Stereospecific Cross Couplings To Set Benzylic, All-Carbon Quaternary Stereocenters in High Enantiopurity

Asymmetric
preparation of all-carbon quaternary stereocenters is
an important goal. Despite advances in formation of highly enantioenriched
products with quaternary stereocenters proximal to a functional group,
methods to install quaternary stereocenters isolated from functional
groups are limited. Transition metal catalysis offers a potential
solution, but prior cross couplings are limited to allylic substrates
or deliver little to no enantiomeric enrichment. We report a stereospecific,
nickel-catalyzed Suzuki–Miyaura arylation of tertiary benzylic
acetates to deliver products with diaryl and triaryl quaternary stereocenters
in high yields and ee’s. This reaction employs an inexpensive,
air-stable Ni­(II) salt and commercially available phosphine ligand
to transform tertiary alcohol derivatives, which are easily available
in exceptional ee, into valuable products with stereoretention.

全碳季碳手性中心的不对称构建是一项重要研究目标。尽管紧邻官能团的高对映富集季碳手性中心产物的构建已取得诸多进展，但构建与官能团隔离的季碳手性中心的方法仍十分有限。过渡金属催化为该问题提供了潜在解决方案，然而此前的交叉偶联反应仅适用于烯丙基底物，且几乎无法实现对映选择性富集。本研究报道了一种立体专一性的镍催化叔苄基乙酸酯的铃木-宫浦（Suzuki–Miyaura）芳基化反应，可高产率、高对映体过量（ee）值地获得含二芳基、三芳基季碳手性中心的产物。该反应使用廉价、空气稳定的二价镍盐（Ni(II)）与商业化可得的膦配体，将极易以优异对映体过量值制备的叔醇衍生物转化为具有立体构型保留的高价值产物。