Palladium(ii)-catalyzed 1,3-heteroaryl acyloxylation of propargylic electrophiles

Abstract

We report a 1,3-heteroaryl acyloxylation of 3-substituted propargylic esters with readily available heteroarenes, including indoles, pyrroles, furans and thiophenes, under palladium catalysis. Heteroaryl-functionalized Z-enol ester products were obtained in a single step with complete levels of γ-regioselectivity and anti-hydroacyloxylation stereo-control. The use of the palladium-tri(2-furyl)phosphine complex in polyfluorinated alcoholic solvents was shown to be crucial to the reactivity of the desired pathway based on control experiments. High atom economy, mild conditions (30 °C) and broad tolerance to functional groups make this protocol attractive. Finally, the synthetic utility of this method was demonstrated by gram-scale synthesis and downstream derivatizations of the product.