Enantioselective formal synthesis of tridemethylisovelleral

A simple and efficient synthetic route to the bicyclic α,β-unsaturated β-keto ester methyl (3aS,7aS)-6-oxo-2,3,3a,6,7,7a-hexahydro-1H-indene-5-carboxylate, a versatile intermediate in the synthesis of biologically active unsaturated 1,4-dialdehydes, is described. The synthesis includes a chirality introducing nonenzymatic asymmetric desymmetrization (ADS) reaction of a cyclic meso-anhydride 4 and a modified Hofmann method for preparing exocyclic dienes. The ester was synthesized in a moderate overall yield (19%) from 6 and with an excellent enantioselectivity (>90%).