Mechanisms and stereoselectivities of the Rh(I)-catalyzed carbenoid carbon insertion reaction of benzocyclobutenol with diazoester.

In this study, a density functional theory (DFT) study has been carried out to investigate the mechanisms of Rh(I)-catalyzed carbenoid carbon insertion into a C-C bond reaction between benzocyclobutenol (R1) and diazoester (R2). The calculated results indicate that the reaction proceeds through five stages: deprotonation of R1, cleavage of the C-C bond, carbenoid carbon insertion, intramolecular aldol reaction, and protonation of the alkoxyl-Rh(I) intermediate. We have suggested and studied two possible pathways according to different coordination patterns (including ketone-type and enol-type coordination forms) in the fourth stage and found that the enol-type pathway is favorable, making the coordination mode of the Rh(I) center in the oxa-π-allyl Rh(I) intermediate clear in this reaction system. Moreover, four possible protonation channels have been calculated in the fifth stage, and the computational results show that the H2O-assisted proton transfer channel is the most favorable. The first step of the third stage is rate-determining, and the first steps in stages 3 and 4 play important roles in determining the stereoselectivities. Moreover, the analyses of distortion/interaction, natural bond orbital (NBO), and molecular orbital (MO) have been performed to better understand this title reaction. Furthermore, the pathway corresponding to the RR configurational product is the most favorable path, which is consistent with the experimental result. This work should be helpful for understanding the detailed reaction mechanism and the origin of stereoselectivities of the title reaction and thus could provide valuable insights into rational design of more efficient catalysts for this type of reactions.