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, [AuI(PPhMe2)­(NCMe)]+, [AuIII(Cl)2(pic)] (pic = 2-picolinate), and PtCl2, 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
[AuI(PPhMe2)­(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 [AuIII(Cl)2(pic)]
and PtCl2 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 [AuI(PPhMe2)­(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 [AuIII(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.