A DFT Study on CuH‐Catalyzed Reductive Relay Hydroamination for Synthesis of Remote‐Chiral Amine

Abstract

AbstractThe reaction mechanism of copper‐hydride‐catalyzed reductive relay hydroamination for remote‐chiral amine was studied. Using density functional theory, we carefully investigated the mechanistic of the generation of R‐ and S‐amines with stereocenters. A series of steps, such as Markovnikov hydrocupration, β‐alkoxide elimination of alkylcopper, insertion of terminal alkene with copper‐hydride catalyst, the electrophile attack, and the formation of C–N bonds have been discussed in the catalytic cycle. The most favorable pathway is obtained by the Re‐attack of the catalyst with the allylic ester. In addition, noncovalent interaction (NCI) analyses show stronger noncovalent interactions in transition state Re‐TS1, frontier molecular orbital (FMO) reveal a larger lowest unoccupied molecular orbital and the highest occupied molecular orbital (LUMO‐HOMO) gap in transition state Si‐TS1, indicating the preference for the S‐configuration chiral amines, which is in good agreement with the experimental observations.