How Does the Catalyst Affect the Reaction Pathway? DFT Analysis of the Mechanism and Selectivity in the 1,6-Diyne Ester Cycloisomerization

The present study reports a detailed theoretical analysis of the mechanistic and chemoselectivity features in 1,6-diyne ester cycloisomerization. The energy profiles for three different catalysts, namely, [Au I (PPhMe 2 )(NCMe)] +, [Au III (Cl) 2 (pic)] (pic = 2-picolinate), and PtCl 2, were investigated. The DFT calculations reveal that all of these catalysts entail similar 1,3-acyloxy migration and 5 -exo-dig cyclization steps, whereas completely distinct reaction pathways are observed after the formation of the putative vinyl metal complex intermediates. In the [Au I (PPhMe 2 )(NCMe)] + system, the configuration of the phosphine ligand can explain the exclusive chemoselectivity of the Friedel–Crafts reaction over the 1,5-acyl migration. On the other hand, in the [Au III (Cl) 2 (pic)] and PtCl 2 systems, the 1,5-acyl migration is assisted by the chloride ligand, offering an alternative mechanism that can justify a reasonable activation barrier and the corresponding stereochemical feature in the reaction. Moreover, the [Au I (PPhMe 2 )(NCMe)] + complex with soft and carbophilic character represents an electron-deficient catalyst with a linear structure; it is particularly unsuitable for the 1,5-acyl migration. In contrast, the [Au III (Cl) 2 (pic)] catalyst reveals a distorted-square-planar geometry that satisfies the condition to form a square-planar moiety with an acyl functionality. Thus, the obtained theoretical results not only well rationalize the experimental observations but provide insights into the details of the 1,5-acyl migration.