Suzuki Hirotsugu, Moro Ryota, Matsuda Takanori
Tenure-Track Program for Innovative Research, University of Fukui, 3-9-1 Bunkyo, Fukui-shi, Fukui, 910-8507, Japan.
Department of Applied Chemistry, Tokyo University of Science, 1-3 Kagurazaka, Shinjuku-ku, Tokyo, 162-8601, Japan.
Angew Chem Int Ed Engl. 2025 Jun 17;64(25):e202505391. doi: 10.1002/anie.202505391. Epub 2025 Apr 21.
Vicinal dicarbofunctionalization of α,β-unsaturated carbonyl compounds is a classical yet versatile method for constructing complex molecular architectures in a single step. However, the regioselectivity is typically governed by the electronic properties of the alkene moiety, leading to the introduction of a nucleophile at the β-position and an electrophile at the α-position. Herein, we report a palladium-catalyzed dicarbofunctionalization of acrylamides via anti-Michael-type addition, achieving reverse regioselectivity relative to traditional approaches. This strategy enables the efficient incorporation of various (hetero)arene nucleophiles at the α-position and carbon electrophiles, including iodoarenes, vinyl iodides, and iodomethane, at the β-position to furnish dicarbofunctionalized amides in good yields. Mechanistic investigations suggest that the reaction proceeds through an alkylpalladium intermediate formed via the α-addition of a nucleophile.
α,β-不饱和羰基化合物的邻位双碳官能团化是一种经典且通用的方法，可一步构建复杂的分子结构。然而，区域选择性通常受烯烃部分的电子性质控制，导致亲核试剂在β位引入，亲电试剂在α位引入。在此，我们报道了一种通过反迈克尔型加成实现的钯催化丙烯酰胺双碳官能团化反应，相对于传统方法实现了反向区域选择性。该策略能够在α位高效引入各种（杂）芳基亲核试剂，在β位引入碳亲电试剂，包括碘代芳烃、碘乙烯和碘甲烷，从而以良好的产率得到双碳官能团化的酰胺。机理研究表明，该反应通过亲核试剂α-加成形成的烷基钯中间体进行。
