Chiral Secondary Alcohols Research Articles

Chiral secondary alcohol-induced asymmetric autocatalysis: correlation between the absolute configuration of the chiral initiators and the product

In the presence of various chiral secondary alcohols as chiral initiators, an enantioselective alkylation of a pyrimidine-5-carbaldehyde using diisopropylzinc was examined: a pyrimidyl alkanol was obtained in high yield and enantiomeric excess. The correlation between the absolute configuration of the chiral secondary alcohols and the pyrimidyl alkanol is discussed.

The origin of an unusually large 19F chemical shift difference between the diastereomeric α‐cyano‐α‐fluoro‐p‐tolylacetic acid (CFTA) esters of 3′,4′,5,7‐tetra‐O‐methylepicatechin

During a study on the relationship between the (19)F chemical shift difference for the diastereomeric alpha-cyano-alpha-fluoro-p-tolylacetic acid (CFTA) esters of chiral secondary alcohols and the absolute configurations of the alcohols, an unusually large 19F chemical shift difference has been observed for the CFTA esters of 3',4',5,7-tetra-O-methylepicatechin. This large chemical shift difference has been reproduced by ab initio calculations of molecular geometry and GIAO calculations of 19F chemical shifts on the stable conformations of the diastereomeric alpha-cyano-alpha-fluorophenylacetic acid (CFPA) esters of cis-flavan-3-ol as model systems. The origin of the large chemical shift difference has been further investigated using NBO analysis. This revealed that the interaction between pi(C=C) of the aryl group in the chiral auxiliary and sigma*(C--F) is a very important determinant of the 19F chemical shifts and this interaction depends on the torsion angle between the plane of aryl group and the C--F bond.

Asymmetric Hydrosilylation of Prochiral Ketones Catalyzed by Nanocrystalline Copper(II) Oxide

AbstractAsymmetric hydrosilylation of aryl alkyl ketones to afford chiral secondary alcohols with good yields and excellent enantioselectivity is realized by using nanocrystalline copper(II) oxide and BINAP in the presence of organosilanes as the stoichiometric reducing agents.

Biocatalytic reduction of a racemic selenocyclohexanone by Brazilian basidiomycetes

An efficient synthesis of the chiral cyclic secondary alcohols, trans-2-(phenylseleno)cyclohexanol 1a and cis-2-(phenylseleno)cyclohexanol 1a, was obtained by enzymatic reduction of 2-(phenylseleno)cyclohexanone 1 using whole fungal cells. Five strains of white-rot basidiomycetes were examined; Irpex lacteus CCB 196, Pycnoporus sanguineus CCB 196, Trametes rigida CCB 285, Trametes versicolor CCB 202 and Trichaptum byssogenum CCB 203. Cells of T. rigida CCB 285 gave alcohols cis-( RS)- 1a and trans-( SS)- 1a in high enantiomeric excesses (ca. 99%).

Oxidative kinetic resolution of racemic secondary alcohols catalyzed by recyclable chiral dimeric Mn(III) salen catalysts

The oxidative kinetic resolution of racemic secondary alcohols was efficiently catalyzed by chiral dimeric Mn(III) salen complexes using PhI(OAc) 2 as an oxidant in the presence of various additives in water/organic solvent mixture. Excellent ee (up to 99%) of chiral secondary alcohols was achieved in 0.5 h. The catalyst 1A was recovered easily and reused five times with retention of enantioselectivity.

Water-soluble chiral monosulfonamide-cyclohexane-1,2-diamine-RhCp ∗ complex and its application in the asymmetric transfer hydrogenation (ATH) of ketones

Monosulfonamide ligands with heteroatom/heterocyclic systems were derived from trans-(1 R,2 R)-cyclohexane-1,2-diamine and complexed with [Ru(benzene)Cl 2] 2, [Cp ∗RhCl 2] 2 in situ and used in the ATH of aromatic ketones with aqueous sodium formate as the hydrogen source. The chiral secondary alcohols were obtained with >93% enantioselectivity and >89% yield. Reduction in water was faster than in isopropanol/KOH. Addition of surfactants showed little or no effects.

Daucus carota and baker’s yeast mediated bio-reduction of prochiral ketones

Stereoselective reduction of prochiral ketones to the corresponding alcohols using biocatalysts has attracted much attention, from the viewpoint of green chemistry. Asymmetric reduction of indanone, tetralone and hydroxyl trimonoterpene ketones to the corresponding enantiomerically pure ( S)-alcohols, using Daucus carota plant homogenate and fermented baker’s yeast cells, is described. The present study illustrates the broad substrate selectivity of the dehydrogenase enzymes present in the D. carota in the synthesis of a wide range of chiral secondary alcohols of biological importance.

Synthesis of polymers containing chiral 1,2-diamine derivatives and their application to asymmetric reactions

Abstract Polymer-supported chiral 1,2-diamine derivatives have been prepared. The polymers containing free 1,2-diamine moiety were applied to enantioselective hydrogenation catalyst by combination with RuCl2-BINAP complex. Asymmetric hydrogenation of aromatic ketones was performed by means of the polymeric catalyst derived from these polymers to give the chiral secondary alcohols with high ee in quantitative conversion. The polymers containing 1,2-diamine monosulfonamide were applied to enantioselective transfer hydrogenation catalyst by combination with RuCl2-p-cymene complex. Asymmetric transfer hydrogenation of aromatic ketones was performed by means of the polymeric catalyst to afford the chiral secondary alcohols. A high level of enantioselectivities up to 99 % ee was attained in neat water by using the polymeric catalyst prepared from quaternary ammonium salt-type polymer support.

Enantioselective phenylacetylene addition to aldehydes and ketones catalyzed by recyclable polymeric Zn(salen) complex

New polymeric Zn(salen) complex was employed in the enantioselective phenylacetylene addition to aldehydes and ketones to produce corresponding chiral secondary propargylic alcohols with yields (up to 96%) and enantioselectivity (up to 72%) and tertiary propargylic alcohols with yields (up to 79%) and enantioselectivity (up to 68%) at room temperature, with added advantage of four times reuse with retention of enantioselectivity.

Enantioselective Dialkylzinc Addition to Aldehydes

Enantioselective dialkylzinc additions to aldehydes to generate chiral secondary alcohols are synthetically and pharmaceutically important intermediates. The authors describe the first example of conjugate acid-base catalysis which is argued to enhance catalytic activity.

New C 2-symmetric bis(sulfonamide)-cyclohexane-1,2-diamine-RhCp ∗ complex and its application in the asymmetric transfer hydrogenation (ATH) of ketones in water

C 2-symmetric bis(sulfonamide) ligands derived from trans-(1 R,2 R)-cyclohexane-1,2-diamine were synthesized and complexed with [Cp ∗RhCl 2] 2 in situ and used in the ATH of aromatic ketones with aqueous sodium formate as the hydrogen source. The chiral secondary alcohols were obtained with 90–99% enantioselectivity and in 50–100% yield. Reductions in water were faster than those in isopropanol/KOH.

新規絶対配置決定手段としてのCFTA法：19F NMRを用いるアルコールおよびアミン類の絶対配置決定への応用

新規絶対配置決定手段としてのCFTA法：19F NMRを用いるアルコールおよびアミン類の絶対配置決定への応用

Determination of the absolute configuration of chiral cyclic alcohols using diamine derivatizing agents by 31P NMR spectroscopy

The absolute configuration and enantiomeric excess of chiral cyclic alcohols can be predicted from the 31P NMR spectra of the two diastereoisomers obtained with organophosphorus diamino-derivatizing agents (CDAs) and the chiral secondary alcohol, according to a simplified model taking into account the spatial location of the substituents of the chiral alcohol center and the 31P NMR signals of the two diastereoisomers.

O-Methylatrolactic acid as a new reagent for determination of the enantiomeric purity and absolute configuration of chiral alcohols and amines

Easily available in both enantiomeric forms, O-methylatrolactic acid (MAA) was successfully used as a new chiral derivatizing agent. Enantiomeric purities and the absolute configurations of chiral secondary alcohols and amines were determined using the observed differences in 1H NMR chemical shifts. The Mosher’s stereochemical model explains the conformational preferences of the respective diastereomeric MAA esters and amides. This was confirmed by the results of DFT calculations for the respective conformers.

Pervaporative separation of ethanol from an alcohol—ester quaternary mixture

As part of a research project focusing on the development of a sustainable biocatalytic process for production of chiral secondary alcohols, the pervaporative separation of ethanol from ethanol/ethyl acetate/1-methoxy-2-propanol/1-methoxy-2-propyl acetate-mixtures through a commercial PVA-based membrane was investigated. Separation behavior of this mixture was studied in a range of mol fractions (10–70%), temperatures relevant for biocatalytic conversions (35–55 °C) and downstream pressures (35–200 mbar). Pervaporation of the non-diluted multicomponent mixture was shown to be strongly influenced by interactions between the permeants and the membrane. Investigation of these interactions contributed to the understanding of the mass transport mechanism of this mixture. Overall, high fluxes were obtained, but small differences between the fastest permeating species were found. The fastest permeating species was ethanol, ethyl acetate or 1-methoxy-2-propanol depending on the feed composition.

Catalytic asymmetric transfer hydrogenation of ketones using terpene-based chiral β-amino alcohols

Catalytic asymmetric transfer hydrogenations of aromatic alkyl ketones have been studied using [RuCl 2( p-cymeme)] 2 and terpene-based β-amino alcohols. The limonene derived amino alcohol, (1 S,2 S,4 R)-1-methyl-4-(1-methylethenyl)-2-(methylamino)cyclohexanol gave the most promising results. Chiral secondary alcohols were obtained in good to excellent yields and moderate enantioselectivities (up to 71%).

An Efficient Method for the Preparation of N-Alkylamides from Alkyl Diphenylphosphinites and Amides by Using Methyl Acrylate

Abstract N,N-Dibenzyltrifluoroacetamide was formed in good yield by treating benzyl diphenylphosphinite with N-benzyltrifluoroacetamide in the presence of easily available methyl acrylate under mild conditions. Yields obtained for the corresponding inverted sulfonamides were good to high in the cases when alkyl diphenylphosphinites derived from chiral secondary alcohols were used.

Biochemical profiling in silico—Predicting substrate specificities of large enzyme families

A general high-throughput method for in silico biochemical profiling of enzyme families has been developed based on covalent docking of potential substrates into the binding sites of target enzymes. The method has been tested by systematically docking transition state--analogous intermediates of 12 substrates into the binding sites of 20 alpha/beta hydrolases from 15 homologous families. To evaluate the effect of side chain orientations to the docking results, 137 crystal structures were included in the analysis. A good substrate must fulfil two criteria: it must bind in a productive geometry with four hydrogen bonds between the substrate and the catalytic histidine and the oxyanion hole, and a high affinity of the enzyme-substrate complex as predicted by a high docking score. The modelling results in general reproduce experimental data on substrate specificity and stereoselectivity: the differences in substrate specificity of cholinesterases toward acetyl- and butyrylcholine, the changes of activity of lipases and esterases upon the size of the acid moieties, activity of lipases and esterases toward tertiary alcohols, and the stereopreference of lipases and esterases toward chiral secondary alcohols. Rigidity of the docking procedure was the major reason for false positive and false negative predictions, as the geometry of the complex and docking score may sensitively depend on the orientation of individual side chains. Therefore, appropriate structures have to be identified. In silico biochemical profiling provides a time efficient and cost saving protocol for virtual screening to identify the potential substrates of the members of large enzyme family from a library of molecules.

Kinetic Resolution of Chiral Secondary Alcohols by Dehydrogenative Coupling with Recyclable Silicon‐Stereogenic Silanes.

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Kinetic Resolution of Chiral Secondary Alcohols by Dehydrogenative Coupling with Recyclable Silicon‐Stereogenic Silanes

Fishing for enantiomers: A novel kinetic resolution of racemic alcohols capable of two-point binding makes use of silanes with silicon-centered chirality. This strategy is based on a diastereoselective dehydrogenative silicon–oxygen coupling under copper catalysis (see scheme). The resolving silane is completely recovered without erosion of stereochemical information at silicon.