Synthesis of Sulfoximine Propargyl Carbamates under Improved Conditions for Rhodium Catalyzed Carbamate Transfer to Sulfoxides

Abstract

Sulfoximines provide aza-analogues of sulfones, with potentially improved properties for medicinal chemistry. The sulfoximine nitrogen also provides an additional vector for the inclusion of other functionality. Here, we report improved conditions for rhodium catalyzed synthesis of sulfoximine (and sulfilimine) carbamates, especially for previously low-yielding carbamates containing π-functionality. Notably we report the preparation of propargyl sulfoximine carbamates to provide an alkyne as a potential click handle. Using Rh₂(esp)₂ as catalyst and a DOE optimization approach provided considerably increased yields.

Sulfoximines, the mono aza analogue of sulfones, have become increasingly important motifs in medicinal chemistry (Figure 1a).¹ The incorporation of sulfoximines in place of sulfonamides or sulfones has afforded attractive biologically active compounds that have entered clinical trials for example as anticancer agents, including roniciclib² and BAY1143572³ (Bayer), and ceralasertib (AstraZeneca).^4,5 Sulfoximines are chemically and configurationally stable⁶ and have been found to exhibit improved physicochemical and metabolic properties.⁷ They also provide an additional vector which is valuable for the attachment of a range of functionality through the sulfoximine nitrogen.^8,9

Figure 1.

Chiral sulfoximines as clinical candidates and rhodium-catalyzed sulfoximine synthesis.

Methods for the synthesis of sulfoximines have expanded greatly in recent years.^8,10 Bolm has pioneered numerous methods for the metal-catalyzed transfer of N-functionality to sulfoxides,^11,12 including notably powerful methods for Rh-catalyzed transfer of trifluoroacetamide (Figure 1b).^11a,13 Bull and Luisi developed conditions for the Rh-catalyzed transfer of carbamates to sulfoxides including Boc and Cbz carbamates.¹⁴ Recent developments include metal-free methods for NH-sulfoximine synthesis from sulfoxides and sulfides using hypervalent iodine(III) reagents and ammonium carbamate as the N-source.¹⁵⁻¹⁷ Willis has developed sulfinylamine (RNSO) reagents, suitable for reaction with nucleophiles to form sulfoximines.¹⁸ We have recently developed sulfonimidoyl fluorides for the preparation of enantioenriched sulfoximines with Grignard reagents.^19,20 The formation of sulfilimines by N-transfer to sulfides has seen similar developments including enantioselective N-transfer,²¹ and these can be oxidized to sulfoximines.^10a,12

Aiming to expand access to sulfoximine derivatives bearing pendant N-functionality we revisited our previous work on carbamate N-transfer to sulfoxides (Figure 1c). The previous conditions were effective for alkyl carbamates (R² = Me, tBu), but much lower yields were obtained with unsaturated carbamate substituents. Allyl carbamate for example gave a 40% yield with methyl p-tolyl sulfoxide.¹⁴ In particular, we envisaged that the direct incorporation of an alkyne as a click handle at the same time as constructing the sulfoximine motif would provide a useful process. Given the prevalence of sulfoxides and sulfones in biologically active compounds,²² as well as sulfoximines themselves,¹ we envisaged that the additional vector afforded by a sulfoximine derived from these other S(IV) and S(VI) derivatives could be of value in labeling and provide a handle for further conjugation, for example attachment of a fluorophore or other derivatization of the alkyne. On this basis we investigated the use of propargyl carbamate as a substrate for the preparation of sulfoximines to install an alkyne motif suitable for click chemistry (Figure 1d).

Here we report improved conditions for the carbamate transfer to sulfoxides for the preparation of sulfoximines. In particular this allows the preparation of propargyl carbamate derivatives. Notably improved yields for the preparation of other carbamate derivatives containing π-electrons were also achieved under the modified conditions broadening the potential to form sulfoximine carbamates and sulfilimine carbamates more generally without requiring preformed activated carbamate reagents.

We initially investigated the transfer of 2-propynyl carbamate to methyl phenylsulfoxide 1a. Applying directly our previously developed reaction conditions using Rh₂(OAc)₄ in CH₂Cl₂ afforded the N-propargylcarbamate sulfoximine with a low 24% yield along with an oxidized sulfone side product (Table 1, entry 1). This was in keeping with our previously reported observations that π-functionality in the carbamate was detrimental, and prompted a program of optimization on this reaction to increase yield. Increasing the reaction concentration and catalyst loading gave a slight improvement, but the undesired sulfone continued to be generated in significant quantities, which was also difficult to separate from the desired sulfoximine product (entry 3). Switching the solvent from CH₂Cl₂ to toluene provided a further improved yield of 2a and reduced the formation of side product 3a (entry 4), while also providing a more attractive solvent for development. Changing the rhodium catalyst to Rh₂(O₂CCF₃)₄ was unsuccessful, whereas using Rh₂(Oct)₄ afforded higher yields with Rh₂(esp)₂ achieving an 87% yield (entries 5–7).²³

Table 1. Selected Optimization for Rhodium Catalyzed Propargylic Carbamate Transfer to Sulfoxide 1a.

			Yield (%)b
entrya	Rh catalyst	solvent (concn)	2a	3a	1a
1	Rh2(OAc)4	CH2Cl2 (0.3 M)	24	12	61
2	Rh2(OAc)4	CH2Cl2 (0.5 M)	30	15	57
3	Rh2(OAc)4c	CH2Cl2 (0.5 M)	43	22	27
4	Rh2(OAc)4	toluene (0.5 M)	53	4	38
5	Rh2(O2CCF3)4	toluene (0.5 M)	trace	7	93
6	Rh2(Oct)4	toluene (0.5 M)	73	5	12
7	Rh2(esp)2	toluene (0.5 M)	87	4	6

^aReactions on 0.3 mmol scale.

^bYields determined by the analysis of ¹H NMR using 1,3,5-trimethoxybenzene as an internal standard.

^c5 mol % Rh₂(OAc)₄ used.

Next a design-of-experiments (DoE) optimization was undertaken to further optimize and improve the reaction conditions accounting for the interplay of conditions. The equivalents of the oxidant and carbamate, the catalyst loading and the reaction temperature were identified as major factors to influence yield. Identical equivalents of oxidant and carbamate were used to group these as a single variable so as to reduce the number of variables in the DOE study and improve model accuracy. Other factors such as the concentration (0.5 M) and the reaction time (24 h) were set to fixed values. Additionally, the DoE custom design examined second-order interactions of these parameters. The correlation between the predicted yield and the parameters was visualized by a three-dimensional response surface of the predicted yield against two major factors (the equivalents of oxidant/carbamate and the catalyst loading), and the dome-shaped surface showed a saddle point at 87% (Figure 2). These conditions gave excellent in situ (90%) and isolated yields (85%) of 2a which were well correlated with the prediction. No difference was observed by comparing the in situ yield after 16 and 24 h, which indicated that the reaction time could be reduced to 16 h for efficiency purposes. Overall, the optimal yield was achieved by increasing the equivalents of the oxidant and carbamate and importantly reducing the catalyst loading, as well as the reaction time and temperature.

Figure 2.

Plot of predicted yield of N-propargylic sulfoximine 2a vs the equivalents of oxidant/carbamate and catalyst loading visualized at fixed concentration (0.5 M) and temperature (30 °C). DoE analysis carried out with JMP Pro 14 with a custom design screen.

With the optimized reaction conditions the scope of the reaction was then investigated on a slightly larger 0.5 mmol scale (Scheme 1). Good to excellent yields were obtained for para- and meta-substituted arylmethylsulfoxide derivatives bearing electron-donating and electron-withdrawing substituents (2a–2g), including halogen and ketone functionality. Enantioenriched (S)-2b was obtained with excellent ee, showing the complete retention of stereochemical information with enantioenriched substrates. Scaling the reaction to 3 mmol scale did not affect the yield significantly (2e). It was noticeable that low yields were observed for ortho-substituted examples 2h and 2i; the corresponding ortho-chloro-derivative (not shown) gave only trace amounts of the sulfoximine product and recovered starting material highlighting the steric and electronic demands on the nucleophilicity at sulfur. In these lower yielding examples, the mass balance was recovered starting material. Good yields were witnessed for alkyl-aryl substrates and their derivatives 2j–m, including the cyclopropyl derivative (2n), a structural feature that has been observed in recent clinical candidates. The reduced yield with isopropyl (2o) was again indicative of steric demands which was also apparent with diphenyl and dibenzyl substrates (2p and 2q). Other dialkyl substrates (2r and 2s) were investigated, and each was successful including tBu derivative 2s. Cyclic sulfoxide 2t gave an excellent yield. A moderate yield was achieved with the 2-pyridyl substrate (2u). This method also showed tolerance of other interesting functional groups, including terminal alcohol (2v) and terminal alkene (2w) where vinyl sulfoximine could be applied as a possible probe structure in chemical biology.¹⁷ Using protected methionine sulfoxide gave the propargylic carbamate derivative of methionine sulfoximine (MSO, 2x), MSO itself being an inhibitor for the biosynthesis of glutathione.

Scheme 1. Substrate Scope of Propargylic Carbamate Transfer.

Reactions on 0.5 mmol scale. All yields correspond to isolated products. R = CH₂CCH.

To make a direct comparison with our previous conditions (see Figure 1),¹⁴ we compared these across a range of carbamate types (Scheme 2). For carbamates with alkyl substituents, such as tert-butyl and methyl carbamate, both methods showed excellent yields on methyl p-tolylsulfoxide (98–99%, 4, 5). In our previous report, the yields dropped significantly to 60% and 54% for benzyl (Cbz) and phenyl carbamates.¹⁴ However, the yields remained at 95% for benzyl carbamate 6 and 90% for phenyl carbamate 7 using the new conditions. In contrast to the disappointing results obtained with allyl and alkynyl carbamates under the previous conditions, allyl 8 and TMS protected propargyl 9 were obtained in 82% and 93% yields.

Scheme 2. Effect of Variation of the Carbamate.

Reactions on 0.5 mmol scale. All yields correspond to isolated products. Yield in square brackets corresponds to the yields under previously reported conditions.

Result as reported in ref (14).

Yield using conditions reported in ref (14).

The developed conditions for carbamate transfer were also applied to sulfide substrates to afford sulfilimines (Scheme 3). Previous examples of sulfilimine carbamates have all applied preformed activated carbamates, bearing N–O or N–X groups.^10,21 Applying our propargyl carbamate transfer to methyl p-tolyl sulfides gave sulfilimine 12 with a 32% yield, where direct oxidation to the corresponding sulfoxide represented the major side product. Moderate to good yields were observed when transferring tert-butyl carbamate to sulfides, affording the products 13, 14, and 15 with different aryl-substituents. Interestingly, switching to Cbz carbamate gave sulfilimine 16 in excellent yield. Additionally, the transfer of tert-butyl carbamate to a sulfenamide was successful, affording the unusual sulfinamidine product 17 with a 38% yield.²⁴

Scheme 3. Sulfilimine Carbamate Synthesis.

Finally, the potential utility of propargyl carbamate-sulfoximine was demonstrated in CuAAC click reactions with alkyl azides (Scheme 4). Using 2a and benzylazide cleanly formed triazole 18. Similarly, biotin azide was suitable to prepare the corresponding triazole (19) as may be valuable in chemical biology.

Scheme 4. Cycloaddition Reactions of Sulfoximine Containing Alkynes with Azides.

In conclusion, improved conditions for the preparation of sulfoximine carbamates are reported where the use of more reactive Rh₂(esp)₂ catalyst and toluene solvent gave improved tolerance of carbamates with unsaturated functionality. This method may further enhance the possibilities for the use of sulfoximines, to exploit that additional vector and directly install a broader range of carbamates with improved yields. The cycloaddition chemistry from the alkynes may provide an alternative way to incorporate small sulfoximine motifs, or allow labeling via other sulfur derivatives. It also provides the first example of the formation of sulfilimine carbamates without the requirement for a preactivated nitrogen source.

Experimental Section

General Experimental Considerations

All nonaqueous reactions were run under an inert atmosphere (argon) with flame-dried or oven-dried glassware using standard techniques. Anhydrous solvents were obtained by filtration through drying columns (CH₂Cl₂) or used directly from commercial sources (^tBuOH, EtOAc, toluene) without drying. Rh₂(esp)₂ (96%) was purchased from Sigma-Aldrich and PhI(OAc)₂ (98%) was purchased from Fluorochem, and used directly without further treatment. Flash column chromatography was performed using 230–400 mesh silica with the indicated solvent system according to standard techniques. Analytical thin-layer chromatography (TLC) was performed on precoated, glassbacked silica gel plates. Visualization of the developed chromatogram was performed by UV absorbance (254 nm) or aqueous potassium permanganate stains. Infrared spectra (ν_max, FTIR ATR) were recorded in reciprocal centimeters (cm^–1). Nuclear magnetic resonance spectra were recorded on 400 MHz spectrometers. Chemical shifts for ¹H NMR spectra are recorded in parts per million from tetramethylsilane with the residual protic solvent resonance as the internal standard (chloroform: δ = 7.27 ppm, DMSO-d₆: δ = 2.50 ppm, MeOD-d₄: δ = 3.31 ppm). Data are reported as follows: chemical shift [multiplicity (s = singlet, d = doublet, t = triplet, quartet = q, pentet = p, m = multiplet and br = broad), coupling constant in Hz, integration, assignment]. ¹³C NMR spectra were recorded with complete proton decoupling. Chemical shifts are reported in parts per million from tetramethylsilane with the solvent resonance as the internal standard (¹³CDCl₃: δ = 77.0 ppm, (¹³CD₃)₂SO: δ = 39.5 ppm, ¹³CD₃OD: δ = 49.0 ppm). J values are reported in Hz. Assignments of ¹H/¹³C spectra were made by the analysis of δ/J values, and COSY, HSQC, and HMBC experiments as appropriate. Melting points are uncorrected. Heating blocks were used for reactions above room temperature.

Reagents: Commercial reagents were used as supplied or purified by standard techniques where necessary. Commercially available sulfoxides (1a, 1b, (S)-1b, 1n, 1p–s, and 1w), carbamates (Boc, Cbz, CO₂Me, and CO₂Ph), and sulfides (10a–c) were used as supplied, and others were prepared from the corresponding commercially available sulfides or thiols as previously reported.²⁵ Sulfenamide 11 was prepared as previously reported.²⁶ Benzyl azide was prepared as previously reported.²⁷ Azide-PEG3-biotin conjugate was purchased from Sigma-Aldrich.

Carbamate Preparation

Prop-2-yn-1-yl Carbamate²⁸

CF₃CO₂H (7.7 mL, 100 mmol, 2.0 equiv) was added dropwise to a stirred solution of propargyl alcohol (2.90 mL, 50 mmol, 1.0 equiv) and NaOCN (6.8 g, 100 mmol, 2.0 equiv) in anhydrous Et₂O (100 mL) at 30 °C. The reaction mixture was stirred at 30 °C overnight. The resulting mixture was diluted with Et₂O (100 mL) and filtered. The filtrate was concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 30% Et₂O in pentane) afforded prop-2-yn-1-yl carbamate as a white solid (2.13 g, 43%). R_f = 0.12 (30% Et₂O in pentane); mp = 48–51 °C; IR (film)/cm^–1 3425, 3307, 3280, 3211, 2952, 1675, 1647, 1607, 1405, 1328, 1062, 865, 702, 634, 563; ¹H NMR (400 MHz, CDCl₃) δ 4.93 (br s, 2H, NH₂), 4.69 (d, J = 2.5 Hz, 2H, CH₂), 2.50 (t, J = 2.5 Hz, 1H, CCH); ¹³C NMR (101 MHz, CDCl₃) δ 155.8 (C=O), 77.9 (CCH), 74.8 (CCH), 52.7 (CH₂). Analytical data (NMR and IR) in agreement with those reported in the literature.²⁹

3-(Trimethylsilyl)prop-2-yn-1-yl Carbamate

CF₃CO₂H (3.1 mL, 40.4 mmol, 2.0 equiv) was added dropwise to a stirred solution of 3-trimethylsilyl-2-propyn-1-ol (3.0 mL, 20.2 mmol, 1.0 equiv) and NaOCN (2.63 g, 40.4 mmol, 2.0 equiv) in anhydrous Et₂O (40 mL) at 30 °C. The reaction mixture was stirred at 30 °C overnight. The resulting mixture was diluted with Et₂O (40 mL) and filtered. The filtrate was concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 30% EtOAc in pentane) afforded 3-(trimethylsilyl)prop-2-yn-1-yl carbamate as a white solid (1.86 g, 54%). R_f = 0.33 (30% EtOAc in pentane); mp = 53–57 °C; IR (film)/cm^–1 3451, 3343, 3292, 3185, 2964, 2181, 1705 (C=O), 1606, 1388, 1320, 1067, 1011, 838, 764, 703; ¹H NMR (400 MHz, CDCl₃) δ 4.84 (br s, 2H, NH₂), 4.69 (s, 2H, CH₂), 0.19 (s, 9H, (CH₃)₃); ¹³C NMR (101 MHz, CDCl₃) δ 155.8 (C=O), 99.2 (CCSi), 92.1 (CCSi), 53.5 (C(CH₃)₃), −0.3 (C(CH₃)₃); HRMS (ESI-TOF) m/z: Calcd. for C₇H₁₄NO₂Si [M + H]⁺: 172.0788, found: 172.0789.

General Procedure for Rhodium-Catalyzed Carbamate Transfer to Sulfoxides and Sulfides (Schemes 1–3)

PhI(OAc)₂ (274 mg, 0.85 mmol, 1.7 equiv) was added to a suspension of the sulfoxide or sulfide (0.5 mmol, 1.0 equiv), carbamate (0.85 mmol, 1.7 equiv), MgO (81 mg, 2.0 mmol, 4.0 equiv), and Rh₂(esp)₂ (7.6 mg, 2.0 mol %) in toluene (1.0 mL) at rt. The resulting mixture was heated to 30 °C and stirred for 16 h. The reaction mixture was diluted with CH₂Cl₂ (1 mL), filtered through Celite, and concentrated under reduced pressure. The resulting residue was purified by flash column chromatography (SiO₂) to afford the corresponding sulfoximine or sulfilimine carbamate.

Prop-2-yn-1-yl (Methyl(oxo)(phenyl)-λ⁶-sulfaneylidene)carbamate (2a)

Prepared using the General Procedure using sulfoxide 1a (69.6 mg, 0.50 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 40% EtOAc in hexane) afforded sulfoximine propargyl carbamate 2a (100.2 mg, 85%) as a pale-yellow gum. R_f = 0.17 (40% EtOAc in hexane); IR (film)/cm^–1 3261, 3014, 2925, 2120, 1668 (C=O), 1444, 1368, 1223, 1084, 977, 867, 783, 742, 683, 559, 504; ¹H NMR (400 MHz, CDCl₃) δ 8.02–7.99 (m, 2H, 2 × Ar–H), 7.71–7.69 (m, 1H, Ar–H), 7.64–7.60 (m, 2H, 2 × Ar–H), 4.70–4.65 (m, 1H, OCHH), 4.65–4.60 (m, 1H, OCHH), 3.34 (s, 3H, SCH₃), 2.43 (t, J = 2.5 Hz, 1H, CCH); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 158.0 (C=O), 138.0 (Ar–C_q), 134.1 (Ar–C), 129.7 (2 × Ar–C), 127.4 (2 × Ar–C), 77.9 (CCH), 74.6 (CCH), 53.4 (CH₂), 44.5 (SCH₃); HRMS (ESI-TOF) m/z: Calcd. for C₁₁H₁₂NO₃S [M + H]⁺: 238.0538, found: 238.0533.

Prop-2-yn-1-yl (Methyl(oxo)(p-tolyl)-λ⁶-sulfaneylidene)carbamate (2b)

Prepared using the General Procedure using sulfoxide 1b (76.6 mg, 0.50 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 40% EtOAc in hexane) afforded sulfoximine propargyl carbamate 2b (108.1 mg, 86%) as a pale-yellow gum. R_f = 0.22 (40% EtOAc in hexane); IR (film)/cm^–1 3260, 3016, 2924, 2120, 1668 (C=O), 1593, 1368, 1224, 1086, 978, 866, 812, 631, 512, 493; ¹H NMR (400 MHz, CDCl₃) δ 7.88 (d, J = 8.4 Hz, 2H, 2 × Ar–H), 7.42–7.40 (m, 2H, 2 × Ar–H), 4.70–4.66 (m, 1H, OCHH), 4.65–4.61 (m, 1H, OCHH), 3.32 (s, 3H, SCH₃), 2.47 (s, 3H, Ar–CH₃), 2.43 (t, J = 2.5 Hz, 1H, CCH); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 158.1 (C=O), 145.3 (Ar–C_q), 134.8 (Ar–C_q), 130.4 (2 × Ar–C), 127.4 (2 × Ar–C), 78.0 (CCH), 74.6 (CCH), 53.4 (CH₂), 44.6 (SCH₃), 21.6 (Ar–CH₃); HRMS (ESI-TOF) m/z: Calcd. for C₁₂H₁₄NO₃S [M + H]⁺: 252.0694, found: 252.0682.

Prop-2-yn-1-yl (S)-(Methyl(oxo)(p-tolyl)-λ⁶-sulfaneylidene)carbamate ((S)-2b)

Prepared using General Procedure using sulfoxide (S)-1b (77.2 mg, 0.50 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 40% EtOAc in hexane) afforded sulfoximine propargyl carbamate (S)-2b (102.5 mg, 82%, > 99% ee) as a pale-yellow gum. R_f = 0.22 (40% EtOAc in hexane); Spectroscopic data same as those for 2b above. [α]²¹_D = +52 (c 1.0, CHCl₃). HPLC conditions: Chiralpak IB column, 90:10 n-hexane:iPrOH, flow rate: 1 mL min^–1, 35 °C, UV detection wavelength: 250 nm, ((S)-2b) retention time: 38 min. ((rac)-2b) retention times: 38 and 42 min.

Prop-2-yn-1-yl ((4-Methoxyphenyl)(methyl)(oxo)-λ⁶-sulfaneylidene)carbamate (2c)

Prepared using General Procedure using sulfoxide 1c (84.7 mg, 0.50 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 30% EtOAc in hexane) afforded sulfoximine propargyl carbamate 2c (101.9 mg, 76%) as a white solid. R_f = 0.08 (30% EtOAc in hexane); mp = 84–85 °C; IR (film)/cm^–1 3265, 3019, 2930, 2848, 2125, 1670 (C=O), 1595, 1498, 1312, 1238, 1088, 984, 867; ¹H NMR (400 MHz, CDCl₃) δ 7.93–7.90 (m, 2H, 2 × Ar–H), 7.08–7.04 (m, 2H, 2 × Ar–H), 4.70–4.66 (m, 1H, OCHH), 4.65–4.60 (m, 1H, OCHH), 3.90 (s, 3H, OCH₃), 3.32 (s, 3H, SCH₃), 2.43 (t, J = 2.5 Hz, 1H, CCH); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 164.1 (Ar–C_q), 158.1 (C=O), 129.6 (2 × Ar–C), 128.8(Ar–C_q), 115.0 (2 × Ar–C), 78.0 (CCH), 74.6 (CCH), 55.8 (OCH₃), 53.3 (CH₂), 44.9 (SCH₃); HRMS (ESI-TOF) m/z: Calcd. for C₁₂H₁₄NO₄S [M + H]⁺: 268.0644, found: 268.0640.

Prop-2-yn-1-yl ((4-Chlorophenyl)(methyl)(oxo)-λ⁶-sulfaneylidene)carbamate (2d)

Prepared using General Procedure using sulfoxide 1d (87.2 mg, 0.50 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 40% Et₂O in pentane) afforded sulfoximine propargyl carbamate 2d (118.9 mg, 88%) as a white gum. R_f = 0.10 (40% Et₂O in pentane); IR (film)/cm^–1 3283, 3083, 3016, 2120, 1672 (C=O), 1573, 1366, 1217, 1081, 977, 866, 783, 684, 462; ¹H NMR (400 MHz, CDCl₃) δ 7.95–7.93 (m, 2H, 2 × Ar–H), 7.61–7.58 (m, 2H, 2 × Ar–H), 4.70–4.66 (m, 1H, OCHH), 4.65–4.60 (m, 1H, OCHH), 3.34 (s, 3H, SCH₃), 2.44 (t, J = 2.5 Hz, 1H, CCH); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 157.8 (C=O), 141.1 (Ar–C_q), 136.4 (Ar–C_q), 130.1 (2 × Ar–C), 128.9 (2 × Ar–C), 77.8 (CCH), 74.8 (CCH), 53.5 (CH₂), 44.5 (SCH₃); HRMS (ESI-TOF) m/z: Calcd. for C₁₁H₁₁NO₃S³⁵Cl [M + H]⁺: 272.0148, found: 272.0151.

Prop-2-yn-1-yl ((4-Bromophenyl)(methyl)(oxo)-λ⁶-sulfaneylidene)carbamate (2e)

Prepared using General Procedure using sulfoxide 1e (110.4 mg, 0.50 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 40% Et₂O in pentane) afforded sulfoximine propargyl carbamate 2e (125.4 mg, 79%) as a colorless gum. R_f = 0.12 (40% Et₂O in pentane); IR (film)/cm^–1 3263, 3083, 3012, 2923, 2120, 1668 (C=O), 1567, 1367, 1224, 1085, 1065, 978, 867, 780, 676, 565, 508; ¹H NMR (400 MHz, CDCl₃) δ 7.85–7.82 (m, 2H, 2 × Ar–H), 7.75–7.72 (m, 2H, 2 × Ar–H), 4.65–4.60 (m, 1H, OCHH), 4.60–4.55 (m, 1H, OCHH), 3.31 (s, 3H, SCH₃), 2.42 (t, J = 2.5 Hz, 1H, CCH); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 157.7 (C=O), 136.8 (Ar–C_q), 132.9 (2 × Ar–C), 129.4 (Ar–C_q), 128.8 (2 × Ar–C), 77.7 (CCH), 74.7 (CCH), 53.4 (CH₂), 44.3 (SCH₃); HRMS (ESI-TOF) m/z: Calcd. for C₁₁H₁₁NO₃S⁷⁹Br [M + H]⁺: 315.9643, found: 315.9650. Three mmol scale synthesis of 2e: PhI(OAc)₂ (1.64 g, 5.1 mmol, 1.7 equiv) was added in three-portions over 5 min to a stirring suspension of sulfoxide 1e (657 mg, 3.0 mmol), prop-2-yn-1-yl carbamate (505 mg, 5.1 mmol, 1.7 equiv), MgO (484 mg, 12.0 mmol, 4.0 equiv) and Rh₂(esp)₂ (45.5 mg, 0.06 mmol, 2.0 mol %) in toluene (6 mL) at rt. The resulting mixture was heated to 30 °C and stirred for 16 h. The reaction mixture was diluted with CH₂Cl₂ (5 mL), filtered through Celite and concentrated under reduced pressure. Purification by flash column chromatography (SiO₂, 40% Et₂O in pentane) afforded 2e as a colorless gum (669 mg, 71%).

Prop-2-yn-1-yl ((4-Acetylphenyl)(methyl)(oxo)-λ⁶-sulfaneylidene)carbamate (2f)

Prepared using General Procedure using sulfoxide 1f (90.6 mg, 0.50 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 40% EtOAc in hexane) afforded sulfoximine propargyl carbamate 2f (94.6 mg, 68%) as a colorless gum. R_f = 0.10 (40% EtOAc in hexane); IR (film)/cm^–1 3272, 3032, 2926, 1682 (C=O), 1663 (C=O), 1367, 1251, 1229, 968, 920, 863, 789, 621, 500; ¹H NMR (400 MHz, CDCl₃) δ 8.17–8.15 (m, 2H, 2 × Ar–H), 8.12–8.10 (m, 2H, 2 × Ar–H), 4.69–4.64 (m, 1H, OCHH), 4.64–4.60 (m, 1H, OCHH), 3.35 (s, 3H, SCH₃), 2.68 (s, 3H, COCH₃), 2.43 (t, J = 2.5 Hz, 1H, CCH); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 196.4 (C=O), 157.8 (C=O), 141.9 (Ar–C_q), 141.1 (Ar–C_q), 129.4 (2 × Ar–C), 127.9 (2 × Ar–C), 77.7 (CCH), 74.8 (CCH), 53.6 (CH₂), 44.2 (SCH₃), 26.9 (COCH₃); HRMS (ESI-TOF) m/z: Calcd. for C₁₃H₁₄NO₄S [M + H]⁺: 280.0644, found: 280.0638.

Prop-2-yn-1-yl ((3-Bromophenyl)(methyl)(oxo)-λ⁶-sulfaneylidene)carbamate (2g)

Prepared using General Procedure using sulfoxide 1g (108.5 mg, 0.50 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 50% Et₂O in hexane) afforded sulfoximine propargyl carbamate 2g (127.6 mg, 81%) as a colorless gum. R_f = 0.13 (50% Et₂O in hexane); IR (film)/cm^–1 3273, 3079, 3019, 2930, 2125, 1670 (C=O), 1365, 1230, 1103, 977, 872, 775, 671; ¹H NMR (400 MHz, CDCl₃) δ 8.12–8.09 (m, 1H, Ar–H), 7.91–7.88 (m, 1H, Ar–H), 7.80–7.77 (m, 1H, Ar–H), 7.49–7.45 (m, 1H, Ar–H), 4.65–4.61 (m, 1H, OCHH), 4.60–4.55 (m, 1H, OCHH), 3.32 (s, 3H, SCH₃), 2.42 (t, J = 2.5 Hz, 1H, CCH); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 157.6 (C=O), 139.7 (Ar–C_q), 137.1 (Ar–C), 131.1 (Ar–C), 130.2 (Ar–C), 125.8 (Ar–C), 123.5 (Ar–C_q), 77.7 (CCH), 74.8 (CCH), 53.4 (CH₂), 44.3 (SCH₃); HRMS (ESI-TOF) m/z: Calcd. for C₁₁H₁₁NO₃S⁷⁹Br [M + H]⁺: 315.9643, found: 315.9649.

Prop-2-yn-1-yl ((2-Fluorophenyl)(methyl)(oxo)-λ⁶-sulfaneylidene)carbamate (2h)

Prepared using General Procedure using sulfoxide 1h (80.0 mg, 0.51 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 40% EtOAc in hexane) afforded sulfoximine propargyl carbamate 2h (25.4 mg, 20%) as a colorless gum. R_f = 0.22 (40% EtOAc in hexane); IR (film)/cm^–1 3273, 3019, 2937, 2125, 1670 (C=O), 1476, 1230, 1126, 1074, 977, 865, 760; ¹H NMR (400 MHz, CDCl₃) δ 8.09 (ddd, J = 8.0, 7.1, 1.8 Hz, 1H, Ar–H), 7.71 (dddd, J = 8.3, 7.5, 5.0, 1.8 Hz, 1H, Ar–H), 7.46–7.38 (m, 1H, Ar–H), 7.31–7.26 (m, 1H, Ar–H), 4.66 (dd, J = 15.6, 2.5 Hz, 1H, OCHH), 4.59 (dd, J = 15.6, 2.5 Hz, 1H, OCHH), 3.47 (d, J = 0.6 Hz, 3H, SCH₃), 2.42 (t, J = 2.5 Hz, 1H, CCH). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 159.7 (C=O), 157.3 (Ar–C_q), 136.6 (Ar–C), 131.0 (Ar–C), 125.5 (Ar–C_q), 125.1 (Ar–C), 117.4 (Ar–C), 77.8 (CCH), 74.7 (CCH), 53.5 (OCH₂), 43.5 (SCH₃). HRMS (ESI-TOF) m/z: Calcd. for C₁₁H₁₁NO₃SF [M + H]⁺: 256.0444, found: 256.0452.

Prop-2-yn-1-yl (Methyl(oxo)(o-tolyl)-λ⁶-sulfaneylidene)carbamate (2i)

Prepared using General Procedure using sulfoxide 1i (77.0 mg, 0.50 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 40% EtOAc in hexane) afforded sulfoximine propargyl carbamate 2i (39.9 mg, 32%) as a colorless gum. R_f = 0.27 (40% EtOAc in hexane); IR (film)/cm^–1 3265, 3019, 2937, 2125, 1670 (C=O), 1446, 1223, 1118, 977, 865, 753; ¹H NMR (400 MHz, CDCl₃) δ 8.11–8.09 (m, 1H, Ar–H), 7.58–7.54 (m, 1H, Ar–H), 7.46–7.42 (m, 1H, Ar–H), 7.39–7.37 (m, 1H, Ar–H), 4.68–4.64 (m, 1H, OCHH), 4.64–4.59 (m, 1H, OCHH), 3.34 (s, 3H, SCH₃), 2.71 (s, 3H, Ar–CH₃), 2.41 (t, J = 2.5 Hz, 1H, CCH); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 157.8 (C=O), 137.2 (Ar–C_q), 136.0 (Ar–C_q), 134.0 (Ar–C), 133.3 (Ar–C), 129.6 (Ar–C), 127.1 (Ar–C), 78.0 (CCH), 74.6 (CCH), 53.4 (OCH₂), 43.3 (SCH₃), 20.5 (Ar–CH₃); HRMS (ESI-TOF) m/z: Calcd. for C₁₂H₁₄NO₃S [M + H]⁺: 252.0694, found: 252.0699.

Prop-2-yn-1-yl (Benzyl(oxo)(phenyl)-λ⁶-sulfaneylidene)carbamate (2j)

Prepared using General Procedure using sulfoxide 1j (109.0 mg, 0.50 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, CH₂Cl₂:Et₂O:hexane = 20:30:50) afforded sulfoximine propargyl carbamate 2j (117.4 mg, 74%) as a white solid. R_f = 0.25 (CH₂Cl₂:Et₂O:hexane = 20:30:50); mp = 100–102 °C; IR (film)/cm^–1 3250, 3064, 2132, 1655 (C=O), 1520, 1446, 1267, 1074, 992, 880, 790, 738; ¹H NMR (400 MHz, CDCl₃) δ 7.64–7.59 (m, 3H, 3 × Ar–H), 7.46–7.42 (m, 2H, 2 × Ar–H), 7.32–7.27 (m, 1H, Ar–H), 7.22–7.18 (m, 2H, 2 × Ar–H), 6.96–6.94 (m, 2H, 2 × Ar–H), 4.77 (d, J = 15.9 Hz, 1H, SCHH), 4.73 (d, J = 15.9 Hz, 1H, SCHH), 4.72 (dd, J = 15.6, 2.5 Hz, 1H, OCHH), 4.65 (dd, J = 15.6, 2.5 Hz, 1H, OCHH), 2.45 (t, J = 2.5 Hz, 1H, CCH); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 158.3 (C=O), 134.4 (Ar–C_q), 134.0 (Ar–C_q), 131.1 (2 × Ar–C), 129.2 (Ar–C), 129.0 (2 × Ar–C), 128.6 (2 × Ar–C), 128.5 (2 × Ar–C), 126.6 (Ar–C), 78.0 (CCH), 74.6 (CCH), 62.0 (SCH₂), 53.4 (OCH₂); HRMS (ESI-TOF) m/z: Calcd. for C₁₇H₁₆NO₃S [M + H]⁺: 314.0851, found: 314.0851.

Prop-2-yn-1-yl (Oxo(phenethyl)(p-tolyl)-λ⁶-sulfaneylidene)carbamate (2k)

Prepared using General Procedure using sulfoxide 1k (123.4 mg, 0.50 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, CH₂Cl₂:Et₂O:hexane = 20:15:65) afforded sulfoximine propargyl carbamate 2k (118.9 mg, 70%) as a white solid. R_f = 0.29 (CH₂Cl₂:Et₂O:hexane = 20:15:65); mp = 79–81 °C; IR (film)/cm^–1 3310, 3034, 2982, 2182, 1670 (C=O), 1595, 1498, 1372, 1215, 1118, 984, 775, 626, 492; ¹H NMR (400 MHz, CDCl₃) δ 7.86 (d, J = 8.4 Hz, 2H, 2 × Ar–H), 7.42–7.39 (m, 2H, 2 × Ar–H), 7.28–7.21 (m, 3H, 3 × Ar–H), 7.11–7.09 (m, 2H, 2 × Ar–H), 4.69–4.65 (m, 1H, OCHH), 4.64–4.60 (m, 1H, OCHH), 3.71 (ddd, J = 14.0, 11.9, 5.1 Hz, 1H, SCHH), 3.59 (ddd, J = 13.9, 11.7, 5.0 Hz, 1H, SCHH), 3.10 (ddd, J = 13.8, 11.7, 5.0 Hz, 1H, PhCHH), 2.97 (ddd, J = 13.8, 11.9, 5.0 Hz, 1H, PhCHH), 2.43 (t, J = 2.4 Hz, 1H, CCH); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 158.1 (C=O), 145.3 (Ar–C_q), 136.6 (Ar–C_q), 133.0 (Ar–C_q), 130.3 (2 × Ar–C), 128.8 (2 × Ar–C), 128.3 (2 × Ar–C), 128.0 (2 × Ar–C), 127.0 (Ar–C_q), 78.0 (CCH), 74.6 (CCH), 57.2 (SCH₂), 53.4 (OCH₂), 28.3 (PhCH₂), 21.6 (Ar–CH₃); HRMS (ESI-TOF) m/z: Calcd. for C₁₉H₂₀NO₃S [M + H]⁺: 342.1164, found: 342.1168.

Prop-2-yn-1-yl (Benzyl(oxo)(phenyl)-λ⁶-sulfaneylidene)carbamate (2l)

Prepared using General Procedure using sulfoxide 1l (85.0 mg, 0.51 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, CH₂Cl₂:Et₂O:hexane = 30:20:50) afforded sulfoximine propargyl carbamate 2l (85.5 mg, 63%) as a colorless gum. R_f = 0.3 (CH₂Cl₂:Et₂O:hexane = 30:20:50); IR (film)/cm^–1 3340, 3263, 2937, 2125, 1677 (C=O), 1521, 1431, 1208, 1074, 969, 738. ¹H NMR (400 MHz, CDCl₃) δ 7.80 (d, J = 8.3 Hz, 2H, 2 × Ar–H), 7.39 (d, J = 8.1 Hz, 2H, 2 × Ar–H), 4.66–4.61 (m, 1H, OCHH), 4.60–4.56 (m, 1H, OCHH), 3.49–3.42 (m, 1H, SCHH), 3.41–3.34 (m, 1H, SCHH) 2.45 (s, 3H, Ar–CH₃), 2.40 (t, J = 2.5 Hz, 1H, CCH), 1.25 (t, J = 7.4 Hz, 3H, CH₃); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 158.0 (C=O), 145.1 (Ar–C_q), 132.2 (Ar–C_q), 130.2 (2 × Ar–C), 128.0 (2 × Ar–C), 77.9 (CCH), 74.4 (CCH), 53.1 (OCH₂), 50.6 (SCH₂), 21.5 (Ar–CH₃), 6.8 (CH₃); HRMS (ESI-TOF) m/z: Calcd. for C₁₃H₁₆NO₃S [M + H]⁺: 266.0851, found: 266.0848.

Prop-2-yn-1-yl ((Chloromethyl)(oxo)(p-tolyl)-λ⁶-sulfaneylidene)carbamate (2m)

Prepared using General Procedure using sulfoxide 1m (94.0 mg, 0.50 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 20% EtOAc in hexane) afforded sulfoximine propargyl carbamate 2m (115.4 mg, 77%) as a white solid. R_f = 0.22 (20% EtOAc in hexane); mp = 83–84 °C; IR (film)/cm^–1 3271, 3014, 2944, 2122, 1671 (C=O), 1592, 1432, 1368, 1234, 1084, 975, 923, 881, 780, 633, 522; ¹H NMR (400 MHz, CDCl₃) δ 7.93–7.91 (m, 2H, 2 × Ar–H), 7.45–7.42 (m, 2H, 2 × Ar–H), 5.20 (d, J = 11.9 Hz, 1H, SCHH), 4.87 (d, J = 12.0 Hz, 1H, SCHH), 4.76–4.72 (m, 1H, OCHH), 4.72–4.68 (m, 1H, OCHH), 2.49 (s, 3H, Ar–CH₃), 2.48 (t, J = 2.5 Hz, 1H, CCH); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 157.7 (C=O), 146.6 (Ar–C_q), 130.3 (2 × Ar–C), 129.5 (Ar–C_q), 129.4 (2 × Ar–C), 77.7 (CCH), 75.0 (CCH), 58.5 (SCH₂), 53.8 (OCH₂), 21.7 (Ar–CH₃); HRMS (ESI-TOF) m/z: Calcd. for C₁₂H₁₃NO₃S³⁵Cl [M + H]⁺: 286.0305, found: 286.0298.

Prop-2-yn-1-yl (Cyclopropyl(oxo)(phenyl)-λ⁶-sulfaneylidene)carbamate (2n)

Prepared using General Procedure using sulfoxide 1n (83.4 mg, 0.50 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 50% Et₂O in hexane) afforded sulfoximine propargyl carbamate 2n (91.3 mg, 70%) as a colorless gum. R_f = 0.12 (50% Et₂O in hexane); IR (film)/cm^–1 3265, 3056, 2945, 2117, 1677 (C=O), 1446, 1245, 1088, 977, 880, 783; ¹H NMR (400 MHz, CDCl₃) δ 7.93–7.91 (m, 2H, 2 × Ar–H), 7.68–7.64 (m, 1H, Ar–H), 7.61–7.56 (m, 2H, 2 × Ar–H), 4.63–4.58 (m, 1H, OCHH), 4.58–4.53 (m, 1H, OCHH), 2.68–2.62 (m, 1H, SCH), 2.39 (d, J = 2.5 Hz, 1H, CCH), 1.68–1.59 (m, 1H, CH), 1.28–1.19 (m, 2H, 2 × CH), 1.05–0.94 (m, 1H, CH); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 157.7 (C=O), 138.3 (Ar–C_q), 133.6 (Ar–C), 129.5 (2 × Ar–C), 127.4 (2 × Ar–C), 77.9 (CCH), 74.5 (CCH), 53.2 (OCH₂), 33.4 (SCH), 6.8 (CH₂), 5.2 (CH₂); HRMS (ESI-TOF) m/z: Calcd. for C₁₃H₁₄NO₃S [M + H]⁺: 264.0694, found: 264.0695.

Prop-2-yn-1-yl (Isopropyl(oxo)(p-tolyl)-λ⁶-sulfaneylidene)carbamate (2o)

Prepared using General Procedure using sulfoxide 1o (90.0 mg, 0.50 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, CH₂Cl₂:Et₂O:hexane = 30:30:40) afforded sulfoximine propargyl carbamate 2o (48.5 mg, 35%) as a pale-yellow gum; R_f = 0.43 (CH₂Cl₂:Et₂O:hexane = 30:30:40); IR (film)/cm^–1 3265, 2937, 2125, 1677 (C=O), 1431, 1372, 1238, 1088, 977, 872, 723, 641; ¹H NMR (400 MHz, CDCl₃) δ 7.77 (d, J = 8.4 Hz, 2H, 2 × Ar–H), 7.40–7.38 (m, 2H, 2 × Ar–H), 4.66–4.62 (m, 1H, OCHH), 4.61–4.57 (m, 1H, OCHH), 3.54 (hept, J = 6.8 Hz, 1H, SCH), 2.46 (s, 3H, Ar–CH₃), 2.40 (t, J = 2.5 Hz, 1H, CCH), 1.41 (d, J = 6.8 Hz, 3H, CHCH₃), 1.24 (d, J = 6.8 Hz, 3H, CHCH₃); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 158.3 (C=O), 145.1 (Ar–C_q), 130.8 (Ar–C_q), 130.2 (2 × Ar–C), 129.0 (2 × Ar–C), 78.2 (CCH), 74.4 (CCH), 56.4 (SCH), 53.3 (CH₂), 21.6 (Ar–CH₃), 15.6 (CHCH₃), 15.0 (CHCH₃); HRMS (ESI-TOF) m/z: Calcd. for C₁₄H₁₈NO₃S [M + H]⁺: 280.1007, found: 280.0999.

Prop-2-yn-1-yl (Oxodiphenyl-λ⁶-sulfaneylidene)carbamate (2p)

Prepared using General Procedure using sulfoxide 1p (101.0 mg, 0.50 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 40% Et₂O in pentane) afforded sulfoximine propargyl carbamate 2p (57.6 mg, 38%) as a colorless gum. R_f = 0.13 (40% Et₂O in pentane). IR (film)/cm^–1 3271, 3084, 3056, 2124, 1667 (C=O), 1443, 1368, 1226, 1135, 1074, 982, 962, 877, 679, 575, 554. ¹H NMR (400 MHz, CDCl₃) δ 8.03–8.00 (m, 4H, 4 × Ar–H), 7.62–7.58 (m, 2H, 2 × Ar–H), 7.55–7.51 (m, 4H, 4 × Ar–H), 4.65 (d, J = 2.4 Hz, 2H, OCH₂), 2.41 (t, J = 2.5 Hz, 1H, CCH). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 157.8 (C=O), 139.1 (2 × Ar–C_q), 133.5 (2 × Ar–C), 129.5 (4 × Ar–C), 127.7 (4 × Ar–C), 77.9 (CCH), 74.6 (CCH), 53.5 (CH₂). HRMS (ESI-TOF) m/z: Calcd. for C₁₆H₁₄NO₃S [M + H]⁺: 300.0694; found: 300.0700.

Prop-2-yn-1-yl (Dibenzyl(oxo)-λ⁶-sulfaneylidene)carbamate (2q)

Prepared using General Procedure using sulfoxide 1q (115.2 mg, 0.50 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, CH₂Cl₂:Et₂O:hexane = 20:30:50) afforded sulfoximine propargyl carbamate 2q (84.1 mg, 51%) as a white solid. R_f = 0.28 (CH₂Cl₂:Et₂O:hexane = 20:30:50); mp = 124–126 °C; IR (film)/cm^–1 3289, 3058, 2983, 2933, 2118, 1651 (C=O), 1491, 1428, 1377, 1271, 1230, 1152, 1096, 1069, 964, 918, 873, 694, 600, 480; ¹H NMR (400 MHz, CDCl₃) δ 7.44–7.38 (m, 10H, 10 × Ar–H), 4.71 (d, J = 2.4 Hz, 2H, OCH₂), 4.59 (d, J = 13.9 Hz, 2H, 2 × SCHH), 4.53 (d, J = 13.9 Hz, 2H, 2 × SCHH), 2.49 (t, J = 2.5 Hz, 1H, CCH); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 158.4 (C=O), 131.3 (4 × Ar–C), 129.6 (2 × Ar–C), 129.1 (4 × Ar–C), 126.2 (2 × Ar–C_q), 78.3 (CCH), 74.5 (CCH), 56.5 (2 × SCH₂), 53.5 (OCH₂); HRMS (ESI-TOF) m/z: Calcd. for C₁₈H₁₈NO₃S [M + H]⁺: 328.1007, found: 328.1012.

Prop-2-yn-1-yl (Dibutyl(oxo)-λ⁶-sulfaneylidene)carbamate (2r)

Prepared using General Procedure using sulfoxide 1r (81.4 mg, 0.50 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, CH₂Cl₂:Et₂O:hexane = 20:30:50) afforded sulfoximine propargyl carbamate 2r (60.9 mg, 47%) as a colorless gum. R_f = 0.24 (CH₂Cl₂:Et₂O:hexane = 20:30:50); IR (film)/cm^–1 3250, 2960, 2878, 2125, 1662 (C=O), 1461, 1230, 1074, 977, 865, 783, 671; ¹H NMR (400 MHz, CDCl₃) δ 4.67 (d, J = 2.5 Hz, 2H, OCH₂), 3.42–3.26 (m, 4H, 2 × SCH₂), 2.44 (t, J = 2.5 Hz, 1H, CCH), 1.90–1.74 (m, 4H, 2 × SCH₂CH₂), 1.53–1.44 (m, 4H, CH₃CH₂), 0.97 (d, J = 7.3 Hz, 6H, 2 × CH₃); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 158.3 (C=O), 78.1 (CCH), 74.5 (CCH), 53.3 (OCH₂), 51.1 (2 × SCH₂), 24.0 (2 × SCH₂CH₂), 21.6 (2 × CH₂CH₃), 13.5 (2 × CH₃); HRMS (ESI-TOF) m/z: Calcd. for C₁₂H₂₂NO₃S [M + H]⁺: 260.1320, found: 260.1317.

Prop-2-yn-1-yl (tert-Butyl(methyl)(oxo)-λ⁶-sulfaneylidene)carbamate (2s)

Prepared using General Procedure using sulfoxide 1s (57.8 mg, 0.48 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 40% EtOAc in hexane) afforded sulfoximine propargyl carbamate 2s (41.0 mg, 39%) as a colorless oil. R_f = 0.15 (40% EtOAc in hexane); IR (film)/cm^–1 3265, 2915, 2125, 1670 (C=O), 1461, 1260, 992, 872, 783, 723; ¹H NMR (400 MHz, CDCl₃) δ 4.73–4.69 (m, 1H, OCHH), 4.86–4.64 (m, 1H, OCHH), 3.28 (s, 3H, SCH₃), 2.45 (t, J = 2.5 Hz, CCH), 1.51 (s, 9H, C(CH₃)₃); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 159.2 (C=O), 78.3 (CCH), 74.5 (CCH), 60.5 (C(CH₃)₃), 53.3 (OCH₂), 32.1 (SCH₃), 22.9 (C(CH₃)₃); HRMS (ESI-TOF) m/z: Calcd. for C₉H₁₆NO₃S [M + H]⁺: 218.0851, found: 218.0854.

Prop-2-yn-1-yl (1-Oxido-1λ⁶-thietan-1-ylidene)carbamate (2t)

Prepared using General Procedure using sulfoxide 1t (45.6 mg, 0.50 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 50% EtOAc in hexane) afforded sulfoximine propargyl carbamate 2t (79.2 mg, 85%) as a pale-red gum. R_f = 0.16 (50% EtOAc in hexane). IR (film)/cm^–1 3264, 3029, 2957, 2121, 1654 (C=O), 1369, 1225, 1115, 992, 871, 782, 689, 553. ¹H NMR (400 MHz, CDCl₃) δ 4.69–4.67 (m, 2H, OCH₂), 4.42–4.33 (m, 2H, 2 × SCHH), 4.30–4.22 (m, 2H, 2 × SCHH), 2.47–2.46 (m, 1H, CCH), 2.44–2.34 (m, 2H, CH₂). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 158.4 (C=O), 77.8 (CCH), 74.8 (CCH), 62.9 (2 × SCH₂), 53.5 (OCH₂), 9.4 (CH₂). HRMS (ESI-TOF) m/z: Calcd. for C₇H₁₀NO₃S [M + H]⁺: 188.0381, found: 188.0375.

Prop-2-yn-1-yl (Methyl(oxo)(pyridin-2-yl)-λ⁶-sulfaneylidene)carbamate (2u)

Prepared using General Procedure using sulfoxide 1u (69.7 mg, 0.49 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 60% EtOAc in hexane) afforded sulfoximine propargyl carbamate 2u (57.2 mg, 49%) as a pale-red gum. R_f = 0.21 (60% EtOAc in hexane); IR (film)/cm^–1 3265, 3019, 2930, 2125, 1670 (C=O), 1431, 1223, 1111, 984, 872, 760; ¹H NMR (400 MHz, CDCl₃) δ 8.74 (ddd, J = 4.7, 1.7, 0.9 Hz, 1H, Ar–H), 8.29 (dt, J = 7.9, 1.0 Hz, 1H, Ar–H), 8.02 (td, J = 7.8, 1.7 Hz, 1H, Ar–H), 7.59 (ddd, J = 7.7, 4.7, 1.1 Hz, 1H, Ar–H), 4.63 (dd, J = 15.6, 2.5 Hz, 1H, OCHH), 4.56 (dd, J = 15.6, 2.5 Hz, 1H, OCHH), 3.47 (s, 3H, SCH₃), 2.40 (t, J = 2.5 Hz, 1H, CCH); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 157.9 (C=O), 156.0 (Ar–C_q), 150.1 (Ar–C), 138.3 (Ar–C), 127.6 (Ar–C), 123.5 (Ar–C), 77.8 (CCH), 74.7 (CCH), 53.4 (OCH₂), 39.8 (SCH₃); HRMS (ESI-TOF) m/z: Calcd. for C₁₀H₁₁N₂O₃S [M + H]⁺: 239.0490, found: 239.0498.

Prop-2-yn-1-yl ((2-Hydroxyethyl)(oxo)(phenyl)-λ⁶-sulfaneylidene)carbamate (2v)

Prepared using General Procedure using sulfoxide 1v (86.8 mg, 0.51 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 60% EtOAc in hexane) afforded sulfoximine propargyl carbamate 2v (52.0 mg, 38%) as a colorless gum. R_f = 0.24 (60% EtOAc in hexane); IR (film)/cm^–1 3429, 3273, 3064, 2937, 2125, 1670 (C=O), 1446, 1372, 1223, 1081, 969, 872, 783, 686; ¹H NMR (400 MHz, CDCl₃) δ 7.99–7.97 (m, 2H, 2 × Ar–H), 7.75–7.71 (m, 1H, Ar–H), 7.66–7.62 (m, 2H, 2 × Ar–H), 4.65 (dd, J = 15.6, 2.5 Hz, 1H, OCHH), 4.60 (dd, J = 15.6, 2.5 Hz, 1H, OCHH), 4.19–4.11 (m, 1H, CHHOH), 4.08–4.00 (m, 1H, CHHOH), 3.68–3.62 (m, 1H, SCHH), 3.52–3.46 (m, 1H, SCHH), 3.41–3.37 (m, 1H, OH); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 157.7 (C=O), 136.7 (Ar–C_q), 134.4 (Ar–C), 129.9 (2 × Ar–C), 127.9 (2 × Ar–C), 77.7 (CCH), 74.8 (d, CCH), 58.9 (SCH₂), 55.8 (SCH₂CH₂), 53.6 (OCH₂); HRMS (ESI-TOF) m/z: Calcd. for C₁₂H₁₃NO₄NaS [M + Na]⁺: 290.0463, found: 290.0451.

Prop-2-yn-1-yl (Oxo(phenyl)(vinyl)-λ⁶-sulfaneylidene)carbamate (2w)

Prepared using General Procedure using sulfoxide 1w (78.8 mg, 0.52 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 50% Et₂O in hexane) afforded sulfoximine propargyl carbamate 2w (79.0 mg, 63%) as a colorless gum. R_f = 0.12 (50% Et₂O in hexane). IR (film)/cm^–1 3263, 3055, 2121, 1673 (C=O), 1443, 1368, 1230, 1082, 972, 873, 744, 686, 635, 536, 494. ¹H NMR (400 MHz, CDCl₃) δ 7.98–7.96 (m, 2H, 2 × Ar–H), 7.68–7.65 (m, 1H, Ar–H), 7.61–7.57 (m, 2H, 2 × Ar–H), 6.75 (dd, J = 16.3, 9.6 Hz, 1H, SCH), 6.54 (dt, J = 16.3, 1.1 Hz, 1H, SCHCHH), 6.21 (dd, J = 9.6 Hz, 1.1 Hz, 1H, SCHCHH), 4.70–4.65 (m, 1H, OCHH), 4.65–4.61 (m, 1H, OCHH), 2.43 (t, J = 2.5 Hz, 1H, CCH). ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 157.7 (C=O), 137.0 (Ar–C_q), 136.5 (SCH), 134.0 (Ar–C), 129.6 (2 × Ar–C), 129.5 (HCCH₂), 127.9 (2 × Ar–C), 77.9 (CCH), 74.7 (CCH), 53.5 (OCH₂). HRMS (ESI-TOF) m/z: Calcd. for C₁₂H₁₂NO₃S [M + H]⁺: 250.0538, found: 250.0533.

tert-Butyl 2-((tert-Butoxycarbonyl)amino)-4-(S-methyl-N-((prop-2-yn-1-yloxy)carbonyl)sulfonimidoyl)-butanoate (2x)

Prepared using General Procedure using sulfoxide 1x (161.4 mg, 0.50 mmol) and prop-2-yn-1-yl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 35% EtOAc in hexane) afforded sulfoximine propargyl carbamate 2x (160.8 mg, 77%) as a colorless gum. R_f = 0.22 (35% EtOAc in hexane); IR (film)/cm^–1 3355, 3280, 2982, 2125, 1707 (C=O), 1670 (C=O), 1513, 1372, 1238, 1148, 1044, 992, 872, 783, 634, 497; ¹H NMR (400 MHz, CDCl₃) δ 5.30–5.28 (m, 1H, NH), 4.65–4.64 (m, 2H, OCH₂), 4.24–4.21 (m, 1H, HCCO₂), 3.55–3.31 (m, 2H, SCH₂), 3.26 (d, J = 7.3 Hz, 3H, SCH₃), 2.45–2.44 (m, 1H, CCH), 2.43–2.35 (m, 1H, SCH₂CHH), 2.21–2.08 (m, 1H, SCH₂CHH), 1.45 (s, 9H, CHCO₂(CH₃)₃), 1.41 (s, 9H, NHCO₂(CH₃)₃); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 169.9 (C=O), 158.1 (C=O), 155.4 (C=O), 83.2 (C(CH₃)₃), 80.3 (C(CH₃)₃), 77.9 (CCH), 74.7 (CCH), 53.3 (OCH₂), 52.3 (CHCO₂), 50.6 (SCH₂), 39.3 (d, SCH₃), 28.2 (C(CH₃)₃), 27.8 (C(CH₃)₃), 25.7 (d, SCH₂CH₂); HRMS (ESI-TOF) m/z: Calcd. for C₁₈H₃₀N₂O₇SNa [M + Na]⁺: 441.1671, found: 441.1668.

tert-Butyl (Methyl(oxo)(p-tolyl)-λ⁶-sulfaneylidene)carbamate (4)

Prepared using General Procedure using sulfoxide 1b (76.8 mg, 0.50 mmol) and tert-butylcarbamate (99.6 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 50% EtOAc in hexane) afforded N-Boc sulfoximine 4 (132.9 mg, 99%) as a white solid. R_f = 0.5 (50% EtOAc in hexane); mp = 108–112 °C; IR (film)/cm^–1 3027, 2974, 2109, 1662 (C=O), 1364, 1267, 1148, 984, 865, 790; ¹H NMR (400 MHz, CDCl₃) δ 7.84 (d, J = 8.4 Hz, 2H, 2 × Ar–H), 7.37 (d, J = 8.4 Hz, 2H, 2 × Ar–H), 3.21 (s, 3H, SCH₃), 2.44 (s, 3H, Ar–CH₃), 1.37 (s, 9H, C(CH₃)₃); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 157.6 (C=O), 144.7 (Ar–C_q), 135.6 (Ar–C_q), 130.2 (2 × Ar–C), 127.3 (2 × Ar–C), 80.4 (C(CH₃)₃), 44.8 (SCH₃), 27.9 (C(CH₃)₃), 21.5 (Ar–CH₃). Analytical data (NMR and IR) in agreement with those reported in the literature.¹⁴

Methyl (Methyl(oxo)(p-tolyl)-λ⁶-sulfaneylidene)carbamate (5)

Prepared using General Procedure using sulfoxide 1b (75.9 mg, 0.49 mmol) and methyl carbamate (63.8 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 50% EtOAc in hexane) afforded N-CO₂Me sulfoximine 5 (111.5 mg, 99%) as a colorless oil. R_f = 0.26 (50% EtOAc in hexane); mp = 92–96 °C; IR (film)/cm^–1 3019, 2930, 2117, 1670 (C=O), 1431, 1223, 1088, 984, 872, 790; ¹H NMR (400 MHz, CDCl₃) δ 7.87 (d, J = 8.4 Hz, 2H, 2 × Ar–H), 7.40 (d, J = 8.2 Hz, 2H, 2 × Ar–H), 3.67 (s, 3H, CO₂CH₃), 3.30 (s, 3H, SCH₃), 2.46 (s, 3H, Ar–CH₃); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 159.4 (C=O), 145.1 (Ar–C_q), 135.1 (Ar–C_q), 130.3 (2 × Ar–C), 127.4 (2 × Ar–C), 53.1 (CO₂CH₃), 44.6 (SCH₃), 21.6 (Ar–CH₃). Analytical data (NMR and IR) in agreement with those reported in the literature.¹⁴

Benzyl (Methyl(oxo)(p-tolyl)-λ⁶-sulfaneylidene)carbamate (6)

Prepared using General Procedure using sulfoxide 1b (76.8 mg, 0.50 mmol) and benzyl carbamate (128.5 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 50% EtOAc in hexane) afforded N-Cbz sulfoximine 6 (144.8 mg, 95%) as a white solid. R_f = 0.4 (50% EtOAc in hexane); mp = 90–94 °C; IR (film)/cm^–1 3027, 2922, 2110, 1655 (C=O), 1379, 1215, 1088, 969, 895 775; ¹H NMR (400 MHz, CDCl₃) δ 7.82 (d, J = 8.4 Hz, 2H, 2 × Ar–H), 7.35 (d, J = 8.4 Hz, 2H, 2 × Ar–H), 7.29–7.22 (m, 5H, 5 × Ar–H), 5.09 (d, J = 12.3 Hz, 1H, OCHH), 5.01 (d, J = 12.3 Hz, 1H, OCHH), 3.25 (s, 3H, SCH₃), 2.43 (s, 3H, Ar–CH₃); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 158.4 (C=O), 144.9 (Ar–C_q), 136.1 (Ar–C_q), 134.9 (Ar–C_q), 130.1 (2 × Ar–C), 128.1 (2 × Ar–C), 128.0 (2 × Ar–C), 127.7 (Ar–C), 127.2 (2 × Ar–C), 67.5 (OCH₂), 44.5 (SCH₃), 21.4 (Ar–CH₃). Analytical data (NMR and IR) in agreement with those reported in the literature.¹⁴

Phenyl (Methyl(oxo)(p-tolyl)-λ⁶-sulfaneylidene)carbamate (7)

Prepared using General Procedure using sulfoxide 1b (76.0 mg, 0.49 mmol) and phenyl carbamate (116.6 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 50% EtOAc in hexane) afforded N-CO₂Ph sulfoximine 7 (128.7 mg, 91%) as a white solid. R_f = 0.5 (50% EtOAc in hexane); mp = 110–116 °C; IR (film)/cm^–1 3042, 2072, 1670 (C=O), 1491, 1260, 1185, 977, 880, 716; ¹H NMR (400 MHz, CDCl₃) δ 7.92 (d, J = 8.4 Hz, 2H, 2 × Ar–H), 7.43–7.41 (m, 2H, 2 × Ar–H), 7.34–7.30 (m, 2H, 2 × Ar–H), 7.18–7.11 (m, 3H, 3 × Ar–H), 3.38 (s, 3H, SCH₃), 2.47 (s, 3H, Ar–CH₃); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 157.2 (C=O), 151.3 (Ar–C_q), 145.2 (Ar–C_q), 134.6 (Ar–C_q), 130.3 (2 × Ar–C), 129.0 (2 × Ar–C), 127.2 (2 × Ar–C), 125.1 (Ar–C), 121.5 (2 × Ar–C), 44.3 (SCH₃), 21.5 (Ar–CH₃). Analytical data (NMR and IR) in agreement with those reported in the literature.¹⁴

Allyl (Methyl(oxo)(p-tolyl)-λ⁶-sulfaneylidene)carbamate (8)

Prepared using General Procedure using sulfoxide 1b (77.0 mg, 0.50 mmol) and allyl carbamate (85.9 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 30% EtOAc in hexane) afforded sulfoximine allyl carbamate 8 (104.4 mg, 82%) as a colorless oil. R_f = 0.13 (30% EtOAc in hexane); IR (film)/cm^–1 3019, 2930, 2110, 1670 (C=O), 1446, 1357, 1223, 1088, 977, 872, 790; ¹H NMR (400 MHz, CDCl₃) δ 7.84 (d, J = 8.2 Hz, 2H, 2 × Ar–H), 7.38 (d, J = 8.2 Hz, 2H, 2 × Ar–H), 5.92–5.82 (m, 1H, CHCH₂), 5.28–5.22 (m, 1H, CHCHH), 5.17–5.13 (m, 1H, CHCHH), 4.56–4.51 (m, 1H, OCHH), 4.51–4.46 (m, 1H, OCHH), 3.27 (s, 3H, SCH₃), 2.43 (s, 3H, Ar–CH₃); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 158.5 (C=O), 145.0 (Ar–C_q), 135.0 (Ar–C_q), 132.4 (CHCH₂), 130.2 (2 × Ar–C), 127.3 (2 × Ar–C), 117.7 (CHCH₂), 66.5 (OCH₂), 44.5 (SCH₃), 21.5 (Ar–CH₃). Analytical data (NMR and IR) in agreement with those reported in the literature.¹⁴

3-(Trimethylsilyl)prop-2-yn-1-yl (Methyl(oxo)(p-tolyl)-λ⁶-sulfaneylidene)carbamate (9)

Prepared using General Procedure using sulfoxide 1b (76.4 mg, 0.50 mmol) and TMS-protected propargyl carbamate (145.6 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 30% EtOAc in hexane) afforded sulfoximine propargyl carbamate 9 (150.0 mg, 93%) as a colorless gum. R_f = 0.38 (30% EtOAc in hexane); IR (film)/cm^–1 3027, 2960, 2117, 1670 (C=O), 1372, 1230, 1088, 1029, 977, 842, 760;¹H NMR (400 MHz, CDCl₃) δ 7.84–7.82 (m, 2H, 2 × Ar–H), 7.38–7.35 (m, 2H, 2 × Ar–H), 4.64–4.59 (m, 1H, OCHH), 4.58–4.54 (m, 1H, OCHH), 3.27 (s, 3H, SCH₃), 2.42 (s, 3H, Ar–CH₃), 0.11 (s, 9H, (CH₃)₃); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 158.0 (C=O), 145.1 (Ar–C_q), 134.6 (Ar–C_q), 130.2 (2 × Ar–C), 127.2 (2 × Ar–C), 99.3 (CCSi), 91.5 (CCSi), 54.1 (OCH₂), 44.4 (SCH₃), 21.5 (Ar–CH₃), −0.5 ((CH₃)₃). HRMS (ESI-TOF) m/z: Calcd. for C₁₅H₂₂NO₃SSi [M + H]⁺: 324.1090, found: 324.1081.

Prop-2-yn-1-yl (Z)-(Methyl(p-tolyl)-λ⁴-sulfaneylidene)carbamate (12)

Prepared using General Procedure using sulfide 10a (69.1 mg, 0.50 mmol) and 2-propynyl carbamate (84.2 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, EtOAc) afforded sulfilimine propargyl carbamate 12 (38.1 mg, 32%) as a colorless gum. R_f = 0.36 (EtOAc); IR (film)/cm^–1 3235, 3019, 2922, 2117, 1759, 1625 (C=O), 1245, 1074, 954, 813, 671; ¹H NMR (400 MHz, CDCl₃) δ 7.68 (d, J = 8.3 Hz, 2H, 2 × Ar–H), 7.34 (d, J = 8.2 Hz, 2H, 2 × Ar–H), 4.67 (dd, J = 15.6, 2.4 Hz, 1H, OCHH), 4.63 (dd, J = 15.7, 2.4 Hz, 1H, OCHH), 2.82 (s, 3H, SCH₃), 2.42 (s, 3H, Ar–CH₃), 2.40 (t, J = 2.5 Hz, 1H, CCH); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 163.6 (C=O), 143.3 (Ar–C_q), 132.7 (Ar–C_q), 130.6 (2 × Ar–C), 126.4 (2 × Ar–C), 79.1 (CCH), 73.9 (CCH), 53.2 (OCH₂), 36.1 (SCH₃), 21.4 (Ar–CH₃). HRMS (ESI-TOF) m/z: Calcd. for C₁₂H₁₄NO₂S [M + H]⁺: 236.0745, found: 236.0755.

tert-Butyl [(Z)-Methyl(p-tolyl)-λ⁴-sulfanylidene]carbamate (13)

Prepared using General Procedure using sulfide 10a (69.1 mg, 0.50 mmol) and tert-butyl carbamate (99.6 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, EtOAc) afforded N-Boc sulfilimine 13 (64.0 mg, 51%) as a white solid. R_f = 0.3 (EtOAc); mp = 152–155 °C; IR (film)/cm^–1 3011, 2975, 2925, 1625, 1361, 1275, 1163, 1079, 985, 835, 817, 786, 753; ¹H NMR (400 MHz, CDCl₃) δ 7.64 (d, J = 8.1 Hz, 2H, 2 × Ar–H), 7.31 (d, J = 8.2 Hz, 2H, 2 × Ar–H), 2.76 (s, 3H, SCH₃), 2.39 (s, 3H, Ar–CH₃), 1.44 (s, 9H, (CH₃)₃); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 164.4 (C=O), 142.8 (Ar–C_q), 133.6 (Ar–C_q), 130.5 (2 × Ar–C), 126.1 (2 × Ar–C), 78.9 (C(CH₃)₃), 35.8 (SCH₃), 28.4 (C(CH₃)₃), 21.4 (Ar–CH₃). Analytical data (NMR and IR) in agreement with those reported in the literature.¹⁴

tert-Butyl (Z)-((4-Methoxyphenyl)(methyl)-λ⁴-sulfaneylidene)carbamate (14)

Prepared using General Procedure using sulfide 10b (77.5 mg, 0.50 mmol) and tert-butyl carbamate (99.6 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, EtOAc) afforded N-Boc sulfilimine 14 (77.3 mg, 61%) as a white solid. R_f = 0.15 (EtOAc); mp = 146–149 °C; IR (film)/cm^–1 3086, 3012, 1625 (C=O), 1498, 1260, 1156, 984, 835; ¹H NMR (400 MHz, CDCl₃) δ 7.72 (d, J = 9.0 Hz, 2H, 2 × Ar–H), 7.02 (d, J = 8.8 Hz, 2H, 2 × Ar–H), 3.86 (s, 3H, OCH₃), 2.78 (s, 3H, SCH₃), 1.46 (s, 9H, (CH₃)₃); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 164.5 (C=O), 162.7 (Ar–C_q), 128.2 (2 × Ar–C), 127.5 (Ar–C_q), 115.3 (2 × Ar–C), 78.8 (C(CH₃)₃), 55.6 (OCH₃), 35.9 (SCH₃), 28.4 (C(CH₃)₃). HRMS (ESI-TOF) m/z: Calcd. for C₁₃H₂₀NO₃S [M + H]⁺: 270.1164, found: 270.1162.

tert-Butyl (Z)-((4-Chlorophenyl)(methyl)-λ⁴-sulfaneylidene)carbamate (15)

Prepared using General Procedure using sulfide 10c (79.9 mg, 0.50 mmol) and tert-butyl carbamate (99.6 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, EtOAc) afforded N-Boc sulfilimine 15 (103.6 mg, 74%) as a white solid. R_f = 0.18 (EtOAc); mp = 142–144 °C; IR (film)/cm^–1 3012, 1625 (C=O), 1476, 1282, 1163, 835; ¹H NMR (400 MHz, CDCl₃) δ 7.72 (d, J = 8.6 Hz, 2H, 2 × Ar–H), 7.52 (d, J = 8.6 Hz, 2H, 2 × Ar–H), 2.80 (s, 3H, SCH₃), 1.46 (s, 9H, (CH₃)₃); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 164.4 (C=O), 138.5 (Ar–C_q), 135.6 (Ar–C_q), 130.2 (2 × Ar–C), 127.4 (2 × Ar–C), 79.3 (C(CH₃)₃), 35.8 (SCH₃), 28.3 (C(CH₃)₃). HRMS (ESI-TOF) m/z: Calcd. for C₁₂H₁₇NO₂S³⁵Cl [M + H]⁺: 274.0669, found: 274.0662.

Benzyl (Z)-(Methyl(p-tolyl)-λ⁴-sulfaneylidene)carbamate (16)

Prepared using General Procedure using sulfide 10a (70.9 mg, 0.51 mmol) and benzyl carbamate (128.5 mg, 0.85 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, EtOAc) afforded N-Cbz sulfilimine 16 (131.1 mg, 89%) as a colorless oil. R_f = 0.19 (EtOAc); IR (film)/cm^–1 3027, 2922, 2095, 1625 (C=O), 1446, 1252, 1074, 969, 813, 746; ¹H NMR (400 MHz, CDCl₃) δ 7.67 (d, J = 8.1 Hz, 2H, 2 × Ar–H), 7.40–7.38 (m, 2H, 2 × Ar–H), 7.34–7.24 (m, 5H, 5 × Ar–H), 5.13 (d, J = 12.4 Hz, 1H, OCHH), 5.07 (d, J = 12.4 Hz, 1H, OCHH), 2.80 (s, 3H, SCH₃), 2.41 (s, 3H, Ar–CH₃); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 164.5 (C=O), 143.1 (Ar–C_q), 137.3 (Ar–C_q), 133.1 (Ar–C_q), 130.6 (2 × Ar–C), 128.2 (2 × Ar–C), 128.1 (2 × Ar–C), 127.6 (Ar–C), 126.3 (2 × Ar–C), 67.5 (OCH₂), 36.1 (SCH₃), 21.4 (Ar–CH₃). HRMS (ESI-TOF) m/z: Calcd. for C₁₆H₁₈NO₂S [M + H]⁺: 288.1058, found: 288.1059.

tert-Butyl (Z)-(Phenyl(piperidin-1-yl)-λ⁴-sulfaneylidene)carbamate (17)

Prepared using General Procedure using 1-(phenylsulphenyl)piperidylamide 11 (58.0 mg, 0.3 mmol) and tert-butyl carbamate (59.7 mg, 0.51 mmol, 1.7 equiv). Purification by flash column chromatography (SiO₂, 30% EtOAc in pentane) afforded sulfinamidine 17 (35.2 mg, 38%) as a colorless oil. R_f = 0.26 (30% EtOAc in pentane); IR (film)/cm^–1 2972, 2936, 2853, 2116, 1630 (C=O), 1273, 1247, 1161, 1029, 848, 751, 688, 548; ¹H NMR (400 MHz, CDCl₃) δ 7.91–7.83 (m, 2H, 2 × Ar–H), 7.53–7.47 (m, 3H, 3 × Ar–H), 3.18 (ddd, J = 11.6, 6.6, 4.1 Hz, 2H, NCH₂), 2.95 (ddd, J = 11.7, 6.7, 3.9 Hz, 2H, NCH₂), 1.77–1.55 (m, 4H, 2 × CH₂), 1.53 (s, 9H, C(CH₃)₃), 1.53–1.50 (m, 2H, CH₂); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 165.0 (C=O), 134.6 (Ar–C_q), 131.2 (Ar–C), 128.9 (2 × Ar–C), 128.1 (2 × Ar–C), 78.7 (C(CH₃)₃), 48.2 (2 × NCH₂), 28.4 (C(CH₃)₃), 26.1 (2 × NCH₂CH₂), 23.5 (NCH₂CH₂CH₂); HRMS (ESI-TOF) m/z: Calcd. for C₁₆H₂₅N₂O₂S [M + H]⁺: 309.1637, found: 309.1630.

(1-Benzyl-1H-1,2,3-triazol-4-yl)methyl (Methyl(oxo)(phenyl)-λ⁶-sulfaneylidene)carbamate (18)

CuSO₄ anhydrous (2.4 mg, 0.015 mol, 5 mol %) was added to sulfoximine 2a (71.2 mg, 0.3 mmol, 1.0 equiv), benzyl azide (47.9 mg, 0.36 mmol, 1.2 equiv), and sodium ascorbate (11.9 mg, 0.06 mmol, 20 mol %) in tert-butyl alcohol (1.0 mL) and H₂O (0.5 mL) at rt. The resulting mixture was stirred at rt for 24 h, then quenched with saturated aqueous NH₄Cl solution (1.0 mL), and extracted with CH₂Cl₂ (3 × 5 mL). The combined organic layer was dried over Na₂SO₄, and the solvent was removed under reduced pressure. Purification by flash column chromatography (SiO₂, 5% EtOH in EtOAc) afforded triazole 18 (77.1 mg, 72%) as a white solid. R_f = 0.52 (5% EtOH in EtOAc); mp = 131–134 °C; IR (film)/cm^–1 3129, 3089, 3062, 2957, 2923, 2106, 1660 (C=O), 1443, 1338, 1249, 1224, 1084, 945, 859, 720, 683; ¹H NMR (400 MHz, CDCl₃) δ 7.92–7.89 (m, 2H, 2 × Ar–H), 7.65–7.61 (m, 1H, Ar–H), 7.54–7.50 (m, 2H, 2 × Ar–H), 7.48 (s, 1H, CCH), 7.35–7.30 (m, 3H, 3 × Ar–H), 7.23–7.20 (m, 2H, 2 × Ar–H), 5.47 (d, J = 14.9 Hz, 1H, NCHH), 5.43 (d, J = 14.9 Hz, 1H, NCHH), 5.14 (d, J = 12.8 Hz, 1H, OCHH), 5.09 (d, J = 12.8 Hz, 1H, OCHH), 3.25 (s, 3H, SCH₃); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 158.3 (C=O), 143.3 (Ar–C_q), 137.8 (CCH), 134.4 (Ar–C_q), 133.9 (Ar–C), 129.5 (2 × Ar–C), 128.9 (2 × Ar–C), 128.5 (Ar–C), 127.9 (2 × Ar–C), 127.1 (2 × Ar–C), 123.4 (CCH), 59.2 (OCH₂), 53.9 (NCH₂), 44.3 (SCH₃); HRMS (ESI-TOF) m/z: Calcd. for C₁₈H₁₉N₄O₃S [M + H]⁺: 371.1178, found: 371.1183.

(1-(13-Oxo-17-((3aR,4R,6aS)-2-oxohexahydro-1H-thieno[3,4-d]imidazol-4-yl)-3,6,9-trioxa-12-azaheptadecyl)-1H-1,2,3-triazol-4-yl)methyl (Methyl(oxo)(phenyl)-λ⁶-sulfaneylidene)carbamate (19)

Sulfoximine 2a (5.3 mg, 0.0225 mmol, 1.0 equiv), biotin-PEG3-azide (12.0 mg, 0.027 mmol, 1.2 equiv), and sodium ascorbate (1.1 mg, 0.0054 mmol, 20 mol %) were added to a microwave vial and sealed. The vial was degassed and backfilled with argon three times. CuSO₄ anhydrous (2.1 mg, 0.0135 mmol) was dissolved in a mixture of tBuOH (750 μL) and H₂O (375 μL), degassed, and backfilled with argon three times. CuSO₄ (0.11 mL in tBuOH and H₂O, 0.00135 mmol, 5 mol %) was added to the reaction vial and stirred at rt for 24 h. Purification by flash column chromatography (SiO₂, 5% MeOH in CH₂Cl₂) afforded the biotin-PEG3-triazole 19 as a white gum (14.7 mg, 96%). R_f = 0.18 (5% MeOH in CH₂Cl₂); IR (film)/cm^–1 3295, 2922, 2867, 1698 (C=O), 1669 (C=O), 1541, 1449, 1253, 1119, 1090, 977, 893, 740, 687, 546, 512; ¹H NMR (400 MHz, CDCl₃) δ 7.99 (d, J = 7.6 Hz, 2H, 2 × Ar–H), 7.70 (t, J = 7.3 Hz, 1H, Ar–H), 7.62 (t, J = 7.5 Hz, 2H, 2 × Ar–H), 6.84 (s, 1H, NH), 6.40 (s, 1H, NH), 5.52 (s, 1H, NH), 5.19 (s, 2H, OCH₂), 4.54 (s, 3H, 3 × CH), 4.35 (s, 1H, CH), 3.88 (s, 2H, CH₂), 3.59–3.53 (m, 10H, 5 × CH₂), 3.41 (s, 2H, CH₂), 3.35 (s, 3H, SCH₃), 2.21 (s, 2H, CH₂), 1.67 (s, 4H, 2 × CH₂), 1.43 (s, 2H, CH₂); ¹³C{¹H} NMR (101 MHz, CDCl₃) δ 173.4 (C=O), 158.6 (C=O), 138.0 (Ar–C_q), 134.1 (Ar–C), 129.8 (2 × Ar–C), 127.4 (2 × Ar–C), 77.2 (SCH), 70.5 (OCH₂), 70.4 (OCH₂), 70.3 (OCH₂), 70.0 (OCH₂), 69.9 (OCH₂), 69.3 (OCH₂), 61.8 (CONHCH), 60.3 (CONHCH), 59.3 (OCH₂), 55.5 (NCH₂), 50.5 (NCH₂), 44.5 (SCH₃), 39.1 (CH₂), 35.9 (CH₂), 28.2 (2 × CH₂), 25.6 (CH₂); HRMS (ESI-TOF) m/z: Calcd. for C₂₉H₄₄N₇O₈S₂ [M + H]⁺: 682.2693, found: 682.2711. Note: Broadening of the ¹H and ¹³C NMR signals of the triazole ring (C and CH signals) occurred to an extent that these were not visible. Similarly the ¹³C NMR signal for the biotin urea carbonyl (HN-CO-NH) is not observed.

All characterization data for the synthesized compounds can be found at https://doi.org/10.14469/hpc/11861.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acs.joc.2c02083.

• Details of DOE investigation. Copies of ¹H and ¹³C NMR spectra. (PDF)

The authors declare no competing financial interest.