Copper(I)-Catalyzed Enantioconvergent Borylation of Racemic Benzyl Chlorides Enabled by Quadrant-by-Quadrant Structure Modification of Chiral Bisphosphine Ligands

Angew Chem Int Ed Engl. 2019 Aug 5;58(32):11112-11117. doi: 10.1002/anie.201906011. Epub 2019 Jul 3.


The first copper(I)-catalyzed enantioselective borylation of racemic benzyl chlorides has been realized by a quadrant-by-quadrant structure modulation of QuinoxP*-type bisphosphine ligands. This reaction converts racemic mixtures of secondary benzyl chlorides into the corresponding chiral benzylboronates with high enantioselectivity (up to 92 % ee). The results of mechanistic studies suggest the formation of a benzylic radical intermediate. The results of DFT calculations indicate that the optimal bisphosphine-copper(I) catalyst engages in noncovalent interactions that efficiently recognize the radical intermediate, and leads to high levels of enantioselectivity.

Keywords: P-chirogenic ligands; copper catalysis; density functional calculations; enantioselective borylation; radical reactions.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't