Reduction Of Carbonyl Compounds Research Articles

Cross-linked poly(diallyldimethylammonium chloride) as an efficient solid–liquid phase transfer catalyst in reduction of carbonyl compounds with sodium borohydride

Cross-linked poly(diallyldimethylammonium chloride) resin was synthesized as an efficient polymeric phase transfer catalyst. This quaternized polymer catalyzed the chemoselective reduction of aldehydes and ketones by NaBH 4 to give the corresponding alcohols in high yields under mild conditions.

Ni-mediated Liquid Phase Reduction of Carbonyl Compounds in the Presence of Atmospheric Hydrogen

Abstract An efficient reduction system of benzaldehyde with hydrogen under ambient pressure was developed using facile NiO catalyst. The non-aromatic solvents such as cyclohexane, tetrahydrofuran (THF) and n-hexane, and the additive with strong basicity e.g. KOH, were necessary for smooth conversion of the substrate. That the catalyst can be recovered and reused for nine times without loss of catalytic activity indicates that this catalyst is a recyclable one for benzaldehyde reduction.

酵素・微生物触媒反応を基盤とする有用物質合成への展開

This article describes our recent studies on enzyme-and microorganism-mediated reactions, and application to the preparation of useful compounds based on the complementary chemo-enzymatic synthesis. First, lipase-catalyzed reactions were focused especially on the preparation of enantiomerically pure compounds, such as N-Boc-indoline-2-carboxylic acid, indanoxazolidinone and symbioramide. Next, the control of nitrile-hydrolyzing enzyme in Rhodococcus rhodochrous was summarized. A one-pot chemo-enzymatic transformation of aldehydes to amides was established. The third topic is the application of yeast-mediated asymmetric reduction of carbonyl compounds. The preparation of a couple of enantiomerically pure starting materials for natural product synthesis by the combination with chemical transformation was disclosed.

Ruthenium hydroxide on magnetite as a magnetically separable heterogeneous catalyst for liquid-phase oxidation and reduction

Three kinds of reactions, (i) aerobic oxidation of alcohols, (ii) aerobic oxidation of amines, and (iii) reduction of carbonyl compounds to alcohols using 2-propanol as a hydrogen donor, could efficiently be promoted by an easily prepared ruthenium hydroxide catalyst on magnetite (Ru(OH)x/Fe3O4). A wide variety of substrates including aromatic, aliphatic, and heterocyclic ones could be converted to the desired products in high to excellent yields without any additives such as bases and electron transfer mediators. After the reaction, the catalyst/product(s) separation could be easily achieved with a permanent magnet and more than 99% of Ru(OH)x/Fe3O4 catalyst could usually be recovered for each reaction. The catalysis for these reactions was intrinsically heterogeneous, and Ru(OH)x/Fe3O4 recovered after these reactions could be reused without appreciable loss of the catalytic performance.

Fast and efficient method for reduction of carbonyl compounds with NaBH4 /wet SiO2 under solvent free condition

Reduction of structurally different carbonyl compounds such as aldehydes, ketones, alpha,beta-unsaturated enals and enones, alpha-diketones and acyloins were accomplished efficiently by sodium borohydride in the presence of wet SiO2 (30% m/m) under solvent free condition. The reactions were performed at room temperature or 75-80 ºC with high to excellent yields of the corresponding products. The chemoselective reduction of aldehydes over ketones was achieved successfully with this reducing system.

Water as a Green Solvent for Fast and Efficient Reduction of Carbonyl Compounds with NaBH4under Microwave Irradiation

Reduction of varieties of carbonyl compounds such as aldehydes, ketones, α,β-unsaturated aldehydes and ketones, α-diketones and acyloins was carried out very fast and efficiently by sodium borohydride in water under microwave irradiation. The corresponding product alcohols were obtained in high to excellent yields.

Synthetic Scope and Mechanistic Studies of Ru(OH)x/Al2O3‐Catalyzed Heterogeneous Hydrogen‐Transfer Reactions

Three kinds of hydrogen-transfer reactions, namely racemization of chiral secondary alcohols, reduction of carbonyl compounds to alcohols using 2-propanol as a hydrogen donor, and isomerization of allylic alcohols to saturated ketones, are efficiently promoted by the easily prepared and inexpensive supported ruthenium catalyst Ru(OH)x/Al2O3. A wide variety of substrates, such as aromatic, aliphatic, and heterocyclic alcohols or carbonyl compounds, can be converted into the desired products, under anaerobic conditions, in moderate to excellent yields and without the need for additives such as bases. A larger scale, solvent-free reaction is also demonstrated: the isomerization of 1-octen-3-ol with a substrate/catalyst ratio of 20,000/1 shows a very high turnover frequency (TOF) of 18,400 h(-1), with a turnover number (TON) that reaches 17,200. The catalysis for these reactions is intrinsically heterogeneous in nature, and the Ru(OH)x/Al2O3 recovered after the reactions can be reused without appreciable loss of catalytic performance. The reaction mechanism of the present Ru(OH)x/Al2O3-catalyzed hydrogen-transfer reactions were examined with monodeuterated substrates. After the racemization of (S)-1-deuterio-1-phenylethanol in the presence of acetophenone was complete, the deuterium content at the alpha-position of the corresponding racemic alcohol was 91%, whereas no deuterium was incorporated into the alpha-position during the racemization of (S)-1-phenylethanol-OD. These results show that direct carbon-to-carbon hydrogen transfer occurs via a metal monohydride for the racemization of chiral secondary alcohols and reduction of carbonyl compounds to alcohols. For the isomerization, the alpha-deuterium of 3-deuterio-1-octen-3-ol was selectively relocated at the beta-position of the corresponding ketones (99% D at the beta-position), suggesting the involvement of a 1,4-addition of ruthenium monohydride species to the alpha,beta-unsaturated ketone intermediate. The ruthenium monohydride species and the alpha,beta-unsaturated ketone would be formed through alcoholate formation/beta-elimination. Kinetic studies and kinetic isotope effects show that the Ru-H bond cleavage (hydride transfer) is included in the rate-determining step.

Aromatic Carbonyl Compound Reduction and Pinacol Coupling Processes Mediated by Titanocene(III)/Zn in Water

A novel procedure for the reduction and pinacol coupling of aromatic aldehydes and ketones mediated by titanocene(III)/Zn in water is described. The titanocene-catalyzed version in sea water proved to be especially convenient for the reduction of aryl ketones. Mechanistically, the reaction presumably proceeds via free-radical chemistry.

NaBH4/NaHSO4×H2O, a Heterogeneous Acidic System for a Mild and Convenient Reduction of Carbonyl Compounds under Protic Condition.

NaBH 4 in the presence of sodium bisulfate (NaHSO 4 .H 2 O), a weakly acidic reagent, efficiently reduces a variety of carbonyl compounds such as aldehydes, ketones, a, β-unsaturated aldehydes and ketones, α-diketones and acyloins to their corresponding alcohols in acetonitrile under heterogeneous condition. Reduction reactions were accomplished at room temperature or under reflux condition.

X-ray Structures of NADPH-dependent Carbonyl Reductase from Sporobolomyces salmonicolor Provide Insights into Stereoselective Reductions of Carbonyl Compounds

The X-ray structures of red yeast Sporobolomyces salmonicolor carbonyl reductase (SSCR) and its complex with a coenzyme, NADPH, have been determined at a resolution of 1.8A and 1.6A, respectively. SSCR was crystallized in an orthorhombic system with the space group P2(1)2(1)2(1) and cell dimensions of a=54.86 A, b=83.49 A, and c=148.72 A. On its cocrystallization with NADPH, isomorphous crystals of the SSCR/NADPH complex were obtained. The structure of SSCR was solved by a single wavelength anomalous diffraction measurement using a selenomethionine-substituted enzyme, and that of the SSCR/NADPH complex was solved by a molecular replacement method using the solved structure of SSCR. The structures of SSCR and the SSCR/NADPH complex were refined to an R-factor of 0.193 (R(free)=0.233) and 0.211 (R(free)=0.238), respectively. SSCR has two domains, an NADPH-binding domain and a substrate-binding domain, and belongs to the short-chain dehydrogenases/reductases family. The structure of the NADPH-binding domain and the interaction between the enzyme and NADPH are very similar to those found in other structure-solved enzymes belonging to the short-chain dehydrogenases/reductases family, while the structure of the substrate-binding domain is unique. SSCR has stereoselectivity in its catalytic reaction, giving rise to excessive production of (S)-alcohols from ethyl 4-chloro-3-oxobutanoate. The X-ray structure of the SSCR/NADPH complex and preliminary modeling show that the formation of the hydrophobic channel induced by the binding of NADPH is closely related to the stereoselective reduction by SSCR.

Reaction Profiles and Substituent Effects for the Reduction of Carbonyl Compounds with Monomer and Dimer Simple Metal Hydride Reagents

Reaction profiles and energetics for the reactions of substituted benzaldehydes with a series of different simple metal hydrides (BH(3), BMeH(2), BMe(2)H, AlH(3), and AlMe(2)H) are examined computationally. B3LYP/6-31G optimizations and MP2/6-311G single point energy calculations revealed that the Al reagents are more reactive than B reagents. Replacement of H with Me on BH(3) or AlH(3) makes the reduction transition state (TS) less stable. Accordingly the overall reactivity is in the order AlH(3) > AlMe(2)H > BH(3) > BMe(2)H. The Hammett rho value for substituted benzaldehydes (BAs) is negative for the initial complex formation and positive for the hydride-transfer step. The size and the sign of the apparent rho value depend on the relative stabilities of the separated reactants and the complex. The TS structures vary according to the Hammond postulate for substituted BAs and the variation is reflected in carbonyl-carbon and aldehyde-deuterium isotope effects. Comparison of the reaction profiles of the monomer and dimer reagents reveals that the real reacting species is the monomer in the gas phase for BH(3) but the dimer for BMe(2)H.

Wet THF as a Suitable Solvent for a Mild and Convenient Reduction of Carbonyl Compounds with NaBH4.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Selective Reduction of Carbonyl Compounds with B‐Phenoxydiisopinocampheylborane: Comparison of Its Reactivity to the Cyclohexoxy Derivative.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of Pinacols Through Electrochemical Reduction of Carbonyl Compounds at Platinum Cathode in Non‐aqueous Weakly Acidic Medium.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Selective Reduction of the Nitro‐Group Using Co2(CO)8—H2O.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Wet THF as a Suitable Solvent for a Mild and Convenient Reduction of Carbonyl Compounds with NaBH4

Abstract NaBH4 in wet THF can readily reduce varieties of carbonyl compounds such as aldehydes, ketones, conjugated enones, acyloins, and α-diketones to their corresponding alcohols in good to excellent yields. Reduction reactions were performed at room temperature or under reflux condition. In addition, the chemoselective reduction of aldehydes over ketones was accomplished successfully with this reducing system.

Reduction of Carbonyl Compounds with Polyethylsiloxane in the Presence of Titanium Compounds.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Selective Reduction of Carbonyl Compounds with B-Phenoxydiisopinocampheylborane: Comparison of Its Reactivity to the Cyclohexoxy Derivative

In the previous communication, we reported that Bcyclohexoxydiisopinocampheylborane, a new alicyclic derivative of diisopinocampheylborane, is one of the mildest reducing agents, which can reduce only an aldehyde function among the reducible general organic functionalities. The reagent readily reduces a variety of aldehydes at room temperature, but very slowly at 0 C. It is evident that the reduction proceeds via a cyclic boatilike transition state being considered as a Meerwein-Ponndorf-Verley (MPV) type reaction. In the mechanistic point of view, the key step of such reactions must be the coordination of boron atom of reagent to the carbonyl oxygen of substrate. We believe that the reactivity of diisopino-campheylborane derivatives correlates to their Lewis acidity and steric requirement: stronger the coordination, faster the reduction rate. Accordingly, we decided to examine the reducing characteristics of Bphenoxydiisopinocampheylborane (Ipc2BOPh), an aromatic derivative, and compare its reactivity to that of the cyclohexoxy derivative (Ipc2BOChex), in hopes of better understanding the nature of reagent and exploring its role in organic synthesis.

Selective Reduction of the Nitro-group Using Co2(CO)8-H2O

Recently, we reported a new reducing agent prepared from Co2(CO)8 and H2O for the selective 1,4-reduction of α ,βunsaturated carbonyl compounds 1 as well as a tandem reductive Pauson-Khand reaction. 2 We became interested in the reduction power especially the reactivity and the selectivity of this new reducing agent in reducing other functional groups. Reduction of aromatic nitro compounds to amines is a very useful synthetic transformation for which a vast array of reagents has been developed. 3 Though the most general methodology for this conversion is catalytic hydrogenation 4 as it is an economical and effective method, particularly in large scale reactions, the reaction has a limited utility in the presence of other reducible functional groups. 5 The selective reduction of nitro group in presence of other reducible functional groups were also achieved using metal based reduction systems. 6 However, the selective reduction of the nitro group in presence of carbonyl group could not easily be attainable under these conditions. Therefore we became interested in a possibility of the selective reduction of nitro groups in presence of other reducible functional groups including carbonyl groups and halides. Herein, we report that various nitro compounds are selectively and readily reduced to their corresponding amino derivatives in presence of other functional groups. The reaction was tested on p-chloronitrobenzene with the reaction conditions used in the previous report of unsaturated carbonyl compound reduction. 1 Since the nitro group requires more reducing agent than unsaturated carbonyl groups, 2 equivalent of Co 2(CO)8 was used for the reaction with the corresponding amount of water. Dimethoxyethane (DME) was used as the solvent since DME was the optimal solvent for the reduction of the unsaturated carbonyl compounds. To our delight, the reaction completed in 30 minutes and the reaction mixture contained only the desired aniline compound without any trace of other byproducts. When a less amount than 2 equivalent of Co2(CO)8 was used, the reduction was not complete. Then, the reaction was applied to aromatic nitro

Enantioselective reduction of carbonyl compounds by whole-cell biotransformation, combining a formate dehydrogenase and a (R)-specific alcohol dehydrogenase

A whole-cell biotransformation system for the reduction of prochiral carbonyl compounds, such as methyl acetoacetate, to chiral hydroxy acid derivatives [methyl (R)-3-hydroxy butanoate] was developed in Escherichia coli by construction of a recombinant oxidation/reduction cycle. Alcohol dehydrogenase from Lactobacillus brevis catalyzes a highly regioselective and enantioselective reduction of several ketones or keto acid derivatives to chiral alcohols or hydroxy acid esters. The adh gene encoding for the alcohol dehydrogenase of L. brevis was expressed in E. coli. As expected, whole cells of the recombinant strain produced only low quantities of methyl (R)-3-hydroxy butanoate from the substrate methyl acetoacetate. Therefore, the fdh gene from Mycobacterium vaccae N10, encoding NAD+-dependent formate dehydrogenase, was functionally coexpressed. The resulting two-fold recombinant strain exhibited an in vitro catalytic alcohol dehydrogenase activity of 6.5 units mg-1 protein in reducing methyl acetoacetate to methyl (R)-3-hydroxy butanoate with NADPH as the cofactor and 0.7 units mg-1 protein with NADH. The in vitro formate dehydrogenase activity was 1.3 units mg-1 protein. Whole resting cells of this strain catalyzed the formation of 40 mM methyl (R)-3-hydroxy butanoate from methyl acetoacetate. The product yield was 100 mol% at a productivity of 200 micromol g-1 (cell dry weight) min-1. In the presence of formate, the intracellular [NADH]/[NAD+] ratio of the cells increased seven-fold. Thus, the functional overexpression of alcohol dehydrogenase in the presence of formate dehydrogenase was sufficient to enable and sustain the desired reduction reaction via the relatively low specific activity of alcohol dehydrogenase with NADH, instead of NADPH, as a cofactor.