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.

• Authors: Anjan Das, Anthony Choi, Iain Coldham
• Journal: Organic letters (Org Lett) Vol. 25 Issue 6 Pg. 987-991 (02 17 2023) ISSN: 1523-7052 [Electronic] United States
• PMID: 36735675 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Piperazines

Topics

• Humans
• Piperazines
• Alzheimer Disease
• Kinetics
• Phosphorylation
• Catalysis