Cooperative Catalysis of Chiral Guanidine and Rh2(OAc)4 in Asymmetric O–H Insertion of Carboxylic Acid: A Theoretical Investigation

We reported mechanistic study on asymmetric O-H insertion reaction of α-diazoester with carboxylic acid, using Rh2(OAc)4/chiral guanidine-amide co-catalyst by density functional theory (B3LYP-D3(BJ)/def2-TZVP//B3LYP-D3(BJ)/[6-31G**, SDD] (SMD, Et2O)). The catalytic reaction included two stages: i) formation of Rh-carbene species, subsequently by the construction of C-O bond forming enol, and ii) chiral guanidinium salt-assisted H-transfer to the enol. In cooperative catalysis, Rh2(OAc)4 helped to form an enol intermediate via high reactivity Rh-carbene species, while the in situ formed guanidium carboxylate acted as a chiral proton shuttle to construct a hydrogen bonding net for the stereo-determinant protonation. The repulsions between the phenyl group of enol intermediate and the cyclohexyl as well as ortho-substituted isopropyl group of chiral guanidine played important roles in controlling the stereoselectivity. A disadvantageous steric arrangement in si-face attack weakened the stabilizing electrostatic and orbital interaction of reacting species in H-transfer step, enhancing the pathway to form predominantly product with R-configuration in the two competing pathways. A model was proposed to explain the asymmetric induction of chiral guanidine-amide in protonation.