Palladium-Catalyzed Aryl C–H Olefination with Unactivated, Aliphatic Alkenes

Palladium-catalyzed coupling between aryl halides and alkenes (Mizoroki–Heck reaction) is one of the most popular reactions for synthesizing complex organic molecules. The limited availability, problematic synthesis, and higher cost of aryl halide precursors (or their equivalents) have encouraged exploration of direct olefination of aryl carbon–hydrogen (C–H) bonds (Fujiwara–Moritani reaction). Despite significant progress, the restricted substrate scope, in particular noncompliance of unactivated aliphatic olefins, has discouraged the use of this greener alternative. Overcoming this serious limitation, we report here a palladium-catalyzed chelation-assisted ortho C–H bond olefination of phenylacetic acid derivatives with unactivated, aliphatic alkenes in good to excellent yields with high regio- and stereoselectivities. The versatility of this operationally simple method has been demonstrated through drug diversification and sequential C–H olefination for synthesizing divinylbenzene derivatives.

钯催化芳基卤化物与烯烃的偶联反应（Mizoroki–Heck反应）是合成复杂有机分子的最常用反应之一。芳基卤化物前体（或其等价物）存在获取受限、合成难度大以及成本较高的问题，这推动了芳基碳-氢键（C–H键）直接烯烃化反应（Fujiwara–Moritani反应）的研究探索。尽管该领域已取得显著进展，但底物范围受限——尤其是未活化脂肪族烯烃无法适配该反应——极大限制了这一更绿色替代方案的应用。本研究攻克了这一重大局限，报道了一种钯催化、螯合辅助的苯乙酸衍生物邻位C–H键烯烃化反应，可与未活化脂肪族烯烃高效反应，产物收率介于中等至优异水平，且具有极高的区域选择性和立体选择性。本方法操作简便，通过药物分子多样化修饰以及用于合成二乙烯基苯衍生物的连续C–H烯烃化反应，验证了该方法的普适性。