LiCl-Accelerated Multimetallic Cross-Coupling of Aryl Chlorides with Aryl Triflates

J Am Chem Soc. 2019 Jul 17;141(28):10978-10983. doi: 10.1021/jacs.9b05461. Epub 2019 Jul 9.

Abstract

While the synthesis of biaryls has advanced rapidly in the past decades, cross-Ullman couplings of aryl chlorides, the most abundant aryl electrophiles, have remained elusive. Reported here is the first general cross-Ullman coupling of aryl chlorides with aryl triflates. The selectivity challenge associated with coupling an inert electrophile with a reactive one is overcome using a multimetallic strategy with the appropriate choice of additive. Studies demonstrate that LiCl is essential for effective cross-coupling by accelerating the reduction of Ni(II) to Ni(0) and counteracting autoinhibition of reduction at Zn(0) by Zn(II) salts. The modified conditions tolerate a variety of functional groups on either coupling partner (42 examples), and examples include a three-step synthesis of flurbiprofen.

Publication types

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

MeSH terms

  • Coordination Complexes / chemical synthesis*
  • Coordination Complexes / chemistry
  • Hydrocarbons, Chlorinated / chemistry*
  • Lithium Chloride / chemistry*
  • Mesylates / chemistry*
  • Molecular Structure
  • Nickel / chemistry*
  • Zinc / chemistry*

Substances

  • Coordination Complexes
  • Hydrocarbons, Chlorinated
  • Mesylates
  • Nickel
  • Lithium Chloride
  • Zinc
  • trifluoromethanesulfonic acid