Asymmetric One-Pot Mukaiyama Michael/Michael Reaction Catalyzed by Diphenylprolinol Silyl Ether

The asymmetric catalytic Mukaiyama Michael reaction between alpha,beta-unsaturated aldehydes and silyl enol ether derived from a cyclic ketone was catalyzed by diphenylprolinol silyl ether to afford Michael products with excellent diastereo- and enantioselectivities. Bicyclo[2.2.2]octanone derivatives can be synthesized as a single isomer in a nearly optically pure form via a two-step, one-pot reaction, comprising the sequential Mukaiyama Michael reaction and intramolecular Michael reaction starting from dienol silyl ether and alpha,beta-unsaturated aldehydes, catalyzed by diphenylprolinol silyl ether. In the second Michael reaction, positive kinetic resolution occurred to increase the enantioselectivity.