Mechanistic Investigation of Au(III)‐Catalyzed Cycloisomerizations of N‐Propargylcarboxamides

Abstract

DFT calculations of the AuCl3‐catalyzed cycloisomerization of N‐(propargyl)benzamide (1) have been conducted to reveal the detailed mechanism resulting in the bioactive 2,5‐disubstituted oxazole. A viable mechanism is established, featuring the co‐catalysis of the oxazoline‐AuCl3 adduct. An oxazoline intermediate is afforded firstly by AuCl3 coordination with 1, 5‐exo‐dig‐cyclization, stepwise 1‐assisted protodeauration and coordination exchange. Once formed, the oxazoline species would replace 1 to assist the protodeauration, generating the oxazoline‐AuCl3 adduct. In the last stage, significantly different from the simple deprotonation followed by protodeauration reported previously, the exo‐cyclic C atom of the oxazoline accepts the adjacent allyl H atom of the oxazoline‐AuCl3 to produce a zwitterionic intermediate, from which the allyl H atom of oxazoline fragment transfers to the allyl C atom of the adduct moiety, affording the final oxazole product and regenerating the oxazoline‐AuCl3. The present theoretical study provides new insight into the mechanism of the unusual cycloisomerization reaction.