Harnessing Regiodivergence and Enantioselectivity in Hydroamidation of Methylenecyclopropanes by Ligand Control

Abstract

Hydroamination/hydroamidation has been recognized as a highly important reaction for delivering complex amines. Hydroamination of aliphatic olefins may occur with ipso- and remote selectivity. Yet, controlling or even reversing the regioisomeric outcomes of the hydroamination of aliphatic olefins constitutes a challenging task. In particular, remote and asymmetric hydroamination of olefins catalyzed by base metals has remained largely underexplored. Reported herein is the Ni-catalyzed, ligand-dependent, and regiodivergent hydroamidation of methylenecyclopropanes (MCPs) with dioxazolones as the amidating reagent. In the case of a substituted bipy ligand, the reaction gives a linear, achiral N-homoallyl amide. In contrast, the employment of a chiral bisoxazoline ligand affords a branched allylic amide in high regio- and enantioselectivity, which occurs via a chain-walking-derived nickel allyl species. Mechanistic studies have been conducted to rationalize the regio- and enantioselectivity. The ring scission of MCP is mediated by a Ni(II) hydride, and the subsequent associative chain walking is enantio-determining in the case of the branch-selective hydroamidation.