Accurate control on nucleophilic addition of H2O to internal al-kynes:
Ag catalyzed regiospecific hydration strategy
Abstract
In 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 al-kynes. 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
bioac-tive organic molecules and gram-scale experiments further
showcased the application potential of the strategy. The catalyst
control prin-ciples are expected to advance efforts towards the
development of general site-selective addition of nucleophile to
unsaturated sub-strates, removing the requirement for neighboring
activating groups.