Multicomponent, Enantioselective Michael-Michael-Aldol-ß-Lactonizations Delivering Complex ß-Lactones.

Optically active, tertiary amine Lewis bases react with unsaturated acid chlorides to deliver chiral, α,ß-unsaturated acylammonium salts. These intermediates participate in a catalytic, enantioselective, three-component process delivering bi- and tricyclic ß-lactones through a Michael-Michael-aldol-ß-lactonization. In a single operation, the described multicomponent, organocascade process forms complex bi- and tricyclic ß-lactones by generating four new bonds, two rings, and up to four contiguous stereocenters. In the racemic series, yields of 22-75% were achieved using 4-pyrrolidinopyridine as Lewis base. In the enantioselective series employing isothiourea catalysts, a kinetic resolution of the initially formed racemic Michael adduct appears operative, providing yields of 46% to quantitative (based on 50% max) with up to 94:6 er. Some evidence for a dynamic kinetic asymmetric transformation for tricyclic-ß-lactone 1d was obtained following optimization (yields up to 61%, 94:6 er) through a presumed reversible Michael.