DFT/MM study on copper-catalyzed cyclopropanation – Enantioselectivity with no enthalpy barrier

The enantioselectivity in the reaction of [Cu(adam-box)(CHCO₂Me)] {adam-box = 2,2-isopropylidenebis[(4R)-(1-adamantyl)-2-oxazoline]} with Ph₂C=CH₂ was analyzed computationally by ONIOM(B3LYP:UFF) calculations. The lack of transition states in the potential-energy surface precludes the use of conventional approaches and requires the definition of reaction paths in an approximate Gibbs free-energy surface. The procedure is time consuming and intrinsically less accurate than the usual approaches based on enthalpic energy surfaces, but it produces results in reasonable agreement with experiment, which furthermore allow identification of the key interactions responsible for chiral discrimination.