Crossing the Reactivity Threshold: Phosphonate-Directed, Gold-Catalyzed Oxygen Transfer to Alkynyl Phosphonates

Abstract The first gold-catalyzed oxygen-transfer reaction of alkynyl phosphonates is reported, providing regioselective access to oxazol-4-yl phosphonates through a formal (2+2+1) assembly. The low intrinsic reactivity of alkynyl phosphonates was overcome by pairing the weakly activating phosphonate group with a strongly π-acidic phosphite–gold(I) catalyst and an electronically attenuated O-transfer reagent. The synthetic value is underscored by a gram-scale synthesis, downstream elaborations to the phosphonic acids, and access to phosphonate analogues of bioactive oxazoles.