Ligand bite governs enantioselectivity:: Electronic and steric control in Pd-catalyzed allylic alkylations by modular fenchyl phosphinites (FENOPs)

Modular fenchyl phosphinites (FENOPs) containing different aryl units-phenyl (1), 2-anisyl (2), or 2-pyridyl (3)-are efficiently accessible from (-)-fenchone. For comparison of the influence of the different aryl units on enantioselectivities and reactivities, these FENOPs were employed in Pd-catalyzed allylic alkylations. The strongly chelating character of P,N-bidentate 3 is apparent from X-ray structures with PdCl2 ([Pd(3)Cl-2]), and with allyl-Pd units in ([Pd(3)(eta(1)-allyl)] and [Pd(3)(eta(3)-allyl)]). FENOP3 gives rise to a PdL* catalyst of moderate enantioselectivity (42% ee, R product). Surprisingly, higher enantioselectivities are found for the hemilabile, monodentate FENOPs 1 (83% ee, S enantiomer) and 2 (69% ee, S enantiomer). Only small amounts of I or 2 generate selective PdL* catalysts, while complete abolition of enantioselectivity appears with unselective PdL*2 species with higher FENOP concentrations in the cases of 1 or 2. Computational transition structure analyses reveal steric and electronic origins of enantioselectivities. The nucleophile is electronically guided trans to phosphorus. endo-Allyl arrangements are favored over exo-allyl orientations for 1 and 2 due to Pd-pi-pyridyl interactions with short side-on Pd-aryl interactions. More remote edge-on Pd-pi-aryl interactions in 3 with Pd-N(1p) coordination favor endo-allyl units slightly more and explain the switch of enantioselectivity from I (S) and 2 (S) to 3 (R).