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...
Saved in:
Published in | Journal of organic chemistry Vol. 87; no. 13; pp. 8819 - 8823 |
---|---|
Main Authors | , , , |
Format | Journal Article |
Language | English |
Published |
WASHINGTON
American Chemical Society
01.07.2022
Amer Chemical Soc |
Subjects | |
Online Access | Get full text |
Cover
Loading…
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. |
---|---|
Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3263 1520-6904 |
DOI: | 10.1021/acs.joc.2c00862 |