Enantioselective remote meta-C-H arylation and alkylation via a chiral transient mediator

Nature. 2018 Jun;558(7711):581-585. doi: 10.1038/s41586-018-0220-1. Epub 2018 Jun 18.

Abstract

Enantioselective carbon-hydrogen (C-H) activation reactions by asymmetric metallation could provide new routes for the construction of chiral molecules1,2. However, current methods are typically limited to the formation of five- or six-membered metallacycles, thereby preventing the asymmetric functionalization of C-H bonds at positions remote to existing functional groups. Here we report enantioselective remote C-H activation using a catalytic amount of a chiral norbornene as a transient mediator, which relays initial ortho-C-H activation to the meta position. This was used in the enantioselective meta-C-H arylation of benzylamines, as well as the arylation and alkylation of homobenzylamines. The enantioselectivities obtained using the chiral transient mediator are comparable across different classes of substrates containing either neutral σ-donor or anionic coordinating groups. This relay strategy could provide an alternative means to remote chiral induction, one of the most challenging problems in asymmetric catalysis3,4.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Benzylamines / chemistry
  • Carbon / chemistry*
  • Catalysis
  • Hydrogen / chemistry*
  • Norbornanes / chemistry
  • Stereoisomerism

Substances

  • Benzylamines
  • Norbornanes
  • 2-norbornene
  • Carbon
  • Hydrogen