Catalytic asymmetric aziridination of α,β-unsaturated aldehydes

Abstract

The development, scope, and application of the highly enantioselective organocatalytic aziridination of α,β-unsaturated aldehydes is presented. The aminocatalytic azirdination of α,β-unsaturated aldehydes enables the asymmetric formation of β-formyl aziridines with up to >19:1 d.r. and 99 % ee. The aminocatalytic aziridination of α-monosubstituted enals gives access to terminal α-substituted- α-formyl aziridines in high yields and up to 99 % ee. In the case of the organocatalytic aziridination of disubstituted α,β-unsaturated aldehydes, the transformations were highly diastereo- and enantioselective and give nearly enantiomerically pure β-formyl-functionalized aziridine products (99 % ee). A highly enantioselective one-pot cascade sequence based on the combination of asymmetric amine and N-heterocyclic carbene catalysis (AHCC) is also disclosed. This one-pot three-component co-catalytic transformation between α,β-unsaturated aldehydes, hydroxylamine derivatives, and alcohols gives the corresponding N-tert-butoxycarbonyl and N-carbobenzyloxy- protected β-amino acid esters with ee values ranging from 92-99 %. The mechanisms and stereochemistry of all these catalytic transformations are also discussed. Go domino! A highly enantioselective organocatalytic aziridination of α,β-unsaturated aldehydes and one-pot cascade sequence based on the combination of asymmetric amine and N-heterocyclic carbene catalysis is disclosed (see scheme). Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.