Synthesis of Enantiomerically Pure (-)-Wine Lactone Based on a Palladium-Catalyzed Enantioselective Allylic Substitution

摘要

The first enantioselective synthesis of enantiomerically pure (-)-wine lactone, (-)-la, a fragrance constituent of various white wines, and its epimer (+)-lb, was carried out. The key steps are allylic substitution of (±)-2-cyclohexen-1-yl acetate (2) with dimethylmalonate using palladium complexes of phosphanyldihydrooxazol L1 or of the phosphanylcarboxylic acid L2 as catalyst, subsequent decarboxylation, iodolactonization and elimination, furnishing enantiomerically pure bicyclic lactone (+)-7 in 47% overall yield. The diastereoselective introduction of methyl groups by S_N2'-type substitution with an organocopper compound and by enolate alkylation gave lactone (-)-la in 43% overall yield from (+)-7.