Primary α-tertiary amine synthesis via α-C–H functionalization

Abstract

A quinone-mediated general synthetic platform for the construction of primary α-tertiary amines from abundant primary α-branched amine starting materials is described. This procedure pivots on the efficientin situgeneration of reactive ketimine intermediates and subsequent reaction with carbon-centered nucleophiles such as organomagnesium and organolithium reagents, and TMSCN, creating quaternary centers. Furthermore, extension to reverse polarity photoredox catalysis enables reactivity with electrophiles,viaa nucleophilic α-amino radical intermediate. This efficient, broadly applicable and scalable amine-to-amine synthetic platform was successfully applied to library and API synthesis and in the functionalization of drug molecules.

Authors: Dhananjayan Vasu,^aAngel L. Fuentes de Arriba,^aJamie A. Leitch,^aAntoine de Gombert^aandDarren J. Dixon*^a

Link: https://pubs.rsc.org/en/content/articlelanding/2019/sc/c8sc05164j#!divAbstract