Enantioselective Synthesis of Hexahydroisobenzofuran and Hexahydro­isoindole Derivatives with Quaternary Stereocenters

Abstract

Oxo esters with pyrrolidine and tetrahydrofuran rings were converted into optically active isobenzofuran and isoindole derivatives. The key step of the sequence was a copper-catalyzed asymmetric Michael reaction with methyl vinyl ketone and en-amines prepared from the oxo esters and L-valine diethylamide. The chiral auxiliary was cleaved from the products during workup and 1,5-diketones with a quaternary stereocenter are obtained with 97-99% ee. Subsequent annulation reactions were achieved in two steps via the intermediate aldol products.