Highly enantioselective δ-protonation and formal [3 + 3] annulation promoted by N-heterocyclic carbene

Abstract

An N-heterocyclic carbene (NHC) catalyzed highly enantioselective δ-protonation of α,β-γ,δ-diunsaturated aldehydes is described. In this work, a chiral NHC catalyst reacts with α,β-γ,δ-diunsaturated aldehydes to generate the extended Breslow intermediate. Upon highly enantioselective δ-protonation and tautomerization, the resulting α,β-unsaturated acyl azolium undergoes a [3 + 3] annulation with enamines to afford various dihydropyridinones with excellent enantioselectivities and good yields (up to 99% ee). This unique intermediate also provides access to δ-chiral esters with potential enantioselectivities.