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Enantioselective alkene hydroalkylation overcoming heteroatom constraints via cobalt catalysis

  • Yan Li,
  • Deguang Liu,
  • Xiao Hu,
  • Jun-Yang Zhang,
  • Qing-Wei Zhu,
  • Boru Men,
  • Gen-Wei Gao,
  • Pei-Wen Chen,
  • Yi-Zhou Tong,
  • Zhe Chang,
  • Zhen Li,
  • Xi Lu,
  • Yao Fu

摘要

Alkene hydroalkylation enables efficient and selective formation of C(sp3)–C(sp3) bonds with unique advantages, such as exceptional chemoselectivity and remarkable tolerance of functional groups. However, eliminating the heteroatom-containing substrate-specific constraints in achieving precise enantioselectivity remains a challenge in alkene hydroalkylation reactions. Here we report the cobalt-hydride-catalysed enantioselective hydroalkylation of 1,1-disubstituted alkenes, enabling the efficient construction of chiral tertiary carbon centres at the benzyl position. The enantioselective control mode does not rely on Lewis basic or polar heteroatom functional groups; instead, an efficient stereochemical control environment is established between substrates and catalysts through weak C–H···π interactions in the alkene hydrometalation step. This work adds a differentiated case to the Giese-type addition reaction and metal-hydride-catalysed alkene hydroalkylation precedents towards breaking substrate-specific constraints in the enantioselective control mode.