Synthesis of constrained bicycloalkanes through bibase-promoted brook rearrangement/radical-polar crossover cyclization
Xinke Ouyang, Bingyao Shi, Yuanyuan Zhao, Zhimin Zhu, Ziyang Li, Yuxin Yang, Chao Shu
Abstract
Highly constrained bicyclic scaffolds are ubiquitous and attracting increasing interest in pharmaceutical and biotechnology discoveries owing to the enhanced activities. Herein, we report a protocol to access highly substituted constrained bicycloalkanes from readily accessible α-silyl alcohols and olefins through a bibase-promoted Brook rearrangement/radical-polar crossover cyclization (RPCC) process. Of note, the practical procedure features broad substrate scope and good group tolerance under mild and operationally simple conditions, using an inexpensive organic photocatalyst. Gram-scale preparation and diverse synthetic transformations demonstrate opportunities to rapidly construct molecular complexity. Mechanistic studies have indicated that the transformation involves a bibase-promoted radical transfer rearrangement addition/radical-polar crossover cyclization relay sequence, which differs from traditional solitary RPCC reactions.