Control of asymmetric biaryl conformations with terpenol moieties: syntheses, structures and energetics of new enantiopure C2-symmetric diols.

New enantiopure, C(2)-symmetric biphenyl-2,2'-diols based on (-)-menthone (BIMOL), (-)-verbenone (BIVOL) and (-)-carvone (BICOL and hydrogenated BIMEOL), are accessible via short, synthetic routes. All diols form intramolecular hydrogen bonds and hence can be employed as chelating ligands for catalyst design, as it demonstrated for the (-)-fenchone based BIFOL. The sense of asymmetry of the biphenyl axes is controlled by the chiral terpene units and is conformationally surprisingly stable. X-ray analyses reveal M biphenyl conformation for BIMOL and P biphenyl conformation for each of BIVOL, BICOL and BIMEOL. The origins of the conformational biphenyl preferences are confirmed by computational ONIOM evaluations of the diols and their diastereomeric conformers. The experimentally observed biphenyl conformations are all energetically preferred, i.e. with 1.3 kcal/mol for (M)-BIMOL, with 5.1 kcal/mol for (P)-BIVOL, with 5.8 kcal/mol for (P)-BICOL, and with 5.4 kcal/mol for (P)-BIMEOL.

A dispensable methoxy group? Phenyl fencholate as a chiral modifier of n-butyllithium.

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.

An exceptional P-H phosphonite: biphenyl-2,2'-bisfenchylchlorophosphite and derived ligands (BIFOPs) in enantioselective copper-catalyzed 1,4-additions.

Biphenyl-2,2'-bisfenchol (BIFOL) based chlorophosphite, BIFOP-Cl, exhibits surprisingly high stabilities against hydrolysis as well as hydridic and organometallic nucleophiles. Chloride substitution in BIFOP-Cl proceeds only under drastic conditions. New enantiopure, sterically demanding phosphorus ligands such as a phosphoramidite, a phosphite and a P-H phosphonite (BIFOP-H) are hereby accessible. In enantioselective Cu-catalyzed 1,4-additions of ZnEt2 to 2-cyclohexen-1-one, this P-H phosphonite (yielding 65% ee) exceeds even the corresponding phosphite and phosphoramidite.

Chiral modular n-butyllithium aggregates: nbuli complexes with anisyl fencholates.

Chiral, enantiopure aggregates are formed spontaneously by mixing solutions of n-butyllithium with anisyl fenchols. X-ray crystal analyses reveal the structures of these aggregates with different ortho substituents in the anisyl moieties (X), X = H (1-H), SiMe3 (2-H), tBu (3-H) SiMe2(tBu) (4-H) and Me (5-H). While the complex of 1-BuLi shows a 3:1 composition, 2-BuLi, 3-BuLi and 4-BuLi yield 2:2 stoichiometries. The aggregate 5-BuLi crystallizes with a 2:4 composition and hence is a derivative of hexameric n-butyllithium, in which two trans-situated nBuLi molecules are substituted by lithium fencholate moieties. The variety in the synthesized chiral nBuLi aggregates demonstrates the high propensity of anisyl fencholates to chirally modify nBuLi. Variations in the modular ligand structures by alterations of the ortho-substituents (X) enable tunings of compositions and also of enantioselectivities in nBuLi additions to benzaldehyde.

Remote C-H activation of phenyl-substituted alkenes by BH(3).THF: mechanism and applications.

[reaction: see text] The hydroboration of tetrasubstituted alkenes and, in particular, bicyclic alkenes with BH(3).THF at 50 degrees C provides, via a highly stereoselective 1,2-rearrangement and a remote C-H activation, a diol in which the relative stereochemistry of three centers has been controlled. A mechanistic study provides general rules for remote C-H activation and leads to new synthetic applications.

Phosphinofenchol or metastable phosphorane? Phosphorus derivatives of fenchol.

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.

(Phosphanyloxazoline)palladium complexes, part I: (Eta3-1,3-dialkylallyl)(phosphanyloxazoline)palladium complexes: X-ray crystallographic studies, NMR investigations, and quantum-chemical calculations.

A series of systematically varied (eta3-1,3-dialkylallyl)palladium complexes of (4S)-[2-(2-diphenylphosphanyl)phenyl]-4,5-dihydrooxazole (PHOX) ligands were characterized by X-ray crystal structure analysis and NMR spectroscopy. Complexes with identical substituents in the 1,3-positions of the allyl group can form eight stereoisomers. In solution four to six isomers were observed and their conformations assigned with the aid of NOE experiments. The dynamic behavior of the complexes was analyzed. In addition, quantum-chemical calculations (restricted Hartree-Fock (HF), density functional theory (DFT)) were carried out and gave satisfactory agreement with experimental findings.

Steroid binding by antibodies and artificial receptors: exploration of theoretical methods to determine the origins of binding affinities and specificities.

Binding mode calculations for complexes between an artificial paracyclophane receptor and digoxins, cholic acids as well as cortisone steroids show encapsulation of different ring combinations. Docking experiments were performed between the 26-10 antibody and digoxins. Coordination affinity arises from hydrophobic desolvation and van der Waals interactions rather than from hydrogen bonds. The specificity and affinity arises mainly from shape complementarity. Computed binding free energies and Kohonen neural network computations both point to physicochemical and structural similarities of natural antibodies and artificial receptors.

Rationalization of enantioselectivities in dialkylzinc additions to benzaldehyde catalyzed by fenchone derivatives.

Three (-)-fenchyl alcohol derivatives, ¿(1R,2R,4S)-exo-(2-Ar)-1,3, 3-trimethylbicyclo[2.2.1] heptan-2-ol, Ar = o-anisyl (2), 2-N-methylimidazolyl (3), 2-N,N-dimethylbenzylamine (4)¿ were synthesized, characterized by X-ray analyses, and employed as precatalysts in diethyl zinc additions to benzaldehyde. Directions and relative degrees of enantioselectivities are rationalized by QM/MM ONIOM computations of mu-O transition structure models. Enantioselectivities arise from repulsive interactions between "transferring" or "passive" alkyl groups at the zinc centers and the substituents at donor groups or the bicyclo[2.2.1]heptane moieties. These results enable predictions for ligand-tuning to improve catalyst efficiency of fenchone-based ligands in dialkylzinc additions to aldehydes.