Chiral Β-amino Alcohols Research Articles

Unravelling a new class of chiral organocatalyst for asymmetric ring-opening reaction of meso epoxides with anilines.

Chiral sulfinamide based organocatalyst 11 was synthesized from readily available starting materials and used for the asymmetric ring-opening (ARO) reaction of meso epoxides with anilines. A high yield (up to 95%) of chiral β-amino alcohols with excellent enantioselectivity (ee up to 99%) was achieved in 24-30 h at rt under optimized reaction conditions. A probable mechanism for the catalytic ARO reaction is envisaged by (1)H and (13)C NMR experiments.

Synthesis of chiral benzene-based tetraoxazolines and their application in asymmetric Friedel–Crafts alkylation of indole derivatives with nitroalkenes

A series of new chiral benzene-based tetraoxazoline ligands were prepared in good yields through the reaction of 1,2,4,5-benzenetetracarboxylic acid and chiral β-amino alcohols by continuous removal of water, and the asymmetric Friedel–Crafts alkylation of indole derivatives with nitroalkenes was tested using the chiral catalysts, which were generated in situ by refluxing the above ligands and anhydrous zinc chloride in solvent. In most case, good yields (up to 99%) and excellent enantioselectivities (up to 98% ee) were obtained.

Magnetic Nano Fe3O4 Catalyzed Solvent-Free Stereo- and Regioselective ­Aminolysis of Epoxides by Amines; a Green Method for the Synthesis of β-Amino Alcohols

We report the use of magnetic nano Fe3O4 as a mild heterogeneous catalyst for the aminolysis of epoxides with amines. The approach constitutes a green method for the formation of a variety of β-amino alcohols with very high stereo- and regioselectivity under solvent-free and ambient reaction conditions. The aminolysis of chiral epoxides with amines gave the corresponding chiral β-amino alcohols with complete inversion of stereochemistry. The magnetic nano Fe3O4 catalyst can be easily recovered and recycled.

Enantiomeric differentiation of β-amino alcohols under electrospray ionization mass spectrometric conditions

The enantiomeric differentiation of a series of chiral β-amino alcohols (A) is attempted, for the first time, by applying the kinetic method using L-proline, L-tryptophan, 4-iodo-L-phenylalanine or 3, 5-diiodo-L-tyrosine as the chiral references (Ref) and Cu(2+) or Ni(2+) ion (M) as the central metal ion. The trimeric diastereomeric adduct ions, [M+(Ref)2+A-H](+), formed under electrospray ionization conditions, are subjected for collision-induced dissociation (CID) experiments. The products ions, formed by the loss of either a reference or an analyte, detected in the CID spectra are evaluated for the enantiomeric differentiation. All the references showed enantiomeric differentiation and the R(chiral) values are better for the aromatic alcohols than for aliphatic alcohols. Notably, the R(chiral) values of the aliphatic amino alcohols enhanced when Ni(2+) is used as the central metal ion. The experimental results are well supported by computational studies carried out on the diastereomeric dimeric complexes. The computational data of amino alcohols is correlated with that of amino acids to understand the structural interaction of amino alcohols with reference molecule and central metal ion and their role on the stabilization of the dimeric complexes. Application of flow injection MS/MS method is also demonstrated for the enantiomeric differentiation of the amino alcohols.

Catalytic Asymmetric Reduction of Prochiral Ketones with Chiral β-Amino Alcohol N-Boranes and the Corresponding Tris(oxazaborolidine)borazines

Chiral β-amino alcohol-derived N-borane catalysts, namely noncyclic (2S)- and (2R)-2-amino-2-phenylethanol N-borane and their corresponding cyclic trimeric borazine derivatives, were synthesized and their catalytic activities in the asymmetric reduction of prochiral ketones were examined. Both the noncyclic and cyclic catalysts successfully catalyzed this reaction, giving the desired secondary alcohols in up to 82% isolated yield and with up to 80% enantioselectivity. The noncyclic catalyst was stable in aqueous and organic solvents, whereas the polycyclic borazine was stable only in nonprotic dry organic solvents.

ChemInform Abstract: Enantioselective Ring Opening of meso‐Epoxides with Aromatic Amines Catalyzed by Dinuclear Magnesium Complexes.

The dinuclear magnesium complexes generated in situ from the reaction of chiral multidentate semi-azacrown ether ligands with n-Bu2Mg were found to be efficient catalysts for enantioselective ring-opening of meso-epox- ides with aniline derivatives, affording the corresponding chiral β-amino alcohols in good yields with up to 90% ee.

Green Asymmetric Synthesis: β‐Amino Alcohol‐Catalyzed Direct Asymmetric Aldol Reactions in Aqueous Micelles

The ability of chiral β-amino alcohols to catalyze the direct asymmetric aldol reaction was evaluated for the first time in aqueous micellar media. A family of cheap and easily accessible β-amino alcohols, obtained in one step from naturally occurring amino acids, was shown to successfully catalyze the asymmetric aldol reaction between a series of ketones and aromatic aldehydes. These aldol reactions furnished the corresponding β-hydroxy ketones with up to 93% isolated yield and 89% ee. (S)-2-phenylglycinol and Triton X-100 proved to be the best organocatalyst and surfactant, respectively.

Asymmetric Organocatalytic Efficiency of Synthesized Chiral β-Amino Alcohols in Ring-Opening of Glycidol with Phenols

A series of novel chiral β-amino alcohols 3–5 and 7–10 were synthesized by regioselective ring opening of epoxides and chiral amines with a straightforward method in high yields (up to 99 %). Kinetic resolution of racemic glycidol with phenols was achieved by using chiral amino alcohols as organocatalysts. Amino alcohols 5, 8 and 10 exhibited the highest enantioselectivities with p-cresol, phenol, and p-methoxyphenol by 63, 65, 58 % ee, respectively. The moderate enantioselectivities were observed with catalyst 9b towards all the nucleophiles (34–48 % ee). The ee values of the desired 3-aryloxy-1,2-diols were determined by HPLC. This study presents an attractive tool for the synthesis of β-blockers and structurally complex molecules.

Chiral β-Amino Alcohols as Ligands for the Ruthenium-Catalyzed Asymmetric Transfer Hydrogenation of N-Phosphinyl Ketimines

Some chiral β-amino alcohols have been evaluated as potential ligands for the ruthenium-catalyzed asymmetric transfer hydrogenation (ATH) of N-phosphinyl ketimines in isopropyl alcohol. The ruthenium complex prepared from [RuCl2(p-cymene)]2 and (1S,2R)-1-amino-2-indanol has shown to be an efficient catalyst for the ATH of several N-(diphenylphosphinyl)imines, affording the reduction products in very good isolated yields and enantiomeric excesses up to 82%. The inherent rigidity of the indane ring system present in the ligand seems to be very important to achieve good enantioselectivities.

Iron(II)-catalyzed enantioselective meso-epoxide-opening with anilines

A highly enantioselective method for the catalytic opening of aromatic meso-epoxides with aniline derivatives was developed. The desired chiral β-amino alcohols were obtained in mostly good to very good yields with excellent enantioselectivities. Structural evidence of the pre-catalyst revealed a scarcely disclosed heptadentate Fe(II) complex with the chiral bipyridine ligand.

A reversal phenomenon of enantioface selectivity by the cooperative operation of two chiral catalysts

The reversal phenomenon of enantioface selectivity in the asymmetric addition of diisopropylzinc to aldehydes was observed by mixing two chiral β-amino alcohol catalysts. The opposite enantiomeric product was formed on using a mixture of two chiral catalysts that possess individual enantioselectivity.

ChemInform Abstract: A Facile Synthesis of Chiral N-Protected β-Amino Alcohols.

Abstract Chiral N-protected β-amino alcohols are easily obtained by NaBH 4 reduction of mixed anhydrides of N-protected α-amino acids in an organic/aqueous medium. The alcohols obtained from side chain or main chain reduction of N-protected aspartic acid are converted in good yields into lactones.

ChemInform Abstract: Enantioselective Catalytic Borane Reductions of Achiral Ketones: Syntheses and Application of Two Chiral β-Amino Alcohols from (S)- 2-Indoline Carboxylic Acid.

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ChemInform Abstract: Enantioselective Catalytic Borane Reductions of Achiral Ketones: Synthesis and Application of New Chiral β-Amino Alcohols from L- Methionine.

Abstract The in situ formed chiral oxazaborolidine catalysts from optically active β-amino alcohols 1-3 from L-methionine ethyl carboxylate 4 have been used successfully in the enantioselective catalytic homogenous borane reductions of various aromatic ketones. The corresponding optically active alcohols are obtained in high optical purity (up to 100% ee ).

ChemInform Abstract: Asymmetric Synthesis of Amines by the Reductive Amination of Ketones Using (+)- and (-)-Norephedrine Followed by Periodate Oxidation.

A new route for the synthesis of aralkyl primary amines is reported, where the commercially available (+) or (−) norephedrine is condensed with aralkyl ketones followed by hydrogenation of the Schiff base using platinum catalyst. The chiral β-aminoalcohols thus obtained were oxidized by periodate to yield the aralkyl primary amines in 54–66% enantiomeric excess.

ChemInform Abstract: Synthesis of Chiral N-Protected β-Amino Alcohols by the Use of UNCAs.

Abstract A facile synthesis of a wide variety of N-protected β-amino alcohol derivatives under mild conditions is described. N-urethane protected amino acid N-carboxyanhydrides (UNCAs) were used as starting material and reduced into the corresponding alcohols with the appropriate hydride, sodium borohydride. The reaction is simple, unexpensive, easily scaled up, and proceeds without observable racemization.

A new C2-symmetric azolium compound for Cu-catalyzed asymmetric conjugate addition of R 2Zn to cyclic enone

A new chiral N-heterocyclic carbene (NHC) ligand was designed. Thus, an efficient synthetic route to C 2-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 Bu 2Zn at room temperature.

ChemInform Abstract: New Chiral Ligands Derived from (S)-Leucine for the Enantioselective Addition of Diethylzinc to Aldehydes.

Abstract A new series of chiral β-amino alcohols derived from ( S )-leucine has been synthesized. The amino alcohol possessing a piperidine ring and a phenethyl group on the carbinol carbon atom was found to be an efficient ligand to catalyze the enantioselective addition of diethylzinc to aromatic (up to 97% ee) and aliphatic (up to 95% ee) aldehydes.

ChemInform Abstract: Synthesis of Chiral, Non-racemic Aldols from Chiral β-Hydroxy-Weinreb Amides Prepared by Enantioselective Reformatsky-Like Reaction Induced by Chiral β-Aminoalcohols.

Abstract Chiral 1,2-aminoalcohols catalyze enantioselective Reformatsky addition of zinc derivatives of α-bromo Weinreb amides. Reaction of Grignard reagents with the resulting β-hydroxy N -methoxy- N -methyl amides allowed the preparation of β-hydroxy ketones regio- and enantioselectively.

Concise methods for the synthesis of chiral polyoxazolines and their application in asymmetric hydrosilylation

Seven polyoxazoline ligands were synthesized in high yield in a one-pot reaction by heating polycarboxylic acids or their esters and chiral β-amino alcohols under reflux with concomitant removal of water or the alcohol produced in the reaction. The method is much simpler and more efficient in comparison to those methods reported in the literature.The compounds were used as chiral ligands in the rhodium-catalyzed asymmetric hydrosilylation of aromatic ketones, and the effects of the linkers and the substituents present on the oxazoline rings on the yield and enantioselectivity investigated. Compound 2 was identified as the best ligand of this family for the hydrosilylation of aromatic ketones.