Reduction Of Carbonyl Compounds Research Articles

Counterintuitive chemoselectivity in the reduction of carbonyl compounds.

The reactivity of carbonyl functional groups largely depends on the substituents on the carbon atom. Reversal of the commonly accepted order of reactivity of different carbonyl compounds requires novel synthetic approaches. Achieving selective reduction will enable the transformation of carbon resources such as plastic waste, carbon dioxide and biomass into valuable chemicals. In this Review, we explore the reduction of less reactive carbonyl groups in the presence of those typically considered more reactive. We discuss reductions, including the controlled reduction of ureas, amides and esters to aldehydes, as well as chemoselective reductions of carbonyl groups, including the reduction of ureas over carbamates, amides and esters; the reduction of amides over esters, ketones and aldehydes; and the reduction of ketones over aldehydes.

Photoinduced catalytical reduction of carbonyl compounds using water as a hydrogen source

A photoinduced iridium-catalyzed PPh3/H2O system for the hydrogenation of carbonyl compounds has been developed, providing a sustainable method for the synthesis of primary alcohols, secondary alcohols, and secondary amines with high atom economy.

Strategic use of crude H2 for the catalytic reduction of carbonyl compounds

Toward a more efficient use of crude H2 without its energy-consuming purification and/or composition regulation processes, this study employs gaseous mixtures of H2, CO, CO2, and CH4 for the catalytic hydrogenation of aldehydes and ketones in the presence of strategically designed triarylboranes and 4-methyltetrahydropyrane as a greener ethereal solvent. The present results emphasize the unexplored utility of less-toxic main-group catalysis for the catalytic hydrogenation using CO- and CO2-rich crude H2. This stands in contrast to the well-established transition-metal catalysis that generally requires purified H2.

The Reduction of Carbonyl Compounds with Dicyclopentylzinc: A New Example of Asymmetric Amplifying Autocatalysis

A previously unknown reduction of carbonyl compounds with dicyclopentylzinc is reported. Aldehydes react in mild conditions yielding corresponding primary alcohols and cyclopentene. Although cyclohexanone and acetophenone are inert to dicyclopentylzinc, a variety of heterocyclic ketones reacted readily, yielding reasonable to high yields of corresponding secondary alcohols. When the reaction was catalyzed with (–)-(1R,2S)-ephedrine, 3-acetylpyridine (10) resulted in a high yield of (S)-1-(pyridin-3-yl)ethanol (19) with >99% ee. 5-Acetyl-2-bromopyridine (11) also provided the corresponding optically active alcohol 20, albeit with a much lower optical yield. When 10% of 19 with 92% ee was used as an autocatalyst, 55% yield of the same compound was obtained, with 95% ee and 96% ee in two independent experiments. A three-stage reaction sequence starting from “no chirality” reaction yielded 19 with 6% ee. Thus, amplifying autocatalysis was detected in the reaction of ketone 10 with dicylopentylzinc.

Geometrically Constrained Organoboron Species as Lewis Superacids and Organic Superbases.

This report unveils an advancement in the formation of a Lewis superacid (LSA) and an organic superbase by the geometrical deformation of an organoboron species towards a T-shaped geometry. The boron dication [2]2+ supported by an amido diphosphine pincer ligand features both a large fluoride ion affinity (FIA>SbF5 ) and hydride ion affinity (HIA>B(C6 F5 )3 ), which qualifies it as both a hard and soft LSA. The unusual Lewis acidic properties of [2]2+ are further showcased by its ability to abstract hydride and fluoride from Et3 SiH and AgSbF6 respectively, and effectively catalyze the hydrodefluorination, defluorination/arylation, as well as reduction of carbonyl compounds. One and two-electron reduction of [2]2+ affords stable boron radical cation [2]⋅+ and borylene 2, respectively. The former species has an extremely high spin density of 0.798e at the boron atom, whereas the latter compound has been demonstrated to be a strong organic base (calcd. pKBH + (MeCN)=47.4) by both theoretical and experimental assessment. Overall, these results demonstrate the strong ability of geometric constraining to empower the central boron atom.

Geometrically Constrained Organoboron Species as Lewis Superacids and Organic Superbases

AbstractThis report unveils an advancement in the formation of a Lewis superacid (LSA) and an organic superbase by the geometrical deformation of an organoboron species towards a T‐shaped geometry. The boron dication [2]2+ supported by an amido diphosphine pincer ligand features both a large fluoride ion affinity (FIA>SbF5) and hydride ion affinity (HIA>B(C6F5)3), which qualifies it as both a hard and soft LSA. The unusual Lewis acidic properties of [2]2+ are further showcased by its ability to abstract hydride and fluoride from Et3SiH and AgSbF6 respectively, and effectively catalyze the hydrodefluorination, defluorination/arylation, as well as reduction of carbonyl compounds. One and two‐electron reduction of [2]2+ affords stable boron radical cation [2]⋅+ and borylene 2, respectively. The former species has an extremely high spin density of 0.798e at the boron atom, whereas the latter compound has been demonstrated to be a strong organic base (calcd. pKBH+ (MeCN)=47.4) by both theoretical and experimental assessment. Overall, these results demonstrate the strong ability of geometric constraining to empower the central boron atom.

Highly Selective Reduction of Carbonyl Compounds and O‐Acetylation of Arylalcohols in the Presence of a Nickel Ion‐Containing 1,4‐Diazabicyclo[2.2.2]octane (DABCO)‐Based Ionic Liquid

AbstractDuring this study, an easy procedure is presented for the preparation of a new nickel ion‐containing DABCO based ionic liquid. The prepared reagent was characterized using FT‐IR, FESEM, EDX, XRD, ICP‐OES, TGA and DRS analyses. In continue the catalytic activity of this reagent which is formulated as [C4(DABCO)2].NiCl4 was investigated in the reduction of a variety of carbonyl compounds to their corresponding alcohols with NaBH4. The promoting ability of this catalyst was also confirmed in the acetylation of alcohols with CH3COCl. All reactions were carried out in short times with high to excellent yields. The catalyst was also recoverable and reusable in the studied reactions.

Native amine dehydrogenases can catalyze the direct reduction of carbonyl compounds to alcohols in the absence of ammonia

Native amine dehydrogenases (nat-AmDHs) catalyze the (S)-stereoselective reductive amination of various ketones and aldehydes in the presence of high concentrations of ammonia. Based on the structure of CfusAmDH from Cystobacter fuscus complexed with Nicotinamide adenine dinucleotide phosphate (NADP+) and cyclohexylamine, we previously hypothesized a mechanism involving the attack at the electrophilic carbon of the carbonyl by ammonia followed by delivery of the hydride from the reduced nicotinamide cofactor on the re-face of the prochiral ketone. The direct reduction of carbonyl substrates into the corresponding alcohols requires a similar active site architecture and was previously reported as a minor side reaction of some native amine dehydrogenases and variants. Here we describe the ketoreductase (KRED) activity of a set of native amine dehydrogenases and variants, which proved to be significant in the absence of ammonia in the reaction medium but negligible in its presence. Conducting this study on a large set of substrates revealed the heterogeneity of this secondary ketoreductase activity, which was dependent upon the enzyme/substrate pairs considered. In silico docking experiments permitted the identification of some relationships between ketoreductase activity and the structural features of the enzymes. Kinetic studies of MsmeAmDH highlighted the superior performance of this native amine dehydrogenases as a ketoreductase but also its very low activity towards the reverse reaction of alcohol oxidation.

Zn-Catalyzed Regioselective and Chemoselective Reduction of Aldehydes, Ketones and Imines.

An operationally convenient Zn-catalyzed synthesis of alcohols by the reduction of aldehydes, ketones, and α,β-unsaturated aldehydes/ketones is reported. It is a rare example of using mild and sustainable HBpin as a reductant for catalytic reduction of carbonyl compounds in the absence of acid or base as hydrolysis reagent. The reaction is upscalable and proceeds in high selectivity without the formation of boronate ester by-products, and tolerates sensitive functionalities, such as iodo, bromo, chloro, fluoro, nitro, trifluoromethyl, aminomethyl, alkynyl, and amide. The Zn(OAc)2/HBpin combination has been also proved to be chemoselective for the C=N reduction of imine analogs.

Understanding the electrochemical hydrogenation of acetone on Pt single crystal electrodes

• Pt(1 1 0) electrode is the only basal plane active for the acetone electroreduction. • The inclusion of (1 1 1) steps on (1 1 0) terraces slightly alters the behavior of Pt(1 1 0). • Insertion of (1 0 0) steps on (1 1 0) terraces decreases the activity. • Sulfate competes with acetone for the surface sites. The heterogeneous upgrading of biomass by means of electrocatalytic hydrogenation is an attractive way to refine products for industrial and pharmaceutical purposes. Also, the efficient electrochemical reduction of carbonyl compounds can act as hydrogen vectors, and therefore energy vectors. In this manuscript, we render further fundamental insights into the electrochemical reduction of acetone as a model molecule of carbonyl compounds. The structural sensitivity of the reaction is demonstrated by using platinum single crystal electrodes with low Miller indices and stepped electrodes with (1 1 0) terraces and either (1 1 1) or (1 0 0) monoatomic steps. Among the basal planes, Pt(1 1 0) is the only one active for the electroreduction of acetone. The inclusion of (1 1 1) steps on the (1 1 0) terraces does not significantly alter the behavior of Pt(1 1 0), but increasing the (1 0 0) step density has been observed to decrease the activity. We attribute this different performance to a geometrical effect of the active sites. By using different supporting electrolytes, we have found that sulfate competes with acetone for the surface sites, thus modifying the adlayer interfacial structure and hampering acetone reactivity.

Organoaluminum derived from Schiff bases: Synthesis, characterization and catalytic performance in hydroboration

In the process of the development of green chemistry, non-noble metal catalysts have become one of the research hotspots. The abundant aluminum has entered the research scope of chemists. Four organoaluminum derived from halogen-substituted Schiff bases were prepared: (2-(((2,6-difluorophenyl)imino)methyl)phenoxy)dimethylaluminum (C1), (2-(((3-chloro-4-fluorophenyl)imino)methyl)phenoxy)dimethylaluminum (C2), (2-(((2-chlorophenyl)imino)methyl)phenoxy)diethylaluminum (C3), (2-(((4-chlorophenyl)imino)methyl)phenoxy)diethylaluminum (C4). All organoaluminum compounds were characterized using 1H NMR, 13C NMR, 19F NMR spectroscopy, and X-ray single crystal diffraction. XRD proved that the aluminum centers of these organoaluminum compounds are all twisted six-membered ring structures. They were used for the hydroboration of aldehydes and ketones, showing excellent results. This provided an additional catalyst for the reduction of carbonyl compounds.

Baker’s yeast (Saccharomyces cerevisiae) catalyzed synthesis of bioactive heterocycles and some stereoselective reactions

Abstract Saccharomyces cerevisiae, commonly known as baker’s yeast, has gained significant importance as a mild, low-cost, environmentally benign biocatalyst. Initially it was mostly employed as an efficient catalyst for the enantioselective reduction of carbonyl compounds. Over the last decade, baker’s yeast has found versatile catalytic applications in various organic transformations. Many multicomponent reactions were also catalyzed by baker’s yeast. Various heterocyclic scaffolds with immense biological activities were synthesized by employing baker’s yeast as catalyst at room temperature. In this communication, we have summarized baker’s yeast catalyzed various organic transformations focusing primarily on heterocyclic synthesis.

Electrochemical Reduction of Aldehydes and Ketones for the Synthesis of Alcohols and Diols under Ambient Conditions

AbstractA sustainable, practical, and direct strategy for the reduction of carbonyl compounds, including aldehydes and ketones, by an electrochemical pathway is presented, affording a variety of alcohols or diols as major products with decent yields. The reaction proceeds smoothly in the air at ambient temperatures with DABCO as the sacrificial reductant. Mechanistic studies revealed that direct electrochemical reduction followed by either protonation or radical–radical homocoupling is the main pathway.

Synergistic effect of acid sites and a gallium-based modified meso-/microporous catalyst for the pyrolysis of biomass

Single-metal and bimetal catalysts were synthesized by the modification of a meso-/microporous composite catalyst (ZSM-5@SBA-15) with the oxides of gallium, zinc, and nickel by ion exchange (iex) and impregnation (imp). The catalysts were characterized by XRD, SEM, TEM, XPS, Py-IR, N2-adsorption-desorption and other techniques. The results revealed that the metal is successfully introduced into the catalyst and that the presence of the metal promotes the conversion of the Brönsted acid to the Lewis acid. The catalysts were applied for biomass pyrolysis to produce bio-oil, and the results revealed that the yields of high value-added products of hydrocarbons (e.g., toluene and naphthalene) obtained by catalytic pyrolysis over bimetal catalysts are significantly improved in comparison with those over a non-metal modified catalyst. Moreover, the possible mechanism for catalytic pyrolysis over the best-performing catalyst of Ga/Zn-ZSM-5@SBA-15-iex (gallium, zinc-modified meso-/microporous ZSM-5@SBA-15 by the ion-exchange method) with the highest aromatic selectivity and effective reduction of carbonyl compounds (e.g., carboxides) was proposed by assuming the systematic comparison of structural features and catalytic performances of various metal/ZSM-5@SBA-15-type catalysts. The study provides guidance for the development of multifunctional catalysts with a synergistic effect of acid sites in the presence of a metal.

Rhodium-Catalyzed Regioselective and Chemoselective Deoxygenative Reduction of 1,3-Diketones

The deoxygenative reduction of carbonyl compounds has been well established. However, most protocols developed typically require harsh reaction conditions or highly reactive/toxic reagents, and the deoxygenative reduction of 1,3-diketones is rarely explored despite their importance to synthetic chemistry and materials science. We describe here a rhodium-catalyzed regioselective and chemoselective deoxygenative reduction of 1,3-diketones under mild reaction conditions. This approach exhibited exceptionally high regioselectivity toward the aliphatic carbonyl reduction over aromatic carbonyl reduction. Moreover, the reaction showed good functional group tolerance and broad substrate scope as well as great potential in the late-stage modification and synthesis of natural products and pharmaceutical skeletons. Preliminary mechanistic studies and DFT calculations revealed that this reaction involved the deoxygenation of 1,3-diketone to α, β-unsaturated ketone and its subsequent 1,4-reduction. The noticeably lower energy barrier of the aliphatic C═O insertion into [Rh]-Bpin versus the aromatic C═O insertion was responsible for the high regioselectivity in this reduction.

Chemoselective Electrosynthesis Using Rapid Alternating Polarity.

Challenges in the selective manipulation of functional groups (chemoselectivity) in organic synthesis have historically been overcome either by using reagents/catalysts that tunably interact with a substrate or through modification to shield undesired sites of reactivity (protecting groups). Although electrochemistry offers precise redox control to achieve unique chemoselectivity, this approach often becomes challenging in the presence of multiple redox-active functionalities. Historically, electrosynthesis has been performed almost solely by using direct current (DC). In contrast, applying alternating current (AC) has been known to change reaction outcomes considerably on an analytical scale but has rarely been strategically exploited for use in complex preparative organic synthesis. Here we show how a square waveform employed to deliver electric current-rapid alternating polarity (rAP)-enables control over reaction outcomes in the chemoselective reduction of carbonyl compounds, one of the most widely used reaction manifolds. The reactivity observed cannot be recapitulated using DC electrolysis or chemical reagents. The synthetic value brought by this new method for controlling chemoselectivity is vividly demonstrated in the context of classical reactivity problems such as chiral auxiliary removal and cutting-edge medicinal chemistry topics such as the synthesis of PROTACs.

NiO–Ni/graphitic carbon nitride as a selective catalyst for transfer hydrogenation of carbonyl compounds using NaH2PO2 as a hydrogen source

The selective hydrogenation of a chemical functionality in the presence of other groups is an excellent strategy to avoid multiple synthetic steps. Earth abundant Ni metal supported on graphitic carbon nitride (NiO–Ni/GCN) has been explored as a mild catalyst for the selective reduction of carbonyl compounds. Sodium hypophosphite (NaH2PO2) is used as a hydrogen donor for transfer hydrogenation of aldehydes and ketones. In the presence of NaH2PO2the NiO nanoparticles are in-situ reduced to catalytically active Ni(0) catalyst. NiO–Ni/GCN catalyst has been characterized by various techniques such as PXRD, IR, SEM, TEM, XPS, and TGA etc. In addition, nickel is a cost-effective and earth abundant metal which makes Ni-GCN as a viable hydrogenation catalyst. In contrast to Pd-GCN and Ru-GCN the present catalyst does not lead to hydrodehalogenation of haloaryl compounds in the presence of a hydrogen donor. Moreover, the catalyst is recyclable and can run efficiently for the multiple cycles without significant loss of activity.

Synergistic Effect of Acid Sites and a Gallium-Based Modified Meso-/Microporous Catalyst for the Pyrolysis of Biomass

Single-metal and bimetal catalysts were synthesized by the modification of a meso-/microporous composite catalyst (ZSM-5@SBA-15) with the oxides of gallium, zinc, and nickel by ion exchange (iex) and impregnation (imp), followed by their application in the catalytic upgrading of bio-oil via the pyrolysis of biomass.The results revealed that the yields of high value-added products of hydrocarbons (e.g., toluene and naphthalene) significantly catalytic pyrolysis over bimetal catalysts improved comparison with that over a non-metal modified catalyst, that is, product yield increased from 2.9 area% to 10.6 area%. Moreover, the possible mechanism for catalytic pyrolysis over the best-performing catalyst of Ga/Zn-ZSM-5@SBA-15-iex (gallium, zinc-modified meso-/microporous ZSM-5@SBA-15 by ion-exchange method) with the highest aromatic selectivity and effective reduction of carbonyl compounds (e.g., carboxides) was proposed by assuming the systematic comparison of structural features and catalytic performances of various metal/ZSM-5@SBA-15-type catalysts and fundamental investigation of the synergetic effects dominated by acidic sites, type of metal and bimetal catalysts.

Nickel nanoparticles anchored over porous triazine-thiourea-sulfonamide to explore the reduction of carbonyl compounds

Nickel nanoparticles anchored over porous triazine-thiourea-sulfonamide to explore the reduction of carbonyl compounds

Reduction of carbonyl compounds via hydrosilylation catalyzed by well-defined PNP-Mn(I) hydride complexes

Reduction reactions of unsaturated compounds are fundamental transformations in synthetic chemistry. In this context, the reduction of polarized double bonds such as carbonyl or C=C motifs can be achieved by hydrogenation reactions. We describe here a highly chemoselective Mn(I)-based PNP pincer catalyst for the hydrosilylation of aldehydes and ketones employing polymethylhydrosiloxane (PMHS) as inexpensive hydrogen donor.Graphic abstract