Not the expected phosphinofenchol 1 but phosphorane 2 is obtained after reaction of 2-lithio(diphenylphosphino)benzene with (-)-fenchone. Surprisingly, ONIOM(B3LYP/6-31G*:UFF) computations of 1 and 2 as well as B3LYP analyses of smaller model systems point to a lower thermodynamic stability of phosphoranes relative to their isomeric alkoxyphosphines. An analogue inherent instability is computed for the methylphosphorane 10, which is also synthesized and characterized by X-ray analysis. Decreasing ring size in cyclic phosphoranes, that is, from five- to four-membered ring systems, destabilizes cyclic phosphoranes even more. This computational prediction is verified experimentally by reaction of lithiomethyl(diphenylphosphine) with (-)-fenchone and subsequent isolation of the corresponding phosphinofenchol. Protonation or alkylation of phosphoranide intermediates can account for the formation of metastable phosphoranes.
Phenyl fenchol forms a 3:1 aggregate with n-butyllithium (3-BuLi), showing unique lithium-HC agostic interactions both in toluene solution (1H,7Li-HOESY) and in the solid state (X-ray analysis). Although methoxy-lithium coordination is characteristic for many mixed aggregates of anisyl fencholates with n-butyllithium, endo-methyl coordination to lithium ions compensates for the missing methoxy groups in 3-BuLi. This gives rise to a different orientation of the fenchane moiety, encapsulating and chirally modifying the butylide unit.
The fenchol-based P-H phosphonite BIFOP-H exeeds with 65% ee other monodentate ligands in the Pd-catalyzed substitution of 1-phenyl-2-propenyl acetate with dimethylmalonate.
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).
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