Epoxycyclohexanones via Organocatalytic Asymmetric Domino Reactions

Significance

An organocatalytic asymmetric domino reaction for the synthesis of optically active epoxycyclohexanones in good overall yields, enantioselectivities, and diastereoselectivities has been reported. Michael addition of γ-chloro-β-keto­esters 1 to α,β-unsaturated aldehydes 2 in the presence of 10 mol% of chiral α,α-diarylprolinol silyl ether 3 and 50 mol% of sodium acetate is followed by subsequent aldol addition. Finally, potassium carbonate mediates the intramolecular S_N2 reaction to give bicyclic compounds of type 4. One example has been demonstrated to undergo highly diastereoselective transformations yielding various optically active products. Furthermore, mechanistic considerations including kinetic studies as well as computational investigations are provided.