Catalytic Asymmetric Aziridination of α,β-Unsaturated Aldehydes

The development, scope, and application of the highly enantioselective organocatalytic aziridination of alpha,beta-unsaturated aldehydes is presented. The aminocatalytic azirdination of alpha,beta-unsaturated aldehydes enables the asymmetric formation of beta-formyl aziridines with up to >19:1 d.r. and 99% ee. The aminocatalytic aziridination of alpha-monosubstituted enals gives access to terminal alpha-substituted-alpha-formyl aziridines in high yields and up to 99% ee. In the case of the organocatalytic aziridination of disubstituted alpha,beta-unsaturated aldehydes, the transformations were highly diastereo- and enantioselective and give nearly enantiomerically pure beta-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 alpha,beta-unsaturated aldehydes, hydroxylamine derivatives, and alcohols gives the corresponding N-tert-butoxycarbonyl and N-carbobenzyloxy-protected beta-amino acid esters with ee values ranging from 92-99%. The mechanisms and stereochemistry of all these catalytic transformations are also discussed.