Enantioselective remote methylene C-H (hetero)arylation of cycloalkane carboxylic acids

• 成果类型: Article
• 署名作者: Zhang, Tao; Zhang, Zi-Yu; Kang, Guowei; Sheng, Tao; Yan, Jie-Lun; Yang, Yuan-Bin; Ouyang, Yuxin; Yu, Jin-Quan
• 署名单位: Scripps Research Institute
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8765
• DOI: 10.1126/science.ado1246
• 发表日期: 2024-05-17
• 页码: 793-798
• 关键词: arylation; functionalization; activation

摘要

Stereoselective construction of gamma- and delta-stereocenters in carbonyl compounds is a pivotal objective in asymmetric synthesis. Here, we report chiral bifunctional oxazoline-pyridone ligands that enable enantioselective palladium-catalyzed remote gamma-C-H (hetero)arylations of free cycloalkane carboxylic acids, which are essential carbocyclic building blocks in organic synthesis. The reaction establishes gamma-tertiary and alpha-quaternary stereocenters simultaneously in up to >99% enantiomeric excess, providing access to a wide range of cyclic chiral synthons and bioactive molecules. The sequential enantioselective editing of two methylene C-H bonds can be achieved by using chiral ligands with opposite configuration to construct carbocycles containing three chiral centers. Enantioselective remote delta-C-H (hetero)arylation is also realized to establish delta-stereocenters that are particularly challenging to access using classical methodologies.