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Building Up a Piperazine Ring from a Primary Amino Group via Catalytic Reductive Cyclization of Dioximes.

ABSTRACT: Piperazine is one of the most frequently found scaffolds in small-molecule FDA-approved drugs. In this study, a general approach to the synthesis of piperazines bearing substituents at carbon and nitrogen atoms utilizing primary amines and nitrosoalkenes as synthons was developed. The method relies on sequential double Michael addition of nitrosoalkenes to amines to give bis(oximinoalkyl)amines, followed by stereoselective catalytic reductive cyclization of the oxime groups. The method that we developed allows a straightforward structural modification of bioactive molecules (e.g., α-amino acids) by the conversion of a primary amino group into a piperazine ring.

SUBMITTER: Pospelov EV

PROVIDER: S-EPMC10380651 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Building Up a Piperazine Ring from a Primary Amino Group via Catalytic Reductive Cyclization of Dioximes.

Pospelov Evgeny V EV Sukhorukov Alexey Yu AY

International journal of molecular sciences 20230722 14

Piperazine is one of the most frequently found scaffolds in small-molecule FDA-approved drugs. In this study, a general approach to the synthesis of piperazines bearing substituents at carbon and nitrogen atoms utilizing primary amines and nitrosoalkenes as synthons was developed. The method relies on sequential double Michael addition of nitrosoalkenes to amines to give bis(oximinoalkyl)amines, followed by stereoselective catalytic reductive cyclization of the oxime groups. The method that we d ...[more]

PMID: 37511552

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