Center of Basic Molecular Science (CBMS), Department of Chemistry, Tsinghua University, Beijing, China.
Nat Commun. 2021 Jun 18;12(1):3776. doi: 10.1038/s41467-021-24012-z.
Chiral tertiary boronic esters are important precursors to bioactive compounds and versatile synthetic intermediates to molecules containing quaternary stereocenters. The development of conjugate boryl addition to α,β-unsaturated amide has been hampered by the intrinsic low electrophilicity of the amide group. Here we show the catalytic asymmetric synthesis of enantioenriched tertiary boronic esters through hydroboration of β,β-disubstituted α,β-unsaturated amides. The Rh-catalyzed hydroboration occurs with previously unattainable selectivity to provide tertiary boronic esters in high enantioselectivity. This strategy opens a door for the hydroboration of inert Michael acceptors with high stereocontrol and may provide future applications in the synthesis of biologically active molecules.
手性叔硼酸酯是生物活性化合物的重要前体，也是含有季立体中心的分子的多功能合成中间体。由于酰胺基团的固有低亲电性，共轭硼基加成到α,β-不饱和酰胺的发展受到了阻碍。在这里，我们展示了通过β,β-二取代的α,β-不饱和酰胺的硼氢化反应来催化不对称合成对映体富集的叔硼酸酯。铑催化的硼氢化反应具有以前无法达到的选择性，以高对映选择性提供叔硼酸酯。该策略为具有高立体控制的惰性迈克尔受体的硼氢化反应打开了一扇门，并且可能为生物活性分子的合成提供未来的应用。
