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.
The direct α-amination of ketones, n class="Chemical">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.
Authors: F Ivy Carroll; Bruce E Blough; Philip Abraham; Andrew C Mills; J Ashley Holleman; Scott A Wolckenhauer; Ann M Decker; Antonio Landavazo; K Timothy McElroy; Hernán A Navarro; Michael B Gatch; Michael J Forster Journal: J Med Chem Date: 2009-11-12 Impact factor: 7.446