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

摘要

The 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, b-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 (LUMOHOMO) gap in transition state Si-TS1, indicating the preference for the S-configuration chiral amines, which is in good agreement with the experimental observations.