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Palladium-Catalyzed Desulfitative Arylation by C−O Bond Cleavage of Aryl Triflates with Sodium Arylsulfinates Chao Zhou, Qingjiang Liu, Yaming Li,* Rong Zhang, Xinmei Fu, and Chunying Duan* State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, China S Supporting Information *
ABSTRACT: An efficient Pd-catalyzed desulfitative coupling reaction of sodium arylsulfinates as arylation reagents by C−O bond cleavage of aryl triflates was developed. With only 2 mol % of Pd(OAc)2 as catalyst and XPhos as ligand, the reaction proceeded well for a range of substrates.
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couple with olefins,7 azoles,8 indoles9 and heteroarenes10 through C−H activation but also reacted with nitriles11 and α,β-unsaturated carbonyl compounds12 via addition reaction, which were used to compose sulphones.13 Moreover, the Li group developed the rhodium-catalyzed coupling of aldehdyes with sodium arylsulfinates at high temperature (165 °C).14 To the best of our knowledge, few successful example has been reported to date on the Pd-catalyzed desulfitative coupling reaction of sodium arylsulfinates as arylation reagents by C−O bond cleavage of aryl triflates, which can be readily synthesized from the corresponding phenols in high yields, utilizing sodium arylsulfinates as arylation reagents. We have reported a palladium-catalyzed desulfitative conjugate addition of arylsulfinic acids with α,β-unsaturated carbonyl compounds and provided the mechanistic studies by ESI-MS.12b In this work, we investigate the utilization of sodium arylsulfinates in the regioselective C−C bond formation and disclose an efficient route for the rapid synthesis of unsymmetrical biaryls via palladium-catalyzed desulfitative arylation of sodium arylsulfinates with C−O bond cleavage of aryl triflates (Scheme 1, eq 3). Initially, we investigated the desulfitative cross-coupling reaction by using 2-cyanophenyl triflate (1a) with sodium phenylsulfinate (2a) as a model reaction and screened several experimental parameters (ligand, solvent, etc.) shown in Table 1. We were pleased to find that with 2 mol % Pd(OAc)2/dppp as the catalyst and dioxane as solvent, the reaction gave 2cyanobiphenyl (3a) in 52% GC yield (Table 1, entry 1). Phosphine-type ligands such as dppf and PPh3 were much more active than the nitrogen-type ligand phenanthroline (Table 1, entries 2−4). The biaryl phosphine-type ligand XPhos, which was relatively cheaper and more effective in the decarboxylative coupling reaction and C−O bond cleavage,15 gave 3a in 66% GC yield (Table 1, entry 5), and after prolonging the reaction time, 95% of 2-cyanobiphenyl (3a) was obtained (Table 1, entriy 7). Screening of solvents revealed that the toluene was the best solvent, and 99% GC yield is achieved even at 120 °C
nsymmetrical biaryls are common building blocks for the synthesis of pharmaceuticals, natural products, and functional materials.1 The palladium-catalyzed Suzuki-type cross-coupling reactions using organoboron as aryl donors provide a general and efficient route of C−C bond formation and have been widely applied to various industrial and academic research (Scheme 1, eq 1).2 On the other hand, Scheme 1. Methods for the Preparation of Unsymmetrical Biaryls
decarboxylative cross-coupling of aryl carboxylic acids has emerged in the past few years as an alternative to traditional transition-metal-catalyzed cross-coupling of preformed organometallic reagents (Scheme 1, eq 2).3 Nevertheless, high reaction temperature (>170 °C) or microwave heating is required for the decarboxylation step. Recently, increasing attention has been attracted to the desulfitative coupling for the construction of C−C bonds via releasing SO2 under relatively mild conditions.4 Pioneering studies of desulfitative biaryl coupling were reported in 1970 by Garbes,5 who first applied aryl sulfinic acids and their salts as aryl donors for the C−C bond-forming reactions. In 1992, Sato and Okoshi reported an efficient palladium-catalyzed desulfitative synthesis of biaryls with sodium arylsulfinates and aromatic bromides at 150 °C using N-methyl-2-pyrrolidone as solvent.6 Recently, sodium arylsulfinates were not only investigated to © 2012 American Chemical Society
Received: September 27, 2012 Published: October 31, 2012 10468
dx.doi.org/10.1021/jo302005s | J. Org. Chem. 2012, 77, 10468−10472
The Journal of Organic Chemistry
Note
Table 1. Optimization of Reaction Conditionsa
Table 2. Desulfitative Arylation of 2a with Various Aryl Triflatesa
entry
ligand/mol %
solvent
time (h)
yieldb (%)
1 2 3 4 5 6 7 8 9 10 11 12e 13f 14e,g
dppp/2 dppf/2 PPh3/4 phenanthroline/4 XPhosc/4 dppp/2 XPhos/4 XPhos/4 XPhos/4 XPhos/4 XPhos/4 XPhos/4 XPhos/4 XPhos/4
dioxane dioxane dioxane dioxane dioxane dioxane dioxane NMP digylme dioxane/DMSO (9:1) toluene toluene toluene toluene
16 16 16 16 16 40 24 24 24 24 24 24 24 24
52 35 37 nd 66 71 99 (95d) 15 88 37 97 99 (97d) 77 trace
a Reaction conditions: 1a (0.2 mmol), 2a (0.24 mmol), Pd(OAc)2 (2 mol %), and ligand in a solvent (1 mL) under nitrogen at 150 °C unless otherwise noted. bGC yield based on 1a. c2-(Dicyclohexylphosphino)-2′,4′,6′-triisopropylbiphenyl. dYield after column chromatography. e120 °C. f100 °C. gCu(OAc)2 (1 equiv).
(Table 1, entry 12). It is noteworthy that different from the decarboxylative coupling, the addition of Cu(OAc)2 did not have a beneficial effect on the desulfitative cross-coupling reaction (Table 1, entry 14). Under optimized conditions (2 mol % Pd(OAc)2, 4 mol % XPhos, toluene, N2, 120 °C, 24 h), the scope of the new protocol with regard to the aryl triflates coupling with sodium phenylsulfinate (2a) was investigated (Table 2). Notably, both electron-withdrawing groups as well as electron-donating groups at aryl triflates gave target products in good to excellent yields (Table 2, entries 1−6). Substituents, such as cyano, formyl, methoxy, and chloro, at the ortho-position did not show steric effects on the C−O bond cleavage and were all coupled in good yields (Table 2, entries 1−3 and 6). The yield of the 4methoxyphenyl triflate was moderate (Table 2, entry 7). When there is a nitro group at the aryl triflate, the reaction almost did not take place, presumably due to the catalyst inactivation since the precipitation of Pd black was observed (Table 2, entries 8 and 9). Moreover, the 1-naphthyl and 2-naphthyl triflates substrates also reacted with 2a smoothly (Table 2, entries 10 and 11). Since 2-cyanobiphenyl compounds are key intermediates in the synthesis of angiotensin II receptor antagonists, for example, Losartan, Irbesartan, Valsartan, and Candesartan,16 we further explored the scope of the desulfitative process with respect to various sodium arylsulfinate structures coupled with 2-cyanophenyltriflates (1a), which is summarized in Table 3. Sodium arylsulfinates bearing 4-methyl, methoxy, trifluoromethyl, and chloro groups coupled with 2-cyanophenyl triflate (1a) provided the target products in excellent yields (Table 3, entries 1 and 3−5). The yields of sodium arylsulfinates bearing 2-methyl and fluoro groups were moderate (Table 3, entries 2 and 7). Similar to the nitro aryl triflates (Table 2, entries 7 and 8), the reaction of sodium arylsulfinate bearing the nitro group almost did not take place (Table 3, entry 8). This may be
a
Reaction conditions: 1a (0.2 mmol), 2a (0.24 mmol), Pd(OAc)2 (2 mol %), XPhos (4 mol %), and toluene (1 mL) in a sealed tube stirred at 120 °C for 24 h under nitrogen. bGC yield. c40 h.
related to the poor solubility of the substrates and the catalyst inactivation, since the precipitation of Pd black in the reaction was also observed. Gratifyingly, the method was suitable for 2naphthyl sodium sulfinate and heteroaromatic sodium sulfinate, which gave the desired product (3u) in excellent yield (92%) (Table 3, entries 9 and 10). In conclusion, we have developed an efficient protocol for the Pd(II)-catalyzed desulfitative coupling reaction of sodium arylsulfinates with aryl triflates for the construction of C−C bonds. With only 2 mol % of Pd(OAc)2 as catalyst and XPhos as ligand, aryl triflates and sodium arylsulfinates reacted smoothly at 120 °C, giving corresponding biaryls with moderate to excellent yields. This protocol, which is particularly suitable for arenesulfinates substrates, represents an important route in the evolution of desulfitative couplings into true synthetic alternatives to traditional couplings of preformed organometallic reagents.
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EXPERIMENTAL SECTION
Preparation of Aryl Triflates.17 Aryl triflates can be prepared by slowly adding a solution of Tf2O (6 mmol) at a rate to maintain the reaction temperature
