Copper-catalyzed asymmetric allylic C–H amination of alkenes using N-arylhydroxylamines

Abstract

The first copper-catalyzed asymmetric allylic C–H amination of alkenes using N-arylhydroxylamines as aminating agents is disclosed. Enantioselective C–N bond formation reactions are promoted in the presence of Cu(MeCN)₄PF₆ as a pre-catalyst and R-(+)-BINAM as a chiral ligand. This protocol delivers chiral N-aryl allylamines in good yields and enantioselectivities. Data regarding the effect of ligand structure and solvents on the efficiency and enantioselectivity of amination reactions are presented. Furthermore, isolation of the metal–ligand–nitroso complex, ESI-MS reaction monitoring analysis and computational calculations provided additional insights into the mechanistic pathway. DFT modeling of the reaction pathway suggests that the stereoselectivity is determined in the conversion of (BINAM)Cu(PhNO)(η²-alkene)⁺ to (BINAM)Cu(N-aryl allylhydroxylamine) via a concerted, asynchronous transition state for C–N bond formation. This catalytic approach features operational simplicity, high product yields with good enantioselectivity, and no byproducts except for water.