Alkoxylation of alkynes by mono or dual gold catalysis

Bearing the complexity for the alkoxylation of alkynes to get alkenes selectively, gold complexes are first class agents to catalyze such type of reaction. Herein we present a revisit of the nucleophilic attack recently presented by Belanzoni and coworkers with a simplified Au based catalyst. The mechanism of the monoaurated nucleophilic attack of alcohols on alkynes becomes difficult from a kinetic and thermodynamic point of view, with barriers above 20 kcal/mol, whereas the digold mechanism display a barrier lower than 10 kcal/mol. Moreover, the simplification of the N-heterocyclic carbene (NHC) ligand in the calculations might decrease the enthalpy barrier. Moving to the real catalyst, the barrier for the alkoxylation of the former alkyne asks for more than 30 kcal/mol, which is not feasible at the temperature present in the experiments. The hydroxyalkoxylation should be favored through a dual gold based mechanism. Here a thorough investigation of the mechanistic aspects of the dual gold-catalyzed hydroalkoxylation of alkynes is faced, using computational methods, in order to probe the new reactivity exhibited in this transformation by recent experiments. These studies revealed that the reaction is second order in digold, first order in alkyne and negative order in phenol. The latter is surprising, but has been rationalized based on the demonstrated involvement of phenol at several stages of the reaction. In addition, we have also explored an extended range of reactions in order to fully define the scope and limitations of our methodology, either changing the nature of the alcohol or the alkyne substrate for the monogold catalyzed mechanism. Tools like sterical maps to characterize the sterics of the catalysts allow giving mechanistic details about the structure. On the other hand, conceptual DFT through the concepts of chemical hardness or electrophilicity allow the rationalization of the potential catalytic performance using different kind of alkyne substrates and alcohols, concluding that the alkoxylation is favoured for electroattractive agents like CF3, and the presence of alkylic alcohols like methanol or ethanol instead of arylic solvents like pheno