Biology; Elsevier, 1975; pp 285–318. [DOI] [PubMed] [Google Scholar]; c Asai A.; Sakai Y.; Ogawa H.; Yamashita Y.; Kakita S.; Ochiai K.; Asmzawa T.; Mihara A.; Mizukami T.; Nakano H. Pyrronamycin a and B, Novel Antitumor Antibiotics Containing Pyrrole-Amide Repeating Unit, Produced by Streptomyces Sp. J. Antibiot. 2000, 53, 66–69. 10.7164/antibiotics.53.66. [DOI] [PubMed] [Google Scholar]
Han X.; Liu Z.; Zhang Z.; Zhang X.; Zhu T.; Gu Q.; Li W.; Che Q.; Li D. Geranylpyrrol a and Piericidin F from Streptomyces Sp. Chq-64 Δrdmf. J. Nat. Prod. 2017, 80, 1684–1687. 10.1021/acs.jnatprod.7b00016. [DOI] [PubMed] [Google Scholar]
a Knorr L. Synthese Von Pyrrolderivaten. Chem. Ber. 1884, 17, 1635–1642. 10.1002/cber.18840170220. [DOI] [Google Scholar]; b Paal C. Synthese Von Thiophen- Und Pyrrolderivaten. Chem. Ber. 1885, 18, 367–371. 10.1002/cber.18850180175. [DOI] [Google Scholar]; c Huisgen R.; Laschtuvka E. Eine Neue Synthese Von Derivaten Des Pyrrols. Chem. Ber. 1960, 93, 65–81. 10.1002/cber.19600930113. [DOI] [Google Scholar]; d Hantzsch A. Neue Bildungsweise Von Pyrrolderivaten. Chem. Ber. 1890, 23, 1474–1476. 10.1002/cber.189002301243. [DOI] [Google Scholar]; e Xuan D. D. Recent Progress in the Synthesis of Pyrroles. Curr. Org. Chem. 2020, 24, 622–657. 10.2174/1385272824666200228121627. [DOI] [Google Scholar]
a Gewald K.; Schäfer H.; Bellmann P.; Hain U. Zur Synthese Von 3-Amino-Pyrrolen Durch Thorpe-Ziegler-Cyclisierung. J. Prakt. Chem. 1992, 334, 491–496. 10.1002/prac.19923340608. [DOI] [Google Scholar]; b Cobb J.; Demetropoulos I. N.; Korakas D.; Skoulika S.; Varvounis G. Synthesis and Reactions of 1-Aryl-2-Nitropyrroles. Structural and Conformational Study of Ethyl N-[2′-[1′-(2-Nitropyrrolyl)]Phenyl]-N-Toluene-4-Sulfonamide Glycinate. Tetrahedron 1996, 52, 4485–4494. 10.1016/0040-4020(96)00096-8. [DOI] [Google Scholar]; c Galenko E. E.; Galenko A. V.; Khlebnikov A. F.; Novikov M. S.; Shakirova J. R. Synthesis and Intramolecular Azo Coupling of 4-Diazopyrrole-2-Carboxylates: Selective Approach to Benzo and Hetero [C]-Fused 6h-Pyrrolo[3,4-C]Pyridazine-5-Carboxylates. J. Org. Chem. 2016, 81, 8495–8507. 10.1021/acs.joc.6b01662. [DOI] [PubMed] [Google Scholar]
a Raushel J.; Fokin V. V. Efficient Synthesis of 1-Sulfonyl-1,2,3-Triazoles. Org. Lett. 2010, 12, 4952–4955. 10.1021/ol102087r. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Yoo E. J.; Ahlquist M.; Kim S. H.; Bae I.; Fokin V. V.; Sharpless K. B.; Chang S. Copper-Catalyzed Synthesis of N-Sulfonyl-1,2,3-Triazoles: Controlling Selectivity. Angew. Chem., Int. Ed. 2007, 46, 1730–1733. 10.1002/anie.200604241. [DOI] [PubMed] [Google Scholar]
a Miura T.; Murakami M.. Reactions of Α-Imino Rhodium(II) Carbene Complexes Generated from N-Sulfonyl-1,2,3-Triazoles. Rhodium Catalysis in Organic Synthesis; Wiley-VCH, 2019; pp 449–470. [Google Scholar]; b Davies H. M. L.; Alford J. S. Reactions of Metallocarbenes Derived from N-Sulfonyl-1,2,3-Triazoles. Chem. Soc. Rev. 2014, 43, 5151–5162. 10.1039/C4CS00072B. [DOI] [PubMed] [Google Scholar]; c Anbarasan P.; Yadagiri D.; Rajasekar S. Recent Advances in Transition-Metal-Catalyzed Denitrogenative Transformations- of 1,2,3-Triazoles and Related Compounds. Synthesis 2014, 46, 3004–3023. 10.1055/s-0034-1379303. [DOI] [Google Scholar]; d Chattopadhyay B.; Gevorgyan V. Transition-Metal-Catalyzed Denitrogenative Transannulation: Converting Triazoles into Other Heterocyclic Systems. Angew. Chem., Int. Ed. 2012, 51, 862–872. 10.1002/anie.201104807. [DOI] [PMC free article] [PubMed] [Google Scholar]; e Bakulev V.; Dehaen W.; Beryozkina T.. Thermal Rearrangements and Transformations of 1,2,3-Triazoles. Chemistry of 1,2,3-Triazoles; Springer, 2014; pp 1–49. [Google Scholar]; f Pal K.; Volla C. M. R. Catalytic Insertion Reactions of Α-Imino Carbenoids. Chem. Rec. 2021, 21, 4032–4058. 10.1002/tcr.202100238. [DOI] [PubMed] [Google Scholar]
a Wang Y.; Wu Y.; Li Y.; Tang Y. Denitrogenative Suzuki and Carbonylative Suzuki Coupling Reactions of Benzotriazoles with Boronic Acids. Chem. Sci. 2017, 8, 3852–3857. 10.1039/C7SC00367F. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Li Y.-L.; Zhang P.-C.; Wu H.-H.; Zhang J. Palladium-Catalyzed Asymmetric Tandem Denitrogenative Heck/Tsuji-Trost of Benzotriazoles with 1,3-Dienes. J. Am. Chem. Soc. 2021, 143, 13010–13015. 10.1021/jacs.1c07212. [DOI] [PubMed] [Google Scholar]; c Zhang P. C.; Han J.; Zhang J. Pd/Pc-Phos-Catalyzed Enantioselective Intermolecular Denitrogenative Cyclization of Benzotriazoles with Allenes and N-Allenamides. Angew. Chem., Int. Ed. 2019, 58, 11444–11448. 10.1002/anie.201904805. [DOI] [PubMed] [Google Scholar]; d Wang Y.; Li Y.; Fan Y.; Wang Z.; Tang Y. Palladium-Catalyzed Denitrogenative Functionalizations of Benzotriazoles with Alkenes and 1,3-Dienes. Chem. Commun. 2017, 53, 11873–11876. 10.1039/C7CC07543J. [DOI] [PubMed] [Google Scholar]
a Schultz E. E.; Sarpong R. Application of in Situ-Generated Rh-Bound Trimethylenemethane Variants to the Synthesis of 3,4-Fused Pyrroles. J. Am. Chem. Soc. 2013, 135, 4696–4699. 10.1021/ja401380d. [DOI] [PubMed] [Google Scholar]; b Miura T.; Hiraga K.; Biyajima T.; Nakamuro T.; Murakami M. Regiocontrolled Synthesis of Polysubstituted Pyrroles Starting from Terminal Alkynes, Sulfonyl Azides, and Allenes. Org. Lett. 2013, 15, 3298–3301. 10.1021/ol401340u. [DOI] [PubMed] [Google Scholar]; c Kwok S. W.; Zhang L.; Grimster N. P.; Fokin V. V. Catalytic Asymmetric Transannulation of Nh-1,2,3-Triazoles with Olefins. Angew. Chem., Int. Ed. 2014, 53, 3452–3456. 10.1002/anie.201306706. [DOI] [PMC free article] [PubMed] [Google Scholar]; d Shang H.; Wang Y.; Tian Y.; Feng J.; Tang Y. The Divergent Synthesis of Nitrogen Heterocycles by Rhodium(II)-Catalyzed Cycloadditions of 1-Sulfonyl 1,2,3-Triazoles with 1,3-Dienes. Angew. Chem., Int. Ed. 2014, 53, 5662–5666. 10.1002/anie.201400426. [DOI] [PubMed] [Google Scholar]; e Xing Y.; Sheng G.; Wang J.; Lu P.; Wang Y. Preparation of Triazoloindoles Via Tandem Copper Catalysis and Their Utility as Α-Imino Rhodium Carbene Precursors. Org. Lett. 2014, 16, 1244–1247. 10.1021/ol5002347. [DOI] [PubMed] [Google Scholar]; f Zhang L.; Sun G.; Bi X. Rhodium/Silver-Cocatalyzed Transannulation of N-Sulfonyl-1,2,3-Triazoles with Vinyl Azides: Divergent Synthesis of Pyrroles and 2 H-Pyrazines. Chem.—Asian J. 2016, 11, 3018–3021. 10.1002/asia.201601164. [DOI] [PubMed] [Google Scholar]; g Alcaide B.; Almendros P.; Cembellín S.; Martínez del Campo T.; Palop G. Allenols Versus Allenones: Rhodium-Catalyzed Regiodivergent and Tunable Allene Reactivity with Triazoles. Chem.—Eur. J. 2017, 23, 13754–13759. 10.1002/chem.201702468. [DOI] [PubMed] [Google Scholar]; h Li F.; Pei C.; Koenigs R. M. Rhodium-Catalyzed Cascade Reactions of Triazoles with Organoselenium Compounds - a Combined Experimental and Mechanistic Study. Chem. Sci. 2021, 12, 6362–6369. 10.1039/D1SC00495F. [DOI] [PMC free article] [PubMed] [Google Scholar]
a Miura T.; Yamauchi M.; Murakami M. Nickel-Catalysed Denitrogenative Alkyne Insertion Reactions of N-Sulfonyl-1,2,3-Triazoles. Chem. Commun. 2009, 1470–1471. 10.1039/b819162j. [DOI] [PubMed] [Google Scholar]; b Chattopadhyay B.; Gevorgyan V. Rh-Catalyzed Transannulation of N-Tosyl-1,2,3-Triazoles with Terminal Alkynes. Org. Lett. 2011, 13, 3746–3749. 10.1021/ol2014347. [DOI] [PMC free article] [PubMed] [Google Scholar]; c Shi Y.; Gevorgyan V. Intramolecular Transannulation of Alkynyl Triazoles Via Alkyne-Carbene Metathesis Step: Access to Fused Pyrroles. Org. Lett. 2013, 15, 5394–5396. 10.1021/ol4027655. [DOI] [PMC free article] [PubMed] [Google Scholar]
a Rajasekar S.; Anbarasan P. Rhodium-Catalyzed Transannulation of 1,2,3-Triazoles to Polysubstituted Pyrroles. J. Org. Chem. 2014, 79, 8428–8434. 10.1021/jo501043h. [DOI] [PubMed] [Google Scholar]; b Kim C.-E.; Park S.; Eom D.; Seo B.; Lee P. H. Synthesis of Pyrroles from Terminal Alkynes, N-Sulfonyl Azides, and Alkenyl Alkyl Ethers through 1-Sulfonyl-1,2,3-Triazoles. Org. Lett. 2014, 16, 1900–1903. 10.1021/ol500718s. [DOI] [PubMed] [Google Scholar]; c Feng J.; Wang Y.; Li Q.; Jiang R.; Tang Y. Facile Synthesis of Pyrroles via Rh(II)-Catalyzed Transannulation of 1-Tosyl-1,2,3-Triazoles with Silyl or Alkyl Enol Ethers. Tetrahedron Lett. 2014, 55, 6455–6458. 10.1016/j.tetlet.2014.09.134. [DOI] [Google Scholar]; d Ran R.-Q.; He J.; Xiu S.-D.; Wang K.-B.; Li C.-Y. Synthesis of 3-Pyrrolin-2-Ones by Rhodium-Catalyzed Transannulation of 1-Sulfonyl-1,2,3-Triazole with Ketene Silyl Acetal. Org. Lett. 2014, 16, 3704–3707. 10.1021/ol501514b. [DOI] [PubMed] [Google Scholar]; e Kim C.-E.; Park Y.; Park S.; Lee P. H. Diastereoselective Synthesis of Tetrahydrofurano- and Tetrahydropyrano- Dihydropyrroles Containing N,O-Acetal Moieties Via Rhodium-Catalyzed Transannulation of N-Sulfonyl-1,2,3-Triazoles with Oxacycloalkenes. Adv. Synth. Catal. 2015, 357, 210–220. 10.1002/adsc.201400604. [DOI] [Google Scholar]; f Yang H.; Hou S.; Tao C.; Liu Z.; Wang C.; Cheng B.; Li Y.; Zhai H. Rhodium-Catalyzed Denitrogenative [3 + 2] Cycloaddition: Access to Functionalized Hydroindolones and the Framework of Montanine-Typeamaryllidaceaealkaloids. Chem.—Eur. J. 2017, 23, 12930–12936. 10.1002/chem.201702893. [DOI] [PubMed] [Google Scholar]; g Rajasekar S.; Anbarasan P. A General Proline-Catalyzed Synthesis of 4,5-Disubstituted N-Sulfonyl-1,2,3-Triazoles from 1,3-Dicarbonyl Compounds and Sulfonyl Azide. Chem.—Asian J. 2019, 14, 4563–4567. 10.1002/asia.201901015. [DOI] [PubMed] [Google Scholar]; h Bi J.; Tan Q.; Wu H.; Liu Q.; Zhang G. Rhodium-Catalyzed Denitrogenative Transannulation of N-Sulfonyl-1,2,3-Triazoles with Glycals Giving Pyrroline-Fused N-Glycosides. Org. Lett. 2021, 23, 6357–6361. 10.1021/acs.orglett.1c02141. [DOI] [PubMed] [Google Scholar]
Parr B. T.; Green S. A.; Davies H. M. L. Rhodium-Catalyzed Conversion of Furans to Highly Functionalized Pyrroles. J. Am. Chem. Soc. 2013, 135, 4716–4718. 10.1021/ja401386z. [DOI] [PubMed] [Google Scholar]
a Spangler J. E.; Davies H. M. L. Catalytic Asymmetric Synthesis of Pyrroloindolines Via a Rhodium(II)-Catalyzed Annulation of Indoles. J. Am. Chem. Soc. 2013, 135, 6802–6805. 10.1021/ja4025337. [DOI] [PubMed] [Google Scholar]; b Alford J. S.; Davies H. M. L. Mild Aminoacylation of Indoles and Pyrroles through a Three-Component Reaction with Ynol Ethers and Sulfonyl Azides. J. Am. Chem. Soc. 2014, 136, 10266–10269. 10.1021/ja5058967. [DOI] [PubMed] [Google Scholar]; c Bora P. P.; Luo Z.-L.; Chen L.; Kang Q. Rh(II)-Catalyzed Intramolecular Dearomatizing Annulation of N-Sulfonyl-1,2,3-Triazoles: Synthesis of Polycyclic Spiroindolines. Tetrahedron 2016, 72, 1467–1471. 10.1016/j.tet.2016.01.049. [DOI] [Google Scholar]; d Fu L.; Davies H. M. L. Scope of the Reactions of Indolyl- and Pyrrolyl-Tethered N-Sulfonyl-1,2,3-Triazoles: Rhodium(II)-Catalyzed Synthesis of Indole- and Pyrrole-Fused Polycyclic Compounds. Org. Lett. 2017, 19, 1504–1507. 10.1021/acs.orglett.7b00180. [DOI] [PMC free article] [PubMed] [Google Scholar]
a Miura T.; Funakoshi Y.; Murakami M. Intramolecular Dearomatizing [3 + 2] Annulation of Α-Imino Carbenoids with Aryl Rings Furnishing 3,4-Fused Indole Skeletons. J. Am. Chem. Soc. 2014, 136, 2272–2275. 10.1021/ja412663a. [DOI] [PubMed] [Google Scholar]; b Kim H.; Kim S.-E.; Jeon W. H.; Lee K.; Lee P. H. Synthesis of 3a,7a-Dihydroindoles Via Rhodium-Catalyzed Intermolecular Formal [3 + 2] Transannulation Reactions of Triazoles with Alkyl-Substituted Benzene Derivatives. Bull. Korean Chem. Soc. 2017, 38, 1299–1305. 10.1002/bkcs.11283. [DOI] [Google Scholar]; c Jana S.; Vroemans R.; Dehaen W. Synthesis of Polycyclic Dihydroindoles by Selective Decomposition of Bis(1,2,3-Triazoles) Mediated by Rhodium Catalysis. Adv. Synth. Catal. 2017, 359, 3085–3089. 10.1002/adsc.201700756. [DOI] [Google Scholar]; d Lu J.-T.; Shi Z.-F.; Cao X.-P. Total Synthesis of (−)-Chanoclavine I and an Oxygen-Substituted Ergoline Derivative. J. Org. Chem. 2017, 82, 7774–7782. 10.1021/acs.joc.7b00573. [DOI] [PubMed] [Google Scholar]; e Yuan H.; Guo Z.; Luo T. Synthesis of (+)-Lysergol and Its Analogues to Assess Serotonin Receptor Activity. Org. Lett. 2017, 19, 624–627. 10.1021/acs.orglett.6b03779. [DOI] [PubMed] [Google Scholar]; f Wilkerson-Hill S. M.; Haines B. E.; Musaev D. G.; Davies H. M. L. Synthesis of [3a,7a]-Dihydroindoles by a Tandem Arene Cyclopropanation/3,5-Sigmatropic Rearrangement Reaction. J. Org. Chem. 2018, 83, 7939–7949. 10.1021/acs.joc.8b00812. [DOI] [PMC free article] [PubMed] [Google Scholar]; g Anna; Chen Z.; Qiao H.; Gao J.; Zhu M.; Li C. Synthesis of Xanthones from 4-(2-Phenoxyphenyl)-1-Tosyl-1h-1,2,3-Triazole Via Rhodium-Catalyzed Annulation/Oxidation. Catal. Commun. 2021, 161, 106360. 10.1016/j.catcom.2021.106360. [DOI] [Google Scholar]
a Cheng W.; Tang Y.; Xu Z.-F.; Li C.-Y. Synthesis of Multifunctionalized 2-Carbonylpyrrole by Rhodium-Catalyzed Transannulation of 1-Sulfonyl-1,2,3-Triazole with Β-Diketone. Org. Lett. 2016, 18, 6168–6171. 10.1021/acs.orglett.6b03179. [DOI] [PubMed] [Google Scholar]; b Mi P.; Yuan H.; Wang H.; Liao P.; Zhang J.; Bi X. Divergent Reactions between Α-Imino Rhodium Carbenoids and 1,3-Diketones: Substrate-Controlled O-H Versus C-H Insertion. Eur. J. Org. Chem. 2017, 2017, 1289–1293. 10.1002/ejoc.201700009. [DOI] [Google Scholar]; c Miura T.; Tanaka T.; Hiraga K.; Stewart S. G.; Murakami M. Stereoselective Synthesis of 2,3-Dihydropyrroles from Terminal Alkynes, Azides, and Α,Β-Unsaturated Aldehydes Via N-Sulfonyl-1,2,3-Triazoles. J. Am. Chem. Soc. 2013, 135, 13652–13655. 10.1021/ja407166r. [DOI] [PubMed] [Google Scholar]; d Ma X.; Liu L.; Wang J.; Xi X.; Xie X.; Wang H. Rhodium-Catalyzed Annulation of Α-Imino Carbenes with Α,Β-Unsaturated Ketones: Construction of Multisubstituted 2,3-Dihydropyrrole/Pyrrole Rings. J. Org. Chem. 2018, 83, 14518–14526. 10.1021/acs.joc.8b01835. [DOI] [PubMed] [Google Scholar]; e Ma X.; Xie X.; Liu L.; Xia R.; Li T.; Wang H. Facile Synthesis of Pyrroloindoles Via a Rhodium(II)-Catalyzed Annulation of 3-Benzylidene-Indolin-2-Ones and Α-Imino Carbenes. Chem. Commun. 2018, 54, 1595–1598. 10.1039/C7CC08438B. [DOI] [PubMed] [Google Scholar]; f He J.; Man Z.; Shi Y.; Li C.-Y. Synthesis of Β-Amino-Α,Β-Unsaturated Ketone Derivatives Via Sequential Rhodium-Catalyzed Sulfur Ylide Formation/Rearrangement. J. Org. Chem. 2015, 80, 4816–4823. 10.1021/acs.joc.5b00521. [DOI] [PubMed] [Google Scholar]
Jia R.; Meng J.; Leng J.; Yu X.; Deng W.-P. Rhodium(II)-Catalyzed Reaction of 1-Tosyl-1,2,3-Triazoles with Morita-Baylis-Hillman Adducts: Synthesis of 3,4-Fused Pyrroles. Chem.—Asian J. 2018, 13, 2360–2364. 10.1002/asia.201800057. [DOI] [PubMed] [Google Scholar]
Alford J. S.; Spangler J. E.; Davies H. M. L. Conversion of Cyclic Ketones to 2,3-Fused Pyrroles and Substituted Indoles. J. Am. Chem. Soc. 2013, 135, 11712–11715. 10.1021/ja405043g. [DOI] [PubMed] [Google Scholar]
Yadagiri D.; Reddy A. C. S.; Anbarasan P. Rhodium Catalyzed Diastereoselective Synthesis of 2,2,3,3-Tetrasubstituted Indolines from N-Sulfonyl-1,2,3-Triazoles and Ortho-Vinylanilines. Chem. Sci. 2016, 7, 5934–5938. 10.1039/C6SC01075J. [DOI] [PMC free article] [PubMed] [Google Scholar]
a Li L.; Xia X.-H.; Wang Y.; Bora P. P.; Kang Q. Synthesis of Benzofuransviatandem Rhodium-Catalyzed C(sp³)-H Insertion and Copper-Catalyzed Dehydrogenation. Adv. Synth. Catal. 2015, 357, 2089–2097. 10.1002/adsc.201500396. [DOI] [Google Scholar]; b Lindsay V. N. G.; Viart H. M. F.; Sarpong R. Stereodivergent Intramolecular C(sp³)-H Functionalization of Azavinyl Carbenes: Synthesis of Saturated Heterocycles and Fused N-Heterotricycles. J. Am. Chem. Soc. 2015, 137, 8368–8371. 10.1021/jacs.5b04295. [DOI] [PubMed] [Google Scholar]; c Shen M.-H.; Pan Y.-P.; Jia Z.-H.; Ren X.-T.; Zhang P.; Xu H.-D. An Efficient Approach to 1,2,3-Trisubstituted Indole Via Rhodium Catalyzed Carbene Csp3-H Bond Insertion. Org. Biol. Chem. 2015, 13, 4851–4854. 10.1039/C5OB00085H. [DOI] [PubMed] [Google Scholar]; d Senoo M.; Furukawa A.; Hata T.; Urabe H. Rhodium-Catalyzed Intramolecular C-H Bond Activation with Triazoles: Preparation of Stereodefined Pyrrolidines and Other Related Cyclic Compounds. Chem.—Eur. J. 2016, 22, 890–895. 10.1002/chem.201503823. [DOI] [PubMed] [Google Scholar]; e Shen H.; Fu J.; Yuan H.; Gong J.; Yang Z. Synthesis of 2,3-Disubstituted Indoles and Benzofurans by the Tandem Reaction of Rhodium(II)-Catalyzed Intramolecular C-H Insertion and Oxygen-Mediated Oxidation. J. Org. Chem. 2016, 81, 10180–10192. 10.1021/acs.joc.6b00611. [DOI] [PubMed] [Google Scholar]
a Rajagopal B.; Chou C.-H.; Chung C.-C.; Lin P.-C. Synthesis of Substituted 3-Indolylimines and Indole-3-Carboxaldehydes by Rhodium(II)-Catalyzed Annulation. Org. Lett. 2014, 16, 3752–3755. 10.1021/ol501618z. [DOI] [PubMed] [Google Scholar]; b Tang X.-Y.; Zhang Y.-S.; He L.; Wei Y.; Shi M. Intramolecular Annulation of Aromatic Rings with N-Sulfonyl 1,2,3-Triazoles: Divergent Synthesis of 3-Methylene-2,3-Dihydrobenzofurans and 3-Methylene-2,3-Dihydroindoles. Chem. Commun. 2015, 51, 133–136. 10.1039/C4CC08343A. [DOI] [PubMed] [Google Scholar]; c Schultz E. E.; Lindsay V. N. G.; Sarpong R. Expedient Synthesis of Fused Azepine Derivatives Using a Sequential Rhodium(II)-Catalyzed Cyclopropanation/1-Aza-Cope Rearrangement of Dienyltriazoles. Angew. Chem., Int. Ed. 2014, 53, 9904–9908. 10.1002/anie.201405356. [DOI] [PMC free article] [PubMed] [Google Scholar]; d Xu H.-D.; Jia Z.-H.; Xu K.; Zhou H.; Shen M.-H. One-Pot Protocol to Functionalized Benzopyrrolizidine Catalyzed Successively by Rh2(Oac)4 and Cu(Otf)2: A Transition Metal-Lewis Acid Catalysis Relay. Org. Lett. 2015, 17, 66–69. 10.1021/ol503247t. [DOI] [PubMed] [Google Scholar]; e Tian Y.; Wang Y.; Shang H.; Xu X.; Tang Y. Rhodium(II)-Catalyzed Intramolecular Formal [4 + 3] Cycloadditions of Dienyltriazoles: Rapid Access to Fused 2,5-Dihydroazepines. Org. Biol. Chem. 2015, 13, 612–619. 10.1039/C4OB01910E. [DOI] [PubMed] [Google Scholar]; f Shen M.-H.; Xu H.-D.; Xu K.; Zhou H.; Jia Z.-H.; Wu H.; Lu X.-L. Ring-Strain-Driven Catalytic Carbene Formation-Cyclopropanation-Aza-Cope Rearrangement Cascade: A Facile Entry to Fused Dihydroazepines from 1,3-Dienyltriazoles. Synthesis 2015, 47, 641–646. 10.1055/s-0034-1379636. [DOI] [Google Scholar]; g Li Y.; Zhang Q.; Du Q.; Zhai H. Rh-Catalyzed [3 + 2] Cycloaddition of 1-Sulfonyl-1,2,3-Triazoles: Access to the Framework of Aspidosperma and Kopsia Indole Alkaloids. Org. Lett. 2016, 18, 4076–4079. 10.1021/acs.orglett.6b01968. [DOI] [PubMed] [Google Scholar]; h Sontakke G. S.; Pal K.; Volla C. M. R. Rh(II)-Catalyzed Denitrogenative Transannulation of N-Sulfonyl-1,2,3-Triazolyl Cyclohexadienones for the Synthesis of Benzofurans and Cyclopropa[Cd]Indole-Carbaldehydes. J. Org. Chem. 2019, 84, 12198–12208. 10.1021/acs.joc.9b01924. [DOI] [PubMed] [Google Scholar]; i Lee K. R.; Ahn S.; Lee S.-g. Synergistic Pd(0)/Rh(II) Dual Catalytic [6 + 3] Dipolar Cycloaddition for the Synthesis of Monocyclic Nine-Membered N,O-Heterocycles and Their Alder-Ene Rearrangement to Fused Bicyclic Compounds. Org. Lett. 2021, 23, 3735–3740. 10.1021/acs.orglett.1c01135. [DOI] [PubMed] [Google Scholar]
a Selander N.; Worrell B. T.; Chuprakov S.; Velaparthi S.; Fokin V. V. Arylation of Rhodium(II) Azavinyl Carbenes with Boronic Acids. J. Am. Chem. Soc. 2012, 134, 14670–14673. 10.1021/ja3062453. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Parr B. T.; Davies H. M. L. Rhodium-Catalyzed Tandem Cyclopropanation/Cope Rearrangement of 4-Alkenyl-1-Sulfonyl-1,2,3-Triazoles with Dienes. Angew. Chem., Int. Ed. 2013, 52, 10044–10047. 10.1002/anie.201304310. [DOI] [PubMed] [Google Scholar]; c Miura T.; Tanaka T.; Matsumoto K.; Murakami M. One-Pot Synthesis of 2,5-Dihydropyrroles from Terminal Alkynes, Azides, and Propargylic Alcohols by Relay Actions of Copper, Rhodium, and Gold. Chem.—Eur. J. 2014, 20, 16078–16082. 10.1002/chem.201405357. [DOI] [PubMed] [Google Scholar]; d Fu J.; Shen H.; Chang Y.; Li C.; Gong J.; Yang Z. Concise Stereoselective Synthesis of Oxaspirocycles with 1-Tosyl-1,2,3-Triazoles: Application to the Total Syntheses of (±)-Tuberostemospiroline and (±)-Stemona-Lactam R. Chem.—Eur. J. 2014, 20, 12881–12888. 10.1002/chem.201403756. [DOI] [PubMed] [Google Scholar]; e Murakami M.; Miura T.; Zhao Q.; Funakoshi Y. Site-Selective Introduction of an Enamido Group at the C(3)-Position of Indoles. Heterocycles 2015, 91, 1579–1584. 10.3987/COM-15-13261. [DOI] [Google Scholar]; f Wang H.; Qiao H.; Zhang H.; Yang H.; Zhao Y.; Fu H. Rhodium-Catalyzed Hydrosilylation Reaction of N-Sulfonyl-1,2,3-Triazoles with Triphenylsilane: Access to Diverse Compounds. Eur. J. Org. Chem. 2015, 2015, 4471–4480. 10.1002/ejoc.201500455. [DOI] [Google Scholar]; g Cheng X.; Yu Y.; Mao Z.; Chen J.; Huang X. Facile Synthesis of Substituted 3-Aminofurans through a Tandem Reaction of N-Sulfonyl-1,2,3-Triazoles with Propargyl Alcohols. Org. Biol. Chem. 2016, 14, 3878–3882. 10.1039/C6OB00377J. [DOI] [PubMed] [Google Scholar]; h Man Z.; Dai H.; Shi Y.; Yang D.; Li C.-Y. Synthesis of 5-Iodo-1,2,3,4-Tetrahydropyridines by Rhodium-Catalyzed Tandem Nucleophilic Attacks Involving 1-Sulfonyl-1,2,3-Triazoles and Iodides. Org. Lett. 2016, 18, 4962–4965. 10.1021/acs.orglett.6b02428. [DOI] [PubMed] [Google Scholar]; i Kubiak R. W.; Davies H. M. L. Rhodium-Catalyzed Intermolecular C-H Functionalization as a Key Step in the Synthesis of Complex Stereodefined Β-Arylpyrrolidines. Org. Lett. 2018, 20, 3771–3775. 10.1021/acs.orglett.8b01362. [DOI] [PMC free article] [PubMed] [Google Scholar]; j Liu Z.; Chen L.; Zhu D.; Zhu S. Formal Allylation and Enantioselective Cyclopropanation of Donor/Acceptor Rhodium(II) Azavinyl Carbenes. Org. Lett. 2021, 23, 1275–1279. 10.1021/acs.orglett.0c04251. [DOI] [PubMed] [Google Scholar]
a Bosmani A.; Guarnieri-Ibáñez A.; Goudedranche S.; Besnard C.; Lacour J. Polycyclic Indoline-Benzodiazepines through Electrophilic Additions of Α-Imino Carbenes to Tröger Bases. Angew. Chem., Int. Ed. 2018, 57, 7151–7155. 10.1002/anie.201803756. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Bosmani A.; Guarnieri-Ibáñez A.; Lacour J. Configurational Lability of Imino-Substituted Ethano Trögerbases. Insight on the Racemization Mechanism. Helv. Chim. Acta 2019, 102, e1900021. 10.1002/hlca.201900021. [DOI] [Google Scholar]; c Saleh N.; Bosmani A.; Besnard C.; Bürgi T.; Jacquemin D.; Lacour J. Access to Chiral Rigid Hemicyanine Fluorophores from Tröger Bases and Α-Imino Carbenes. Org. Lett. 2020, 22, 7599–7603. 10.1021/acs.orglett.0c02726. [DOI] [PubMed] [Google Scholar]; d Guarnieri-Ibáñez A.; de Aguirre A.; Besnard C.; Poblador-Bahamonde A. I.; Lacour J. Regiodivergent Synthesis of Pyrazino-Indolines Vs. Triazocines Via Α-Imino Carbenes Addition to Imidazolidines. Chem. Sci. 2021, 12, 1479–1485. 10.1039/D0SC05725H. [DOI] [PMC free article] [PubMed] [Google Scholar]
a Lei X.; Li L.; He Y.-P.; Tang Y. Rhodium(II)-Catalyzed Formal [3 + 2] Cycloaddition of N-Sulfonyl-1,2,3-Triazoles with Isoxazoles: Entry to Polysubstituted 3-Aminopyrroles. Org. Lett. 2015, 17, 5224–5227. 10.1021/acs.orglett.5b02570. [DOI] [PubMed] [Google Scholar]; b Rostovskii N. V.; Ruvinskaya J. O.; Novikov M. S.; Khlebnikov A. F.; Smetanin I. A.; Agafonova A. V. Switchable Synthesis of Pyrroles and Pyrazines Via Rh(II)-Catalyzed Reaction of 1,2,3-Triazoles with Isoxazoles: Experimental and Dft Evidence for the 1,4-Diazahexatriene Intermediate. J. Org. Chem. 2017, 82, 256–268. 10.1021/acs.joc.6b02389. [DOI] [PubMed] [Google Scholar]
a Zhao Y.-Z.; Yang H.-B.; Tang X.-Y.; Shi M. Rh(II)-Catalyzed [3 + 2] Cycloaddition of 2 H-Azirines with N-Sulfonyl-1,2,3-Triazoles. Chem.—Eur. J. 2015, 21, 3562–3566. 10.1002/chem.201406460. [DOI] [PubMed] [Google Scholar]; b Wang Y.; Lei X.; Tang Y. Rh(II)-Catalyzed Cycloadditions of 1-Tosyl 1,2,3-Triazoles with 2h-Azirines: Switchable Reactivity of Rh-Azavinylcarbene as [2c]- or Aza-[3c]-Synthon. Chem. Commun. 2015, 51, 4507–4510. 10.1039/C5CC00268K. [DOI] [PubMed] [Google Scholar]; c Khaidarov A. R.; Rostovskii N. V.; Starova G. L.; Khlebnikov A. F.; Novikov M. S. Synthesis of Spirocyclic 3H-Pyrrol-4-Amines from 2h-Azirines and 1-Sulfonyl-1,2,3-Triazoles. Chem. Heterocycl. Compd. 2018, 54, 946–950. 10.1007/s10593-018-2378-8. [DOI] [Google Scholar]; d Khaidarov A. R.; Rostovskii N. V.; Zolotarev A. A.; Khlebnikov A. F.; Novikov M. S. Synthesis of 1-(2-Aminovinyl)Indoles and 1,3′-Biindoles by Reaction of 2,2-Diaryl-Substituted 2h-Azirines with Α-Imino Rh(II) Carbenoids. J. Org. Chem. 2019, 84, 3743–3753. 10.1021/acs.joc.8b03205. [DOI] [PubMed] [Google Scholar]
a Ye T.; McKervey M. A. Organic Synthesis With.Alpha.-Diazo Carbonyl Compounds. Chem. Rev. 1994, 94, 1091–1160. 10.1021/cr00028a010. [DOI] [Google Scholar]; b Gillingham D.; Fei N. Catalytic X-H Insertion Reactions Based on Carbenoids. Chem. Soc. Rev. 2013, 42, 4918–4931. 10.1039/c3cs35496b. [DOI] [PubMed] [Google Scholar]
a Chuprakov S.; Worrell B. T.; Selander N.; Sit R. K.; Fokin V. V. Stereoselective 1,3-Insertions of Rhodium(II) Azavinyl Carbenes. J. Am. Chem. Soc. 2014, 136, 195–202. 10.1021/ja408185c. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Lee D. J.; Yoo E. J. Efficient Synthesis of C-N-Coupled Heterobiaryls by Sequential N-H Functionalization Reactions. Org. Lett. 2015, 17, 1830–1833. 10.1021/acs.orglett.5b00625. [DOI] [PubMed] [Google Scholar]; c He X.; Wu Y.; Zhou T.; Zuo Y.; Xie M.; Li R.; Duan J.; Shang Y. Rh-Catalyzed C-N Coupling of N-Sulfonyl-1,2,3-Trizales with Secondary Amines for Regioselective Synthesis of Phenylvinyl-1,2-Diamines. Synth. Commun. 2020, 50, 2685–2697. 10.1080/00397911.2020.1781185. [DOI] [Google Scholar]
Miura T.; Biyajima T.; Fujii T.; Murakami M. Synthesis of Α-Amino Ketones from Terminal Alkynes Via Rhodium-Catalyzed Denitrogenative Hydration of N-Sulfonyl-1,2,3-Triazoles. J. Am. Chem. Soc. 2012, 134, 194–196. 10.1021/ja2104203. [DOI] [PubMed] [Google Scholar]
The (Z)-geometry was confirmed by NOESY studies on a selection of substrates: 17b, 17d, 17g.
Espino C. G.; Fiori K. W.; Kim M.; Du Bois J. Expanding the Scope of C-H Amination through Catalyst Design. J. Am. Chem. Soc. 2004, 126, 15378–15379. 10.1021/ja0446294. [DOI] [PubMed] [Google Scholar]
Hashimoto S.-i.; Watanabe N.; Sato T.; Shiro M.; Ikegami S. Enhancement of Enantioselectivity in Intramolecular C-H Insertion Reactions of Α-Diazo Β-Keto Esters Catalyzed by Chiral Dirhodium(II) Carboxylates. Tetrahedron Lett. 1993, 34, 5109–5112. 10.1016/S0040-4039(00)60689-5. [DOI] [Google Scholar]
Xu Z.-F.; An Y.; Chen Y.; Duan S. Rhodium-Catalysed Synthesis of Fused Pyrimidine Derivatives Employing N-Sulfonyl-1,2,3-Triazoles as a 1-Aza-[4c] Synthon. Tetrahedron Lett. 2019, 60, 1849–1853. 10.1016/j.tetlet.2019.06.023. [DOI] [Google Scholar]
Cornel V.; Lovely C. J.. Boron Trifluoride Etherate. Encyclopedia of Reagents for Organic Synthesis; John Wiley & Sons, 1995; pp 664–672. [Google Scholar]
a Hayashi Y. Pot Economy and One-Pot Synthesis. Chem. Sci. 2016, 7, 866–880. 10.1039/C5SC02913A. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Yasuda N.The Art of Process Chemistry; Wiley-VCH, 2010. [Google Scholar]; c Zhang T. Y. Process Chemistry: The Science, Business, Logic, and Logistics. Chem. Rev. 2006, 106, 2583–2595. 10.1021/cr040677v. [DOI] [PubMed] [Google Scholar]; d Tietze L. F. Domino Reactions in Organic Synthesis. Chem. Rev. 1996, 96, 115–136. 10.1021/cr950027e. [DOI] [PubMed] [Google Scholar]
Miura T.; Tanaka T.; Yada A.; Murakami M. Doyle-Kirmse Reaction Using Triazoles Leading to One-Pot Multifunctionalization of Terminal Alkynes. Chem. Lett. 2013, 42, 1308–1310. 10.1246/cl.130521. [DOI] [Google Scholar]
Javorskis T.; Orentas E. Chemoselective Deprotection of Sulfonamides under Acidic Conditions: Scope, Sulfonyl Group Migration, and Synthetic Applications. J. Org. Chem. 2017, 82, 13423–13439. 10.1021/acs.joc.7b02507. [DOI] [PubMed] [Google Scholar]
Yoo E. J.; Ahlquist M.; Kim S. H.; Bae I.; Fokin V. V.; Sharpless K. B.; Chang S. Copper-Catalyzed Synthesis Ofn-Sulfonyl-1,2,3-Triazoles: Controlling Selectivity. Angew. Chem., Int. Ed. 2007, 46, 1730–1733. 10.1002/anie.200604241. [DOI] [PubMed] [Google Scholar]
Liu Y.; Wang X.; Xu J.; Zhang Q.; Zhao Y.; Hu Y. Highly Controlling Selectivity of Copper(I)-Catalyzed Azide/Alkyne Cycloaddition (Cuaac) between Sulfonyl Azids and Normal Alkynes or Propynoates. Tetrahedron 2011, 67, 6294–6299. 10.1016/j.tet.2011.06.017. [DOI] [Google Scholar]
Chuprakov S.; Malik J. A.; Zibinsky M.; Fokin V. V. Catalytic Asymmetric C-H Insertions of Rhodium(II) Azavinyl Carbenes. J. Am. Chem. Soc. 2011, 133, 10352–10355. 10.1021/ja202969z. [DOI] [PMC free article] [PubMed] [Google Scholar]
Cano I.; Nicasio M. C.; Pérez P. J. Copper(I) Complexes as Catalysts for the Synthesis of N-Sulfonyl-1,2,3-Triazoles from N-Sulfonylazides and Alkynes. Org. Biomol. Chem. 2010, 8, 536–538. 10.1039/B912835B. [DOI] [PubMed] [Google Scholar]
Tachdjian C.; Barton D. H. R.; Chern C.-Y.; Tachdjan C. Preparation of New Thiohydroxamic Acid Derivatives: Synthesis of Substituted 1-Hydroxy-1,2-Dihydoroimidazole-2-Thiones. Heterocycles 1994, 37, 793. 10.3987/COM-93-S55. [DOI] [Google Scholar]
Schmidt R. R.; Dimmler M.; Hemmerich P. Heterocyclische 8π-Systeme, 8:1,4-Dihydropyrazine Und 1,4-Dihydropyrazin-Anionen. Chem. Ber. 1976, 109, 2395–2404. 10.1002/cber.19761090706. [DOI] [Google Scholar]
Jiang T.-S.; Dai L.; Zhou Y.; Zhang X. Palladium-Catalyzed Tandem Oxidative Annulation of Α-Amino Ketones Leading to 2-Aroylindoles. Tetrahedron 2020, 76, 130917. 10.1016/j.tet.2019.130917. [DOI] [Google Scholar]
Kallmayer H.-j.; Wagner E. Zur Farbe Der N-(4′-Nitrophenacyl)-Arylamine. Arch. Pharm. 1980, 313, 315–323. 10.1002/ardp.19803130407. [DOI] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

jo2c00434_si_001.pdf^{(10.1MB, pdf)}

[ref1] a Singh N.; Singh S.; Kohli S.; Singh A.; Asiki H.; Rathee G.; Chandra R.; Anderson E. A. Recent Progress in the Total Synthesis of Pyrrole-Containing Natural Products (2011–2020). Org. Chem. Front. 2021, 8, 5550–5573. 10.1039/D0QO01574A. [DOI] [Google Scholar]; b Young I. S.; Thornton P. D.; Thompson A. Synthesis of Natural Products Containing the Pyrrolic Ring. Nat. Prod. Rep. 2010, 27, 1801–1839. 10.1039/c0np00014k. [DOI] [PubMed] [Google Scholar]; c Fürstner A. Chemistry and Biology of Roseophilin and the Prodigiosin Alkaloids: A Survey of the Last 2500 Years. Angew. Chem., Int. Ed. 2003, 42, 3582–3603. 10.1002/anie.200300582. [DOI] [PubMed] [Google Scholar]

[ref2] a Bhardwaj V.; Gumber D.; Abbot V.; Dhiman S.; Sharma P. Pyrrole: A Resourceful Small Molecule in Key Medicinal Hetero-Aromatics. RSC Adv. 2015, 5, 15233–15266. 10.1039/C4RA15710A. [DOI] [Google Scholar]; b Li Petri G.; Spanò V.; Spatola R.; Holl R.; Raimondi M. V.; Barraja P.; Montalbano A. Bioactive Pyrrole-Based Compounds with Target Selectivity. Eur. J. Med. Chem. 2020, 208, 112783. 10.1016/j.ejmech.2020.112783. [DOI] [PMC free article] [PubMed] [Google Scholar]

[ref3] a Curran D.; Grimshaw J.; Perera S. D. Poly(Pyrrole) as a Support for Electrocatalytic Materials. Chem. Soc. Rev. 1991, 20, 391–404. 10.1039/cs9912000391. [DOI] [Google Scholar]; b Maeda H. Supramolecular Chemistry of Pyrrole-Based Π-Conjugated Molecules. Bull. Chem. Soc. Jpn. 2013, 86, 1359–1399. 10.1246/bcsj.20130219. [DOI] [Google Scholar]; c Loudet A.; Burgess K. Bodipy Dyes and Their Derivatives: Syntheses and Spectroscopic Properties. Chem. Rev. 2007, 107, 4891–4932. 10.1021/cr078381n. [DOI] [PubMed] [Google Scholar]

[ref4] a Finlay A. C.; Hochstein F. A.; Sobin B. A.; Murphy F. X. Netropsin, a New Antibiotic Produced by a Streptomyces. J. Am. Chem. Soc. 1951, 73, 341–343. 10.1021/ja01145a113. [DOI] [Google Scholar]; b Nguyen G. T. H.; Leung W. Y.; Tran T. N.; Wang H.; Murray V.; Donald W. A. Mechanism for the Binding of Netropsin to Hairpin DNA Revealed Using Nanoscale Ion Emitters in Native Mass Spectrometry. Anal. Chem. 2020, 92, 1130–1137. 10.1021/acs.analchem.9b04209. [DOI] [PubMed] [Google Scholar]; c Lewis E. A.; Munde M.; Wang S.; Rettig M.; Le V.; Machha V.; Wilson W. D. Complexity in the Binding of Minor Groove Agents: Netropsin Has Two Thermodynamically Different DNA Binding Modes at a Single Site. Nucleic Acids Res. 2011, 39, 9649–9658. 10.1093/nar/gkr699. [DOI] [PMC free article] [PubMed] [Google Scholar]

[ref5] a Arcamone F.; Penco S.; Orezzi P.; Nicolella V.; Pirelli A. Structure and Synthesis of Distamycin A. Nature 1964, 203, 1064–1065. 10.1038/2031064a0. [DOI] [PubMed] [Google Scholar]; b Zimmer C.Effects of the Antibiotics Netropsin and Distamycin a on the Structure and Function of Nucleic Acids. In Progress in Nucleic Acid Research and Molecular Biology; Elsevier, 1975; pp 285–318. [DOI] [PubMed] [Google Scholar]; c Asai A.; Sakai Y.; Ogawa H.; Yamashita Y.; Kakita S.; Ochiai K.; Asmzawa T.; Mihara A.; Mizukami T.; Nakano H. Pyrronamycin a and B, Novel Antitumor Antibiotics Containing Pyrrole-Amide Repeating Unit, Produced by Streptomyces Sp. J. Antibiot. 2000, 53, 66–69. 10.7164/antibiotics.53.66. [DOI] [PubMed] [Google Scholar]

[ref6] Han X.; Liu Z.; Zhang Z.; Zhang X.; Zhu T.; Gu Q.; Li W.; Che Q.; Li D. Geranylpyrrol a and Piericidin F from Streptomyces Sp. Chq-64 Δrdmf. J. Nat. Prod. 2017, 80, 1684–1687. 10.1021/acs.jnatprod.7b00016. [DOI] [PubMed] [Google Scholar]

[ref7] a Knorr L. Synthese Von Pyrrolderivaten. Chem. Ber. 1884, 17, 1635–1642. 10.1002/cber.18840170220. [DOI] [Google Scholar]; b Paal C. Synthese Von Thiophen- Und Pyrrolderivaten. Chem. Ber. 1885, 18, 367–371. 10.1002/cber.18850180175. [DOI] [Google Scholar]; c Huisgen R.; Laschtuvka E. Eine Neue Synthese Von Derivaten Des Pyrrols. Chem. Ber. 1960, 93, 65–81. 10.1002/cber.19600930113. [DOI] [Google Scholar]; d Hantzsch A. Neue Bildungsweise Von Pyrrolderivaten. Chem. Ber. 1890, 23, 1474–1476. 10.1002/cber.189002301243. [DOI] [Google Scholar]; e Xuan D. D. Recent Progress in the Synthesis of Pyrroles. Curr. Org. Chem. 2020, 24, 622–657. 10.2174/1385272824666200228121627. [DOI] [Google Scholar]

[ref8] a Gewald K.; Schäfer H.; Bellmann P.; Hain U. Zur Synthese Von 3-Amino-Pyrrolen Durch Thorpe-Ziegler-Cyclisierung. J. Prakt. Chem. 1992, 334, 491–496. 10.1002/prac.19923340608. [DOI] [Google Scholar]; b Cobb J.; Demetropoulos I. N.; Korakas D.; Skoulika S.; Varvounis G. Synthesis and Reactions of 1-Aryl-2-Nitropyrroles. Structural and Conformational Study of Ethyl N-[2′-[1′-(2-Nitropyrrolyl)]Phenyl]-N-Toluene-4-Sulfonamide Glycinate. Tetrahedron 1996, 52, 4485–4494. 10.1016/0040-4020(96)00096-8. [DOI] [Google Scholar]; c Galenko E. E.; Galenko A. V.; Khlebnikov A. F.; Novikov M. S.; Shakirova J. R. Synthesis and Intramolecular Azo Coupling of 4-Diazopyrrole-2-Carboxylates: Selective Approach to Benzo and Hetero [C]-Fused 6h-Pyrrolo[3,4-C]Pyridazine-5-Carboxylates. J. Org. Chem. 2016, 81, 8495–8507. 10.1021/acs.joc.6b01662. [DOI] [PubMed] [Google Scholar]

[ref9] a Raushel J.; Fokin V. V. Efficient Synthesis of 1-Sulfonyl-1,2,3-Triazoles. Org. Lett. 2010, 12, 4952–4955. 10.1021/ol102087r. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Yoo E. J.; Ahlquist M.; Kim S. H.; Bae I.; Fokin V. V.; Sharpless K. B.; Chang S. Copper-Catalyzed Synthesis of N-Sulfonyl-1,2,3-Triazoles: Controlling Selectivity. Angew. Chem., Int. Ed. 2007, 46, 1730–1733. 10.1002/anie.200604241. [DOI] [PubMed] [Google Scholar]

[ref10] a Miura T.; Murakami M.. Reactions of Α-Imino Rhodium(II) Carbene Complexes Generated from N-Sulfonyl-1,2,3-Triazoles. Rhodium Catalysis in Organic Synthesis; Wiley-VCH, 2019; pp 449–470. [Google Scholar]; b Davies H. M. L.; Alford J. S. Reactions of Metallocarbenes Derived from N-Sulfonyl-1,2,3-Triazoles. Chem. Soc. Rev. 2014, 43, 5151–5162. 10.1039/C4CS00072B. [DOI] [PubMed] [Google Scholar]; c Anbarasan P.; Yadagiri D.; Rajasekar S. Recent Advances in Transition-Metal-Catalyzed Denitrogenative Transformations- of 1,2,3-Triazoles and Related Compounds. Synthesis 2014, 46, 3004–3023. 10.1055/s-0034-1379303. [DOI] [Google Scholar]; d Chattopadhyay B.; Gevorgyan V. Transition-Metal-Catalyzed Denitrogenative Transannulation: Converting Triazoles into Other Heterocyclic Systems. Angew. Chem., Int. Ed. 2012, 51, 862–872. 10.1002/anie.201104807. [DOI] [PMC free article] [PubMed] [Google Scholar]; e Bakulev V.; Dehaen W.; Beryozkina T.. Thermal Rearrangements and Transformations of 1,2,3-Triazoles. Chemistry of 1,2,3-Triazoles; Springer, 2014; pp 1–49. [Google Scholar]; f Pal K.; Volla C. M. R. Catalytic Insertion Reactions of Α-Imino Carbenoids. Chem. Rec. 2021, 21, 4032–4058. 10.1002/tcr.202100238. [DOI] [PubMed] [Google Scholar]

[ref11] a Wang Y.; Wu Y.; Li Y.; Tang Y. Denitrogenative Suzuki and Carbonylative Suzuki Coupling Reactions of Benzotriazoles with Boronic Acids. Chem. Sci. 2017, 8, 3852–3857. 10.1039/C7SC00367F. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Li Y.-L.; Zhang P.-C.; Wu H.-H.; Zhang J. Palladium-Catalyzed Asymmetric Tandem Denitrogenative Heck/Tsuji-Trost of Benzotriazoles with 1,3-Dienes. J. Am. Chem. Soc. 2021, 143, 13010–13015. 10.1021/jacs.1c07212. [DOI] [PubMed] [Google Scholar]; c Zhang P. C.; Han J.; Zhang J. Pd/Pc-Phos-Catalyzed Enantioselective Intermolecular Denitrogenative Cyclization of Benzotriazoles with Allenes and N-Allenamides. Angew. Chem., Int. Ed. 2019, 58, 11444–11448. 10.1002/anie.201904805. [DOI] [PubMed] [Google Scholar]; d Wang Y.; Li Y.; Fan Y.; Wang Z.; Tang Y. Palladium-Catalyzed Denitrogenative Functionalizations of Benzotriazoles with Alkenes and 1,3-Dienes. Chem. Commun. 2017, 53, 11873–11876. 10.1039/C7CC07543J. [DOI] [PubMed] [Google Scholar]

[ref13] a Miura T.; Yamauchi M.; Murakami M. Nickel-Catalysed Denitrogenative Alkyne Insertion Reactions of N-Sulfonyl-1,2,3-Triazoles. Chem. Commun. 2009, 1470–1471. 10.1039/b819162j. [DOI] [PubMed] [Google Scholar]; b Chattopadhyay B.; Gevorgyan V. Rh-Catalyzed Transannulation of N-Tosyl-1,2,3-Triazoles with Terminal Alkynes. Org. Lett. 2011, 13, 3746–3749. 10.1021/ol2014347. [DOI] [PMC free article] [PubMed] [Google Scholar]; c Shi Y.; Gevorgyan V. Intramolecular Transannulation of Alkynyl Triazoles Via Alkyne-Carbene Metathesis Step: Access to Fused Pyrroles. Org. Lett. 2013, 15, 5394–5396. 10.1021/ol4027655. [DOI] [PMC free article] [PubMed] [Google Scholar]

[ref15] Parr B. T.; Green S. A.; Davies H. M. L. Rhodium-Catalyzed Conversion of Furans to Highly Functionalized Pyrroles. J. Am. Chem. Soc. 2013, 135, 4716–4718. 10.1021/ja401386z. [DOI] [PubMed] [Google Scholar]

[ref16] a Spangler J. E.; Davies H. M. L. Catalytic Asymmetric Synthesis of Pyrroloindolines Via a Rhodium(II)-Catalyzed Annulation of Indoles. J. Am. Chem. Soc. 2013, 135, 6802–6805. 10.1021/ja4025337. [DOI] [PubMed] [Google Scholar]; b Alford J. S.; Davies H. M. L. Mild Aminoacylation of Indoles and Pyrroles through a Three-Component Reaction with Ynol Ethers and Sulfonyl Azides. J. Am. Chem. Soc. 2014, 136, 10266–10269. 10.1021/ja5058967. [DOI] [PubMed] [Google Scholar]; c Bora P. P.; Luo Z.-L.; Chen L.; Kang Q. Rh(II)-Catalyzed Intramolecular Dearomatizing Annulation of N-Sulfonyl-1,2,3-Triazoles: Synthesis of Polycyclic Spiroindolines. Tetrahedron 2016, 72, 1467–1471. 10.1016/j.tet.2016.01.049. [DOI] [Google Scholar]; d Fu L.; Davies H. M. L. Scope of the Reactions of Indolyl- and Pyrrolyl-Tethered N-Sulfonyl-1,2,3-Triazoles: Rhodium(II)-Catalyzed Synthesis of Indole- and Pyrrole-Fused Polycyclic Compounds. Org. Lett. 2017, 19, 1504–1507. 10.1021/acs.orglett.7b00180. [DOI] [PMC free article] [PubMed] [Google Scholar]

[ref17] a Miura T.; Funakoshi Y.; Murakami M. Intramolecular Dearomatizing [3 + 2] Annulation of Α-Imino Carbenoids with Aryl Rings Furnishing 3,4-Fused Indole Skeletons. J. Am. Chem. Soc. 2014, 136, 2272–2275. 10.1021/ja412663a. [DOI] [PubMed] [Google Scholar]; b Kim H.; Kim S.-E.; Jeon W. H.; Lee K.; Lee P. H. Synthesis of 3a,7a-Dihydroindoles Via Rhodium-Catalyzed Intermolecular Formal [3 + 2] Transannulation Reactions of Triazoles with Alkyl-Substituted Benzene Derivatives. Bull. Korean Chem. Soc. 2017, 38, 1299–1305. 10.1002/bkcs.11283. [DOI] [Google Scholar]; c Jana S.; Vroemans R.; Dehaen W. Synthesis of Polycyclic Dihydroindoles by Selective Decomposition of Bis(1,2,3-Triazoles) Mediated by Rhodium Catalysis. Adv. Synth. Catal. 2017, 359, 3085–3089. 10.1002/adsc.201700756. [DOI] [Google Scholar]; d Lu J.-T.; Shi Z.-F.; Cao X.-P. Total Synthesis of (−)-Chanoclavine I and an Oxygen-Substituted Ergoline Derivative. J. Org. Chem. 2017, 82, 7774–7782. 10.1021/acs.joc.7b00573. [DOI] [PubMed] [Google Scholar]; e Yuan H.; Guo Z.; Luo T. Synthesis of (+)-Lysergol and Its Analogues to Assess Serotonin Receptor Activity. Org. Lett. 2017, 19, 624–627. 10.1021/acs.orglett.6b03779. [DOI] [PubMed] [Google Scholar]; f Wilkerson-Hill S. M.; Haines B. E.; Musaev D. G.; Davies H. M. L. Synthesis of [3a,7a]-Dihydroindoles by a Tandem Arene Cyclopropanation/3,5-Sigmatropic Rearrangement Reaction. J. Org. Chem. 2018, 83, 7939–7949. 10.1021/acs.joc.8b00812. [DOI] [PMC free article] [PubMed] [Google Scholar]; g Anna; Chen Z.; Qiao H.; Gao J.; Zhu M.; Li C. Synthesis of Xanthones from 4-(2-Phenoxyphenyl)-1-Tosyl-1h-1,2,3-Triazole Via Rhodium-Catalyzed Annulation/Oxidation. Catal. Commun. 2021, 161, 106360. 10.1016/j.catcom.2021.106360. [DOI] [Google Scholar]

[ref18] a Cheng W.; Tang Y.; Xu Z.-F.; Li C.-Y. Synthesis of Multifunctionalized 2-Carbonylpyrrole by Rhodium-Catalyzed Transannulation of 1-Sulfonyl-1,2,3-Triazole with Β-Diketone. Org. Lett. 2016, 18, 6168–6171. 10.1021/acs.orglett.6b03179. [DOI] [PubMed] [Google Scholar]; b Mi P.; Yuan H.; Wang H.; Liao P.; Zhang J.; Bi X. Divergent Reactions between Α-Imino Rhodium Carbenoids and 1,3-Diketones: Substrate-Controlled O-H Versus C-H Insertion. Eur. J. Org. Chem. 2017, 2017, 1289–1293. 10.1002/ejoc.201700009. [DOI] [Google Scholar]; c Miura T.; Tanaka T.; Hiraga K.; Stewart S. G.; Murakami M. Stereoselective Synthesis of 2,3-Dihydropyrroles from Terminal Alkynes, Azides, and Α,Β-Unsaturated Aldehydes Via N-Sulfonyl-1,2,3-Triazoles. J. Am. Chem. Soc. 2013, 135, 13652–13655. 10.1021/ja407166r. [DOI] [PubMed] [Google Scholar]; d Ma X.; Liu L.; Wang J.; Xi X.; Xie X.; Wang H. Rhodium-Catalyzed Annulation of Α-Imino Carbenes with Α,Β-Unsaturated Ketones: Construction of Multisubstituted 2,3-Dihydropyrrole/Pyrrole Rings. J. Org. Chem. 2018, 83, 14518–14526. 10.1021/acs.joc.8b01835. [DOI] [PubMed] [Google Scholar]; e Ma X.; Xie X.; Liu L.; Xia R.; Li T.; Wang H. Facile Synthesis of Pyrroloindoles Via a Rhodium(II)-Catalyzed Annulation of 3-Benzylidene-Indolin-2-Ones and Α-Imino Carbenes. Chem. Commun. 2018, 54, 1595–1598. 10.1039/C7CC08438B. [DOI] [PubMed] [Google Scholar]; f He J.; Man Z.; Shi Y.; Li C.-Y. Synthesis of Β-Amino-Α,Β-Unsaturated Ketone Derivatives Via Sequential Rhodium-Catalyzed Sulfur Ylide Formation/Rearrangement. J. Org. Chem. 2015, 80, 4816–4823. 10.1021/acs.joc.5b00521. [DOI] [PubMed] [Google Scholar]

[ref19] Jia R.; Meng J.; Leng J.; Yu X.; Deng W.-P. Rhodium(II)-Catalyzed Reaction of 1-Tosyl-1,2,3-Triazoles with Morita-Baylis-Hillman Adducts: Synthesis of 3,4-Fused Pyrroles. Chem.—Asian J. 2018, 13, 2360–2364. 10.1002/asia.201800057. [DOI] [PubMed] [Google Scholar]

[ref20] Alford J. S.; Spangler J. E.; Davies H. M. L. Conversion of Cyclic Ketones to 2,3-Fused Pyrroles and Substituted Indoles. J. Am. Chem. Soc. 2013, 135, 11712–11715. 10.1021/ja405043g. [DOI] [PubMed] [Google Scholar]

[ref21] Yadagiri D.; Reddy A. C. S.; Anbarasan P. Rhodium Catalyzed Diastereoselective Synthesis of 2,2,3,3-Tetrasubstituted Indolines from N-Sulfonyl-1,2,3-Triazoles and Ortho-Vinylanilines. Chem. Sci. 2016, 7, 5934–5938. 10.1039/C6SC01075J. [DOI] [PMC free article] [PubMed] [Google Scholar]

[ref22] a Li L.; Xia X.-H.; Wang Y.; Bora P. P.; Kang Q. Synthesis of Benzofuransviatandem Rhodium-Catalyzed C(sp³)-H Insertion and Copper-Catalyzed Dehydrogenation. Adv. Synth. Catal. 2015, 357, 2089–2097. 10.1002/adsc.201500396. [DOI] [Google Scholar]; b Lindsay V. N. G.; Viart H. M. F.; Sarpong R. Stereodivergent Intramolecular C(sp³)-H Functionalization of Azavinyl Carbenes: Synthesis of Saturated Heterocycles and Fused N-Heterotricycles. J. Am. Chem. Soc. 2015, 137, 8368–8371. 10.1021/jacs.5b04295. [DOI] [PubMed] [Google Scholar]; c Shen M.-H.; Pan Y.-P.; Jia Z.-H.; Ren X.-T.; Zhang P.; Xu H.-D. An Efficient Approach to 1,2,3-Trisubstituted Indole Via Rhodium Catalyzed Carbene Csp3-H Bond Insertion. Org. Biol. Chem. 2015, 13, 4851–4854. 10.1039/C5OB00085H. [DOI] [PubMed] [Google Scholar]; d Senoo M.; Furukawa A.; Hata T.; Urabe H. Rhodium-Catalyzed Intramolecular C-H Bond Activation with Triazoles: Preparation of Stereodefined Pyrrolidines and Other Related Cyclic Compounds. Chem.—Eur. J. 2016, 22, 890–895. 10.1002/chem.201503823. [DOI] [PubMed] [Google Scholar]; e Shen H.; Fu J.; Yuan H.; Gong J.; Yang Z. Synthesis of 2,3-Disubstituted Indoles and Benzofurans by the Tandem Reaction of Rhodium(II)-Catalyzed Intramolecular C-H Insertion and Oxygen-Mediated Oxidation. J. Org. Chem. 2016, 81, 10180–10192. 10.1021/acs.joc.6b00611. [DOI] [PubMed] [Google Scholar]

[ref25] a Bosmani A.; Guarnieri-Ibáñez A.; Goudedranche S.; Besnard C.; Lacour J. Polycyclic Indoline-Benzodiazepines through Electrophilic Additions of Α-Imino Carbenes to Tröger Bases. Angew. Chem., Int. Ed. 2018, 57, 7151–7155. 10.1002/anie.201803756. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Bosmani A.; Guarnieri-Ibáñez A.; Lacour J. Configurational Lability of Imino-Substituted Ethano Trögerbases. Insight on the Racemization Mechanism. Helv. Chim. Acta 2019, 102, e1900021. 10.1002/hlca.201900021. [DOI] [Google Scholar]; c Saleh N.; Bosmani A.; Besnard C.; Bürgi T.; Jacquemin D.; Lacour J. Access to Chiral Rigid Hemicyanine Fluorophores from Tröger Bases and Α-Imino Carbenes. Org. Lett. 2020, 22, 7599–7603. 10.1021/acs.orglett.0c02726. [DOI] [PubMed] [Google Scholar]; d Guarnieri-Ibáñez A.; de Aguirre A.; Besnard C.; Poblador-Bahamonde A. I.; Lacour J. Regiodivergent Synthesis of Pyrazino-Indolines Vs. Triazocines Via Α-Imino Carbenes Addition to Imidazolidines. Chem. Sci. 2021, 12, 1479–1485. 10.1039/D0SC05725H. [DOI] [PMC free article] [PubMed] [Google Scholar]

[ref26] a Lei X.; Li L.; He Y.-P.; Tang Y. Rhodium(II)-Catalyzed Formal [3 + 2] Cycloaddition of N-Sulfonyl-1,2,3-Triazoles with Isoxazoles: Entry to Polysubstituted 3-Aminopyrroles. Org. Lett. 2015, 17, 5224–5227. 10.1021/acs.orglett.5b02570. [DOI] [PubMed] [Google Scholar]; b Rostovskii N. V.; Ruvinskaya J. O.; Novikov M. S.; Khlebnikov A. F.; Smetanin I. A.; Agafonova A. V. Switchable Synthesis of Pyrroles and Pyrazines Via Rh(II)-Catalyzed Reaction of 1,2,3-Triazoles with Isoxazoles: Experimental and Dft Evidence for the 1,4-Diazahexatriene Intermediate. J. Org. Chem. 2017, 82, 256–268. 10.1021/acs.joc.6b02389. [DOI] [PubMed] [Google Scholar]

[ref27] a Zhao Y.-Z.; Yang H.-B.; Tang X.-Y.; Shi M. Rh(II)-Catalyzed [3 + 2] Cycloaddition of 2 H-Azirines with N-Sulfonyl-1,2,3-Triazoles. Chem.—Eur. J. 2015, 21, 3562–3566. 10.1002/chem.201406460. [DOI] [PubMed] [Google Scholar]; b Wang Y.; Lei X.; Tang Y. Rh(II)-Catalyzed Cycloadditions of 1-Tosyl 1,2,3-Triazoles with 2h-Azirines: Switchable Reactivity of Rh-Azavinylcarbene as [2c]- or Aza-[3c]-Synthon. Chem. Commun. 2015, 51, 4507–4510. 10.1039/C5CC00268K. [DOI] [PubMed] [Google Scholar]; c Khaidarov A. R.; Rostovskii N. V.; Starova G. L.; Khlebnikov A. F.; Novikov M. S. Synthesis of Spirocyclic 3H-Pyrrol-4-Amines from 2h-Azirines and 1-Sulfonyl-1,2,3-Triazoles. Chem. Heterocycl. Compd. 2018, 54, 946–950. 10.1007/s10593-018-2378-8. [DOI] [Google Scholar]; d Khaidarov A. R.; Rostovskii N. V.; Zolotarev A. A.; Khlebnikov A. F.; Novikov M. S. Synthesis of 1-(2-Aminovinyl)Indoles and 1,3′-Biindoles by Reaction of 2,2-Diaryl-Substituted 2h-Azirines with Α-Imino Rh(II) Carbenoids. J. Org. Chem. 2019, 84, 3743–3753. 10.1021/acs.joc.8b03205. [DOI] [PubMed] [Google Scholar]

[ref28] a Ye T.; McKervey M. A. Organic Synthesis With.Alpha.-Diazo Carbonyl Compounds. Chem. Rev. 1994, 94, 1091–1160. 10.1021/cr00028a010. [DOI] [Google Scholar]; b Gillingham D.; Fei N. Catalytic X-H Insertion Reactions Based on Carbenoids. Chem. Soc. Rev. 2013, 42, 4918–4931. 10.1039/c3cs35496b. [DOI] [PubMed] [Google Scholar]

[ref29] a Chuprakov S.; Worrell B. T.; Selander N.; Sit R. K.; Fokin V. V. Stereoselective 1,3-Insertions of Rhodium(II) Azavinyl Carbenes. J. Am. Chem. Soc. 2014, 136, 195–202. 10.1021/ja408185c. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Lee D. J.; Yoo E. J. Efficient Synthesis of C-N-Coupled Heterobiaryls by Sequential N-H Functionalization Reactions. Org. Lett. 2015, 17, 1830–1833. 10.1021/acs.orglett.5b00625. [DOI] [PubMed] [Google Scholar]; c He X.; Wu Y.; Zhou T.; Zuo Y.; Xie M.; Li R.; Duan J.; Shang Y. Rh-Catalyzed C-N Coupling of N-Sulfonyl-1,2,3-Trizales with Secondary Amines for Regioselective Synthesis of Phenylvinyl-1,2-Diamines. Synth. Commun. 2020, 50, 2685–2697. 10.1080/00397911.2020.1781185. [DOI] [Google Scholar]

[ref30] Miura T.; Biyajima T.; Fujii T.; Murakami M. Synthesis of Α-Amino Ketones from Terminal Alkynes Via Rhodium-Catalyzed Denitrogenative Hydration of N-Sulfonyl-1,2,3-Triazoles. J. Am. Chem. Soc. 2012, 134, 194–196. 10.1021/ja2104203. [DOI] [PubMed] [Google Scholar]

[ref31] The (Z)-geometry was confirmed by NOESY studies on a selection of substrates: 17b, 17d, 17g.

[ref32] Espino C. G.; Fiori K. W.; Kim M.; Du Bois J. Expanding the Scope of C-H Amination through Catalyst Design. J. Am. Chem. Soc. 2004, 126, 15378–15379. 10.1021/ja0446294. [DOI] [PubMed] [Google Scholar]

[ref33] Hashimoto S.-i.; Watanabe N.; Sato T.; Shiro M.; Ikegami S. Enhancement of Enantioselectivity in Intramolecular C-H Insertion Reactions of Α-Diazo Β-Keto Esters Catalyzed by Chiral Dirhodium(II) Carboxylates. Tetrahedron Lett. 1993, 34, 5109–5112. 10.1016/S0040-4039(00)60689-5. [DOI] [Google Scholar]

[ref34] Xu Z.-F.; An Y.; Chen Y.; Duan S. Rhodium-Catalysed Synthesis of Fused Pyrimidine Derivatives Employing N-Sulfonyl-1,2,3-Triazoles as a 1-Aza-[4c] Synthon. Tetrahedron Lett. 2019, 60, 1849–1853. 10.1016/j.tetlet.2019.06.023. [DOI] [Google Scholar]

[ref35] Cornel V.; Lovely C. J.. Boron Trifluoride Etherate. Encyclopedia of Reagents for Organic Synthesis; John Wiley & Sons, 1995; pp 664–672. [Google Scholar]

[ref36] a Hayashi Y. Pot Economy and One-Pot Synthesis. Chem. Sci. 2016, 7, 866–880. 10.1039/C5SC02913A. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Yasuda N.The Art of Process Chemistry; Wiley-VCH, 2010. [Google Scholar]; c Zhang T. Y. Process Chemistry: The Science, Business, Logic, and Logistics. Chem. Rev. 2006, 106, 2583–2595. 10.1021/cr040677v. [DOI] [PubMed] [Google Scholar]; d Tietze L. F. Domino Reactions in Organic Synthesis. Chem. Rev. 1996, 96, 115–136. 10.1021/cr950027e. [DOI] [PubMed] [Google Scholar]

[ref37] Miura T.; Tanaka T.; Yada A.; Murakami M. Doyle-Kirmse Reaction Using Triazoles Leading to One-Pot Multifunctionalization of Terminal Alkynes. Chem. Lett. 2013, 42, 1308–1310. 10.1246/cl.130521. [DOI] [Google Scholar]

[ref38] Javorskis T.; Orentas E. Chemoselective Deprotection of Sulfonamides under Acidic Conditions: Scope, Sulfonyl Group Migration, and Synthetic Applications. J. Org. Chem. 2017, 82, 13423–13439. 10.1021/acs.joc.7b02507. [DOI] [PubMed] [Google Scholar]

[ref39] Yoo E. J.; Ahlquist M.; Kim S. H.; Bae I.; Fokin V. V.; Sharpless K. B.; Chang S. Copper-Catalyzed Synthesis Ofn-Sulfonyl-1,2,3-Triazoles: Controlling Selectivity. Angew. Chem., Int. Ed. 2007, 46, 1730–1733. 10.1002/anie.200604241. [DOI] [PubMed] [Google Scholar]

[ref40] Liu Y.; Wang X.; Xu J.; Zhang Q.; Zhao Y.; Hu Y. Highly Controlling Selectivity of Copper(I)-Catalyzed Azide/Alkyne Cycloaddition (Cuaac) between Sulfonyl Azids and Normal Alkynes or Propynoates. Tetrahedron 2011, 67, 6294–6299. 10.1016/j.tet.2011.06.017. [DOI] [Google Scholar]

[ref41] Chuprakov S.; Malik J. A.; Zibinsky M.; Fokin V. V. Catalytic Asymmetric C-H Insertions of Rhodium(II) Azavinyl Carbenes. J. Am. Chem. Soc. 2011, 133, 10352–10355. 10.1021/ja202969z. [DOI] [PMC free article] [PubMed] [Google Scholar]

[ref42] Cano I.; Nicasio M. C.; Pérez P. J. Copper(I) Complexes as Catalysts for the Synthesis of N-Sulfonyl-1,2,3-Triazoles from N-Sulfonylazides and Alkynes. Org. Biomol. Chem. 2010, 8, 536–538. 10.1039/B912835B. [DOI] [PubMed] [Google Scholar]

[ref43] Tachdjian C.; Barton D. H. R.; Chern C.-Y.; Tachdjan C. Preparation of New Thiohydroxamic Acid Derivatives: Synthesis of Substituted 1-Hydroxy-1,2-Dihydoroimidazole-2-Thiones. Heterocycles 1994, 37, 793. 10.3987/COM-93-S55. [DOI] [Google Scholar]

[ref44] Schmidt R. R.; Dimmler M.; Hemmerich P. Heterocyclische 8π-Systeme, 8:1,4-Dihydropyrazine Und 1,4-Dihydropyrazin-Anionen. Chem. Ber. 1976, 109, 2395–2404. 10.1002/cber.19761090706. [DOI] [Google Scholar]

[ref45] Jiang T.-S.; Dai L.; Zhou Y.; Zhang X. Palladium-Catalyzed Tandem Oxidative Annulation of Α-Amino Ketones Leading to 2-Aroylindoles. Tetrahedron 2020, 76, 130917. 10.1016/j.tet.2019.130917. [DOI] [Google Scholar]

[ref46] Kallmayer H.-j.; Wagner E. Zur Farbe Der N-(4′-Nitrophenacyl)-Arylamine. Arch. Pharm. 1980, 313, 315–323. 10.1002/ardp.19803130407. [DOI] [Google Scholar]

PERMALINK

Modular Synthesis of Highly Substituted 3-Azapyrroles by Rh(II)-Catalyzed N–H Bond Insertion and Cyclodehydration

Matthew B Williams

Alistair Boyer

Abstract

Introduction

Figure 1.

Scheme 1. General Reactivity of 1-Sufonyl-1,2,3-triazoles and Selected Application to the Synthesis of Pyrroles and Indoles.

Scheme 2. Approaches to 3-Azapyrroles from 1-Sufonyl-1,2,3-triazoles and This Approach.

Results

Scheme 3. Synthesis of α-Aminoketones 16 and 1-STs 4 Used in This Work.

Table 1. Optimization of N–H Insertiona.

Table 2. Optimization of Cyclodehydrationa.

Scheme 4. Scope of Arylamine in the Pyrrole Synthesis.

Scheme 5. Scope of Ketone in the Pyrrole Synthesis.

Scheme 6. Scope of 1-ST in the Pyrrole Synthesis.

Scheme 7. Three-Step, One-Pot Synthesis of Pyrroles 18 from Alkynes 21, Sulfonyl Azides 22, and α-Aminoketones 16.

Conclusion

Experimental Details

General Information and Methods

General Procedure 1: CuAAC to Form 1STs

4-(4-Tolyl)-1-tosyl-1,2,3-triazole (4a)

4-(Thiophen-2-yl)-1-tosyl-1,2,3-triazole (4m)

4-(4-Methoxyphenyl)-1-tosyl-1,2,3-triazole (4n)

4-(Cyclohexen-1-yl)-1-tosyl-1,2,3-triazole (4o)

1-Methanesulfonyl-4-(4-tolyl)-1,2,3-triazole (4p)

1-(4-Nitrobenzenesulfonyl)-4-(4-tolyl)-1,2,3-triazole (4q)

1-(4-Methoxylphenylsulfonyl)-4-(4-tolyl)-1,2,3-triazole (4r)

General Procedure 2: Formation of α-Aminoketones

1-(4-Tolyl)-2-(4-tolylamino)ethan-1-one (16a)

2-(4-Chlorophenylamino)-1-(4-tolyl)ethan-1-one (16b)

1-(4-Tolyl)-2-(3-trifluoromethylphenylamino)ethan-1-one (16c)

2-(4-Methoxyphenylamino)-1-(4-tolyl)ethan-1-one (16d)

1-(4-Tolyl)-2-(2,4,6-trimethylphenylamino)ethan-1-one (16e)

2-(Naphth-2-ylamino)-1-(4-tolyl)ethan-1-one (16f)

1-(4-Tolyl)-2-(4-tolylamino)propan-1-one (16g)

1-(Naphth-2-yl)-2-(4-tolylamino)ethan-1-one (16h)

1-(4-Methoxyphenyl)-2-(4-tolylamino)ethan-1-one (16i)

1-(4-Nitrophenyl)-2-(4-tolylamino)ethan-1-one (16j)

1-(4-Cyanophenyl)-2-(4-tolylamino)ethan-1-one (16k)

1-(4-Chlorophenyl)-2-(4-tolylamino)ethan-1-one (16l)

1-Cyclopropyl-2-(4-tolylamino)ethan-1-one (16u)

1-(2-Tolyl)-2-(4-tolylamino)ethan-1-one (16v)

General Procedure 3: Rh(II)-Catalyzed N–H Bond Insertion

1-[(2-Oxo-2-(4-tolyl)ethyl)(4-tolyl)amino]-1-(4-tolyl)-2-(tosylamino)ethene (17a)

1-[(4-Chlorophenyl)(2-oxo-2-(4-tolyl)ethyl)amino]-1-(4-tolyl)-2-(tosylamino)ethene (17b)

1-[(2-Oxo-2-(4-tolyl)ethyl)(3-trifluoromethylphenyl)amino]-1-(4-tolyl)-2-(tosylamino)ethene (17c)

1-[(4-Methoxyphenyl)(2-oxo-2-(4-tolyl)ethyl)amino]-1-(4-tolyl)-2-(tosylamino)ethene (17d)

1-[(1-Oxo-1-(4-tolyl)prop-2-yl)(4-tolyl)amino]-1-(4-tolyl)-2-(tosylamino)ethene (17g)

1-[(2-(Naphth-2-yl)-2-oxoethyl)(4-tolyl)amino]-1-(4-tolyl)-2-(tosylamino)ethene (17h)

1-[(2-(4-Methoxyphenyl)-2-oxoethyl)(4-tolyl)amino]-1-(4-tolyl)-2-(tosylamino)ethene (17i)

1-[(2-(4-Nitrophenyl)-2-oxoethyl)(4-tolyl)amino]-1-(4-tolyl)-2-(tosylamino)ethene (17j)

1-[(2-(4-Cyanophenyl)-2-oxoethyl)(4-tolyl)amino]-1-(4-tolyl)-2-(tosylamino)ethene (17k)

1-[(2-(4-Chlorophenyl)-2-oxoethyl)(4-tolyl)amino]-1-(4-tolyl)-2-(tosylamino)ethene (17l)

1-[(2-Oxo-2-(4-tolyl)ethyl)(4-tolyl)amino]-1-(thiophen-2-yl)-2-(tosylamino)ethene (17m)

1-(4-Methoxyphenyl)-1-[(2-oxo-2-(4-tolyl)ethyl)(4-tolyl)amino]-2-(tosylamino)ethene (17n)

1-(Cyclohexen-1-yl)-1-[(2-oxo-2-(4-tolyl)ethyl)(4-tolyl)amino]-2-(tosylamino)ethene (17o)

2-(4-Methoxybenzenesulfonylamino)-1-[(2-oxo-2-(4-tolyl)ethyl)(4-tolyl)amino]-1-(4-tolyl)ethene (17p)

2-(4-Nitrobenzenesulfonylamino)-1-[(2-oxo-2-(4-tolyl)ethyl)(4-tolyl)amino]-1-(4-tolyl)ethene (17q)

2-(Mesylamino)-1-[(2-oxo-2-(4-tolyl)ethyl)(4-tolyl)amino]-1-(4-tolyl)ethene (17r)

General Procedure 4: Cyclodehydration

General Procedure 5: One-Pot Pyrrole Synthesis

3-Tosylamino-1,2,4-tri(4-tolyl)pyrrole (18a)

1-(4-Chlorophenyl)-2,4-di(4-tolyl)-3-tosylaminopyrrole (18b)

2,4-Di(4-tolyl)-3-tosyl-1-(3-trifluoromethylphenyl)aminopyrrole (18c)

2,4-Di(4-tolyl)-1-(4-methoxyphenyl)-3-tosylaminopyrrole (18d)

2,4-Di(4-tolyl)-3-tosyl-1-(2,4,6-trimethylphenyl)aminopyrrole (18e)

2,4-Di(4-tolyl)-1-naphth-2-yl-3-tosylaminopyrrole (18f)

5-Methyl-3-tosylamino-1,2,4-tri(4-tolyl)pyrrole (18g)

1,2-Di(4-tolyl)-4-(naphth-2-yl)-3-tosylaminopyrrole (18h)

1,2-Di(4-tolyl)-4-(4-methoxyphenyl)-3-tosylaminopyrrole (18i)

1,2-Di(4-tolyl)-4-(4-nitrophenyl)-3-tosylaminopyrrole (18j)

4-(4-Cyanophenyl)-1,2-di(4-tolyl)-3-tosylaminopyrrole (18k)

4-(4-Chlorophenyl)-1,2-di(4-tolyl)-3-tosylaminopyrrole (18l)

1,4-Di(4-tolyl)-2-(thiophen-2-yl)-3-tosylaminopyrrole (18m)

1,4-Di(4-tolyl)-2-(4-methoxyphenyl)-3-tosylaminopyrrole (18n)

1,4-Di(4-tolyl)-2-(cyclohexen-1-yl)-3-tosylaminopyrrole (18o)

3-(4-Methoxybenzenesulfonylamino)-1,2,4-tri(4-tolyl)pyrrole (18p)

3-(4-Nitrobenzenesulfonylamino)-1,2,4-tri(4-tolyl)pyrrole (18q)

3-Mesylamino-1,2,4-tri(4-tolyl)pyrrole (18r)

Table 1. Optimization of N–H Insertion^a.

Table 2. Optimization of Cyclodehydration^a.