Palladium-catalyzed C(sp3)-H arylation of diarylmethanes at room temperature: synthesis of triarylmethanes via deprotonative-cross-coupling processes

J Am Chem Soc. 2012 Aug 22;134(33):13765-72. doi: 10.1021/ja3047816. Epub 2012 Aug 7.

Abstract

Although metal-catalyzed direct arylation reactions of non- or weakly acidic C-H bonds have recently received much attention, chemists have relied heavily on substrates with appropriately placed directing groups to steer reactivity. To date, examples of intermolecular arylation of unactivated C(sp(3))-H bonds in the absence of a directing group remain scarce. We report herein the first general, high-yielding, and scalable method for palladium-catalyzed C(sp(3))-H arylation of simple diarylmethane derivatives with aryl bromides at room temperature. This method facilitates access to a variety of sterically and electronically diverse hetero- and nonheteroaryl-containing triarylmethanes, a class of compounds with various applications and interesting biological activity. Key to the success of this approach is an in situ metalation of the substrate via C-H deprotonation under catalytic cross-coupling conditions, which is referred to as a deprotonative-cross-coupling process (DCCP). Base and catalyst identification were performed by high-throughput experimentation (HTE) and led to a unique base/catalyst combination [KN(SiMe(3))(2)/Pd-NiXantphos] that proved to efficiently promote the room-temperature DCCP of diarylmethanes. Additionally, the DCCP exhibits remarkable chemoselectivity in the presence of substrates that are known to undergo O-, N-, enolate-, and C(sp(2))-H arylation.

Publication types

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

MeSH terms

  • Benzene Derivatives / chemical synthesis
  • Benzene Derivatives / chemistry*
  • Benzhydryl Compounds / chemical synthesis
  • Benzhydryl Compounds / chemistry*
  • Bromides / chemical synthesis
  • Bromides / chemistry
  • Catalysis
  • Palladium / chemistry*
  • Protons

Substances

  • Benzene Derivatives
  • Benzhydryl Compounds
  • Bromides
  • Protons
  • Palladium
  • diphenylmethane