Cobalt-catalyzed diastereo- and enantioselective reductive coupling of cyclobutenes and aldehydes through umpolung reactivity

Abstract

Catalytic diastereo- and enantioselective functionalization of cyclobutenes represents a general and modular strategy for the construction of enantioenriched complex cyclobutanes. However, all precedents focused on reactions of cyclobutenes with nucleophilic organometallic intermediates, whereas transformations of cyclobutenes with electrophiles remained unknown. Herein, we report an unprecedented cobalt-catalyzed protocol for diastereo- and enantioselective reductive coupling of unactivated cyclobutenes and aldehydes. This process enabled access to a broad range of densely functionalized enantioenriched cyclobutanes and the introduction of a chiral functionalized alkyl group with high efficiency and stereoselectivity. Mechanistic studies revealed that diastereo- and enantioselective oxidative cyclization of cyclobutenes and aldehydes followed by stereoselective protonation might be involved. DFT (Density Functional Theory) calculations elucidated the origin of stereoselectivity. This study provides a new platform for modular synthesis of enantioenriched cyclobutanes and reveals new reactivity for cobalt catalysis, pushing forward the advancement in organocobalt chemistry.