Regio-controllable [2+2] benzannulation with two adjacent C(sp3)-H bonds

• 成果类型: Article
• 署名作者: Yang, Ji-Min; Lin, Yu-Kun; Sheng, Tao; Hu, Liang; Cai, Xin-Pei; Yu, Jin-Quan
• 署名单位: Scripps Research Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-11080
• DOI: 10.1126/science.adg5282
• 发表日期: 2023-05-11
• 页码: 639-644
• 关键词: c-h activation; derivatives

摘要

Regiocontrol in traditional cycloaddition reactions between unsaturated carbon compounds is often challenging. The increasing focus in modern medicinal chemistry on benzocyclobutene (BCB) scaffolds indicates the need for alternative, more selective routes to diverse rigid carbocycles rich in C(sp(3)) character. Here, we report a palladium-catalyzed double C-H activation of two adjacent methylene units in carboxylic acids, enabled by bidentate amide-pyridone ligands, to achieve a regio-controllable synthesis of BCBs through a formal [2+2] cycloaddition involving s bonds only (two C-H bonds and two aryl-halogen bonds). A wide range of cyclic and acyclic aliphatic acids, as well as dihaloheteroarenes, are compatible, generating diversely functionalized BCBs and hetero-BCBs present in drug molecules and bioactive natural products.