Nickel-catalyzed highly diastereo- and enantioselective hydroaminocarbonylation and hydrocarboxylation of cyclopropenes.

Abstract

The asymmetric hydrocarbonylation of olefins represents a promising and effective strategy for the synthesis of chiral carboxylic acids and their derivatives. However, achieving the synthesis of chiral cyclopropyl primary amides and cyclopropyl carboxylic acids via asymmetric hydroaminocarbonylation and hydrocarboxylation of cyclopropenes remains a significant challenge. Here, we present an efficient catalytic system that enables the utilization of cost-effective NH₄OAc as a practical alternative to gaseous ammonia and simple organic amines in nickel-catalyzed asymmetric hydroaminocarbonylation of cyclopropenes under 1 atm of CO, which provides rapid access to structurally diverse primary amides, secondary amides, and tertiary amides. Notably, the Ni-catalyzed asymmetric hydrocarboxylation reaction is also established with H₂O as a nucleophile to give the corresponding cyclopropyl carboxylic acids in good yields with excellent stereoselectivities. These reactions feature mild reaction conditions, exceptional levels of enantioselectivities and diastereoselectivities while also exhibiting remarkable tolerance towards diverse functional groups. Moreover, our methodology proves to be highly efficient for the synthesis of pharmaceutical compounds such as Levomilnacipran and Bicifadine.