Cation−π Interactions in the Benzylic Arylation of Toluenes with Bimetallic Catalysts

• Published in: Journal of the American Chemical Society 2018-10, Vol.140 (39), p.12415-12423
• Main Authors: Sha, Sheng-Chun, Tcyrulnikov, Sergei, Li, Minyan, Hu, Bowen, Fu, Yue, Kozlowski, Marisa C, Walsh, Patrick J
• Format: Article
• Language: English
• Subjects: Biphenyl Compounds - chemical synthesis; Biphenyl Compounds - chemistry; Catalysis; Cations - chemistry; Potassium - chemistry; Toluene - chemistry
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/jacs.8b05143

A method to directly arylate toluene derivatives with aryl bromides to generate diarylmethanes, which are important building blocks in drug discovery, is described. In this method, KN­(SiMe3)2 in combination with a (NIXANTPHOS)Pd catalyst accomplished the deprotonative activation of toluene derivatives to permit cross-coupling with aryl bromides. Good to excellent yields are obtained with a range of electron-rich to neutral aryl bromides. Both electron-rich and electron-poor toluene derivatives are well tolerated, and even 2-chlorotoluene performs well, providing a platform for introduction of additional functionalization. This discovery hinges on the use of a main group metal to activate toluene for deprotonation by means of a cation−π interaction, which is secured by a bimetallic K­(NIXANTPHOS)Pd assembly. Mechanistic and computational studies support acidification of toluene derivatives by the K+–cation– π interaction, which may prove pertinent in the development of other, new reaction systems.