Biaryls: Gold-Catalyzed Arylation

Biaryls are moieties we often see in natural products, pharmaceuticals, agrochemicals, and organic materials. Guy Lloyd-Jones, Christopher Russell, and their student, Liam Ball, at the University of Bristol reported gold-catalyzed arylation of simple arenes by trimethylsilyl-substituted ones. In the typical condition, the three chemists used 1 or 2 mol% Ph₃PAuOTs as the precatalyst and an oxidant formed in situ from iodobenzene diacetate and camphorsulfonic acid. The solvent was 2% methanol in chloroform, and most reactions were complete at room temperature between 20 and 40 hours. The arylation was regioselective, and its position followed the trends of the electrophilic aromatic substitution, which are also consistent with the results that reactions with sterically hindered or less electron-rich arenes and electron-deficient arylsilanes needed higher temperatures or longer reaction times. The synthetic strategy showed little or no double arylation or homocoupling and tolerated a wide variety of functional groups.

Trimethylsilyl-substituted arenes can be synthesized via silylation methods known in the literature. Ph₃PAuOTs can be prepared according to work by Hubert Schmidbaur and co-workers at the Technical University of Munich based on two commercially available precursors: treatment of Ph₃PAuCl with AgOTs in tetrahydrofuran at –70 °C for 2 hours gave Ph₃PAuOTs in a yield of 95%. Both iodobenzene diacetate and camphorsulfonic acid are commercially accessible.

Lloyd-Jones, Russell, and Ball applied their synthetic protocol to the preparation of diflunisal, a generic anti-inflammatory drug Merck & Co. developed in 1971.

Teleportation gates:

• Article: Ball, L. T.; Lloyd-Jones, G. C.; Russell, C. A. Science 2012, 337, 1644–1648. DOI: 10.1126/science.1225709.
• University of Bristol.
• Guy Lloyd-Jones’s research group.
• Christopher Russell’s research group.
• Electrophilic aromatic substitution on Wikipedia.
• Syntheses of arylsilanes on Organic Chemistry Portal.
• Preparation of Ph₃PAuOTs: Römbke, P.; Schier, A.; Schmidbaur, H. J. Chem. Soc., Dalton Trans. 2001, 2482–2486. DOI: 10.1039/b104001b.
• Diflunisal on Wikipedia.