Enantioselective Reduction Of Ketones Research Articles

A genomic search approach to identify carbonyl reductases in Gluconobacter oxydans for enantioselective reduction of ketones

The versatile carbonyl reductases from Gluconobacter oxydans in the enantioselective reduction of ketones to the corresponding alcohols were exploited by genome search approach. All purified enzymes showed activities toward the tested ketoesters with different activities. In the reduction of 4-phenyl-2-butanone with in situ NAD(P)H regeneration system, (S)-alcohol was obtained with an e.e. of up to 100% catalyzed by Gox0644. Under the same experimental condition, all enzymes catalyzed ethyl 4-chloroacetoacetate to give chiral products with an excellent e.e. of up to 99%, except Gox0644. Gox2036 had a strict requirement for NADH as the cofactor and showed excellent enantiospecificity in the synthesis of ethyl (R)-4-chloro-3-hydroxybutanoate. For the reduction of ethyl 2-oxo-4-phenylbutyrate, excellent e.e. (>99%) and high conversion (93.1%) were obtained by Gox0525, whereas the other enzymes showed relatively lower e.e. and conversions. Among them, Gox2036 and Gox0525 showed potentials in the synthesis of chiral alcohols as useful biocatalysts.

Enantioselective Reduction of Prochiral Ketones with NaBH4/Me2SO4/(S)-Me-CBS

The enantioselective reduction of prochiral ketones with NaBH4/Me2SO4/(S)-Me-CBS is described. Borane is generated in situ via the reaction of NaBH4 with Me2SO4 in tetrahydrofuran, which is as efficient as the commercial one. Such in situ–generated borane reagent was applied to reduce prochiral ketones in the presence of chiral oxazaborolidine catalyst directly. The corresponding chiral secondary alcohols were obtained with excellent enantiomeric excesses (93–99% ee) and good to excellent yield (80–99%).

Whole‐Cell Biocatalysis in Deep‐Eutectic‐Solvents/Aqueous Mixtures

AbstractWhole‐cell biocatalysis with the use of baker’s yeast is demonstrated in different mixtures of water with deep eutectic solvents (DESs; choline chloride/glycerol, 1:2 mol/mol). Enantioselective ketone reduction is observed for long reaction times (>200 h), which suggests that the whole cells remain stable in these neoteric solvents. By changing the proportion of the DES added, a complete inversion of enantioselectivity is observed, from approximately 95 % enantiomeric excess (ee) (S) in pure water to approximately 95 % ee (R) in the pure DES. Presumably, some (S)‐oxidoreductases present in baker’s yeast are inhibited by DESs.

β‐Hydroxyamide‐Based Ligands and Their Use in the Enantioselective Borane Reduction of Prochiral Ketones

Hydroxyamide-based ligands have occupied a considerable place in asymmetric synthesis. Here we report the synthesis of seven β-hydroxyamide-based ligands from the reaction of 2-hydroxynicotinic acid with chiral amino alcohols and test their effect on the enantioselective reduction of aromatic prochiral ketones with borane in tetrahydofuran (THF). They produce the corresponding secondary alcohols with up to 76% enantiomeric excess (ee) and good to excellent yields (86-99%).

ChemInform Abstract: Facile Access to Chiral Alcohols with Pharmaceutical Relevance Using a Ketoreductase Newly Mined from Pichia guilliermondii.

AbstractThe enantioselective reduction of ketones and 3‐keto esters is presented employing a newly mined carbonyl reductase from P.

Reusable Cobalt(III) Complex Catalysts for Enantioselective Borohydride Reduction of Ketones

Abstract A reusable catalytic system was developed for the catalytic enantioselective borohydride reduction of ketones. The optically active 1-chlorovinylketoiminatocobalt(III) complexes were recovered after the reaction by silica gel column chromatography, and then efficiently catalyzed the enantioselective reduction several times without any loss of reactivity as well as enantioselectivity.

β-Hydroxyamide derivatives of salicylic acid as organocatalysts for enantioselective reductions of prochiral ketones

In order to find the most effective catalyst for the enantioselective reduction of a prochiral ketone, a series of novel β-hydroxyamide derivatives of salicylic acid and chiral amino alcohols were synthesized. Different substituted prochiral ketones have been reduced in high yield (up to 99%) and the corresponding secondary alcohols are formed with good enantiomeric excess (up to 86%). The mechanism of this type of catalyst can be explained by considering the reaction mechanism for the CBS catalyst.

Improved Synthesis of the C16–C20 Segment of Resolvin E1 Using Enantioselective Ketone Reduction and Lipase-Catalyzed Resolution

A practical synthesis targeting the C16–C20 segment of the endogenous metabolite Resolvin E1 (RvE1) is described. The original route was revised to avoid the use of source-constrained raw materials and chemistries that were problematic on larger scale. The revised route utilizes commercially available (E)-1-chloropent-1-en-3-one as the key raw material to replace (S)-glycidol. The (E)-vinyl iodide functionality was installed by an addition/elimination sequence to prepare the segment required for a subsequent Sonogashira coupling. The chiral secondary hydroxyl group at C18 was established by Corey–Bakshi–Shibata (CBS) reduction followed by lipase-catalyzed acetylation to achieve chiral purity in excess of 98% ee. The revised route offered a viable multikilogram process to support early clinical production of this pro-resolution therapeutic agent.

ChemInform Abstract: Enantioselective Borohydride Reduction of Aliphatic Ketones Catalyzed by Ketoiminatocobalt(III) Complex with 1‐Chlorovinyl Axial Ligand.

AbstractNewly designed chiral cobalt(III) complexes, e.g. (I), are applied to the enantioselective borohydride reduction of aliphatic ketones using 1,1,1‐trichloroethane to generate the corresponding 1‐chlorovinyl cobalt(III) derivatives as reactive intermediate.

Trichloromethyl ketones: asymmetric transfer hydrogenation and subsequent Jocic-type reactions with amines

Amino-amides are important pharmaceutical building-blocks. The enantioselective reduction of trichloromethyl ketones using ruthenium transfer hydrogenation catalysts is reported. The products react in a range of Jocic-type reactions to give enantiomerically enriched amino-amides.

Synthesis of chiral 2-(anilinophenylmethyl)pyrrolidines and 2-(anilinodiphenylmethyl)pyrrolidine and their application to enantioselective borane reduction of prochiral ketones as chiral catalysts

Chiral diamines, 2-(anilinophenylmethyl)pyrrolidines and 2-(anilinodiphenylmethyl)pyrrolidine, were prepared from N-(tert-butoxycarbonyl)pyrrolidine or (S)-proline as a starting material, respectively. These chiral diamines were efficient for the catalytic enantioselective borane reduction of acetophenone. Using (S)-2-(anilinodiphenylmethyl)pyrrolidine, chiral secondary alcohols were obtained from prochiral ketones with good to excellent enantiomeric excesses (up to 98% ee).

Application of microorganisms towards synthesis of chiral terpenoid derivatives.

Biotransformations are a standard tool of green chemistry and thus are following the rules of sustainable development. In this article, we describe the most common types of reactions conducted by microorganisms applied towards synthesis of chiral terpenoid derivatives. Potential applications of obtained products in various areas of industry and agriculture are shown. We also describe biological activity of presented compounds. Stereoselective hydroxylation, epoxidation, Baeyer–Villiger oxidation, stereo- and enantioselective reduction of ketones, and various kinetic resolutions carried out by bacteria and fungi have been reviewed. Mechanistic considerations regarding chemical and enzymatic reactions are presented. We also briefly describe modern approaches towards enhancing desired enzymatic activity in order to apply modified biocatalysts as an efficient tool and green alternative to chemical catalysts used in industry.

Structure Determination of the Cobalt(III) Complex Catalyst for Enantioselective Borohydride Reduction

Abstract The structure of the reactive cobalt complex catalyst for the enantioselective borohydride reduction of ketones was completely determined by ESI-MS, NMR, and X-ray analyses. It was confirmed that as an axial ligand, 1-chlorovinyl group derived from 1,1,1-trichloroethane was attached. Based on the X-ray analysis, two rotamers on cobalt–carbon bond were found in one unit. The obtained 1-chlorovinylcobalt(III) complex was examined for the enantioselective reduction to afford the reduced product in high yield with a high enantioselectivity.

Enantioselective Borohydride Reduction of Aliphatic Ketones Catalyzed by Ketoiminatocobalt(III) Complex with 1-Chlorovinyl Axial Ligand

Abstract For the enantioselective borohydride reduction of aliphatic ketones, the optically active ketoiminatocobalt(II) catalysts was successfully designed based on their axial ligand. Instead of chloroform for the aryl ketone reduction, various axial ligand precursors were examined for the aliphatic ketone. Consequently, 1,1,1-trichloroethane was found to be the most effective activator of the cobalt(II) complexes to generate the corresponding 1-chlorovinyl cobalt(III) derivatives as the reactive intermediate. Several aliphatic ketones were successfully reduced to afford the corresponding secondary alcohols with high enantioselectivities.

ChemInform Abstract: Iron‐Catalyzed Highly Enantioselective Reduction of Aromatic Ketones with Chiral P2N4‐Type Macrocycles.

AbstractThe catalytic system in situ generated from the iron carbonyl complex and chiral 22‐membered tetraazadiphospha‐macrocycle PAC exhibits high activity and excellent enantioselectivity in the transfer hydrogenation of various aromatic ketones.

ChemInform Abstract: Asymmetric Reduction of Ketones by Phosphoric Acid Derived Catalysts.

AbstractCatalytic systems involving a BINOL‐derived phosphoric acid are developed for the enantioselective reduction of aryl alkyl ketones with catecholborane.

Iron‐Catalyzed Highly Enantioselective Reduction of Aromatic Ketones with Chiral P2N4‐Type Macrocycles

AbstractNovel P2N4‐donors containing chiral 22‐membered macrocyclic ligands have been synthesized and the structures have been determined by an X‐ray diffraction study. The catalytic systems in situ generated from triiron dodecarbonyl, Fe3(CO)12, and the chiral macrocyclic ligand exhibited high activity (TOF up to 1940 h−1) and excellent enantioselectivity with up to 99% ee in the asymmetric transfer hydrogenation of various aromatic ketones.

Catalyst development for organocatalytic hydrosilylation of aromatic ketones and ketimines

A new family of Lewis basic 2-pyridyl oxazolines have been developed, which can act as efficient organocatalysts for the enantioselective reduction of prochiral aromatic ketones and ketimines with trichlorosilane, a readily available and inexpensive reagent. 1-Isoquinolyl oxazoline, derived from mandelic acid, was identified as the most efficient catalyst of the series, capable of delivering high enantioselectivities in the reduction of both ketones (up to 94% ee) and ketimines (up to 89% ee).

ChemInform Abstract: Effect of Substituents on Enantioselectivity in Chiral Oxazaborolidine Mediated Asymmetric Ketone Reduction Reaction.

AbstractThe chiral amine synthesized from L‐valine methyl ester and 5‐chloro salicylaldehyde proves as good catalyst for the enantioselective oxazaborolidine reduction of prochiral ketones.

Asymmetric Reduction of Ketones by Phosphoric Acid Derived Catalysts

Enantioenriched secondary alcohols represent an important class of molecules found in numerous intermediates, chiral building blocks, and biologically active compounds. Asymmetric reduction of prochiral ketones constitutes the most straightforward way to form these important moieties. Traditionally, stoichiometric amounts of chiral ligands were used together with an aluminium or a boron hydride to achieve high levels of enantioselectivity. Various catalytic processes have been developed in the past three decades in an effort to eliminate the use of stoichiometric amounts of chiral regents. The Corey–Bakshi–Shibata (CBS) catalyst and Noyori s ruthenium catalyst represent two of the most wellknown methods for this purpose. Both catalytic systems have been further developed by altering the ligand or by employing different metals in efforts to enhance the selectivity or improve practicality. Despite extensive research, the utilization of simple chiral Bronsted acids as precatalysts for this asymmetric process is still unknown. Chiral phosphoric acids have emerged as highly efficient and selective catalysts for a variety of transformations since their first reports, through independent studies by Akiyama and Terada. Early publications using these catalysts relied on the activation of imine electrophiles. Recently, additional discoveries have shown an ability for these catalysts to activate vinyl ether, aziridines, nitroso compounds, enones, and glyoxylates. However, general carbonyl compounds, like ketones, have not been used as substrates in the presence of chiral phosphoric acid. Recently, our group reported the first highly enantioselective allylboration of aldehydes catalyzed by a chiral phosphoric acid. Protonation of the boronate oxygen by the catalyst was proposed to rationalize both the activation and the enantioselectivity. The broadening of the limited scope of this type of activation is highly desired. Herein, we describe, to the best of our knowledge, the first example of highly enantioselective reduction of ketones catalyzed by a chiral phosphoric acid derivative. However, this chemistry is believed to differ mechanistically in comparison to our previous allyboration. The formation of a new phosphoryl catechol boronate is proposed based on preliminary spectroscopic evidence. The phosphoryl borate formed in situ is believed to act as a novel chiral bifunctional catalytic system. The reduction of acetophenone (1a) with catecholborane was chosen as the starting point for optimization of the reaction conditions. A series of binol-derived phosphoric acids were screened in toluene at room temperature in the presence of 5 molecular sieves (Table 1, entries 1–6). Catalyst P3, with a 9-anthryl group in the 3,3’-position of binol, provided the product with the highest enantioselectivity (Table 1, entry 3). Chiral N-triflyl phosphoramide P7, which is a stronger Bronsted acid than its phosphoric acid counterpart, provided the product with reverse absolute configuration and low ee (Table 1, entry 7). Further solvent