N-Heterocyclic Carbene-Catalyzed Synthesis of Ynones via C-H Alkynylation of Aldehydes with Alkynyliodonium Salts-Evidence for Alkynyl Transfer via Direct Substitution at Acetylenic Carbon

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 mild conditions, at -40 degrees C 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. C-13-labeling and computations determined that the key alkynyl transfer step occurs via an unusual direct substitution at an acetylenic carbon, wherein an iodine-based leaving group is exchanged by a Breslow intermediate nucleophile. 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 are fully reproduced and rationalized by the calculated full free energy profile of the reaction, showing that the largest energy span is located between the protonated form of NHC catalyst and the transition state for the carbene attack on the aldehyde substrate.