Enantioselective Robinson-Type Annulation

Significance

The authors disclose a novel strategy for the enantioselective Robinson-type annulation reaction which is based on a chiral Brønsted acid 2-catalyzed Michael addition of α-alkyl-β-keto esters 1 to methyl vinyl ketone combined with a chiral Brønsted acid 4-catalyzed kinetic resolution of products 3 in the subsequent aldol condensation. Thus, cyclohexenone derivatives 5 were obtained in good yields along with high enantioselectivities. Only for compound 6 derived from methyl 2-oxocyclopentanecarboxylate no kinetic resolution was observed in the aldolization step.

Review: T. Akiyama Chem. Rev. 2007, 107, 5744-5758.