Pathway-divergent coupling of alkynes and cyclobutenes through enantioselective cobalt catalysis.

Abstract

Development of catalytic enantioselective transformations through divergent pathways from a single set of starting materials provides one of the most straightforward and efficient strategies for rapid establishment of a library of molecules in chemical synthesis and drug discovery. Catalytic reactions that generate enantioenriched cyclobutenes and cyclobutanes which are not only important units in medicinal chemistry, natural products and material science, but also useful intermediates in organic synthesis are of importance in the field of catalysis. Here we report a cobalt-catalyzed protocol for pathway-divergent enantioselective coupling of alkynes and cyclobutenes. Such processes that begin with oxidative cyclization followed by protonation or reductive elimination accurately controlled by ligands produce densely functionalized cyclobutanes and cyclobutenes in up to 95% yield with >98:2 regio- and diastereoselectivity and >99.5:0.5 enantiomeric ratio. Mechanistic studies and DFT calculations reveal that the reaction pathways are manipulated precisely by ligands and elucidate the origin of stereoselectivity.