A Density Functional Theory (DFT) Mechanistic Study of Gold(I)-Catalyzed Alkynylation of the Indole and Pyrrole Substrates, Using a Hypervalent Iodine Reagent

Density functional theory (DFT) was utilized to probe the mechanism of AuCl-catalyzed alkynylation of the indole and pyrrole substrates using a hypervalent iodine reagent ([(<u>t</u>ri-<i><u>i</u>so-</i><u>p</u>ropy<u>s</u>ilyl)<u>e</u>thynyl]-1,2-<u>b</u>enziodo<u>x</u>ol-3­(1<i>H</i>)-one (TIPS-EBX)). An unprecedented reaction mechanism was shown to be operative. In this mechanism, the catalytic reaction starts with coordination of the alkyne moiety of the iodine­(III) reagent to the AuCl catalyst, followed by transfer of the alkynyl group from I^III to Au^I. The iodine­(III) center was found to be capable of activating the alkyne triple bond more efficiently than the gold­(I) center. The nucleophilic attack of the aromatic substrates on the I^III-activated alkyne gives a iodine­(III) gold­(I) vinyl complex. According to the calculations, this step was predicted to be the rate-determining step. Starting from the vinyl complex, the product is formed through the interaction of the occupied σ_Au–C-orbital with the vacant σ_I–C^*-orbital, followed by a very fast deprotonation reaction. This process that leads to the reduction of iodine­(III) to iodine­(I) occurs without protonation of the benzoate group of the iodine­(III) moiety and with a small activation energy of 6.6 kcal/mol. It was concluded that the presence of the Au–C σ-bond at the β-position converts the vinyl group to a potent reductant. The regioselectivity for the catalytic C–H alkynylation of arenes is dictated by the stability of the vinyl complex. It was found that the cationic gold complexes such as PMe₃Au⁺ are not effective catalysts for the alkynylation reaction, because they are strongly poisoned by coordination to the benzoate group of the iodine­(III) reagent