A one-pot Knoevenagel reaction/asymmetric epoxidation/domino
ring-opening
cyclization (DROC) has been developed from commercial aldehydes, (phenylsulfonyl)acetonitrile,
cumyl hydroperoxide, 1,2-ethylendiamines, and 1,2-ethanol amines to
provide 3-aryl/alkyl piperazin-2-ones and morpholin-2-ones in yields
of 38 to 90% and up to 99% ee. Two out of the three steps are stereoselectively
catalyzed by a quinine derived urea. The sequence has been applied
for a short enantioselective entry to a key intermediate, in both
absolute configurations, involved in the synthesis of the potent antiemetic
drug Aprepitant.