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Photocatalysis and Kinetic Resolution by Lithiation to Give Enantioenriched 2-Arylpiperazines.

ABSTRACT: Piperazines are important heterocycles in drug compounds. We report the asymmetric synthesis of arylpiperazines by photocatalytic decarboxylative arylation (metallaphotoredox catalysis) then kinetic resolution using n-BuLi/(+)-sparteine. This gave a range of piperazines with very high enantioselectivities. Further functionalizations gave enantioenriched 2,2-disubstituted piperazines, and either N-substituent can be removed selectively. Late-stage functionalizations of enantioenriched piperazine derivatives were demonstrated, including synthesis of a drug compound with glycogen synthase kinase (GSK)-3β inhibitor activity with potential for treating Alzheimer's disease.

SUBMITTER: Das A

PROVIDER: S-EPMC9942196 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Photocatalysis and Kinetic Resolution by Lithiation to Give Enantioenriched 2-Arylpiperazines.

Das Anjan A Choi Anthony A Coldham Iain I

Organic letters 20230203 6

Piperazines are important heterocycles in drug compounds. We report the asymmetric synthesis of arylpiperazines by photocatalytic decarboxylative arylation (metallaphotoredox catalysis) then kinetic resolution using <i>n</i>-BuLi/(+)-sparteine. This gave a range of piperazines with very high enantioselectivities. Further functionalizations gave enantioenriched 2,2-disubstituted piperazines, and either N-substituent can be removed selectively. Late-stage functionalizations of enantioenriched pipe ...[more]

PMID: 36735675

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