Lewis acid acceleration of C-N bond-forming reductive elimination from heteroarylpalladium complexes and catalytic amidation of heteroaryl bromides

A large acceleration of carbon-nitrogen bond-forming reductive elimination from heteroarylpalladium amido complexes by addition of Lewis acids is described. Several lines of data imply that this effect arises from coordination of the Lewis acid to the nitrogen of the heteroaryl group. The presence of this coordination was confirmed by isolation of a Lewis acid base complex with a borane coordinated to the pyridyl nitrogen. This adduct underwent reductive elimination faster than the complex lacking the Lewis acid, and it occurred in high yield. Control experiments showed that this acceleration of reductive elimination was not observed for the reactions of arylpalladium amide complexes. This effect of Lewis acids translated to catalytic C-N bond-forming coupling processes. The binding of Lewis acids to the pyridyl nitrogen led to an acceleration of the amidation of unactivated heteroaryl bromides catalyzed by palladium complexes of Xantphos. The rates were faster and the yields were higher for reactions of BEt3 adducts of basic heteroaryl bromides than for the free heteroaryl bromides. This phenomenon draws parallels to the beneficial effect of Lewis acids on the reductive elimination of nitriles from arylmetal cyanide complexes and the catalytic hydrocyanation of olefins.