Homogeneous Gold Catalysis: Hydration of 1,2-Diphenylacetylene with Methanol in Aqueous Media. A Theoretical Viewpoint Gloria Mazzone, Nino Russo, and Emilia Sicilia* Dipartimento di Chimica and Centro di Calcolo ad Alte Prestazioni per Elaborazioni Parallele e Distribuite-Centro d’Eccellenza MIUR, Universita ̀ della Calabria, I-87036 Arcavacata di Rende, Italy * S Supporting Information ABSTRACT: Hydration of alkynes to the corresponding ketones can be afforded in high yields at room temperature by using gold(I) phosphine complexes as catalyst, with no acidic cocatalysts required. A detailed DFT computational study of the nucleophilic attack of methanol to 1,2- diphenylacetylene assisted by [(Ph 3 P)Au] + catalyst has been carried out to shed light on the mechanistic aspects of such a process. The effect of the presence of an additional molecule of water that assists the reaction has been investigated. Calculations suggest that the rate-determining step of the whole process is the addition of a second nucleophile molecule to the formed enol ether to yield the final ketone product, along the pathway that describes the second part of the reaction. Comparison with an analogous study for the nucleophilic attack of water shows that, according to experimental findings, addition to diphenylacetylene of MeOH is faster than that of H 2 O. ■ INTRODUCTION Gold, a noble metal, was long considered useless as a catalyst; however, in the last 15 years homogeneous Au(I) and Au(III) complexes have emerged as highly competent and selective catalysts to act as soft carbophilic Lewis acids toward C-C multiple bonds. 1 Hence, an understanding of the mechanistic and structural aspects of the reactions mediated by gold complexes has become the subject of an ever-increasing number of publications. 2 A surprising efficiency of Au(I) complexes has been detected, especially toward the addition of methanol to alkynes under mild conditions. This new synthetic strategy has provided an alternative to mercury salts, used for the industrial production of ketones from alkynes 3 until the discovery of their toxicity. Linear dicoordinated gold com- pounds, upon activation by a silver(I) salt, generate a monoligated cationic catalyst which requires strong electronic and steric stabilization from its ancillary ligand. To date, cationic Au(I)-phosphine complexes have been identified as the best gold-based catalysts for selective activation of the triple bond in simple alkynes in aqueous media. 4 The mechanism by which this reaction occurs has been studied for the first time by Teles et al. at the end of the 1990s. In their investigation of methanol addition to alkynes, the authors have detected an efficient catalytic activity of coordinatively unsaturated Au(I) species, of the type R 3 PAu + , generated in situ by the protonolysis of R 3 PAuCH 3 and release of CH 4 . 5 They have shown how in the presence of water ketones are the only products. Furthermore, with the aid of ab initio calculations, the authors have suggested an associative mechanism in which the first interaction between alkyne and catalyst leads to the formation of a linear Au-η 2 -alkyne complex that is then attacked in a syn fashion by a molecule of methanol at the side of the coordinated metal. Similar results were obtained a few years later by Tanaka et al., 3 Laguna, 6 and others, 7 which have shown that alkyne hydration can be performed by organometallic gold(I) complexes, especially in combination with strong acids with heating. More recently, in a series of experiments on gold-catalyzed ketone formation from a wide range of alkynes, Leyva and Corma have demonstrated that water-soluble phosphine ligands combined with a soft noncoordinating anion would make the Au(I) catalytic center sufficiently acidic to achieve the nucleophile addition to alkynes without additives. 8 Catalysts such as R 3 PAuX (PR 3 = PPh 3 , SPhos, P t Bu 3 ; X = Cl, OTf, NTf 2 ) have been formed in situ by treatment of the corresponding chloride complex, R 3 PAuCl, with a silver salt. Moreover, with the purpose of shedding light on the proposed mechanistic hypotheses 3,5,6 for this reaction the authors have carried out a series of kinetic experiments using H 2 O, MeOH, or both as nucleophiles, 1,2-diphenylacetylene as substrate, and AuPR 3 X (PR 3 = PPh 3 , SPhos, P t Bu 3 ; X = Cl, OTf, NTf 2 ) as catalyst with different amounts of water and solvents. The mechanism proposed by the authors on the basis of experimental findings is summarized in Scheme 1. The first steps of the reaction are coordination of the triple bond to the Au(I) complex with formation of the Au-π-alkyne complex I Received: December 13, 2011 Published: March 16, 2012 Article pubs.acs.org/Organometallics © 2012 American Chemical Society 3074 dx.doi.org/10.1021/om2012369 | Organometallics 2012, 31, 3074-3080