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Asymmetric Catalytic Access to Piperazin-2-ones and Morpholin-2-ones in a One-Pot Approach: Rapid Synthesis of an Intermediate to Aprepitant.

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.

SUBMITTER: Meninno S

PROVIDER: S-EPMC10278953 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Asymmetric Catalytic Access to Piperazin-2-ones and Morpholin-2-ones in a One-Pot Approach: Rapid Synthesis of an Intermediate to Aprepitant.

Meninno Sara S Lattanzi Alessandra A

The Journal of organic chemistry 20230221 12

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 int ...[more]

PMID: 36808952

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