Work

Simple Catalytic Mechanism for the Direct Coupling of α-Carbonyls with Functionalized Amines: A One-Step Synthesis of Plavix

Year: 2013

Type: article

Abstract: The direct α-amination of ketones, esters, and aldehydes has been accomplished via copper catalysis. In the presence of catalytic copper(II) bromide, a diverse range of carbonyl and amine substrates undergo fragment coupling to produce synthetically useful α-amino-substituted motifs. The transformation is proposed to proceed via a catalytically generated α-bromo carbonyl species; nucleophilic displacement of the bromide by the amine then delivers the α-amino carbonyl adduct while the catalyst is reconstituted. The practical value of this transformation is highlighted through one-step syntheses of two high-profile pharmaceutical agents, Plavix and amfepramone.

Source: Journal of the American Chemical Society

DOI: 10.1021/ja4096472

Authors: Ryan W. Evans, Jason R. Zbieg, Shaolin Zhu, Wei Li, David W. C. MacMillan

Institution: Princeton University

Language: English

Topic: Catalytic Cross-Coupling Reactions

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funder: National Institute of General Medical Sciences

Award: Combining Nickel and Photoredox Catalysis