Highly Regio- and Enantioselective Hydrosilylation of gem-Difluoroalkenes by Nickel Catalysis
Highly Regio- and Enantioselective Hydrosilylation of gem-Difluoroalkenes by Nickel Catalysis
复制标题
镍催化对偕二氟烯烃进行高度区域和对映选择性硅氢加成
DOI：
10.1002/anie.202114918
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发表时间：
2022-01-12
影响因子：
16.6
通讯作者：
Chang, Junbiao
中科院分区：
文献类型：
--
作者：
Bai, Dachang;Wu, Fen;Chang, Junbiao
具有二氟甲基化立体中心的有机小分子的合成在药物发现中特别有吸引力。在此，我们开发了一种有效的方法，用于直接产生二氟甲基化的立体中心，通过ALE催化的区域选择性和对映选择性硅氢加成的偕-二氟烯烃。该反应也代表了在镍催化下碳（sp（3））-硅键的对映选择性构建，这提供了高价值的光学活性α-二氟甲基硅烷的原子和步骤经济的合成路线。该方案具有易于获得的起始材料和商业手性催化，广泛的底物跨越一系列官能团，具有高产率（高达99%收率）和优异的对映选择性（高达96%ee）。对映体富集的产物经历多种立体特异性转化。进行了初步的机制研究。
The synthesis of small organic molecules with a difluoromethylated stereocenter is particularly attractive in drug discovery. Herein, we have developed an efficient method for the direct generation of difluoromethylated stereo-centers through Ale-catalyzed regio- and enantioselective hydrosilylation of gem-difluoroalkenes. The reaction also represents the enantioselective construction of carbon(sp(3))-silicon bonds with nickel catalysis, which provides an atom- and step-economical synthesis route of high-value optically active a-difluoromethylsilanes. This protocol features readily available starting materials and commercial chiral catalysis, broad substrates spanning a range of functional groups with high yield (up to 99 % yield) and excellent enantioselectivity (up to 96 % ee). The enantioenriched products undergo a variety of stereospecific transformations. Preliminary mechanistic studies were performed.