A DFT study on the reaction mechanism of the gold(I)-catalyzed cycloisomerization of alkynylhydroxyallylamides to 4-Oxa-6-azatricyclo[3.3.0.02,8]octane and 3-Acyl-4-alkenylpyrrolidine

In this study, we use density functional theory calculations to investigate the discrepancy between two experimental results of Au(I)-catalyzed cycloisomerization reactions of alkynylhydroxyallyl tosylamide under similar reaction conditions, with the only variations being reaction temperature and time. The experimental results reported by Yeh and Chung groups, respectively, showed that 3-acyl-4-alkenylpyrrolidines are produced dominantly at ambient temperature, while 4-aza-6-oxatricyclo[3.3.0.0^2,8]octanes are produced in higher yield at elevated temperature. Using (Z)-4-([3-phenylprop-2-yn-1-yl]amino)but-2-en-1-ol and [Au(PPh₃)]⁺ as the model starting material and active catalyst species, respectively, we identified two major pathways leading to 4-aza-6-oxatricyclo[3.3.0.0^2,8]octane (pathway I ) and 3-acyl-4-alkenylpyrrolidine (pathway II ). The overall free energy barrier (ΔG^‡_max) and the energetic span (ΔG^‡_span) of each pathway were 38.3 and 48.4 kcal/mol for pathway I and 29.0 and 37.1 kcal/mol for pathway II . Our analysis shows that the disparate outcomes observed in the experiments by two separate groups mainly originate in the reaction kinetics, with both the overall activation barrier and energetic span being the important factor.