Mechanism and the Origins of Periselectivity in Cycloaddition Reactions of Benzyne with Dienes

Density functional theory calculations have been used to explore the reaction mechanism of (4 + 2) and (2 + 2) cycloadditions of benzyne with classical dienes. The results indicate the following: (1) (4 + 2) products arise via concerted pathways, (2) (2 + 2) products arise via stepwise pathways with diradical intermediates, and (3) these diradical intermediates are formed via isomerization of carbene intermediates. The origins of periselec-tivity in these reactions are analyzed using distortion/interaction analysis for the key steps, and they indicate that the tiny distortion in the very early [4 + 2] transition structure, coupled with an entropic favorability, controls selective (4 + 2) cycloaddition.

Automated summary

Density functional theory calculations were performed to investigate the reaction mechanism of (4 + 2) and (2 + 2) cycloadditions of benzyne with classical dienes. The results indicate that the (4 + 2) products are formed via concerted pathways, while the (2 + 2) products are formed through stepwise pathways with diradical intermediates. These diradical intermediates are generated through isomerization of carbene intermediates. Distortion/interaction analysis of the key steps provides insights into the origin of selectivity, revealing that the slight distortion in the very early [4 + 2] transition structure, coupled with entropic favorability, controls the selective (4 + 2) cycloaddition.