Ligand Bite Governs Enantioselectivity: Electronic and Steric Control in Pd‐Catalyzed Allylic Alkylations by Modular Fenchyl Phosphinites (FENOPs)

Abstract

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 ([Pd3Cl2]), and with allyl-Pd units in ([Pd3(eta1-allyl)] and [Pd3(eta3-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 1 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(lp) coordination favor endo-allyl units slightly more and explain the switch of enantioselectivity from 1 (S) and 2 (S) to 3 (R).

Hemilabile Diamidophosphite-Thioether Ligands with a β-Hydroxy Sulfide Backbone: Palladium(II) Complexes and Asymmetric Allylic Substitution

“…Note that individual [Pd­(allyl)­( L )]­BF 4 complexes should produce only P , S -chelate catalysts (excluding undesirable forms based on possible minor impurities in the initial complexes). In turn, the use of n L + [Pd­(allyl)­Cl] 2 combinations should afford a dynamic mixture of both types of intermediates, due to the presence of donor chloride anions . This fact, as well as the influence of different counterions may lead to distinctions in enantioselectivities when comparing catalytic systems based on individual chelates and in situ formed compositions 1/1.…”

Platinum(II) and Palladium(II) Complexes of Bisphosphine Ligands Bearing o-N,N-Dimethylanilinyl Substituents: A Hint of Catalytic Olefin Hydration

“…The inability of the P-atom to epimerize during the fluxional process is obviously of importance for potential asymmetric catalysis using ligands such as dmapcp. A detailed understanding of the stereochemical implications of fluxional processes in chiral complexes is becoming increasingly important in light of recent discoveries that both chiral and achiral hemilabile ligand groups may act to enhance enantioselectivities in metal-catalyzed asymmetric reactions.…”