Organocatalytic Domino Michael-Knoevenagel Condensation Reaction for the Synthesis of Optically Active 3-Diethoxyphosphoryl-2-oxocyclohex-3-enecarboxylates

A novel, organocatalytic, highly enantio- and diastereoselective synthetic approach towards optically active 6-substituted-3-dietlloxypllosphoryl-2-oxocyclohex-3-enecarboxylates is presented. Our methodology utilizes a Michael-Knoevenagel domino reaction sequence of ethyl 4-diethoxyphosphoryl-3-oxobutanoate and alpha,beta-unsaturated aldehydes catalyzed by a chiral diarylprolinol ether. The cyclohexenecarboxylates obtained are particularly well suited for the preparation of highly functionalized cyclohexene and cyclohexane derivatives, with up to four chiral centers and high levels of stereocontrol.