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. 2021 Dec 23;7(1):1186–1196. doi: 10.1021/acsomega.1c05770

trans-Dichlorobis(XPhos)palladium(II) Precatalyst for Suzuki–Miyaura Cross-Coupling Reactions of Aryl/Vinyl Sulfonates/Halides: Scope, Mechanistic Study, and Synthetic Applications

Fatih Sirindil 1, Romain Pertschi 1, Emma Naulin 1, Delphine Hatey 1, Jean-Marc Weibel 1, Patrick Pale 1, Aurélien Blanc 1,*
PMCID: PMC8756804  PMID: 35036781

Abstract

graphic file with name ao1c05770_0012.jpg

Suzuki–Miyaura cross-coupling reactions of aryl/vinyl sulfonates/halides with various boron species were performed using an easily available trans-dichlorobis(XPhos)palladium(II) precatalyst. Under microwave assistance, more than 30 coupling products were obtained with yields ranging from 23 to 99%, including the synthesis of two bioactive compounds, dubamine and tamoxifen. A mechanistic investigation of the Suzuki–Miyaura reaction was conducted notably by nuclear magnetic resonance (NMR) and high-resolution mass spectroscopy, revealing the nature of the active Pd0 species and of the reducing entity.

Introduction

The Suzuki–Miyaura coupling (SMC) reaction has become the most important and more widely employed method for building Csp2–C bonds.1 To improve its efficacy and expand its scope, various bulky ligands2 have been developed such as Buchwald’s dialkylbiarylphosphines.3 Among them, the 2-dicyclohexylphosphino-2′,4′,6′-triisopropylbiphenyl ligand, so-called XPhos, has demonstrated its efficiency several times in SMC and in related cross-coupling reactions.4 This bulky phosphine ligand was generally used together with palladium(II) salts, such as Pd(OAc)2.5 The resulting mixture in situ formed XPhos-PdII complex(es), which evolved into the active Pd0 species upon spontaneous reduction or upon exposure to a base.6 However, prestirring the ligand and the Pd precursor could have deleterious effects on cross-coupling reactions considering the potential formation of dinuclear6 and polynuclear metal complexes and clusters.7 To avoid such problems, well-defined preformed palladium complexes, i.e., precatalysts,8 have been successfully developed.

Combining the effectiveness of dialkylbiarylphosphine ligands and the advantages of precatalysts, Buchwald et al. have thus developed XPhos-based palladacycle complexes (Scheme 1) for coupling challenging boronic acid partners in SMC and other cross-coupling reactions.9 Despite their excellent catalytic activities, these palladacycle-based precatalysts suffer from some drawbacks, such as their high temperature of activation (Pd G1)9b and low stability (Pd G2)9c or the genotoxicity of the resultant carbazole by-product10 (Pd G2-G4) and more generally their 3–4 step synthesis even if they are now commercially available. Alternative precatalysts have thus been envisaged by combining XPhos and N-heterocyclic carbene or π-allyl ligands (Scheme 1). PdCl2(IPr)(XPhos) developed by Cazin et al.11 was an effective catalyst for aqueous SMC of aryl chloride at a low catalyst loading (0.03 mol %). PdCl(η3crotyl)(XPhos) introduced by Colacot et al.12 was more active than XPhos-Pd G3 in the same coupling with heteroaryl chlorides. A closely related PdCl(η3indenyl)(XPhos) precatalyst was developed by Hazari and Nova13 showing comparable performance to the best-known systems on SMC with heteroaryl partners.

Scheme 1. Precatalysts Containing the XPhos Ligand.

Scheme 1

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Surprisingly, the simplest precatalyst PdCl2(XPhos)2 (Scheme 1), easily prepared in a quantitative manner by mixing PdCl2(MeCN)2 and XPhos (2 equiv) in acetonitrile at reflux,14 has almost never been used in palladium-catalyzed cross-coupling reactions, despite its obvious analogy to trans-dichlorobis(triphenylphosphine)palladium(II), one of the earliest and commonly used L2PdCl2 precatalyst.15

The first description of PdCl2(XPhos)2 was provided by Jong et al. in 2015 during copper-free Sonogashira cross-coupling investigations, where it was only used for comparison to more elaborated dialkylbiarylphosphine ligands (Scheme 2, eq 1).16 In 2018, PdCl2(XPhos)2 was also used as a precatalyst in Suzuki–Miyaura coupling reactions between sulfoxide-based boronates and few electron-poor aryl bromide partners (Scheme 2, eq 2).17 In our hand, PdCl2(XPhos)2 appeared salvaging in the development of the challenging Suzuki–Miyaura cross-coupling reaction with various 2-pyrrolyl tosylates (Scheme 2, eq 3), while mixtures of the XPhos ligand or other ligands with various PdII/0 sources led to unreproducible or poor yields.14 As a result, 2-aryl pyrrole derivatives were obtained in good to excellent yields, allowing the completion of the total synthesis of the rhazinilam natural product.

Scheme 2. Palladium(II) Di(XPhos) Dichloride as the Precatalyst for Cross-Coupling Reactions.

Scheme 2

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The excellent results obtained from rhazinilam total synthesis inspired us to further explore the reactivity of PdCl2(XPhos)2 as a precatalyst and also to understand why this catalyst was so efficient and how it could act. We report here its application to Suzuki–Miyaura cross-coupling reactions of aryl and vinyl sulfonates or halides, and to the synthesis of relevant bioactive molecules. Moreover, a mechanistic investigation of the Suzuki–Miyaura reaction was conducted, notably by NMR and high-resolution mass spectroscopy.

Results and Discussion

As almost unknown (see Scheme 2), we started looking at the reactivity of PdCl2(XPhos)2, and especially for the best partners PdCl2(XPhos)2 was able to couple with in the Suzuki–Miyaura reaction. For that, we first engaged simple toluyl sulfonates and halides with a series of typical phenyl boron species under the conditions we set up for pyrrolyl sulfonates14 (Scheme 3). Whatever the partners, the expected product 4-methyl-1,1′-biphenyl 2a was obtained with yields higher than 70%. Coupled with phenylboronic acid, toluyl tosylate (Ts), para-methoxybenzenesulfonate (Mbs), and mesylate (Ms) partners gave good to excellent results, especially for the Mbs group (97%). As expected from the use of such kind of ligand,3 the corresponding bromide afforded the coupling product 2a in excellent yield (87%), and even the more challenging chloride partner provided 2a in a similar yield (93%). As the boron partner nature is known to be important in the Suzuki–Miyaura coupling,18 we briefly surveyed this aspect. Boron reagents, more stable than boronic acids, were as effective under our reaction conditions.18 With the less reactive toluyl tosylate, neopentylglycol, or catechol boronic esters proved to be the most efficient, yielding 2a in 85%. Phenylboronic pinacol ester was slightly less effective (72%), probably for steric reasons, as was potassium phenyltrifluoroborate which provided similar yields (75%). It is worth noting that the SMC efficiency was weakly affected by decreasing the catalyst loading to 1 mol %, leading to 2a with 74% of yield from the tosylate partner (79% with 5 mol %). Finally, the control experiment run with a mixture of PdCl2(MeCN)2 and XPhos afforded 2a from toluyl tosylate in a poor 27% yield (79% with PdCl2(XPhos)2), confirming that the PdCl2(XPhos)2 precatalyst prevailed over its progenitors under our reaction conditions. Of note, without microwave activation, the SMC proceeds as well but with a long reaction time (18 h at 110 °C in an oil bath vs 30 min under microwave) but generally with lower yields (see the Supporting Information).

Scheme 3. Variation of the Leaving Group and of the Boron Species in the Suzuki–Miyaura Coupling using PdCl2(XPhos)2 as the Precatalyst.

Scheme 3

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TBAOH, n-BuOH/H2O, 110 °C, 30 min, MW.

Yields of isolated pure products.

With 1 mol % of the catalyst.

With a mixture of PdCl2(MeCN)2/XPhos ligands.

Despite better results achieved with arylOMbs and boronic esters, we selected aryl tosylates and boronic acids, the most challenging partners, to tackle the efficiency of PdCl2(XPhos)2 as a precatalyst in the Suzuki–Miyaura reaction. Various combinations of these partners were thus subjected to the same conditions to explore the scope of this SMC variant (Scheme 4). The use of the PdCl2(XPhos)2 precatalyst demonstrated good generality and efficiency (88% in average), except for a few cases (see below). The conditions proved compatible with a wide range of functional groups such as ester, aldehyde, acetal, ether, fluoride, free hydroxy, and even free amine. Heteroaromatics, including the strongly coordinating pyridine, and alkenes also proved compatible.

Scheme 4. Scope of the Palladium-Catalyzed Suzuki–Miyaura Coupling of Aryl Tosylates with Various Boronic Acids.

Scheme 4

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NMR yield.

Degradation occurred.

SMCs are known to be sensitive to electronic effects, which negatively impacts the reaction efficiency at the oxidative addition step for electron-rich aryl halides and related species, and at the transmetalation step for electron-poor boronic derivatives. Although the use of bulky biphenyl ligands should minimize such effects,3b we looked at the effects substituents may have in the presence of the PdCl2(XPhos)2 precatalyst as it is unknown. Therefore, the simple toluyl tosylate was coupled with a variety of phenylboronic acids carrying electron-withdrawing or -donating groups under the abovementioned conditions. para-Alkoxylated phenylboronic acids gave slightly better yields than their para-deactivated counterparts (see 2d, 2g, 2i vs 2b, 2c, 2h), as expected from their higher nucleophilicity, which increases the transmetalation rates. No significant difference could be observed in the coupling of phenyl tosylates carrying electron-donating or -withdrawing substituents (see 2f, 2o–2t). In contrast, the nitro group either on the boronic acid or on the tosylate induced lower yields and the formation of undefined by-products (see 2e). Despite its coordination ability, pyridine either on the boronic acid or on the tosylate led to high to quantitative yields of the coupling products (see 2j, 2s). The fragile thiophene boronic acid gave lower yields, as well as undefined by-products (see 2k). The effect of steric hindrance was also briefly examined. From mono ortho-substituted phenylboronic acids, coupling products 2l, 2m were obtained in high yields. In contrast, 2,6-dimethoxyphenyl boronic acid reacted slowly and only gave low conversion and yield of the corresponding coupling product 2n. The latter result is quite surprising as bulky biphenyl ligands are known for their efficiency in coupling hindered partners.19 Finally, the (E)-2-phenylvinylboronic acid partner reacted efficiently under our reaction conditions, as demonstrated by the formation of the stilbene derivative 2u in high yield, while methylboronic acid failed to afford coupling product 2v.

We then briefly evaluated the compatibility of vinyl partners to our SMC reaction conditions (Scheme 5). Satisfyingly, coupling compounds 2w-2y were obtained in good yields ranging from 73 to 79%, from vinyl bromide (1w, 1x) or tosylate ((E)-1y) derivatives.

Scheme 5. PdCl2(XPhos)2 as the Precatalyst in the Suzuki–Miyaura Coupling of Vinyl Partners.

Scheme 5

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Overall, simple PdCl2(XPhos)2, almost quantitatively prepared in a single step, proved to be a useful and efficient catalyst for SMC of aryl and vinyl sulfonates. However, the way it acts in solution is unknown, we thus investigated its behavior in solution and in the presence of reagents under the set-up conditions.

The precise understanding of palladium-catalyzed cross-coupling reactions has greatly benefited from the detailed investigations mostly performed by Jutand et al., who combined electrochemical and NMR techniques.20 Applying those techniques to the SMC reaction, they were able to identify each elementary step of the catalytic cycle and demonstrated the key influence of several parameters on these elementary steps, complicating the whole cycle.21 In the same vein, Jutand and Grimaud have recently reported the study of in situ formation of XPhos-Pd0 complexes and their reactivity in oxidative addition with aryl halide using cyclic voltammetry and NMR techniques.6 This work revealed the complexity of the process starting from a mixture of XPhos ligand and PdII(OAc)2 with the formation of diverse Pd0 species and PdI–PdI dimers.

As we started here from a preformed catalyst, we wondered if such complexity would still occur, and if not, what would be the key reducing step converting the PdII precatalyst into which active Pd0 species. To gain mechanistic insights into the SMC reaction starting from the PdCl2(XPhos)2 precatalyst, we monitored the evolution of a solution containing PdCl2(XPhos)2 in the presence of a base by combining 31P, 1H NMR spectroscopies and high-resolution mass techniques (Figure 1).

Figure 1.

Figure 1

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31P and 1H NMR monitoring of the PdCl2(XPhos)2 reductive elimination.

The PdCl2(XPhos)2 complex was solubilized under argon in n-butanol at 0.1 M and this solution was diluted with CDCl3 for 1H NMR monitoring. 31P NMR analysis of this mixture indicated a single signal at 45.2 ppm corresponding to the precatalyst (black spectrum, t = 0 min, in Figure 1 left inset). The addition of 1 equiv of an aqueous solution of base (TBAOH or NaOH) and heating at 110 °C induced the rapid formation of a new species at 47.0 ppm (blue-green spectrum, t = 1 min). Irrespective of the nature of the base, the system evolved toward this species with complete disappearance of the initial complex within minutes (red spectrum, t = 10 min). Further monitoring over 60 min showed that the system remained unchanged. Interestingly, the appearance of the 47.0 ppm signal in 31P NMR was accompanied by the concomitant formation of a triplet signal at 9.56 ppm (Figure 1, right inset) in the 1H NMR spectrum. The latter could be assigned to n-butanal. These observations strongly suggested that n-butanol is the reducing agent of the initial PdII complex into a single Pd0 species. This rapid formation and the presence of a single Pd0 species is in sharp contrast with what was observed starting from Pd(OAc)2 and excess XPhos.6 To confirm that n-butanol is the reducing species, the same experiments in the presence of TBAOH or NaOH were performed with tert-butanol as the solvent. In both cases, 31P and 1H NMR monitoring did not show any evolution of the PdCl2(XPhos)2 signal at 45.2 ppm.

To identify the Pd0 species formed in n-butanol, high-resolution mass spectra (ESI-TOF, HR-MS) of the solution were recorded. A set of peaks typical for the isotopic distribution of a palladium entity was observed at an m/z exact mass of 1058.6145. This value accounts for a chemical formula of C66H98P2Pd, which corresponds to the reduced palladium complex Pd0(XPhos)2.

This data set clearly indicates that in n-butanol, PdCl2(XPhos)2 is rapidly converted to Pd0(XPhos)2 in the presence of the base, presumably upon chloride exchange on PdII with n-butanoate, in situ formed upon base addition, followed by β-H-elimination (Scheme 6). It is interesting to note that the solution of the so-formed Pd0(XPhos)2 species, although stable, contains a small amount of free XPhos (δ −12.2 ppm, 31P NMR). This observation suggests an equilibrium between the di- and mono-ligated Pd°, in line with what is known for this type of bulky ligand to ensure oxidative addition19 and with the recent kinetic study demonstrating that the dissociation of Pd0(XPhos)2 is rate-limiting in SMC.6

Scheme 6. PdCl2(XPhos)2In Situ Transformation as Established by 31P and 1H NMR Monitoring (Species in Bracket Could not be Detected).

Scheme 6

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To look at the reactivity of the so-formed Pd0(XPhos)2 species, we added toluyl sulfonate while continuously monitoring the complete cycle of the Suzuki coupling. Unfortunately, all attempts to investigate the coupling with sulfonylated partners by 31P NMR were unsuccessful due to the formation of insoluble species making NMR monitoring impossible. Facing this situation, we decided to use iodobenzene as a coupling partner. Rewardingly, 31P and 1H NMR spectroscopies allowed monitoring of the coupling with this reagent and as before, intermediate species could also be analyzed by high-resolution mass spectrometry (Figure 2).

Figure 2.

Figure 2

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31P and 1H NMR monitoring of the Suzuki–Miyaura coupling between iodobenzene and 1,3-benzodioxole-5-boronic acid using PdCl2(XPhos)2 as the precatalyst.

To facilitate the reading of 1H NMR spectra, NaOH and the 5-(1,3-benzodioxolyl)boronic acid coupling partner were used. Addition of 1 equiv of iodobenzene to the Pd0(XPhos)2 solution obtained above (Figure 2, 31P purple spectrum, t = 10 min), led in 10 min to the formation of a new species at 21.9 ppm concomitantly with another signal at −12.2 ppm, typical of free XPhos (black spectrum, t = 20 min). The chemical shift of the new signal was in close agreement with the one already reported by Skrydstrup22 for the (XPhos)(I)PdPh complex (31P, δ = 21.4 ppm). HR-MS analysis confirmed its nature, with a mass of 659.2977, which corresponded to the (XPhos)Pd(C6H5) complex, that is the oxidative addition product in which iodide was lost under MS conditions.23 Without further addition, a new signal at 36.3 ppm appeared within 10 min and increased until the complete disappearance of the free XPhos signal (blue-green and red spectra, t = 30 and 45 min). HR-MS analysis at that stage revealed a mass of 553.3921 corresponding to a C39H54P formula. The latter is consistent with the phosphonium derivative Ph(XPhos)+, which could be produced from reductive elimination of the oxidative addition complex in the absence of boronic acid and a base.

The addition of 2 equiv of 5-(1,3-benzodioxolyl)boronic acid did not induce a change in the system after another 15 min of stirring (blue spectrum, t = 60 min). However, the addition of 1 equiv of a base caused the disappearance of the oxidative addition complex signal at 21.9 ppm (green spectrum, t = 75 min), in agreement with transmetalation and reductive elimination processes both known to involve Pd(OH) intermediates.21c The XPhos signal also reappeared, due to the release of the ligand, while the already formed Ph(XPhos)+ signal at 36.3 ppm remained persistent.

Parallel 1H NMR monitoring allowed looking at the evolution of the boronic acid partner through its typical 1,3-benzodioxolyl methylene signal at 5.84 ppm for 5-boronic acid and at 5.90 ppm for the 5-coupled product 2f (Figure 2, bottom, with color code identical to the 31P spectra). As observed in 31P NMR, the signal of boronic acid persisted for 30 min until the addition of NaOH (1 equiv; 1H green spectrum, t = 75 min). At this moment, this signal disappeared and concomitantly, a new signal at 5.90 ppm corresponding to 2f appeared (see the 1H gray spectrum of the pure compound for comparison).

In the 1H NMR, traces of the coupling product 2f could already be detected before NaOH addition (red and blue spectra in Figure 2). This 2f formation was probably promoted once boronic acid was added to the slight excess of NaOH, unintentionally introduced during the first base addition necessary for the in situ production of the active catalytic species (see Figure 1). This combined information allowed establishing the full mechanism for the present SMC reaction catalyzed by the preformed PdCl2(XPhos)2 (Scheme 7).

Scheme 7. Proposed Mechanism for the Suzuki–Miyaura Coupling Starting from the PdCl2(XPhos)2 Precatalyst (Species in Bracket Could not be Detected).

Scheme 7

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To exemplify the benefit of this SMC reaction based on the PdCl2(XPhos)2 precatalyst, we applied these conditions to the synthesis of two bioactive compounds (Scheme 8). First, the natural alkaloid dubamine, exhibiting an antiviral effect against cold,24 was readily prepared in 88% yield starting from quinolyl tosylate 1z by coupling with 3,4-methylene-dioxyphenylboronic acid. We then focused our attention on the challenging synthesis of tamoxifen, a drug used since the 1970s for the treatment of breast cancer and as an antiestrogenic agent.25 The latter was readily obtained in a high yield from Z-vinyl tosylate (Z)-1y and boronic acid 3 as coupling partners, despite the hindrance of the former partner. Sodium hydroxide was used instead of TBAOH to minimize the formation of by-products.

Scheme 8. Application of the Suzuki Coupling Conditions to the Synthesis of Dubamine and Tamoxifene.

Scheme 8

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Conclusions

In conclusion, we have demonstrated here that the easily available PdCl2(XPhos)2 was an efficient precatalyst for Suzuki–Miyaura cross-coupling reactions of aryl or vinyl sulfonates/halides with various boron species (35 examples, 23–99%). The conditions proved compatible with a large palette of functional groups, including free OH, free NH2, and the pyridine moiety, the latter two being strongly coordinating. The mechanism of SMC starting from PdCl2(XPhos)2 was also investigated revealing the nature of the active Pd0 species and of the reducing entity. Furthermore, our SMC reaction conditions allowed the synthesis of two bioactive molecules.

Experimental Section

General Information

Proton (1H NMR) and carbon (13C NMR) nuclear magnetic resonance spectra were recorded on 300, 400, or 500 MHz instruments. The chemical shifts are given in part per million (ppm) on the delta scale. The solvent peak was used as reference values. For 1H NMR, CDCl3 = 7.26 ppm. For 13C NMR, CDCl3= 77.16 ppm. Data are presented as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, quint = quintet, m = multiplet, b = broad), coupling constants (J in Hz) and integration, and carbons with the same chemical shift as follows: chemical shift (x carbons). Infrared spectra were recorded neat. Wavelengths of maximum absorbance (νmax) are quoted in wavenumbers (cm–1). High-resolution mass spectrum (HR-MS) data were recorded on a microTOF spectrometer equipped with an orthogonal electrospray interface (ESI). The parent ions [M]+, [M + H]+, [M + K]+ [M + Li]+, or [M + Na]+ are quoted. Analytical thin-layer chromatography (TLC) was carried out on silica gel 60 F254 plates with visualization by ultraviolet light, cerium ammonium molybdate, or potassium permanganate dip. Flash column chromatography was carried out using SiO2 60 (40–63 μm) and the procedures included the subsequent evaporation of solvents in vacuo. All commercially available reagents were used as received, all extractive procedures were performed using technical grade solvents, and all aqueous solutions were saturated unless details are given. All air- and moisture-sensitive reactions were carried out using flame-dried glassware under an argon atmosphere. A microwave monomode CEM Discover SP was used for all of the SMC (power 300 W) reactions. All aryl sulfonates 1 used were known compounds and were prepared from the commercially available phenol derivatives according to the reported procedure.26 (E)-1-Bromocyclooct-1-ene 1w and bromotriphenylethylene 1x were synthesized following a procedure described in the literature.27 Boronic acid 3 was prepared in two steps from 4-iodophenol using a reported procedure.28

General Procedure for Suzuki–Miyaura Coupling Reactions

A microwave reactor (10 mL) was successively loaded with the corresponding aryl/vinyl sulfonate or halide (1 equiv), PdCl2(XPhos)2 (5 mol %), and arylboronic acid (2 equiv). The tube was flushed with argon three times. Then, argon degassed n-BuOH (c = 0.1 M) was added, and the mixture was stirred at room temperature for 5 min. An argon degassed aqueous solution of TBAOH or NaOH [0.3 M] (1 equiv) was then added. The tube was placed in the microwave (300 W) and the reaction mixture was stirred at 110 °C for 30 min. The reaction was quenched with water (2 mL) and diluted with EtOAc (5 mL). The layers were separated, and the aqueous layer was extracted twice with EtOAc (5 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated in vacuo. The crude product was purified by flash column chromatography (cyclohexane/EtOAc or pentane/ether) on silica gel to afford the desired product.

4-Methyl-1,1′-biphenyl (2a)

Prepared following the general procedure in 79% yield (199 mg, 1.18 mmol) from p-tolyl 4-methylbenzenesulfonate (393.5 mg, 1.5 mmol) and phenylboronic acid. 1H NMR (CDCl3, 500 MHz) δ 7.55–7.52 (m, 2H), 7.47–7.43 (m, 2H), 7.40–7.35 (m, 2H), 7.30–7.25 (m, 1H), 7.22–7.18 (m, 2H), 2.35 (s, 3H); 13C NMR (CDCl3, 126 MHz) δ 141.3, 138.5, 137.2, 129.6 (2C), 128.8 (2C), 127.1 (2C), 127.1 (2C), 127.1, 21.3. Consistent with the literature data.29

Prepared following the general procedure in 97% yield (12.6 mg, 0.075 mmol) from p-tolyl 4-methoxybenzenesulfonate (21.6 mg, 0.077 mmol) and phenylboronic acid.

Prepared following the general procedure in 82% yield (15.8 mg, 0.094 mmol) from p-tolyl methanesulfonate (21.3 mg, 0.114 mmol) and phenylboronic acid.

Prepared following the general procedure in 87% yield (23.7 mg, 0.140 mmol) from 1-bromo-4-methylbenzene (27.8 mg, 0.162 mmol) and phenylboronic acid.

Prepared following the general procedure in 93% yield (25.2 mg, 0.150 mmol) from 1-chloro-4-methylbenzene (20.4 mg, 0.161 mmol) and phenylboronic acid.

Prepared following the general procedure in 75% yield (9.0 mg, 0.053 mmol) from p-tolyl 4-methylbenzenesulfonate (18.7 mg, 0.071 mmol) and potassium phenyltrifluoroborate.

Prepared following the general procedure in 72% yield (10.0 mg, 0.059 mmol) from p-tolyl 4-methylbenzenesulfonate (21.5 mg, 0.082 mmol) and phenylboronic acid pinacol ester.

Prepared following the general procedure in 84% yield (5.7 mg, 33.9 μmol) from p-tolyl 4-methylbenzenesulfonate (10.5 mg, 40.0 μmol) of and 5,5-dimethyl-2-phenyl-1,3,2-dioxaborinane.

Prepared following the general procedure in 85% yield (5.8 mg, 34.5 μmol) from p-tolyl 4-methylbenzenesulfonate (10.6 mg, 40.4 μmol) and 2-phenyl-1,3,2-benzodioxaborole.

Methyl 4′-Methyl-[1,1′-biphenyl]-4-carboxylate (2b)

Prepared following the general procedure in 85% yield (17.6 mg, 0.078 mmol) from p-tolyl 4-methylbenzenesulfonate (24.0 mg, 0.091 mmol) and (4-(methoxycarbonyl)phenyl)boronic acid. 1H NMR (CDCl3, 500 MHz) δ 8.12–8.06 (m, 2H), 7.65 (dq, J = 8.5, 2.0 Hz, 2H), 7.56–7.50 (m, 2H), 7.30–7.26 (m, 2H), 3.94 (s, 3H), 2.41 (s, 3H); 13C NMR (CDCl3, 126 MHz) δ 167.2, 145.7, 138.3, 137.2, 130.2 (2C), 129.8 (2C), 128.7, 127.2 (2C), 126.9 (2C), 52.3, 21.3. Consistent with the literature data.30

4-Fluoro-4′-methyl-1,1′-biphenyl (2c)

Prepared following the general procedure in 91% yield (12.8 mg, 0.068 mmol) from p-tolyl 4-methylbenzenesulfonate (19.8 mg, 0.075 mmol) and (4-fluorophenyl)boronic acid. 1H NMR (CDCl3, 500 MHz) δ 7.53 (ddd, J = 8.8, 5.4, 2.7 Hz, 2H), 7.46–7.43 (m, 2H), 7.25 (d, J = 7.7 Hz, 2H), 7.15–7.09 (m, 2H), 2.40 (s, 3H); 13C NMR (CDCl3, 126 MHz) δ 163.4, 161.4, 137.5, 137.2, 129.7 (2C), 128.6, 128.5 127.0 (2C), 115.8, 115.6, 21.2. Consistent with the literature data.31

4-Methoxy-4′-methyl-1,1′-biphenyl (2d)

Prepared following the general procedure in 94% yield (15.7 mg, 0.079 mmol) from p-tolyl 4-methylbenzenesulfonate (22.2 mg, 0.084 mmol) and (4-methoxyphenyl)boronic acid. 1H NMR (CDCl3, 500 MHz) δ 7.80–7.76 (m, 2H), 7.73–7.70 (m, 2H), 7.51–7.47 (m, 2H), 7.25–7.21 (m, 2H), 4.11 (s, 3H), 2.65 (s, 3H); 13C NMR (CDCl3, 126 MHz) δ 159.0, 138.1, 136.5, 133.8, 129.6 (2C), 128.1 (2C), 126.7 (2C), 114.3 (2C), 55.5, 21.2. Consistent with the literature data.32

4-Methyl-4′-nitro-1,1′-biphenyl (2e)

Prepared following the general procedure in 47% yield (34.1 mg, 0.160 mmol) from 4-nitrophenyl 4-methylbenzenesulfonate (100 mg, 0.341 mmol) and p-tolylboronic acid (92.7 mg, 0.682 mmol). 1H NMR (300 MHz, CDCl3) δ 8.28 (d, J = 8.9 Hz, 2H), 7.72 (d, J = 9.0 Hz, 2H), 7.53 (d, J = 8.2 Hz, 2H), 7.33–7.28 (d, J = 9.0 Hz, 2H), 2.43 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 147.7, 145.0, 139.2, 136.0, 130.0 (2C), 127.6 (2C), 127.4 (2C), 124.3 (2C), 21.4.29

5-Phenylbenzo[d][1,3]dioxole (2f)

Prepared following the general procedure in 81% yield (30.5 mg, 0.154 mmol) from p-tolyl benzenesulfonate (47 mg, 0.189 mmol) and 3,4-methylenedioxyphenylboronic acid. 1H NMR (CDCl3, 300 MHz) δ 7.55–7.50 (m, 2H), 7.46–7.38 (m, 2H), 7.33 (tt, J = 7.3, 1.3 Hz, 1H), 7.09–7.05 (m, 2H), 6.90 (dd, J = 7.4, 0.8 Hz, 1H), 6.01 (s, 2H); 13C NMR (CDCl3, 126 MHz) δ 147.5, 146.4, 140.3, 135.0, 128.1 (2C), 126.3 (2C), 120.0, 108.9, 107.1, 100.5. Consistent with the literature data.33

5-(p-Tolyl)benzo[d][1,3]dioxole (2g)

Prepared following the general procedure in 95% yield (15.3 mg, 0.072 mmol) from p-tolyl 4-methylbenzenesulfonate (19.8 mg, 0.076 mmol) and 3,4-methylenedioxyphenylboronic acid. 1H NMR (CDCl3, 500 MHz) δ 7.44–7.37 (m, 2H), 7.22 (d, J = 7.8 Hz, 2H), 7.08–7.01 (m, 2H), 6.87 (d, J = 8.0 Hz, 1H), 5.99 (s, 2H), 2.38 (s, 3H); 13C NMR (CDCl3, 126 MHz) δ 148.2, 146.9, 138.2, 136.8, 135.7, 129.6 (2C), 126.9 (2C), 120.5, 108.7, 107.7, 101.2, 21.2. Consistent with the literature data.34

4′-Methyl-[1,1′-biphenyl]-3-ol (2h)

Prepared following the general procedure in 93% yield (12.2 mg, 0.066 mmol) from p-tolyl 4-methylbenzenesulfonate (18.6 mg, 0.071 mmol) and (3-hydroxyphenyl)boronic acid. 1H NMR (CDCl3, 500 MHz) δ 7.50–7.43 (m, 2H), 7.30 (t, J = 7.9 Hz, 1H), 7.24 (d, J = 8.0 Hz, 2H), 7.16 (dt, J = 7.6, 1.3 Hz, 1H), 7.05 (t, J = 2.1 Hz, 1H), 6.80 (ddd, J = 8.1, 2.6, 1.0 Hz, 1H), 4.73 (d, J = 9.5 Hz, 1H), 2.39 (s, 3H); 13C NMR (CDCl3, 126 MHz) δ 155.9, 143.1, 137.9, 137.5, 130.1, 129.6 (2C), 127.1 (2C), 119.8, 114.0, (2C) 21.3. Consistent with literature data.35

N,N-Dimethyl-2-((4′-methyl-[1,1′-biphenyl]-4-yl)oxy)ethan-1-amine (2i)

Prepared following the general procedure in 96% yield (15.7 mg, 61.5 mmol) from p-tolyl 4-methylbenzenesulfonate (16.8 mg, 63.8 mmol) and (4-(2-(dimethylamino)ethoxy)phenyl)boronic acid (see the Supporting Information). White solid. mp = 83-86°C, TLC Rf = 0.24 (DCM/EtOH 10%); IR (neat) νmax 498, 576, 630, 678, 787, 843, 920, 1035, 1094, 1117, 1159, 1180, 1195, 1216, 1236, 1268, 1314, 1374, 1401, 1452, 1498, 1531, 1581, 1606, 2758, 2815, 2853, 2921; 1H NMR (CDCl3, 500 MHz) δ 7.53–7.47 (m, 2H), 7.47–7.42 (m, 2H), 7.22 (d, J = 7.8 Hz, 2H), 7.01–6.95 (m, 2H), 4.11 (t, J = 5.8 Hz, 2H), 2.76 (t, J = 5.7 Hz, 2H), 2.38 (s, 3H), 2.36 (s, 6H); 13C NMR (CDCl3, 126 MHz) δ 158.2, 137.9, 136.4, 133.8, 129.4 (2C), 127.9 (2C), 126.6 (2C), 114.8 (2C), 66.0, 58.3, 45.9 (2C), 21.1; HR-MS 256.1694 (C17H21NO + H+) calcd 256.1696.

4-(p-Tolyl)pyridine (2j)

Prepared following the general procedure in 99% yield (18.1 mg, 0.107 mmol) from p-tolyl 4-methylbenzenesulfonate (28.0 mg, 0.107 mmol) and pyridin-4-ylboronic acid. 1H NMR (CDCl3, 500 MHz) δ 8.66–8.61 (m, 2H), 7.59–7.52 (m, 2H), 7.52–7.45 (m, 2H), 7.30 (d, J = 7.8 Hz, 2H), 2.42 (s, 3H); 13C NMR (CDCl3, 126 MHz) δ 150.3 (2C), 148.3, 139.3, 135.3, 130.0 (2C), 127.0 (2C), 121.5 (2C), 21.4. Consistent with the literature data.36

3-(p-Tolyl)thiophene (2k)

Prepared following the general procedure in 78% yield (51.5 mg, 0.236 mmol) from p-tolyl 4-methylbenzenesulfonate (100 mg, 0.381 mmol) and thiophen-3-ylboronic acid (97.9 mg, 0.762 mmol). 1H NMR (300 MHz, CDCl3) δ 7.50 (d, J = 8.2 Hz, 2H), 7.43–7.33 (m, 3H), 7.21 (d, J = 8.0 Hz, 2H), 2.38 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 142.5, 137.0, 133.2, 129.6 (2C), 126.5 (2C), 126.4, 126.2, 119.8, 21.3.37

2,4′-Dimethyl-1,1′-biphenyl (2l)

Prepared following the general procedure in 78% yield (54.1 mg, 0.297 mmol) from p-tolyl 4-methylbenzenesulfonate (100 mg, 0.381 mmol) and o-tolylboronic acid. 1H NMR (300 MHz, CDCl3) δ 7.32–7.22 (m, 7H), 2.44 (s, 3H), 2.32 (s, 3H).13C NMR (126 MHz, CDCl3) δ 141.7, 138.9, 136.2, 135.3, 130.2, 129.7, 128.9 (2C), 128.7 (2C), 126.9, 125.6, 21.1, 20.4.38

4′-Methyl-[1,1′-biphenyl]-2-amine (2m)

Prepared following the general procedure in 91% yield (12.7 mg, 0.069 mmol) from p-tolyl 4-methylbenzenesulfonate (20.0 mg, 0.076 mmol) and (2-aminophenyl)boronic acid. 1H NMR (CDCl3, 500 MHz) δ 7.38–7.33 (m, 2H), 7.31–7.20 (m, 2H), 7.18–7.10 (m, 2H), 6.82 (td, J = 7.4, 1.2 Hz, 1H), 6.79–6.74 (m, 1H), 3.76 (s, 2H), 2.41 (s, 3H); 13C NMR (CDCl3, 126 MHz) δ 143.6, 137.0, 136.6, 130.6, 129.6 (2C), 129.1 (2C), 128.4, 127.8, 118.8, 115.7, 21.3. Consistent with the literature data.39

2,6-Dimethoxy-4′-methyl-1,1′-biphenyl (2n)

Prepared following the general procedure in 23% yield (20.0 mg, 0.087 mmol) from p-tolyl 4-methylbenzenesulfonate (100 mg, 0.381 mmol) and (2,6-dimethoxyphenyl)boronic acid. 1H NMR (CDCl3, 500 MHz) δ 7.34–7.23 (m, 5H), 6.68 (d, J = 8.3 Hz, 2H), 3.73 (s, 6H), 2.42 (s, 3H); 13C NMR (CDCl3, 126 MHz) δ 157.6, 136.2, 130.8, 130.6 (2), 128.4 (2C), 128.3, 119.3, 104.0 (2C), 55.8 (2C), 21.3. Consistent with the literature data.40

[1,1′-Biphenyl]-4-carbaldehyde (2o)

Prepared following the general procedure in 91% yield (20.8 mg, 0.114 mmol) from 4-formylphenyl 4-methylbenzenesulfonate (34.7 mg, 0.125 mmol) and phenylboronic acid. 1H NMR (CDCl3, 500 MHz) δ 10.06 (s, 1H), 7.99–7.94 (m, 2H), 7.79–7.74 (m, 2H), 7.64 (dt, J = 6.6, 1.3 Hz, 2H), 7.49 (td, J = 7.2, 6.3, 1.4 Hz, 2H), 7.46–7.39 (m, 1H); 13C NMR (CDCl3, 126 MHz) δ 192.1, 147.3, 139.8, 135.3, 130.4 (2C), 129.2 (2C), 128.6, 127.8 (2C), 127.5 (2C). Consistent with the literature data.41

4-Acetyl-1,1′-biphenyl (2p)

Prepared following the general procedure in 92% yield (31.1 mg, 0.158 mmol) from 4-acetylphenyl 4-methylbenzenesulfonate (50 mg, 0.172 mmol) and phenylboronic acid. 1H NMR (CDCl3, 500 MHz) δ 8.07–8.00 (m, 2H), 7.72–7.67 (m, 2H), 7.66–7.61 (m, 2H), 7.50–7.45 (m, 2H), 7.43–7.38 (m, 1H), 2.64 (s, 3H).; 13C NMR (CDCl3, 126 MHz) δ 197.8, 145.8, 139.9, 135.9, 129.0 (2C), 128.9 (2C), 128.2, 127.3 (2C), 127.2 (2C), 26.7. Consistent with the literature data.42

4-Methoxy-1,1′-biphenyl (2q)

Prepared following the general procedure in 87% yield (29 mg, 0.157 mmol) from 4-methoxyphenyl 4-methylbenzenesulfonate (50 mg, 0.18 mmol) and phenylboronic acid. 1H NMR (CDCl3, 300 MHz) δ 7.57–7.27 (m, 7H), 6.98 (d, J = 9.0 Hz, 2H), 3.86 (s, 3H); 13C NMR (CDCl3, 126 MHz) δ 159.1, 140.8, 133.8, 128.7 (2C), 128.2 (2C), 126.8 (2C), 126.7, 114.2 (2C), 55.4. Consistent with the literature data.43

4-Fluoro-1,1′-biphenyl (2r)

Prepared following the general procedure in 90% yield (29 mg, 0.168 mmol) from 4-fluorophenyl 4-methylbenzenesulfonate (50 mg, 0.187 mmol) and phenylboronic acid. 1H NMR (CDCl3, 300 MHz) δ 7.49–7.43 (m, 4H), 7.39–7.32 (m, 2H), 7.30–7.23 (m, 1H), 7.10–6.99 (m, 2H); 13C NMR (CDCl3, 126 MHz) δ 162.5 (d, J = 251 Hz), 140.3, 137.4 (d, J = 2.5 Hz), 128.8 (2C), 128.7 (d, J = 8.7 Hz, 2C), 127.3, 127.0 (2C), 115.6 (d, J = 21.3, 2C). Consistent with the literature data.43

4-Phenylpyridine (2s)

Prepared following the general procedure in 75% yield (13.6 mg, 0.087 mmol) from pyridin-4-yl 4-methylbenzenesulfonate (29.2 mg, 0.117 mmol) and phenylboronic acid. 1H NMR (500 MHz, CDCl3) δ 8.70–8.65 (m, 2H), 7.65 (dd, J = 7.2, 1.9 Hz, 2H), 7.54–7.50 (m, 2H), 7.49 (d, J = 7.7 Hz, 2H), 7.47–7.44 (m, 1H).; 13C NMR (126 MHz, CDCl3) δ 150.2 (2C), 148.7, 138.2, 129.3 (2C), 129.2, 127.2 (2C), 121.9 (2C). Consistent with the literature data.41

2-(4-Methoxyphenyl)naphthalene (2t)

Prepared following the general procedure in 85% yield (71.8 mg, 0.29 mmol) from naphthalen-2-yl 4-methylbenzenesulfonate (100 mg, 0.335 mmol) and (4-methoxyphenyl)boronic acid (101.9 mg, 0.67 mmol). 1H NMR (300 MHz, CDCl3) δ 8.01–7.97 (m, 1H), 7.93–7.82 (m, 2H), 7.75–7.63 (m, 3H), 7.54– 742 (m, 2H), 7.07–6.99 (m, 2H), 3.88 (s, 3H). 13C NMR (500 MHz, CDCl3) δ 159.4, 138.3, 133.9, 133.7, 132.4, 128.6 (2C), 128.5, 128.2, 127.8, 126.4, 125.8, 125.6, 125.2, 114.4 (2C), 55.5.44

(E)-1-Methyl-4-styrylbenzene (2u)

Prepared following the general procedure in 89% yield (14.8 mg, 0.076 mmol) from p-tolyl 4-methylbenzenesulfonate (22.4 mg, 0.085 mmol) and trans-2-phenylvinylboronic acid. 1H NMR (CDCl3, 500 MHz) δ 7.53 (d, J = 7.6 Hz, 2H), 7.45 (d, J = 7.9 Hz, 2H), 7.38 (t, J = 7.6 Hz, 2H), 7.28 (t, J = 3.8 Hz, 1H), 7.20 (d, J = 7.8 Hz, 2H), 7.11 (d, J = 2.4 Hz, 2H), 2.39 (s, 3H); 13C NMR (CDCl3, 126 MHz) δ 137.7, 134.6, 129.6, 129.5 (2C), 128.8 (2C), 128.7 (2C), 127.8, 127.5 (2C), 126.5 (2C), 21.4. Consistent with literature data.45

(E)-1-Phenylcyclooct-1-ene (2w)

Prepared following the general procedure in 73% yield (43.7 mg, 0.235 mmol) from (E)-1-bromocyclooct-1-ene 1w (60.0 mg, 0.32 mmol) and phenylboronic acid. 1H NMR (CDCl3, 500 MHz) δ 7.44–7.38 (m, 2H), 7.34–7.26 (m, 2H), 7.25–7.17 (m, 1H), 6.01 (t, J = 8.3 Hz, 1H), 2.66–2.60 (m, 2H), 2.33–2.26 (m, 2H), 1.69–1.62 (m, 2H), 1.61–1.56 (m, 2H), 1.57–1.50 (m, 4H); 13C NMR (CDCl3, 126 MHz) δ 143.3, 140.4, 128.3 (2C), 128.1, 126.6, 125.9 (2C), 30.1, 29.6, 28.6, 27.6, 27.0, 26.3. Consistent with the literature data.46

1,1,2,2-Tetraphenylethene (2x)

Prepared following the general procedure in 79% yield (26.1 mg, 0.079 mmol) from 2-bromo-1,1,2-triphenylethylene 1x (33.6 mg, 0.1 mmol) and phenylboronic acid. 1H NMR (CDCl3, 300 MHz) δ 7.15–7.08 (m, 12H), 7.07–6.98 (m, 8H); 13C NMR (CDCl3, 126 MHz) δ 143.9 (4C), 141.1 (2C), 131.5 (8C), 127.8 (8C), 126.5 (4C). Consistent with the literature data.47

4-(1,2-Diphenylbut-1-en-1-yl)phenol (2y)

Prepared following the general procedure using NaOH as the base in 73% yield (11.1 mg, 0.037 mmol, E/Z = 79/21) from (E)-1,2-diphenylbut-1-en-1-yl 4-methylbenzenesulfonate48(E)-1y (19.1 mg, 0.050 mmol) and (4-hydroxyphenyl)boronic acid. 1H NMR (CDCl3, 500 MHz, mixture of E/Z isomers) δ 7.35 (t, J = 7.6 Hz, 2HZ), 7.28–6.97 (m, 18H), 6.90–6.85 (m, 2H), 6.82 (d, J = 8.5 Hz, 2HE), 6.74 (d, J = 8.5 Hz, 2HZ), 6.47 (d, J = 8.5 Hz, 2HZ), 4.74 (bs, 1HE), 4.51 (bs, 1HZ), 2.50 (q, J = 7.5 Hz, 2HE), 2.45 (q, J = 7.5 Hz, 2HZ), 0.94 (t, J = 7.5 Hz, 3HE), 0.92 (t, J = 7.5 Hz, 3HZ); 13C NMR (CDCl3, 126 MHz, mixture of E/Z isomers) δ 154.2, 153.3, 143.7, 143.3, 142.4, 142.3, 142.0, 141.4, 138.2, 138.1, 136.2, 135.7, 132.1, 130.8, 129.7, 129.4, 128.1, 127.9, 127.8, 127.3, 126.5, 126.0, 125.6, 114.9, 114.2, 29.0, 13.6. Consistent with the literature data.49

2-(Benzo[d][1,3]dioxol-5-yl)quinoline (Dubamine)

Prepared following the general procedure in 88% yield (32.6 mg, 0.13 mmol) from quinolin-2-yl 4-methylbenzenesulfonate501z (44.6 mg, 0.148 mmol) and 3,4-methylenedioxyphenylboronic acid. 1H NMR (CDCl3, 500 MHz) δ 8.18 (dd, J = 8.7, 0.8 Hz, 1H), 8.13 (dq, J = 8.4, 0.9 Hz, 1H), 7.83–7.78 (m, 2H), 7.75 (d, J = 1.8 Hz, 1H), 7.71 (ddd, J = 8.4, 6.9, 1.5 Hz, 1H), 7.66 (dd, J = 8.1, 1.8 Hz, 1H), 7.51 (ddd, J = 8.1, 6.9, 1.2 Hz, 1H), 6.95 (d, J = 8.1 Hz, 1H), 6.05 (s, 2H); 13C NMR (CDCl3, 126 MHz) δ 156.8, 149.0, 148.5, 148.3, 136.8, 134.3, 129.8, 129.7, 127.6, 127.1, 126.2, 121.9, 118.8, 108.6, 108.1, 101.5; HR-MS 250.0851 (C13H11NO2+H+) calcd 250.0863. Consistent with the literature data.51

(Z)-2-(4-(1,2-Diphenylbut-1-en-1-yl)phenoxy)-N,N-dimethylethan-1-amine (Tamoxifen)

Prepared following the general procedure using NaOH as the base in 78% yield (14.3 mg, 38.5 μmol) from (Z)-1,2-diphenylbut-1-en-1-yl 4-methylbenzenesulfonate48(Z)-1y (18.6 mg, 49.0 μmol) and (4-(2-(dimethylamino)ethoxy)phenyl)boronic acid273. It was obtained as a white solid; TLC Rf 0.28 (CH2Cl2/EtOH 5%); 1H NMR (CDCl3, 500 MHz) δ 7.39–7.30 (m, 2H), 7.32–7.19 (m, 2H), 7.20–7.05 (m, 6H), 6.76 (d, J = 9.1, 8.6 Hz, 2H), 6.55 (d, 2H), 3.95 (t, J = 5.7 Hz, 2H), 2.68 (t, J = 5.2 Hz, 2H), 2.45 (q, J = 7.4 Hz, 2H), 2.32 (s, 6H), 0.92 (t, J = 7.3 Hz, 3H); 13C NMR (CDCl3, 126 MHz) δ 156.8, 143.9, 142.5, 141.5, 138.3, 135.7, 132.0 (2C), 129.8 (2C), 129.6 (2C), 128.2 (2C), 128.0 (2C), 126.6, 126.1, 113.5 (2C), 65.5, 58.3, 45.9, 29.2 (2C), 13.8; HR-MS 372.2297 (C26H29ON+H+) calcd 372.2322. Consistent with the literature data.28

Acknowledgments

The authors gratefully acknowledge the French Ministry of Research and the CNRS for financial support. F.S. and R.P. thank the French Ministry of Research for Ph.D. fellowships.

Glossary

Abbreviations

SMC

Suzuki–Miyaura Coupling

Ts

tosyl

Mbs

para-methoxybenzenesulfonyl

Ms

mesyl

TBAOH

tetra-butylammonium hydroxide

PhBpin

phenylboronic acid pinacol ester

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.1c05770.

  • Copies of 1H and 13C spectra (PDF)

The authors declare no competing financial interest.

Supplementary Material

ao1c05770_si_001.pdf (4.7MB, pdf)

References

  1. a Miyaura N.; Suzuki A. Palladium-catalyzed cross-coupling reactions of organoboroncompounds. Chem. Rev. 1995, 95, 2457–2483. 10.1021/cr00039a007. [DOI] [Google Scholar]; b D’Alterio M. C.; Casals-Cruanas E.; Tzouras N. V.; Talarico G.; Nolan S. P.; Poater A. Mechanistic aspects of the palladium-catalyzed Suzuki-Miyaura cross-coupling reaction. Chem. – Eur. J. 2021, 27, 13481. 10.1002/chem.202101880. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. a Littke A. F.; Dai C.; Fu G. C. Versatile catalysts for the Suzuki cross-coupling of arylboronic acids with aryl and vinyl halides and triflates under mild conditions. J. Am. Chem. Soc. 2000, 122, 4020–4028. 10.1021/ja0002058. [DOI] [Google Scholar]; b Stambuli J. P.; Kuwano R.; Hartwig J. F. Unparalleled rates for the activation of aryl chlorides and bromides: coupling with amines and boronic acids in minutes at room temperature. Angew. Chem., Int. Ed. 2002, 41, 4746–4748. 10.1002/anie.200290036. [DOI] [PubMed] [Google Scholar]
  3. a Old D. W.; Wolfe J. P.; Buchwald S. L. A highly active catalyst for palladium-catalyzed cross-coupling reactions: Room-temperature Suzuki couplings and amination of unactivated aryl chlorides. J. Am. Chem. Soc. 1998, 120, 9722–9723. 10.1021/ja982250+. [DOI] [Google Scholar]; b Martin R.; Buchwald S. L. Palladium-catalyzed Suzuki–Miyaura cross-coupling reactions employing dialkylbiaryl phosphine ligands. Acc. Chem. Res. 2008, 41, 1461–1473. 10.1021/ar800036s. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. For selected recent examples, see:; a Dong Y.; Sun S.; Yang F.; Zhu Y.; Zhu W.; Qiao H.; Wu Y.; Wu Y. Pd-catalyzed aminocarbonylation of alkynes with amines using Co2(CO)8 as a carbonyl source. Org. Chem. Front. 2016, 3, 720–724. 10.1039/C6QO00075D. [DOI] [Google Scholar]; b Onoabedje E. A.; Okoro U. C.; Knight D. W.; Sarkar A. Functionalization of linear and angular phenothiazine and phenoxazine ring systems via Pd(0)/XPhos mediated Suzuki-Miyaura cross-coupling reactions. J. Heterocycl. Chem. 2016, 53, 1787–1794. 10.1002/jhet.2485. [DOI] [Google Scholar]; c Paraja M.; Barroso R.; Cabal M. P.; Valdes C. Synthesis of dienes by palladium-catalyzed couplings of tosylhydrazones with aryl and alkenyl halides. Adv. Synth. Catal. 2017, 359, 1058–1062. 10.1002/adsc.201601155. [DOI] [Google Scholar]
  5. a Dikova A.; Cheval N. P.; Blanc A.; Weibel J.-M.; Pale P. Aryl and heteroaryl nosylates as stable and cheap partners for Suzuki-Miyaura cross-coupling reactions. Tetrahedron 2016, 72, 1960–1968. 10.1016/j.tet.2016.02.061. [DOI] [Google Scholar]; b Zhang L.; Qing J.; Yang P.; Wu J. Palladium-catalyzed Hiyama cross-coupling reactions of aryl mesylates. Org. Lett. 2008, 10, 4971–4974. 10.1021/ol802049t. [DOI] [PubMed] [Google Scholar]; c Naber J. R.; Buchwald S. L. Palladium-catalyzed Stille cross-coupling reaction of aryl chlorides using a pre-milled palladium acetate and XPhos catalyst system. Adv. Synth. Catal. 2008, 350, 957–961. 10.1002/adsc.200800032. [DOI] [Google Scholar]; d Nguyen H. N.; Huang X.; Buchwald S. L. The first general palladium catalyst for the Suzuki-Miyaura and carbonyl enolate coupling of aryl arenesulfonates. J. Am. Chem. Soc. 2003, 125, 11818–11819. 10.1021/ja036947t. [DOI] [PubMed] [Google Scholar]
  6. Wagschal S.; Perego L. A.; Simon A.; Franco-Espejo A.; Tocqueville C.; Albaneze-Walker J.; Jutand A.; Grimaud L. Formation of XPhos-ligated palladium(0) complexes and reactivity in oxidative additions. Chem. – Eur. J. 2019, 25, 6980–6987. 10.1002/chem.201900451. [DOI] [PubMed] [Google Scholar]
  7. Kashin A. S.; Ananikov V. P. Catalytic C-C and C-heteroatom bond formation reactions: in situ generated or preformed catalysts? Complicated mechanistic picture behind well-known experimental procedures. J. Org. Chem. 2013, 78, 11117–11125. 10.1021/jo402038p. [DOI] [PubMed] [Google Scholar]
  8. a Hazari N.; Melvin P. R.; Beromi M. M. Well-defined nickel and palladium precatalysts for cross-coupling. Nat. Rev. Chem. 2017, 1, 0025 10.1038/s41570-017-0025. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Seechurn C. C. C. J.; Li H.; Colacot T. J.. Pd-Phosphine Precatalysts For Modern Cross-coupling Reactions. In New Trends in Cross-Coupling: Theory and Applications; Royal Society of Chemistry, 2015; Vol. 21, Chapter 3, pp 91–138. [Google Scholar]; c Li H.; Seechurn C. C. C. J.; Colacot T. J. Development of preformed Pd catalysts for cross-coupling reactions, beyond the 2010 Nobel prize. ACS Catal. 2012, 2, 1147–1164. 10.1021/cs300082f. [DOI] [Google Scholar]
  9. a Bruno N. C.; Niljianskul N.; Buchwald S. L. N-Substituted 2-aminobiphenylpalladium methanesulfonate precatalysts and their use in C–C and C–N cross-couplings. J. Org. Chem. 2014, 79, 4161–4166. 10.1021/jo500355k. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Bruno N. C.; Tudge M. T.; Buchwald S. L. Design and preparation of new palladium precatalysts for C-C and C-N cross-coupling reactions. Chem. Sci. 2013, 4, 916–920. 10.1039/C2SC20903A. [DOI] [PMC free article] [PubMed] [Google Scholar]; c Kinzel T.; Zhang Y.; Buchwald S. L. A new palladium precatalyst allows for the fast Suzuki-Miyaura coupling reactions of unstable polyfluorophenyl and 2-heteroaryl boronic acids. J. Am. Chem. Soc. 2010, 132, 14073–14075. 10.1021/ja1073799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. a Brinkmann M.; Blenkle H.; Salowsky H.; Bluhm K.; Schiwy S.; Tiehm A.; Hollert H. Genotoxicity of heterocyclic PAHs in the micronucleus assay with the fish liver cell line RTL-W1. PLoS One 2014, 9, e85692 10.1371/journal.pone.0085692. [DOI] [PMC free article] [PubMed] [Google Scholar]; b Zhanataev A. K.; Eremina N. V.; Chayka Z. V.; Kazey V. I.; Andrianova E. L.; Purmal A. A.; Rydkina E. B.; Durnev A. D. Genotoxicity of two new carbazole derivatives with antifungal activity. Mutat. Res. 2017, 816–817, 24–31. 10.1016/j.mrgentox.2017.03.004. [DOI] [PubMed] [Google Scholar]
  11. Schmid T. E.; Jones D. C.; Songis O.; Diebolt O.; Furst M. R. L.; Slawin A. M. Z.; Cazin C. S. J. Mixed phosphine/N-heterocyclic carbene palladium complexes: synthesis, characterization and catalytic use in aqueous Suzuki-Miyaura reactions. Dalton Trans. 2013, 42, 7345–7353. 10.1039/c2dt32858e. [DOI] [PubMed] [Google Scholar]
  12. DeAngelis A. J.; Gildner P. G.; Chow R.; Colacot T. J. Generating active ″L-Pd(0)″ via neutral or cationic π-allylpalladium complexes featuring biaryl/bipyrazolylphosphines: synthetic, mechanistic, and structure-activity studies in challenging cross-coupling reactions. J. Org. Chem. 2015, 80, 6794–6813. 10.1021/acs.joc.5b01005. [DOI] [PubMed] [Google Scholar]
  13. Melvin P. R.; Nova A.; Balcells D.; Dai W.; Hazari N.; Hruszkewycz D. P.; Shah H. P.; Tudge M. T. Design of a versatile and improved precatalyst scaffold for palladium-catalyzed cross-coupling: (η3-1-tBu-indenyl)2(μ-Cl)2Pd2. ACS Catal. 2015, 5, 3680–3688. 10.1021/acscatal.5b00878. [DOI] [Google Scholar]
  14. Sirindil F.; Weibel J.-M.; Pale P.; Blanc A. Total synthesis of rhazinilam through gold-catalyzed cycloisomerization-sulfonyl migration and palladium-catalyzed Suzuki-Miyaura coupling of pyrrolyl sulfonates. Org. Lett. 2019, 21, 5542–5546. 10.1021/acs.orglett.9b01860. [DOI] [PubMed] [Google Scholar]
  15. a Schoenberg A.; Bartoletti I.; Heck R. F. Palladium-catalyzed carboalkoxylation of aryl, benzyl, and vinylic halides. J. Org. Chem. 1974, 39, 3318–3326. 10.1021/jo00937a003. [DOI] [Google Scholar]; b Miyaura N.; Suzuki A. Palladium-catalyzed reaction of 1-alkenylboronates with vinylic halides: (1Z,3E)-1-phenyl-1,3-octadiene. Org. Synth. 1990, 68, 130–137. 10.15227/orgsyn.068.0130. [DOI] [Google Scholar]
  16. Yang Y.; Lim J. F. Y.; Chew X.; Robins E. G.; Johannes C. W.; Lim Y. H.; Jong H. Palladium precatalysts containing meta-terarylphosphine ligands for expedient copper-free Sonogashira cross-coupling reactions. Catal. Sci. Technol. 2015, 5, 3501–3506. 10.1039/C5CY00507H. [DOI] [Google Scholar]
  17. Čubiňák M.; Eigner V.; Tobrman T. Bench-stable sulfoxide-based boronates: preparation and application in a tandem Suzuki reaction. Adv. Synth. Catal. 2018, 360, 4604–4614. 10.1002/adsc.201801000. [DOI] [Google Scholar]
  18. Lennox A. J. J.; Lloyd-Jones G. C. Selection of boron reagents for Suzuki–Miyaura coupling. Chem. Soc. Rev. 2014, 43, 412–443. 10.1039/C3CS60197H. [DOI] [PubMed] [Google Scholar]
  19. Barder T. E.; Walker S. D.; Martinelli J. R.; Buchwald S. L. Catalysts for Suzuki–Miyaura coupling processes: scope and studies of the effect of ligand structure. J. Am. Chem. Soc. 2005, 127, 4685–4696. 10.1021/ja042491j. [DOI] [PubMed] [Google Scholar]
  20. Jutand A. Contribution of electrochemistry to organometallic catalysis. Chem. Rev. 2008, 108, 2300–2347. 10.1021/cr068072h. [DOI] [PubMed] [Google Scholar]
  21. a Amatore C.; Jutand A.; Le Duc G. Kinetic data for the transmetalation/reductive elimination in palladium-catalyzed Suzuki-Miyaura reactions: unexpected triple role of hydroxide ions used as base. Chem. – Eur. J. 2011, 17, 2492–2503. 10.1002/chem.201001911. [DOI] [PubMed] [Google Scholar]; b Amatore C.; Jutand A.; Le Duc G. Mechanistic origin of antagonist effects of usual anionic bases (OH-, CO32-) as modulated by their countercations (Na+, Cs+, K+) in palladium-catalyzed Suzuki-Miyaura reactions. Chem. – Eur. J. 2012, 18, 6616–6625. 10.1002/chem.201200516. [DOI] [PubMed] [Google Scholar]; c Amatore C.; Le Duc G.; Jutand A. Mechanism of palladium-catalyzed Suzuki-Miyaura reactions: multiple and antagonistic roles of anionic ″bases″ and their countercations. Chem. – Eur. J. 2013, 19, 10082–10093. 10.1002/chem.201300177. [DOI] [PubMed] [Google Scholar]; d Amatore C.; El Kaim L.; Grimaud L.; Jutand A.; Meignie A.; Romanov G. Kinetic data on the synergetic role of amines and water in the reduction of phosphine-ligated palladium(II) to palladium(0). Eur. J. Org. Chem. 2014, 2014, 4709–4713. 10.1002/ejoc.201402519. [DOI] [Google Scholar]
  22. Andersen T. L.; Friis S. D.; Audrain H.; Nordeman P.; Antoni G.; Skrydstrup T. Efficient 11C-carbonylation of isolated aryl palladium complexes for PET: application to challenging radiopharmaceutical synthesis. J. Am. Chem. Soc. 2015, 137, 1548–1555. 10.1021/ja511441u. [DOI] [PubMed] [Google Scholar]
  23. For mechanism of oxidative addition of Pd0 complexes ligated by bulky monophosphines, see:; Kurbangalieva A.; Carmichael D.; Hii K. K.; Jutand A.; Brown J. M. Oxidative addition to palladium(0) diphosphine complexes: observations of mechanistic complexity with iodobenzene as reactant. Chem. – Eur. J. 2014, 20, 1116–1125. 10.1002/chem.201301937. [DOI] [PubMed] [Google Scholar]
  24. Brossi A.The Alkaloids: Chemistry and Pharmacology, Academic Press: San Diego, 1988. [Google Scholar]
  25. Shiina I.; Sano Y.; Nakata K.; Suzuki M.; Yokoyama T.; Sasaki A.; Orikasa T.; Miyamoto T.; Ikekita M.; Nagahara Y.; Hasome Y. An expeditious synthesis of tamoxifen, a representative SERM (selective estrogen receptor modulator), via the three-component coupling reaction among aromatic aldehyde, (cinnamyl)trimethylsilane, and β-chlorophenetole. Bioorg. Med. Chem. 2007, 15, 7599–7617. 10.1016/j.bmc.2007.09.008. [DOI] [PubMed] [Google Scholar]
  26. Lei X.; Jalla A.; Shama M. A. A.; Stafford J. M.; Cao B. Chromatography-free and eco-friendly synthesis of aryl tosylates and mesylates. Synthesis 2015, 47, 2578–2585. 10.1055/s-0034-1378867. [DOI] [Google Scholar]
  27. a Facchini S. V.; Cettolin M.; Bai X.; Casamassima G.; Pignataro L.; Gennari C.; Piarulli U. Efficient synthesis of amines by iron-catalyzed C = N transfer hydrogenation and C=O reductive amination. Adv. Synth. Catal. 2018, 360, 1054–1059. 10.1002/adsc.201701316. [DOI] [Google Scholar]; b Nunes C.; Steffens D.; Monteiro A. Synthesis of tri- and tetrasubstituted olefins by palladium cross-coupling reaction. Synlett 2007, 2007, 0103–0106. 10.1055/s-2006-956467. [DOI] [Google Scholar]
  28. Zhou C.; Larock R. C. Regio- and stereoselective route to tetrasubstituted olefins by the palladium-catalyzed three-component coupling of aryl iodides, internal alkynes, and arylboronic acids. J. Org. Chem. 2005, 70, 3765–3777. 10.1021/jo048265+. [DOI] [PubMed] [Google Scholar]
  29. Zhou W.-J.; Wang K.-H.; Wang J.-X.; Huang D.-F. Reusable, polystyrene-resin-supported, palladium-catalyzed, atom-efficient cross-coupling reaction of aryl halides with triarylbismuths. Eur. J. Org. Chem. 2010, 2010, 416–419. 10.1002/ejoc.200901210. [DOI] [Google Scholar]
  30. Guan B.-T.; Wang Y.; Li B.-J.; Yu D.-G.; Shi Z.-J. Biaryl construction via Ni-catalyzed C-O activation of phenolic carboxylates. J. Am. Chem. Soc. 2008, 130, 14468–14470. 10.1021/ja8056503. [DOI] [PubMed] [Google Scholar]
  31. Döbele M.; Vanderheiden S.; Jung N.; Bräse S. Synthesis of aryl fluorides on a solid support and in solution by utilizing a fluorinated solvent. Angew. Chem., Int. Ed. 2010, 49, 5986–5988. 10.1002/anie.201001507. [DOI] [PubMed] [Google Scholar]
  32. Lü B.; Fu C.; Ma S. Application of a readily available and air stable monophosphine HBF4 salt for the Suzuki coupling reaction of aryl or 1-alkenyl chlorides. Tetrahedron Lett. 2010, 51, 1284–1286. 10.1016/j.tetlet.2009.12.143. [DOI] [Google Scholar]
  33. Su W.; Urgaonkar S.; McLaughlin P. A.; Verkade J. G. Highly active palladium catalysts supported by bulky proazaphosphatrane ligands for Stille cross-coupling: Coupling of aryl and vinyl chlorides, room temperature coupling of aryl bromides, coupling of aryl triflates, and synthesis of sterically hindered biaryls. J. Am. Chem. Soc. 2004, 126, 16433–16439. 10.1021/ja0450096. [DOI] [PubMed] [Google Scholar]
  34. Chow W. K.; So C. M.; Lau C. P.; Kwong F. Y. A general palladium catalyst system for Suzuki-Miyaura coupling of potassium aryltrifluoroborates and aryl mesylates. J. Org. Chem. 2010, 75, 5109–5112. 10.1021/jo100846t. [DOI] [PubMed] [Google Scholar]
  35. Ishikawa S.; Manabe K. Synthetic method for multifunctionalized oligoarenes using pinacol esters of hydroxyphenylboronic acids. Chem. Commun. 2006, 2589–2591. 10.1039/b603574d. [DOI] [PubMed] [Google Scholar]
  36. Fleckenstein C. A.; Plenio H. Highly efficient Suzuki-Miyaura coupling of heterocyclic substrates through rational reaction design. Chem. – Eur. J. 2008, 14, 4267–4279. 10.1002/chem.200701877. [DOI] [PubMed] [Google Scholar]
  37. Hatakeyama T.; Hashimoto S.; Ishizuka K.; Nakamura M. Highly selective biaryl cross-coupling reactions between aryl halides and aryl grignard reagents: a new catalyst combination of N-heterocyclic carbenes and iron, cobalt, and nickel fluorides. J. Am. Chem. Soc. 2009, 131, 11949–11963. 10.1021/ja9039289. [DOI] [PubMed] [Google Scholar]
  38. So C. M.; Lau C. P.; Kwong F. Y. Easily accessible and highly tunable indolyl phosphine pigands for Suzuki–Miyaura coupling of aryl chlorides. Org. Lett. 2007, 9, 2795–2798. 10.1021/ol070898y. [DOI] [PubMed] [Google Scholar]
  39. Stokes B. J.; Jovanović B.; Dong H.; Richert K. J.; Riell R. D.; Driver T. G. Rh2(II)-Catalyzed synthesis of carbazoles from biaryl azides. J. Org. Chem. 2009, 74, 3225–3228. 10.1021/jo9002536. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Becht J.-M.; Catala C.; Le Drian C.; Wagner A. Synthesis of biaryls via decarboxylative Pd-catalyzed cross-coupling reaction. Org. Lett. 2007, 9, 1781–1783. 10.1021/ol070495y. [DOI] [PubMed] [Google Scholar]
  41. Ackermann L.; Potukuchi H. K.; Althammer A.; Born R.; Mayer P. Tetra-ortho-substituted biaryls through palladium-catalyzed Suzuki-Miyaura couplings with a diaminochlorophosphine ligand. Org. Lett. 2010, 12, 1004–1007. 10.1021/ol1000186. [DOI] [PubMed] [Google Scholar]
  42. Alacid E.; Najera C. First cross-coupling reaction of potassium aryltrifluoroborates with organic chlorides in aqueous media catalyzed by an oxime-derived palladacycle. Org. Lett. 2008, 10, 5011–5014. 10.1021/ol802024j. [DOI] [PubMed] [Google Scholar]
  43. Watson D. A.; Su M.; Teverovskiy G.; Zhang Y.; Garcia-Fortanet J.; Kinzel T.; Buchwald S. L. Formation of ArF from LPdAr(F): catalytic conversion of aryl triflates to aryl fluorides. Science 2009, 325, 1661–1664. 10.1126/science.1178239. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Shen H.-C.; Pal S.; Lian J.-J.; Liu R.-S. Ruthenium-catalyzed aromatization of aromatic enynes via the 1,2-migration of halo and aryl groups: a new process involving electrocyclization and skeletal rearrangement. J. Am. Chem. Soc. 2003, 125, 15762–15763. 10.1021/ja0379159. [DOI] [PubMed] [Google Scholar]
  45. Cella R.; Stefani H. A. Ultrasound-assisted synthesis of Z and E stilbenes by Suzuki cross-coupling reactions of organotellurides with potassium organotrifluoroborate salts. Tetrahedron 2006, 62, 5656–5662. 10.1016/j.tet.2006.03.090. [DOI] [Google Scholar]
  46. Rao M. L. N.; Jadhav D. N.; Venkatesh V. Atom-efficient vinylic arylations with triarylbismuths as substoichiometric multicoupling reagents under palladium catalysis. Eur. J. Org. Chem. 2009, 2009, 4300–4306. 10.1002/ejoc.200900487. [DOI] [Google Scholar]
  47. Suleymanov A. A.; Doll M.; Ruggi A.; Scopelliti R.; Fadaei-Tirani F.; Severin K. Synthesis of tetraarylethene luminogens by C–H vinylation of aromatic compounds with triazenes. Angew. Chem., Int. Ed. 2020, 59, 9957–9961. 10.1002/anie.201908755. [DOI] [PubMed] [Google Scholar]
  48. Li B. X.; Le D. N.; Mack K. A.; McClory A.; Lim N.-K.; Cravillion T.; Savage S.; Han C.; Collum D. B.; Zhang H.; Gosselin F. Highly stereoselective synthesis of tetrasubstituted acyclic all-carbon olefins via enol tosylation and Suzuki-Miyaura coupling. J. Am. Chem. Soc. 2017, 139, 10777–10783. 10.1021/jacs.7b05071. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Ganapathy D.; Sekar G. Efficient synthesis of polysubstituted olefins using stable palladium nanocatalyst: applications in synthesis of tamoxifen and isocombretastatin A4. Org. Lett. 2014, 16, 3856–3859. 10.1021/ol5017367. [DOI] [PubMed] [Google Scholar]
  50. Fan S.; Yang J.; Zhang X. Pd-Catalyzed direct cross-coupling of electron-deficient polyfluoroarenes with heteroaromatic tosylates. Org. Lett. 2011, 13, 4374–4377. 10.1021/ol201706t. [DOI] [PubMed] [Google Scholar]
  51. Cheval N. P.; Dikova A.; Blanc A.; Weibel J.-M.; Pale P. Vinyl nosylates: an ideal partner for palladium–catalyzed cross–coupling. Chem. – Eur. J. 2013, 19, 8765–8768. 10.1002/chem.201300127. [DOI] [PubMed] [Google Scholar]

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