Effect of Substituent on the Mechanism and Chemoselectivity of the Gold(I)-Catalyzed Propargyl Ester Tandem Cyclization

This study reports a detailed theoretical analysis of the mechanisms and chemoselectivity for the formation of benzo­[<i>b</i>]­fluorenes or benzofulvenes from propargyl esters catalyzed by an organometallic Au­(I) complex. Three different substitution patterns within the 1,5-diyne ester substrates were explored to rationalize the reaction mechanism and chemoselectivity. DFT calculations reveal that the title reaction proceeds through four main steps: (i) 1,3-acyl-shift, (ii) 6-<i>endo</i>-<i>dig</i> or 5-<i>exo</i>-<i>dig</i> cyclization, (iii) Friedel–Crafts-type, and (iv) proton transfer, with step (ii) being rate-determining in all studied pathways. In the absence of substituents at the aromatic rings of the substrate (R = H), the 6-<i>endo</i>-<i>dig</i> cyclization is favored. In turn, in the presence of one strong electron-donating substituent at the backbone (R = OCH<sub>3</sub>) of the substrate, the 5-<i>exo</i>-<i>dig</i> cyclization is favored. Besides, a modification of the substrate’s acetyl group by a pivaloyl group leads to an activation barrier difference between the 6-<i>endo</i>-<i>dig</i> and 5-<i>exo</i>-<i>dig</i> cyclizations, which increases and suppresses the formation of benzofulvenes. The obtained theoretical data are in a very good agreement with prior experimental evidence, suggesting that the substituent plays a crucial role in the outcome of the final product. High chemoselectivity can be explained by the hindrance (torsional strain) along the forming C–C bond and the carbocation stability provided by substituents.