Copper(I)-N-Heterocyclic Carbene-Catalyzed Enantioselective Conjugate Allylation of α,β-Unsaturated Esters

Enantioenriched β-allyl carbonyl compounds constitute an important class of versatile chiral building blocks that can be transformed into a variety of intermediates and utilized in the synthesis of numerous biologically active natural products. Catalytic enantioselective conjugate allyl addition to simple α,β-unsaturated esters provides one of the most efficient approaches for access to such moieties. However, this reaction has not been accomplished for a long time in synthetic chemistry. The natural tendency for 1,2-addition or the formation of stable π-allyl complexes and reluctance to 1,1-reductive elimination make such a reaction very challenging. Herein, by means of copper(I)-N-heterocyclic carbene (NHC) catalysis, such a problem is successfully addressed, and a broad range of simple α,β-unsaturated esters undergo conjugate allylation with commercially available allylBpin in moderate to high yields with excellent regioselectivity and high enantioselectivity. The hydroxyl group in the NHCs was found to be indispensable for both a high yield and high enantioselectivity. Based on control experiments and DFT calculations, a redox reaction pathway involving reversible oxidative addition of allyl cuprate to simple α,β-unsaturated esters, isomerization of Cu(III) π-allyl species, and unique 3,3'-allyl-allyl reductive elimination is proposed rationally. Finally, the synthetic utility of the present methodology is showcased by its application in efficient asymmetric formal syntheses of three bioactive natural products and transformations of the allylation product.