Investigation of the Electronic Origin of Asymmetric Induction in Palladium-Catalyzed Allylic Substitutions with Phosphinooxazoline (PHOX) Ligands by Hammett and Swain–Lupton Analysis of the13C NMR Chemical Shifts of the (π-Allyl)palladium Intermediates

Abstract

Isomeric 4′- and 5′-substituted phosphinooxazoline (PHOX) ligands are used to probe the electronic origins of enantioselective nucleophilic additions to (1,3-diphenylallyl)palladium PHOX ligand complexes. Hammett analysis of the 13C NMR chemical shifts of the allyl C-1 and C-3 carbons shows that the major exo diastereomer is less susceptible to differential changes at C-1 and C-3 and that the location of the substituent has a smaller impact on these changes. In contrast, the minor endo diastereomer is more susceptible to differential 13C NMR changes at C-1 and C-3 and the location of the substituent has a greater impact on these changes. The endo diastereomer exhibits a pronounced “cis effect” by the ligating nitrogen and phosphorus atoms across the palladium center that explains its lower reactivity and, therefore, how the enantioselectivity typically obtained with PHOX ligands exceeds the approximately 8/1 ratio of exo to endo intermediates. Swain–Lupton analysis reveals the importance of both resonance and field effects by the substituents regardless of their location and supports the overall electronic control model for enantioselection by PHOX ligands. For rational chiral ligand design and electronic tuning of ligand properties, these results suggest that the overall electronic impact of a remote substituent generally depends more on its identity than on its location within the ligand.