Extensive Experimental and Computational Study of Counterion Effect in the Reaction Mechanism of NHC-Gold(I)-Catalyzed Alkoxylation of Alkynes

Herein, we synthesized and characterized through NMR and X-ray techniques a new set of [(NHC)-Au-X] complexes (NHC = 1,3-bis(2,6-diisopropylphenyl)-imidazol-2-ylidene), differing in the counterion X- (X- = OMs-, NO3 -, ClO4 -, 2,2,3,3,4,4,5,5,6,6,7,7,7-tridecafluoroheptanoate (PFHp-)). All of these complexes, together with those already known having NTf2 - and phthalimide (ptm-) as counterions, were tested as catalysts in the methoxylation of 3-hexyne. The results were analyzed together with those obtained previously. The values of activation parameters (ΔH- and ΔS-) for different anions are also reported. The overall catalytic and kinetic evidence, together with an extensive computational work, confirm the general mechanistic picture given recently in which the anion plays an active role in all steps of the reaction mechanism: pre-equilibrium, nucleophilic attack, and protodeauration. Medium-coordinating anions (OMs-, OTs-) containing a highly symmetric anchoring group give the best catalytic performances. This is due to the following reasons: (a) the pre-equilibrium is shifted toward the outer sphere ion pair, (b) their characteristic basicity promotes the nucleophilic attack, and (c) the possible paths leading to the deactivation of the catalyst are inhibited. These highly symmetric tridentate anions destabilize the unreactive tricoordinated gold species, which instead may be formed by anions with a "planar" anchoring group, such as PFHp- and TFA-. A general trend between coordinating ability and catalytic performances in the alkoxylation of alkynes may be established only when the geometric features of the anion are taken into account. The role of the anion has been also investigated in connection with the nature of the nucleophile. In particular, when the alcohol is a poor nucleophile, a large difference in reactivity is observed, while the use of suitably functionalized alcohols, which may contribute to polarizing the -OH bond through intramolecular interactions, flattens the anion effect. © 2016 American Chemical Society.