Accurate Control on the Nucleophilic Addition of H2O to Internal Alkynes: An Ag catalyzed Regiospecific Hydration Strategy

Abstract

AbstractIn the absence of directing auxiliaries, catalytic addition of nucleophiles to unactivated alkynes with accurate control of regioselectivity remains an ongoing challenge in organic chemistry. Herein, we realized a Ag‐catalysed regiospecific hydration process of unactivated alkynes. Computational investigations offered insights into the origin of the regiochemical outcome. The practicability and efficacy of the protocol was exemplified by its simple reaction conditions without incorporation of acidic additives, as well as the tolerance of a wide range of alkynes equipped with various functional groups, leading to the ketone products in up to 98 % yield. Direct modification of bioactive organic molecules and gram‐scale experiments further showcased the application potential of the strategy. The catalyst control principles are expected to advance efforts towards the development of general site‐selective addition of nucleophile to unsaturated substrates, removing the requirement for neighboring activating groups.