Novel chiral bis(oxazolines): synthesis and application as ligands in the copper-catalyzed enantioselective conjugate addition of diethylzinc to enones

Novel chiral C₂-symmetric bis(oxazolines) were prepared from tartaric acid. They were applied as ligands in the copper-catalyzed conjugate addition of diethylzinc to chalcone and 2-cyclohexenone. Maximum enantiomeric excesses of 50% and 53% were obtained, respectively. The sense of induction was found to depend on the configuration of the stereogenic centre in the oxazoline ring, and not on the stereogenic centres of the 1,4-dioxane backbone.     

Novel chiral dibenzo[a,c]cycloheptadiene bis(oxazoline) and catalytic enantioselective cyclopropanation of styrene

A series of chiral C₂-symmetric bis(oxazoline) ligands containing dibenzo[a,c]cycloheptadiene units were synthesized. The copper complexes, prepared in situ from copper (I)-triflate and the new enantiopure oxazoline ligands, were assessed as chiral catalysts in the enantioselective cyclopropanation of styrene with diazoacetate. Enantioselectivities up to 82 and 62%, respectively, for trans- and cis-2-phenylcyclopropanecarboxylate were observed.     

C2型轴对称手性双恶唑啉的合成及其应用研究

本文综述了手性双恶唑啉的合成及其金属配合物作为手性催化剂在催化不对称反应中的应用研究进展。     

Asymmetric glyoxylate-ene reaction catalyzed by C2-symmetric chiral bis(oxazoline)–lanthanide complexes

Efficient C₂-symmetric chiral bis(oxazoline)-lanthanide catalysts are developed for the glyoxylate-ene reaction to afford the α-hydroxy esters in 85% yield and up to 54% ee. An enhanced level of diastereoselectivity (81% de) was obtained in the reaction between menthyl glyoxylate and alkenes catalyzed by bis(oxazoline)–Ln(OTf)₃ complex.     

Amino acid recognition of pyridine bis(oxazoline)-copper(II) complex in aqueous solvent

Enantioselective recognition of amino acids has been studied with C₂-symmetric chiral pyridine bis(oxazoline)-copper(II) complexes at physiological pH condition. UV-visible titration revealed strong binding of submillimolar dissociation constant between pyridine bis(oxazoline)-copper(II) complex and amino acids in aqueous solution. Moderate selectivity of up to 2:1 between d- and l-amino acids was achieved. The enantiomers were baseline resolved by capillary electrophoresis, using the bis(l-lysine)-copper(II) complex as a chiral selector.     

Synthesis of new C1-symmetric bis(oxazoline) ligands with a chelating sidearm for stereoselective Mukaiyama aldol condensations

Novel C₁-symmetric bis(oxazoline) ligands with a secondary binding sidearm were prepared in enantiomerically pure form in good yields, in only four steps starting from commercially available reagents. These new chiral ligands were tested in the enantioselective Mukaiyama aldol condensation between the trimethylsilyl keteneacetal of methyl isobutyrate and a non-chelating substrate such as benzaldehyde to afford the product in up to 55% ee.     

Preparation and Catalytic Enantioselective Reactions of C 3-Symmetric Tris(Oxazoline)s Derived from Kemp's Triacid

Kemp's triacid was elaborated to optically pure tris(β-hydroxylamide)s and tris(oxazoline)s. The resulting C ₃-symmetric compounds were used in diethylzinc additions to benzaldehyde and allylic oxidations of cyclopentene, based on Kharash reaction conditions, to give the corresponding products in good chemical yields and moderate enantioselectivities.     

The synthesis and application of novel C2-symmetric chiral N,N,O,O bisoxazoline ligands with a ferrocene backbone

Novel C₂-symmetric bisoxazoline ligands 5 with a ferrocene backbone and a hydroxyl group at the substituent of the oxazoline ring were designed and prepared. With these ligands, up to 94% ee was obtained for the alkylation of arylaldehyde with diethylzinc.     

Synthesis of non-symmetric bisoxazoline compounds. An easy way to reach tailored chiral ligands

Bisoxazoline compounds have been used as chiral catalyst ligands in a wide variety of reactions. A great deal of effort has been aimed at the synthesis of C₂-symmetric bisoxazolines but very few references exist for non-symmetric ones. As part of our studies into the possible usefulness of non-symmetric bisoxazolines, we report an easy method for the synthesis of bisoxazoline compounds bearing different substituents in each oxazoline ring.     

Tripodal borate ligands from tris(dimethylamino)borane: the first synthesis of a chiral tris(methimazolyl)borate ligand, and the crystal structure of a single diastereomer pseudo-C3-symmetric Ru(II) complex

The activation of tris(dimethylamino)borane towards reaction with a chiral methimazole by N-methylimidazole has been used to prepare the first example of a chiral tris(methimazolyl)borate ligand. Coordination of this neutral ligand to Ru(II) has been achieved by reaction with [(p-cymene)RuCl(2)](2) to provide a single diastereomer complex in which the chirality of the methimazolyl substituents dictate the chirality of the bicyclo[3.3.3]cage formed by the ligand on coordination to the metal. The alternative approach to chiral tris(methimazolyl)borate ligands involving the introduction of a chiral group onto the boron atom has been explored by replacing N-methylimidazole in the above reaction by chiral oxazolines as activating bases in reaction with simple methimazole. However, although the B(NMe(2))(3) is activated to reaction with methimazole by these oxazolines, an intramolecular oxazoline ring-opening by a coordinated methimazolyl sulfur occurs and prevents the successful synthesis of these ligands.     

Synthesis of C2-symmetric chiral crown ethers by lipase-catalyzed reactions

Kinetic resolution of a racemic mixture of C₂-symmetric 18-crown-6 diols (rac-1a) and 15-crown-5 diol (rac-1c) was achieved by lipase-catalyzed acetylation. The enantiomeric excess of the chiral crown diols (95% ee and 82% ee) was determined by ¹H NMR spectroscopy, using (R)-(+)-1-(1-naphthyl)ethylammonium hydrochloride as a shift reagent. The C₂-symmetric chiral 15-crown-5 diol (>95% ee) was also obtained by kinetic resolution of the racemic diacetate (rac-2c) using lipase-catalyzed solvolysis.     

Development of a new class of C1-symmetric bisphosphine ligands for rhodium-catalyzed asymmetric hydrogenation

A new class of C₁-symmetric bisphosphine ligands with three hindered quadrants have been obtained through facile synthesis from chiral BINOL derivatives. Their rhodium complexes have exhibited high enantioselectivities (up to 98% ee) in the asymmetric hydrogenation of various unsaturated prochiral olefins, providing an efficient catalytic system for the enantioselective synthesis of chiral amino acids and amines.     

Asymmetric alkylation of 5-alkyl-2-aminothiazolones using a C2-symmetric chiral tetraamine base

The diastereoselective alkylation of a series of 5-alkyl-2-aminothiazolones utilizing a C₂-symmetric chiral tetraamine base is reported.     

The first examples of supramolecular discotic C3h tris(N-salicylideneamine)s featuring inter- and intra-molecular H-bonding: synthesis and characterization

Supramolecular liquid crystalline tris(N-salicylideneamine)s (TSANs) featuring both inter- and intra-molecular hydrogen bonding have been synthesized and characterized for the first time. These TSANs formed by condensing 3 equiv of 3,4,5-trialkoxybenzoylhydrazine with 1,3,5-triformylphloroglucinol exist as the single C_3h-symmetric keto-enamine product solely, unlike the previously reported TSANs. Their self-assembly into supramolecular fluid hexagonal columnar phase over a wide thermal range is evidenced with the aid of optical microscopic, calorimetric, and powder X-ray diffraction techniques.     

Asymmetric addition of diethylzinc to benzaldehyde catalyzed by novel chiral C2-symmetric tetrakis(sulfonamide)–titanium(IV) complexes

A series of chiral C₂-symmetric tetrakis(sulfonamides) 3a–f, 4a–f were prepared and employed as ligands for titanium(IV) complexes in the asymmetric addition of diethylzinc to benzaldehyde. The chiral secondary alcohols were obtained in high yields and in moderate enantioselectivities.     

Copper(II)-containing C2-symmetric bistetracarboline amides in enantioselective Henry reactions

A series of new C₂-symmetric chiral diamides were synthesized from l-tryptophan and used as chiral ligands chelated with Cu(II) in enantioselective Henry reactions. Ligand 4a with CuCl₂·2H₂O (5%) showed effective catalytic efficiency in Henry reaction. High yields (up to 99%) and excellent enantioselectivities (up to 98%) were achieved for both aromatic and aliphatic aldehyde substrates.     

Chiral N-phosphonyl imine chemistry: asymmetric 1,2-additions of allylmagnesium bromides

Chiral N-phosphonyl homoallylic amines were synthesized by the reaction of allylmagnesium bromide with chiral N-phosphonyl imines. The C₂-symmetric chiral N-phosphonyl group was optimized for this reaction. Excellent yields and good diastereoselectivities were obtained for eight examples.     

Copper‐Catalyzed Enantioselective Synthesis of Oxazolines from Aminotriols via Asymmetric Desymmetrization

A copper‐catalyzed enantioselective transformation of tris(hydroxymethyl)aminomethane‐derived aminotriols was developed to provide multisubstituted oxazolines with a tetrasubstituted carbon center. The present transformation consisted of sequential reactions involving mono‐sulfonylation of aminotriols, subsequent intramolecular cyclization to afford prochiral oxazoline diols, and sulfonylative asymmetric desymmetrization of resultant oxazoline diols. In addition, the kinetic resolution process would be involved in the sulfonylative asymmetric desymmetrization step, which would amplify the enantiopurities of the desired products. Various aminotriols were tolerated in the present reaction, affording the desired oxazolines in good to high yields with excellent enantioselectivities. The synthetic utility of the present reaction was demonstrated by the transformation of the optically active oxazoline into a chiral α‐tertiary amine motif.     

A new C2-symmetric azolium compound for Cu-catalyzed asymmetric conjugate addition of R2Zn to cyclic enone

A new chiral N-heterocyclic carbene (NHC) ligand was designed. Thus, an efficient synthetic route to C₂-symmetric bis(hydroxyamide)-functionalized benzimidazolium salts from chiral β-amino alcohols was developed. The combination of Cu(OTf)₂ and the chiral azolium compound efficiently promoted the conjugate addition reaction of cyclic enone with dialkylzinc to give the corresponding adduct in good yield. Among a series of chiral NHC proligands, the functionalized benzimidazolium chloride possessing a tert-butyl group as a stereodirecting group was found to be the best choice of ligand. Under optimized reaction conditions, an excellent enantioselectivity (96% ee) was realized by allowing 2-cyclohepten-1-one to react with Bu₂Zn at room temperature.     

Regioselective cleavage of the bis-benzylidene acetal of d-mannitol under oxidative and reductive conditions: a new approach to C2-symmetric chiral ligands

A highly regioselective oxidative cleavage of 1,3:4,6-di-O-benzylidene-d-mannitol was carried out using NBS and the resultant product was readily converted to the C₂-symmetric chiral ligand, (R,R)-3,4-dihydroxy-1,5-hexadiene. On the other hand, reductive cleavage of 1,3:4,6-di-O-benzylidene-d-mannitol was achieved in a highly regioselective manner using BF₃·OEt₂ and Et₃SiH to give a highly functionalized benzyl ether, which was converted to a synthetically useful C₂-symmetric bis-amino alcohol derivative.