Department of Chemistry, University of Sheffield, Brook Hill, Sheffield S3 7HF, U.K.
Liverpool ChiroChem, Department of Chemistry, University of Liverpool, Liverpool L69 7ZD, U.K.
J Org Chem. 2022 Jul 1;87(13):8819-8823. doi: 10.1021/acs.joc.2c00862. Epub 2022 Jun 14.
The base -BuLi with sparteine allows a kinetic resolution of -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 -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.
手性仲丁基锂和斯巴醇允许 Boc-2-芳基-4-亚甲基哌啶的动力学拆分。通过高对映体过量值分离出 2,2-二取代产物和回收的起始原料。通过 VT-NMR 光谱和 DFT 研究，-Boc 基团的旋转速率很快。对富集的手性起始原料进行锂化和捕获得到了立体化学保持的 2,2-二取代哌啶。4-亚甲基基团的官能化导致各种 2,4-二取代哌啶，而不会损失手性纯度，这些哌啶可以作为药物发现的有用构建块。
