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

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. L...

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Published inJournal of organic chemistry Vol. 87; no. 13; pp. 8819 - 8823
Main Authors Choi, Anthony, Meijer, Anthony J. H. M., Silvestri, Ilaria Proietti, Coldham, Iain
Format Journal Article
LanguageEnglish
Published WASHINGTON American Chemical Society 01.07.2022
Amer Chemical Soc
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
LITHIATION
INHIBITOR
DERIVATIVES
DISCOVERY
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Summary: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.
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ISSN:0022-3263
1520-6904
DOI:10.1021/acs.joc.2c00862