Catalytic asymmetric constructions of nitrogen, boron and carbon continuous stereogenic centers

Abstract

Abstract Precise construction of molecular chirality is a longstanding scientific challenge in synthetic chemistry. Although methods to enantioselectively assemble consecutive carbon stereocenters are abundant, courses to establish enriched continuous heteroatomic stereocenters have acquired less attention and remain a tremendous challenge. Of those atoms in main group elements, nitrogen and boron are the most intractable ones to control their chirality. The copper-catalyzed asymmetric insertion reaction is one of the most significant transformations to construct C-B bonds in organic synthesis. Herein, we report a protocol to synthesize troublesome continuous heteroatomic stereocenters from cyclic amine boranes and diazo compounds via asymmetric B-H insertion reaction. The protocol is compatible with a wide range of amine boranes and diazo compounds, exhibiting high diastereo- and enantioselectivities. Mechanistic studies reveal a meaningful kinetic resolution pathway involved in the transformation and DFT calculations elucidate the origins of stereoselectivity and diastereoselectivity.