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

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.

Stereoselective Synthesis of Isoxazolidines via Copper-Catalyzed Alkene Diamination

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Sodium Iodide‐Catalyzed Direct α‐Alkoxylation of Ketones with Alcohols via Oxidation of α‐Iodo Ketone Intermediates

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Concise Synthesis of (±)-Clopidogrel via Carboxylation of Benzylamine with CO2

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