Asymmetric Reduction Of Acetophenone Research Articles

Optically Pure Calixarenyl Phosphine via Stereospecific Alkylation on Evans' Oxazolidinone Moiety.

A convenient protocol for the synthesis of 25,26,27-tribenzoyl-28-[((S)-1-diphenylphos- phanyl-propan-2-yl)oxy]-calix[4]arene via stereospecific methylation on Evans' oxazolidinone moiety was reported. According to the 13C NMR analysis of this phosphine, the calix[4]arene skeleton adopted a 1,3-alternate conformation. The latter conformation of the macrocycle and the (S)-chirality of the carbon atom bearing the methyl substituent were confirmed by a single-crystal X-ray diffraction study. After coordination of the phosphinated ligand to the dimeric [RuCl2(p-cymene)]2 organometallic precursor, the resulting arene-ruthenium complex was tested in the asymmetric reduction of acetophenone and alcohol was obtained with modest enantiomeric excess.

Enantioselective Synthesis of (S)-γ-Amino Alcohols by Ru/Rh/Ir Catalyzed Asymmetric Transfer Hydrogenation (ATH) with Tunable Chiral Tetraaza Ligands in Water

(R/S)-γ-Amino alcohols are the key intermediates for the preparation of Fluoxetine, Atomoxetine, Nisoxetine and Duloxetine. In this paper, we describe an effective method to obtain (S)-γ-amino alcohols by Ru/Rh/Ir catalyzed asymmetric transfer hydrogenation with tunable chiral tetraaza ligands (L1–L5) in HCOONa/H2O system. The asymmetric reduction of acetophenone with [Ru(p-cymene)Cl2]2/L1 was utilized as the model ATH reaction to achieve the optimum reaction conditions. The best results were obtained by [RhCp∗Cl2]2/L5 affording the corresponding (S)-γ-amino alcohol with a good 97% conversion and an excellent > 99% ee in the reduction of 3-(N-methyl, N-carbethoxy)-1-phenylpropan-1-one. The influence of electronic and steric effects of the substituents in the ligands on the catalytic activities was also discussed. (S)-γ-Amino alcohols were prepared via asymmetric transfer hydrogenation of β-amino ketones catalyzed by Ru/Rh/Ir complexes in situ with tunable chiral tetraaza ligands in HCOONa/H2O system. A moderate to excellent conversion (~ 99%) and enantioselectivity (~ 99%) were obtained with varied electronic and steric effects of the substituents on ligands and substrates.

Debaryomyces hansenii as a new biocatalyst in the asymmetric reduction of substituted acetophenones

Chiral secondary alcohols are convenient mediator for the synthesis of biologically active compounds and natural products. In this study fifteen yeast strains belonging to three food originated yeast species Debaryomyces hansenii, Saccharomyces cerevisiae and Hanseniaspora guilliermondii were tested for their capability for the asymmetric reduction of acetophenone to 1-phenylethanol as biocatalyst microorganisms. Of these strains, Debaryomyces hansenii P1 strain showed an effective asymmetric reduction ability. Under optimized conditions, substituted acetophenones were converted to the corresponding optically active secondary alcohols in up to 99% enantiomeric excess and at high conversion rates. This is the first report on the enantioselective reduction of acetophenone by D. hansenii P1 from pastırma, a fermented Turkish meat product. The preparative scale asymmetric bio reduction of 3-methoxy acetophenone 1g by D. hansenii P1 gave (R)-1-(3-methoxyphenyl) ethanol 2g 82% yield, and >99% enantiomeric excess. Compound 2g can be used for the synthesis of (+)-NPS-R-568 [3-(2-chlorophenyl)-N-[(1R)-1-(3-methoxyphenly) ethyl] propan-1-amine] which have a great potential for the treatment of primary and secondary hyper-parathyroidism. In addition, D. hansenii P1 successfully reduced acetophenone derivatives. This study showed that this yeast can be used industrially to produce enantiomerically pure chiral secondary alcohols, which can be easily converted to different functional groups.

Asymmetric reduction of acetophenone into R-(+)-1-phenylethanol by endophytic fungus Neofusicoccum parvum BYEF07 isolated from Illicium verum

Seventy-nine strains of endophytic fungi isolated from the healthy leaves, twigs and fruits of Illicium verum were screened for the asymmetric reduction activities to acetophenone. Strain BYEF07, which showed relatively high reduction activities, has been classified as Neofusicoccum parvum, and the main product was confirmed to be (R)-(+)-1-phenylethanol by GC–MS and chiral HPLC methods. The bio-reduction conditions of acetophenone by cells of N. parvum BYEF07 were investigated in detail. Under the conditions of 1.8 g/L of acetophenone, 100 g/L of microorganism cells and 10 g/L of glucose in 40 mL Na2HPO4 KH2PO4 buffer solution at pH7.5, 30 °C and 150 rpm, after 48 h reaction, the production yield of 1-phenylethanol and enantiomeric excess value of (R)-(+)-1-phenylethanol were 78% and 96%, respectively.

The Asymmetric Reduction of Acetophenone and Its Derivatives to (S)-Aromatic Secondary Alcohols by Rhodotorula mucilaginosa CCTCC M2014255 Resting Cells

Enantiomerically enriched aromatic secondary alcohols and its derivatives are important chiral intermediates utilized widely in pharmacy, chemical, hormone, spices and chiral auxiliary materials. Thus, the key factors affecting the asymmetric reduction were successfully analyzed using R. mucilaginosa CCTCC M2014255 resting cells. The optimal temperature, buffer pH, co-substrate and its concentration, resting cells concentration were systematically investigated. Under the optimized conditions, acetophenone and its derivatives were effectively asymmetrically reduced by R.mucilaginosa CCTCC M2014255 while the conversion reached >99.0 % and e.e. of product were >99.0 %, respectively. These results provide a theoretical and technical support for realizing industrialized production of enantiomerically enriched aromatic secondary alcohols by microbial catalytic asymmetric synthesis.

ChemInform Abstract: Ruthenium(II) Complexes Derived from C2‐Symmetric Ferrocene‐Based Chiral Bis(phosphinite) Ligands: Synthesis and Catalytic Activity Towards the Asymmetric Reduction of Acetophenones.

Chiral secondary alcohols are very important building blocks and valuable synthetic intermediates both in organic synthesis and in the pharmaceutical industry for producing biologically active complex molecules. A series of new chiral Ru–phosphinite complexes (1, 2, 3, 4, 5, 6, 7, 8) were prepared from chiral C2-symmetric ferrocenyl phosphinites and corresponding chloro complex, [Ru(η6-p-cymene)(μ-Cl)Cl]2. The complexes were characterized using conventional spectroscopic methods. The binuclear complexes were tested as pre-catalysts and were found to be good pre-catalysts for the asymmetric transfer hydrogenation of substituted acetophenones in basic 2-propanol at 82°C, providing the corresponding optically active alcohols with almost quantitative conversion and modest to high enantioselectivities (46–97%). Amongst the all complexes, complex 6 gave the highest ee of 97% in the reduction of 2-methoxyacetophenone to (S)-1-(2-methoxyphenyl)ethanol at 82°C. Copyright © 2015 John Wiley & Sons, Ltd.

Ruthenium(II) complexes derived from C2‐symmetric ferrocene‐based chiral bis(phosphinite) ligands: synthesis and catalytic activity towards the asymmetric reduction of acetophenones

Chiral secondary alcohols are very important building blocks and valuable synthetic intermediates both in organic synthesis and in the pharmaceutical industry for producing biologically active complex molecules. A series of new chiral Ru–phosphinite complexes (1, 2, 3, 4, 5, 6, 7, 8) were prepared from chiral C2‐symmetric ferrocenyl phosphinites and corresponding chloro complex, [Ru(η6‐p‐cymene)(μ‐Cl)Cl]2. The complexes were characterized using conventional spectroscopic methods. The binuclear complexes were tested as pre‐catalysts and were found to be good pre‐catalysts for the asymmetric transfer hydrogenation of substituted acetophenones in basic 2‐propanol at 82°C, providing the corresponding optically active alcohols with almost quantitative conversion and modest to high enantioselectivities (46–97%). Amongst the all complexes, complex 6 gave the highest ee of 97% in the reduction of 2‐methoxyacetophenone to (S)‐1‐(2‐methoxyphenyl)ethanol at 82°C. Copyright © 2015 John Wiley & Sons, Ltd.

ChemInform Abstract: Tethered Ru(II) Catalysts Containing a Ru—I Bond.

AbstractTwo new iodide‐containing derivatives of widely‐used Ru(II) (arene)(TosDPEN) catalysts are synthesized and evaluated in the asymmetric reduction of acetophenone under both transfer (ATH) and pressure hydrogenation (AH) conditions.

Interaction of β-cyclodextrin as catalyst with acetophenone in asymmetric reaction: a theoretical survey.

The asymmetric reduction of acetophenone with sodium borohydride in the presence of β-cyclodextrin (β-CD) as catalyst can improve selectivity and yield. The interaction between acetophenone and β-CD plays an important role for the reduction of acetophenone. This work studies the reaction of acetophenone in the presence of β-CD using density functional theory (DFT) method. Energy is investigated to find out the lowest energy of two possible complexation models. The geometrical structure confirms that acetophenone inserts into the cavity mainly from the secondary hydroxyl side. Hydrogen bonds are researched on the basis of natural bonding orbital (NBO) analysis, the results confirm the donor-acceptor interactions of complex. Mülliken charge and frontier orbital are employed for revealing the electronic transfer. In addition, (13)C nuclear magnetic resonance ((13)CNMR) spectroscopy shows that the active site concentrates on the carbon atom of carbonyl group. The probable catalytic mechanism of β-CD is discussed in terms of the calculated parameters.

A Photocatalyst/Enzyme Couple That Uses Solar Energy in the Asymmetric Reduction of Acetophenones

A Photocatalyst/Enzyme Couple That Uses Solar Energy in the Asymmetric Reduction of Acetophenones

A Photocatalyst/Enzyme Couple That Uses Solar Energy in the Asymmetric Reduction of Acetophenones

Sonnenanbeter: Ein gekoppeltes Photokatalysator-Enzym-System als neuartiges künstliches Photosynthesesystem sammelt Solarenergie nach dem Vorbild von Grünplanzen über eine Kombination aus Photo- und Biokatalyse und induziert Asymmetrie in einem achiralen Substrat (siehe Bild; ADPR=Adenosindiphosphatribose, NADP=Nicotinamidadenindinucleotidphosphat).

Borane‐mediated asymmetric reduction of acetophenone by enantiopure aminonaphthols and aminoalcohols as catalytic source

Practical, cheap, and stereoselective synthetic methods were applied to the preparation of novel 1-(aminoalkyl)naphthol and gamma-aminoalcohol tridentate ligands. The ligands obtained were conveniently applied with good results as catalytic sources in the borane-mediated enantioselective reduction of acetophenone with borane dimethylsulfide. Conformational analysis through molecular modeling allows the rationalization of observed stereochemical outcomes.

Asymmetric reduction of acetophenone using α,α-disubstituted aziridinemethanols and borane

A series of α,α-disubstituted aziridinemethanols have been designed and synthesized as chiral auxiliaries for the enantioselective reduction of acetophenone. Some of them catalyzed the reduction with excellent ee (up to 97%) under more facile reaction conditions. Furthermore, the results showed that α,α-disubstituted aziridinemethanols with electron-withdrawing groups led to much higher enantioselectivity than those with electron-donating groups, which allowed the rational modification of catalyst structure to achieve optimal enantioselectivity.

The Hydrogenation/Transfer Hydrogenation Network in Asymmetric Reduction of Ketones Catalyzed by [RuCl2(binap)(pica)] Complexes

Chiral binap/pica-Ru(II) complexes (binap=(S)- or (R)-2,2'-bis(diphenylphosphino)-1,1'-binaphthyl; pica=alpha-picolylamine) catalyze both asymmetric hydrogenation (AH) of ketones using H(2) and asymmetric transfer hydrogenation (ATH) using non-tertiary alcohols under basic conditions. The AH and ATH catalytic cycles are linked by the metal-ligand bifunctional mechanism. Asymmetric reduction of pinacolone is best achieved in ethanol containing the Ru catalyst and base under an H(2) atmosphere at ambient temperature, giving the chiral alcohol in 97-98 % ee. The reaction utilizes only H(2) as a hydride source with alcohol acting as a proton source. On the other hand, asymmetric reduction of acetophenone is attained with both H(2) (ambient temperature) and 2-propanol (>60 degrees C) with relatively low enantioselectivity. The degree of contribution of the AH and ATH cycles is highly dependent on the ketone substrates, solvent, and reaction parameters (H(2) pressure, temperature, basicity, substrate concentration, H/D difference, etc.).

Bicyclo[2.2.2]octane-derived chiral ligands—synthesis and application of BODOLs in the asymmetric reduction of acetophenone with catecholborane

An improved synthetic route to the bicyclo[2.2.2]octane-2,6-diol ligands (2,6-BODOLs) allowed an increased structural variation of the ligand side-arm. The addition of aromatic or vinylic Grignard reagents to hydroxyketone 1 was highly selective and ligands 3f– 3l were isolated in 84–97% yield. The addition of alkyl Grignard reagents containing β-hydrogens resulted in lower yields (13–71%) due to competing ketone reduction. A number of 2,5-BODOLs were synthesized using a similar methodology. The ligands, together with Ti(O iPr) 4, were tested in the asymmetric reduction of acetophenone with catecholborane (up to 98% ee). 1-Naphthyl-BODOL 3i was employed as an allylboration reagent to benzaldehyde together with Sc(OTf) 3, resulting in (1 S)-1-phenyl-3-buten-1-ol in 80% ee.

A complex process of the asymmetric reduction of prochiral aromatic ketone by yeast cell with the introduction of an organic solvent as the separation medium

AbstractEnantiomerically pure aromatic alcohols are important chiral building blocks for many single enantiomer pharmaceuticals. The asymmetric reduction of the corresponding prochiral ketone by active yeast cells is one of the most promising synthesis routes for chiral alcohols. But the space‐time productivity is low. To promote the reaction, a complex process of the asymmetric reduction reaction with the introduction of an organic solvent as a separation factor was studied in this work. The asymmetric reduction of acetophenone (ACP) to chiral α‐phenylethyl alcohol (PEA) by Saccharomyces cerevisiae was chosen as the model reaction. It was found that organic solvents with more than 3.5 of logP, such as n‐octane, were favorable for the asymmetric reduction reaction. The yield of the reaction could be remarkably promoted with this technique. The reaction could further be improved by adding ethanol as cosolvent. The initial ACP concentration could be as high as 60 mmol/l, which is about six times larger than that of reacting in a single aqueous phase. Copyright © 2008 Curtin University of Technology and John Wiley & Sons, Ltd.

Isolation of microbe for asymmetric reduction of prochiral aromatic ketone and its reaction characters

The favorable microbes for the asymmetric reduction of prochiral aromatic ketones was isolated from soil using acetophenone as the sole carbon source, when the asymmetric reduction of acetophenone (ACP) to chiral α-phenethyl alcohol (PEA) was chosen as the model reaction. Two microbe strains with excellent catalytic activity were obtained. They were Geotrichum candidum and Pichia pastoris identified by bacteria identification. The product of the asymmetric reduction of ACP catalyzed by Pichia pastoris was mainly R-PEA and that by Geotrichum candidum was mainly S-PEA. The yield and enantiomeric excesses (e.e.) could respectively reach 75% and 90% for Pichia pastoris, and 80% and 70% for Geotrichum candidum, much higher than those catalyzed by baker’s yeast.

Asymmetric Reduction of Acetophenones with NaBH4 in the Presence of Mono-6-(1-methyl-3-imidazolium)-6-deoxy-β-cyclodextrin Tosylate

The asymmetric reduction of acetophenone and its derivatives was achieved with sodium borohydride utilizing a novel chiral ionic liquid of β-cylclodextrin (CD), mono-6-(1-methyl-3-imidazolium)-6-deoxy-β-cyclodextrin tosylate (MIM-β-CDOTs). It was found that this chiral β-CD-based ionic liquid could provide higher enantioselectivity for the product alcohols. Moreover, the enantioselectivity of the product alcohols was highly dependent on the structure of prochiral ketones, structure of CD and reduction temperature.

Asymmetric Reduction of Acetophenones with NaBH4 in the Presence of Mono-6-(1-methyl-3-imidazolium)-6-deoxy-β-cyclodextrin tosylate

Asymmetric Reduction of Acetophenones with NaBH4 in the Presence of Mono-6-(1-methyl-3-imidazolium)-6-deoxy-β-cyclodextrin tosylate

Asymmetric reduction of acetophenone using lithium aluminium hydride modified with some novel amino alcohol Schiff bases

Some new chiral Schiff bases have been prepared in good yields from various carbonyl groups and two 2-amino alcohols. LiAlH 4 was treated with different equivalents of the Schiff bases. Enantioselective reduction of acetophenone is achieved in high chemical yield (up to 93%) with moderate enantiomeric excess (up to 22%) by use of the new reducing agents.