Modular synthesis of chiral pentadentate bis(oxazoline) ligands

Highly modular N,Y,Z,Y,N-ligands (Y=N, O, S; Z=N, NO, OH, OMe) have been prepared using bis(oxazoline) building blocks either as nucleophiles or as electrophiles in coupling reactions with central aromatic units. This way, a great variety of pentadentate bis(oxazoline) ligands in diastereo- and enantiomerically pure form become readily available, which are useful for the construction of helical metal complexes with predetermined chirality.     

The first immobilization of pyridine-bis(oxazoline) chiral ligands

[formula: see text] A chiral pyridine-bis(oxazoline) ligand, functionalized with a vinyl group in the pyridine ring, can be polymerized with styrene and divinylbenzene to obtain supported chiral ligands. As proof of the usefulness of this supported ligands, the corresponding ruthenium complexes are catalysts for the cyclopropanation reaction of styrene with ethyl diazoacetate with up to 85% ee.     

Steric and electronic tuning of chiral bis(oxazoline) ligands with 3,3'-bithiophene backbone

[structure: see text] The role played by the electronic properties and the steric features of bis(oxazoline) ligands in the Cu(I)-catalyzed cyclopropanation of styrene effected with ethyl diazoacetate was investigated. Two pairs of new bis(oxazolines) displaying flexible and atropisomeric 3,3'-bithiophene backbones were synthesized and structurally and electronically characterized. For the first time, the electrochemical oxidative potential was used as a reliable index of the electronic density on the nitrogen atom of the chelating groups of new and, for comparative purposes, of already known bis(oxazolines). The Cu(I) complexes of the new ligands were prepared, and their enantioselection ability and catalytic efficiency were tested. This investigation suggests that steric factors and catalyst geometrical features are clearly more important than any consideration of the electronic properties of the chiral ligands.     

The first solid-phase synthesis of bis(oxazolinyl)pyridine ligands

Chiral Pybox (pyridine-2,6-bis(oxazoline)) ligands can be cleanly and efficiently prepared on polystyrene support via a five-step solid-phase synthetic sequence. Cu(I)-complexed polymer-bound Pybox was used as a catalyst in the first heterogeneously catalyzed asymmetric addition of alkynes to imines. Best enantioselectivity was observed with (t)Bu-substituted oxazolines.     

Helical, nonracemic inorganic-organic hybrid polymers of cadmium halides with pentadentate bis(oxazoline) ligands

A chiral, nonracemic pentadentate pyridine bis(oxazoline) ligand forms unprecedented P-helical inorganic-organic hybrid polymers with cadmium halides. The one-dimensional chains consist of Lambda2-configured pentagonal-bipyramidal cadmium complexes with metal-centered chirality bridged by [CdX4]2- tetrahedra via shared halide atoms. In the solid state, the overall helicity exhibits strongly directed orientation parallel to the crystallographic axis a.     

Polymer-bound bis(oxazoline) as a chiral catalyst

A chiral bis(oxazoline) was grafted on ArgoGel and used in the palladium-catalysed substitution of (±)-1,3-diphenyl-2-propenyl acetate with dimethyl malonate. The enantioselectivity was the same as that observed when the analogous monomeric catalyst was used (94–95% e.e.), despite the fact that the C₂ symmetry of the ligand was affected when coupled to the polymer. The polymer-supported catalyst could be recycled several times after removal of precipitated Pd(0). The polymer-bound bis(oxazoline) was also applied in a zinc-catalysed Diels–Alder reaction but lower selectivity and reactivity than the monomer was observed.     

The synthesis of phosphine oxide-linked bis(oxazoline) ligands and their application in asymmetric allylic alkylation

The phosphine oxide-linked bis(oxazoline) ligands were designed and synthesized in two ways. One is the coupling of Grignard reagent derived from 2-(2-bromophenyl)oxazoline with phenylphosphonic dichloride, another route is the condensation of bis(2-formylphenyl)(phenyl)phosphine oxide with chiral amino alcohols followed by NBS oxidation. These new bis(oxazoline) ligands were applied in Pd-catalyzed asymmetric allylic alkylation reactions and good yields and enantioselectivities were obtained with diphenyl substituted ligand (up to 95% ee).     

Improved synthesis of aza-bis(oxazoline) ligands

A straightforward synthesis of chiral aza-bis(oxazoline) (Azabox) ligands from commercially available amino alcohols is described. The new protocol allows access to previously reported Azabox ligands in considerably improved yields but also to new derivatives, including non-C2-symmetrical ones.     

新型C2对称的手性双(亚)唑啉化合物的合成

手性双噁唑啉化合物因其在不对称合成领域的广泛应用,而成为有机合成的一个研究热点。具有C2对称的手性双噁唑啉化合物因其在不对称合成反应中表现出较好的对映选择活性而倍受关注,其合成方法有由羧基转化为噁唑啉基;     

Strategies for the synthesis of chiral, bidentate bis(perfluoroorganyl)phosphane ligands

Chiral, bidentate phosphane ligands, so-called PP ligands, are most frequently synthesized by reacting chiral ditosylates with diarylphosphanide ions.To use the P(CF₃)₂⁻ ion in nucleophilic substitution reactions, it is necessary to reduce the negative hyperconjugation, which is associated with a C-F activation. For this reason we synthesized different bis(trifluoromethyl)phosphanido complexes of mercury, silver and tungsten and investigated their use in nucleophilic substitution reactions. The most reactive compound, resulting from this study so far, is the pentacarbonylbis(trifluoromethyl)phosphanidotungstenate, [W{P(CF₃)₂}(CO)₅]⁻, which exhibits nearly the same bonding situation for the P(CF₃)₂ unit as in the free P(CF₃)₂⁻ ion. For use in synthesis of bis(trifluoromethyl)phosphane derivatives, Lewis acids are desirable, which stabilize the P(CF₃)₂⁻ ion by an intermediary formation of a donor acceptor adduct and can be split off after the synthesis of bis(trifluoromethyl)phosphane derivatives, as could be achieved using the extremely weak Lewis acids, CS₂ and acetone. These results could be established in the synthesis of the first example of an chiral, bidentate bis(trifluoromethyl)phosphane derivative.To synthesize a chiral, bidentate bis(pentafluorophenyl)phosphane derivative, a different synthetic strategy is necessary that does not involve the P(C₆F₅)₂⁻ ion, which decomposes even at low temperature. The implementation of functional P(CN)₂⁻ ions leads to the synthesis of functional, chiral bidentate dicyanophosphane derivatives which finally can be transformed into the corresponding bis(pentafluorophenyl)phosphane derivatives.     

Catalytic and highly enantioselective reactions of alpha-sulfonyl carbanions with chiral bis(oxazoline)s

The enantioselective reactions of lithiated benzyl trifluoromethyl sulfones with a substoichiometric amount of a bis(oxazoline) and various aldehydes is disclosed. The products were formed with excellent diastereo- and enantioselectivities. Fluorination of the sulfone with N-fluorobenzenesulfonimide and a stoichiometric amount of a bis(oxazoline) gave products with extremely high enantioselectivities (up to 99% ee; ee=enantiomeric excess). The enantioselective reaction was confirmed to proceed through a dynamic thermodynamic resolution pathway.     

Design and synthesis of chiral hybrid spiro (isoxazole–isoxazoline) ligands

Novel chiral hybrid ligands containing an unsymmetrical spiro[4.5]decane skeleton with isoxazole and isoxazoline as the two coordinating units have been synthesized. Pd complexes of these ligands were found to be effective in activating olefins towards enantioselective tandem cyclization of a dialkenyl alcohol, providing the cyclized products in up to 97% ee.     

Asymmetric synthesis of chiral spiro bis(isoxazoline) and spiro (isoxazole–isoxazoline) ligands

Asymmetric synthesis of novel chiral ligands, bis(isoxazoline) on a spiro[4.4]nonane scaffold and isoxazole–isoxazoline on a spiro[4.5]decane scaffold, has been achieved by utilizing an enantiomerically pure alcohol as the starting material.     

The application of bis(oxazoline) ligands in the catalytic enantioselective methallylation of aldehydes

A series of symmetric and non-symmetric bis(oxazoline) ligands were applied in the Nozaki-Hiyama-Kishi methallylation of a range of aromatic and aliphatic aldehydes. A non-symmetrical ligand with tert-butyl/benzyl-substituted oxazolines provided the highest enantioselectivity of 99.5% for the methallylation of benzaldehyde.     

Heterogenization of a chiral bis(oxazoline) catalyst by grafting onto silica

[reaction: see text] We report here the first heterogenization of a bis(oxazoline) ligand on an inorganic (silica) surface. The activity and enantioselectivity of this new material as a catalyst for the Diels-Alder reaction were checked, and it was shown that under certain conditions enantioselectivities similar to those of the homogeneous catalyst are reached. It was also shown that under these conditions the catalyst can be recycled without loss of activity or selectivity.     

Enantioselective synthesis induced by chiral organic-inorganic hybrid silsesquioxane in conjunction with asymmetric autocatalysis

5-Pyrimidyl alkanol with up to 96% ee was formed using chiral organic-inorganic hybrid silsesquioxane in the enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde, in conjunction with asymmetric autocatalysis.     

The supramolecular chemistry of organic-inorganic hybrid materials

The combination of nanomaterials as solid supports and supramolecular concepts has led to the development of hybrid materials with improved functionalities. These "hetero-supramolecular" ideas provide a means of bridging the gap between molecular chemistry, materials sciences, and nanotechnology. In recent years, relevant examples have been reported on functional aspects, such as enhanced recognition and sensing by using molecules on preorganized surfaces, the reversible building of nanometer-sized networks and 3D architectures, as well as biomimetic and gated chemistry in hybrid nanomaterials for the development of advanced functional protocols in three-dimensional frameworks. This approach allows the fine-tuning of the properties of nanomaterials and offers new perspectives for the application of supramolecular concepts.     

Synthesis of highly modular bis(oxazoline) ligands by Suzuki cross-coupling and evaluation as catalytic ligands

New bis(oxazoline) ligands (BOXs) containing biaryl substitutents at the C-4 position and H or CH₂OR substituents at the C-5 position have been synthesized using Suzuki cross-coupling as the main tool for structural diversity. Copper, zinc, and palladium complexes of the prepared BOXs have been evaluated in the following catalytic asymmetric processes: Acylation with kinetic resolution of trans-1,2-cyclohexanediol (Cu), enantioselective Friedel-Crafts alkylation of indole (Zn), and enantioselective alkylation of 3-acetoxy-1,3-diphenylpropene (Pd).