N-Heterocyclic Carbene-Catalyzed Synthesis of Ynones via C–H Alkynylation of Aldehydes with Alkynyliodonium Salts

Alkynylation of aldehydes with alkynyl(aryl)iodonium salts catalyzed by an N-heterocyclic carbene (NHC) has been developed. The application of the organocatalyst and the hypervalent iodine group-transfer reagent allowed for metal-free C–H functionalization and C–C bond formation. The reaction proceeds under exceptionally mild conditions, at –40 ⁰C and in the presence of an amine base, providing access to an array of heteroaryl-propargyl ketones containing various substituents in good to excellent yields. The mechanism of the reaction was investigated by means of both experiments and density functional theory calculations. 13C-labelling and computations determined that the key alkynyl transfer step occurs via an unusual direct SN2 substitution of iodine-based leaving group by Breslow intermediate nucleophile at an acetylenic carbon. Moreover, kinetic studies revealed that the turnover-limiting step of the catalytic cycle is the generation of the Breslow intermediate, whereas the subsequent C–C bond-formation is a fast process. These results were fully reproduced and rationalized by the computed full free energy profile of the reaction, showing that the largest energy span is located between protonated NHC and the transition state for the carbene attack on the aldehyde substrate.