Simple catalytic mechanism for the direct coupling of $alpha$-carbonyls with functionalized amines: a one-step synthesis of plavix Article (Faculty180)

cited authors

  • Evans, Ryan W; Zbieg, Jason R; Zhu, Shaolin; Li, Wei; MacMillan, David WC


  • 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.


publication date

  • 2013

start page

  • 16074


  • 135