Enantioselective Synthesis of Axially Chiral Alkylidenecycloalkanes via Copper-Catalyzed Functionalization of Acyl Allenols
Baihui Gong, Qing‐Bin Lu, R. Li-jiun Sun, Zelin Li, Yihan Chen, Aijun Lin, Hequan Yao, Shang Gao
Abstract
Axially chiral alkylidenecycloalkanes are an important type of stereoisomer, resulting from the perpendicular arrangement of two pairs of substituents. Despite the considerable progress made in the catalytically enantioselective synthesis of atropisomers, the available methods for accessing axially chiral alkylidenecycloalkanes have been underutilized. In this study, we describe a copper-catalyzed enantioselective synthesis of axially chiral alkylidenecycloalkanes using acyl allenols. The axial chirality is established through a central to axial transfer via an enantioenriched allylcopper species. This reaction features mild conditions, >30:1 regioselectivities, and up to 98% ee. Control experiments reveal that the bulky size of the leaving group has a significant influence on the enantioselectivity of the reaction. The alkene and vinylboronate groups of the products provide versatile platforms for further transformations to enrich the structural diversity of products.