Asymmetric Catalytic Access to Piperazin-2-ones and Morpholin-2-ones in a One-Pot Approach: Rapid Synthesis of an
Sara Meninno1, Alessandra Lattanzi1
1Dipartimento di Chimica e Biologia "A. Zambelli", Università di Salerno, Via Giovanni Paolo II, 84084 Fisciano, Italy.
Abstract:
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.
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