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Kinetic Resolution of 2-Aryl-4-methylenepiperidines toward Enantioenriched Functionalizable Piperidine Fragments.

ABSTRACT: The base n-BuLi with sparteine allows a kinetic resolution of N-Boc-2-aryl-4-methylenepiperidines. The 2,2-disubstituted products and recovered starting materials were isolated with high enantiomeric ratios. From VT-NMR spectroscopy and DFT studies, the rate of rotation of the N-Boc group is fast. Lithiation and trapping of the enantioenriched starting materials gave 2,2-disubstituted piperidines with retention of stereochemistry. Functionalization of the 4-methylene group led to a variety of 2,4-disubstituted piperidines without loss of enantiopurity that could be useful building blocks for drug discovery.

SUBMITTER: Choi A

PROVIDER: S-EPMC9490820 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature

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Kinetic Resolution of 2-Aryl-4-methylenepiperidines toward Enantioenriched Functionalizable Piperidine Fragments.

Choi Anthony A Meijer Anthony J H M AJHM Silvestri Ilaria Proietti IP Coldham Iain I

The Journal of organic chemistry 20220614 13

The base n-BuLi with sparteine allows a kinetic resolution of N-Boc-2-aryl-4-methylenepiperidines. The 2,2-disubstituted products and recovered starting materials were isolated with high enantiomeric ratios. From VT-NMR spectroscopy and DFT studies, the rate of rotation of the N-Boc group is fast. Lithiation and trapping of the enantioenriched starting materials gave 2,2-disubstituted piperidines with retention of stereochemistry. Functionalization of the 4-methylene group l ...[more]

PMID: 35699313

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