Origin of Ligand Effects on Stereoinversion in Pd-Catalyzed Synthesis of Tetrasubstituted Olefins

Abstract

The mechanism and origin of ligand effects on stereoinversion of Pd-catalyzed synthesis of tetrasubstituted olefins were investigated using DFT calculations and the approach of energy decomposition analysis (EDA). The results reveal that the stereoselectivity-determining steps are different when employing different phosphine ligands. This is mainly due to the steric properties of ligands. With the bulkier Xantphos ligand, the syn/anti-to-Pd 1,2-migrations determine the stereoselectivity. While using the less hindered P­(o-tol)3 ligand, the 1,3-migration is the stereoselectivity–determining step. The EDA results demonstrate that Pauli repulsion and polarization are the dominant factors for controlling the stereochemistry in 1,2- and 1,3-migrations, respectively. The origins of differences of Pauli repulsion and polarization between the two stereoselective transition states are further identified.

Insights into the mechanism and origin of multifunctional ligand effects on chemoselectivity in Pd-catalyzed unnatural prenylation and geranylation of oxindoles with isoprene

“…In 2021, Lu et al proposed that mono- and bisphosphine ligands could control the stereochemistry in Pd-catalyzed synthesis of tetrasubstituted olefins through Pauli repulsion and polarization. 11 Recently, the Lan group revealed that mono- and bisphosphine ligands could also regulate the reactants undergoing either three-component coupling or Suzuki–Miyaura coupling reactions. 12 However, the mechanism of ligand regulation in the construction of products with different carbon chain lengths is still worth exploring.…”