Palladium-catalyzed cross-coupling of alpha-diazocarbonyl compounds with arylboronic acids.

Suzuki-Miyaura reaction of aryl and vinyl halides or triflates with organoboron reagents has developed into one of the most important C-C bond-forming reactions.1,2 The mild and simple reaction conditions, the availability of various boronic acids that are normally nontoxic and stable, and easy workup and separation of the products are some of the factors that are responsible for the increasing popularity of the Suzuki-Miyaura reaction. Our recent interest is focused on the development of new methodology based on palladium-catalyzed reactions of R-diazocarbonyl compounds.3 Although R-diazocarbonyl compounds have been extensively applied as metal carbene precusors,4 the palladium-catalyzed reaction has received only limited attentions.5-7 We have conceived that the combination of Pd-carbene reaction with the transmetallation of boronic acids would lead to novel transformations. Herein we report a palladium-catalyzed cross-coupling reaction of arylboronic acids with R-diazocarbonyl compounds. The reaction affords R-aryl R,â-unsaturated carbonyl compounds, presumably through migratory insertion reactions of palladium carbene intermediate. On the outset of this study, we have used methyl R-diazopropionate 1 and phenylboronic acid 2a as the substrates. When 1 and 2a were catalyzed with Pd(PPh3)4 in the presence of benzoquinone (BQ) and K2CO3, methyl 2-phenylacrylate 3a was isolated in moderate yield (Table 1, entry 1). In the absence of the oxidant BQ, the reaction gave trace 2-phenylacrylate 3a (entry 2). We went on to screen other reaction parameters, such as temperature, solvent, and base. It was found that the reaction proceeded more efficiently at high-temperature (entry 3). The bases, such as K2CO3, Cs2CO3, and Et3N afforded similar results, while i-Pr2NH was found the most suitable base to promote the reaction with high yield (entries 6, 7). Polar solvent DCE could accelerate the reaction but led to slightly low yield, while MeCN was found not favorable (entries 8, 9). Several other palladium catalysts were then examined. Pd(OAc)2, PdCl2(PPh3)2, and Pd(OAc)2/phosphine ligands all led to lower yields of 3a (entries 10-14). Finally, for comparison the reaction was carried out in the absence of Pd(PPh3)4. No product 3a could be detected. A series of arylboronic acids were then subjected to the optimized reaction conditions with methyl R-diazopropionate 1. The reaction finished in 15 min with high efficiency and afforded methyl R-arylacrylates in moderate to good yields (Table 2). The reaction with o-, m-, and p-monoalkyl substituted arylboronic acids all proceeded efficiently (entries 2∼5). The low yield in the reaction with 3,5-dimethylsubstituted arylboronic acid was due to its low solubility in toluene (entry 6). The reaction was found marginally affected by electronic effects of the substituents of boronic acids. The electron-donating group increased the reaction efficiency as compared with electron-withdrawing groups (entries 7, 8, 9). It is noteworthy that chloro and bromo substituents are tolerated in the reaction conditions, which is advantageous for further transformations (entries 10, 11). Next we studied the scope of the reaction with various R-diazocarbonyl compounds (Table 3). A series of R-alkyl substituted diazocarbonyl compounds were examined and all gave the crosscoupling products in good yields. In the cases where trisubstituted olefins were formed, the E and Z selectivity were low (entries 2, 3, 4). Notably, tetra-substituted olefin, which is difficult to access, can be obtained in moderate yield (entry 5). The reaction also worked well with R-diazoketones, including cyclic substrate (entries 6-9). To elucidate the reaction mechanism of this novel palladiumcatalyzed cross-coupling reaction, we examined the possibility of a process of 1,2-H shift of Pd-carbene intermediate,8 followed by a Heck-Mizoroki-type reaction (eq 1).9 When methyl acrylate and Table 1. Conditions on Pd-Catalyzed Reaction of 1 and 2aa