We performed density functional theory (DFT) simulations for the gold(I)‐catalyzed reaction between the weak nucleophilic groups (phenol hydroxy group and benzamido groups) as present in N‐methyl salicylamide and a terminal or internal alkyne to produce benzoxazinone derivatives. For this seemingly mechanistically simple reaction, there are four possible paths depending on the initial N ‐ or O ‐nucleophilic attack on the internal or external alkyne carbon of the gold(I)‐activated triple bond, thus forming intermediate gold‐carbenoids that are transformed into alkenes. The subsequent 6‐ exo‐trig or 7‐ endo‐trig cyclization proceeds via nucleophilic O ‐ or N ‐attack, respectively, to the internal or external alkene carbon. This allows for a mechanistic manifold that features eight possible reaction paths leading to four unique products, with six‐ or seven‐member ring structures. The DFT predictions showed that the experimentally observed product may be formed either through an initial N ‐attack or O ‐attack on the internal alkyne carbon compared to the external alkyne carbon and a subsequent O ‐attack or N ‐attack step, respectively, in the 6‐ exo‐trig cyclization. The path, including an initial nucleophilic N ‐attack to the internal alkyne carbon, is, however, favored at the starting attack and also due to the energy‐demanding 6‐ exo‐trig cyclization in a late step of the mechanism.
Stylianakis et al. (Thu,) studied this question.