Asymmetric Catalytic Access to Piperazin-2-ones and Morpholin-2-ones in a One-Pot Approach: Rapid Synthesis of an Intermediate to Aprepitant
Sara Meninno, Alessandra Lattanzi
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.
Topics & Concepts
ChemistryCatalysisEnantioselective synthesisDominoAcetonitrileKnoevenagel condensationEthanolArylMedicinal chemistryCombinatorial chemistryAlkylStereochemistryOrganic chemistrySynthesis and Catalytic ReactionsAsymmetric Synthesis and CatalysisSynthetic Organic Chemistry Methods