Palladium-Catalyzed Cross-Coupling of Cyanohydrins with Aryl Bromides: Construction of Biaryl Ketones

Abstract The palladium-catalyzed cross-coupling of the lithium anion of aryl tert-butyldimethylsilyl-protected cyanohydrins with aryl bromides followed by in situ deprotection with fluoride ion provides a convenient and versatile approach to biaryl ketones. This protocol represents the first example of a palladium-catalyzed arylation of a cyanohydrin, which functions as an acyl anion equivalent. Hence, in contrast to classical cross-coupling reactions, the pronucleophile component is incorporated in the product to permit further functionalization. We then highlight the synthetic utility of the new method with applications to bioactive biaryl ketones and the construction of a triaryl diketone that has been used to prepare an extended tetrathiafulvalene.