Metal-Catalysed α-Arylation of Carbonyl and Related Molecules

α-Arylated carbonyl compounds are commonly occurring motifs in biologically interesting molecules. Conventional procedures for their synthesis often result in complications, particularly in scale-up (stoichiometric amounts of reagents; harsh reaction conditions etc).  Over the last decade, metal-catalysed arylations have been developed under mild reaction conditions and these reactions are being used on Kg scale.

A recent excellent review from scientists at Johnson-Matthey (C C C Johansson and T Colacot, Angew Chem Int Ed, 2010, 49, 676-707) explores the scope of the reaction, illustrated by the schemes below, and discusses progress on replacements for the expensive Pd catalysts, which currently give best yields.  Choice of catalyst/ligand, the nature of the aryl halide, the carbonyl component, base, solvent, stoichiometry and temperature can all influence the success and are important parameters for successful scale up.  These are discussed in the article.  As well as the ketones and esters shown below, amides and aldehydes are also arylated successfully.