Regioselective Hydration of Alkynes by Iron(III) 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.