Catalytic enantioselective synthesis of benzocyclobutenols and cyclobutanols via a sequential reduction/C-H functionalization

We report here a sequential enantioselective reduction/C-H functionalization to install contiguous stereogenic carbon centers of benzocyclobutenols and cyclobutanols. This strategy features a practical enantioselective reduction of a ketone and a diastereospecific iridium-catalyzed C-H silylation. Further transformations have been explored, including controllable regioselective ring-opening reactions. In addition, this strategy has been utilized for the synthesis of three natural products, phyllostoxin (proposed structure), grandisol and fragranol.

Automated summary

A sequential enantioselective reduction/C-H functionalization method was developed for installing contiguous stereogenic carbon centers of benzocyclobutenols and cyclobutanols. This strategy involves practical enantioselective reduction of a ketone and diastereospecific iridium-catalyzed C-H silylation, with further transformations explored, including controllable regioselective ring-opening reactions. Additionally, this strategy has been utilized for the synthesis of three natural products.