The first synthesis of organic-inorganic hybrid materials with chiral bis(oxazoline) ligands

Condensation of tetraethoxysilane with silane-functionalized bis(oxazolines) in the presence of dodecylamine leads to hybrid materials whose textural and catalytic properties depend on both the ligand and the spacer structure.     

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.     

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.     

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.     

Modular bis(oxazoline) ligands for palladium catalyzed allylic alkylation: unprecedented conformational behaviour of a bis(oxazoline) palladium eta3-1,3-diphenylallyl complex

New families of enantiopure bis(oxazolines) with 4,5-trans (5 a-g) or 4,5-cis (6 c) stereochemistry at the individual rings have been prepared in high yield. Their eta(3)-allyl palladium complexes (8 a-g, 9 c and 10) have been used as catalytic precursors in allylic alkylation reactions with excellent enantioselectivities (up to 96 %) for the trans oxazoline derivatives, while Pd/6 c system was inactive. NMR studies on palladium eta(3)-1,3-diphenylallyl intermediates (11 a, c and e) showed the presence of syn/syn- and syn/anti-allyl isomers in solution; this resembles the first example of eta(3)-eta(1)-eta(3) isomerism in Pd allylic complexes containing bis(oxazolines) derived from malonic acid.     

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.     

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;     

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).     

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.     

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.     

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).     

Enantioselective reaction of alpha-lithiated dithioacetals using chiral bis(oxazoline)s: new chiral formyl anion equivalents

The enantioselective reaction of various alpha-lithiated dithioacetals with aldehydes or a ketone in the presence of bis(oxazoline)s was examined. Among them, unsymmetrical dithioacetals were found to be the best choice for attaining high enantioselectivity. The reaction of lithiated tert-butylthio(2-pyridylthio)methane with aldehydes proceeded with good diastereoselectivity as well as with good enantioselectivity. The enantioselective reaction was shown to proceed through dynamic thermodynamic resolution. Mercury(II) chloride effected hydrolysis of the dithioacetal moiety of the products to 2-hydroxyaldehydes, which were directly reduced to give the optically active 1,2-diols.     

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.     

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.     

Coordination of a chiral tin(ii) cation bearing a bis(oxazoline) ligand with tetrahydrofuran derivatives

The reaction of SnCl(2) with the lithio derivative of a bis(oxazoline) ligand precursor afforded the enantiomeric chlorostannylene whose chloride ion can be substituted by several neutral or anionic Lewis donors. Abstraction of the chloride ion from the chlorostannylene with silver salts gave the corresponding tetrahydrofuran (THF) complexes of a chiral tin(ii) cation in 1,2-dimethoxyethane (DME) containing THF. That is, the reaction with silver hexafluoroantimonate (AgSbF(6)) afforded the THF complex without interaction with the counteranion. In contrast, reaction with silver triflate (AgOTf) gave the THF complex whose tin center had a pseudo-trigonal bipyramidal structure with two nitrogen atoms of a bidentate ligand and a lone pair at the equatorial positions and one of the oxygen atoms of triflate and an oxygen atom of THF at the apical positions in the solid state. Use of 3-methyltetrahydrofuran (3-MeTHF) instead of THF afforded the 3-MeTHF complexes, where the R-enantiomer of 3-MeTHF predominantly coordinates to the tin center. The previously reported germanium(ii) analogue of the tin(ii) cation indicated a similar enantioselectivity for the coordination of 3-MeTHF on the germanium center.     

Malonate-type bis(oxazoline) ligands with sp hybridized bridge carbon: synthesis and application in Friedel-Crafts alkylation and allylic alkylation

A series of simple and new C₂-symmetric diphenylmethylidene malonate-type bis(oxazoline) ligands were synthesized and applied to the Friedel-Crafts reaction and allylic alkylation. The Cu(II) complex of ligand 4b bearing the benzyl group afforded good to excellent enantioselectivity for the F-C adducts (up to >99% ee) between indole and alkylidene malonate, and the palladium complex of ligand 4c bearing the phenyl group afforded excellent enantioselectivity (up to 94% ee) for the allylic alkylation product.     

On the intermediates in chiral bis(oxazoline)copper(II)-catalyzed enantioselective reactions--experimental and theoretical investigations

The intermediates in the chiral bis(oxazoline)copper(II)-catalyzed reactions have been investigated by means of experimental and theoretical investigations. It is shown that the absolute configuration of the hetero-Diels-Alder adduct obtained from the reaction of ethyl glyoxylate with 1,3-cyclohexadiene in the presence of the chiral bis(phenyloxazoline)copper(II) is dependent on the solvent. In this case, a linear relationship between the enantiomeric excess (ee) and the dielectric constant of the solvent was observed. However, the enantiomeric excess for the adduct obtained with the chiral bis(tert-butyloxazoline)copper(II) complex is independent of the solvent. The addition of different coordinating solvents to the chiral catalysts was investigated and no effect on the enantioselectivity of the reaction was observed. A series of chiral bis(tert-butyloxazoline)-, bis(phenyloxazoline)-, and bis(indaneoxazoline)copper(II) complexes has been prepared and characterized by X-ray analysis, and the similarity between the structures is discussed. For comparison, two related chiral bis(tert-butyloxazoline)- and bis(phenyloxazoline)zinc(II) complexes were also prepared and characterized. A series of chiral bis(oxazoline)copper(II)-substrate (the substrate being glyoxal or methyl glyoxylate) complexes was investigated by means of ab initio calculations. Calculation of the total energy of the optimized structure of 17-, 19-, and 21-electron bis(oxazoline)copper(II)-substrate complexes give the 17-electron complex as the most stable and the most reactive complex, while the 21-electron complex is less stable and also much less reactive. The optimized structures of both the 17-electron bis(tert-butyloxazoline)- and bis(phenyloxazoline)copper(II)-substrate complexes show that the plane of the substrate molecule is twisted by approximately 40-45 degrees out of the bis(oxazoline)copper(II) plane, in agreement with the X-ray structures. On the basis of the experimental results, X-ray structures, and ab initio calculations, the structure of the intermediate(s) and reactivity of the chiral bis(oxazoline)copper(II)-substrate complexes are discussed.