Mild, aqueous α-arylation of ketones : towards new diversification tools for halogenated metabolites and drug molecules

The authors thank the European Research Council (FP7/2007-2013/ERC grant agreement no 614779 to RJMG) and (FP7 2009-2014/ERC agreement no 227817 to SPN) for generous funding. The palladium-catalyzed aqueous α-arylation of ketones was developed and tested for a large variety of reaction partners. These mild conditions enabled the coupling of aryl/ alkyl-ketones with N-protected halotryptophans, heterocyclic haloarenes, and challenging base-sensitive compounds. The synthetic potential of this new methodology for the diversification of complex bioactive molecules was exemplified by derivatising prochlorperazine. The methodology is mild, aqueous and flexible, representing a means of functionalizing a wide range of halo-aromatics and therefore has the potential to be extended to complex molecule diversification. Postprint