Issue 11, 2019

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 efficient in situ generation 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, via a 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.

Graphical abstract: Primary α-tertiary amine synthesis via α-C–H functionalization

Supplementary files

Article information

Article type
Edge Article
Submitted
19 11 2018
Accepted
03 2 2019
First published
08 2 2019
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2019,10, 3401-3407

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

D. Vasu, A. L. Fuentes de Arriba, J. A. Leitch, A. de Gombert and D. J. Dixon, Chem. Sci., 2019, 10, 3401 DOI: 10.1039/C8SC05164J

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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