Regioselective hydration of alkynes by ironIII Lewis/Brønsted catalysis

The triflimide iron(III) salt [Fe(NTf(2))(3)] promotes the direct hydration of terminal and internal alkynes with very good Markovnikov regioselectivities and high yields. The enhanced carbophilic Lewis acidity of the Fe(III) cation mediated by the weakly-coordinating triflimide anion is crucial for the catalytic activity. The iron(III) metal salt can be recycled in the form of the OPPh(3)/[Fe(NTf(2))(3)] system with similar activity and selectivity. However, spectroscopic and kinetic studies show that [Fe(NTf(2))(3)] hydrolyzes under the reaction conditions and that catalytically less active Brønsted species are formed, which points to a Lewis/Brønsted co-catalysis. This triflimide-based catalytic system is regioselective for the hydration of internal aryl-alkynes and opens the door to a new synthetic route to alkyl ketophenones. As a proof of concept, the synthesis of two antipsychotics Haloperidol and Melperone, with general butyrophenone-like structure, is shown.