Carbonyl compounds aliphatic, reduction

SchifT s bases A -Arylimides, Ar-N = CR2, prepared by reaction of aromatic amines with aliphatic or aromatic aldehydes and ketones. They are crystalline, weakly basic compounds which give hydrochlorides in non-aqueous solvents. With dilute aqueous acids the parent amine and carbonyl compounds are regenerated. Reduction with sodium and alcohol gives... 

Ruthenium is excellent for hydrogenation of aliphatic carbonyl compounds (92), and it, as well as nickel, is used industrially for conversion of glucose to sorbitol (14,15,29,75,100). Nickel usually requires vigorous conditions unless large amounts of catalyst are used (11,20,27,37,60), or the catalyst is very active, such as W-6 Raney nickel (6). Copper chromite is always used at elevated temperatures and pressures and may be useful if aromatic-ring saturation is to be avoided. Rhodium has given excellent results under mild conditions when other catalysts have failed (4,5,66). It is useful in reduction of aliphatic carbonyls in molecules susceptible to hydrogenolysis. 

A reiterative application of a two-carbon elongation reaction of a chiral carbonyl compound (Homer-Emmonds reaction), reduction (DIBAL) of the obtained trans unsaturated ester, asymmetric epoxidation (SAE or MCPBA) of the resulting allylic alcohol, and then C-2 regioselective addition of a cuprate (Me2CuLi) to the corresponding chiral epoxy alcohol has been utilized for the construction of the polypropionate-derived chain ]R-CH(Me)CH(OH)CH(Me)-R ], present as a partial structure in important natural products such as polyether, ansamycin, or macro-lide antibiotics [52]. A seminal application of this procedure is offered by Kishi s synthesis of the C19-C26 polyketide-type aliphatic segment of rifamycin S, starting from aldehyde 105 (Scheme 8.29) [53]. 

Metal-induced reductive dimerization of carbonyl compounds is a useful synthetic method for the formation of vicinally functionalized carbon-carbon bonds. For stoichiometric reductive dimerizations, low-valent metals such as aluminum amalgam, titanium, vanadium, zinc, and samarium have been employed. Alternatively, ternary systems consisting of catalytic amounts of a metal salt or metal complex, a chlorosilane, and a stoichiometric co-reductant provide a catalytic method for the formation of pinacols based on reversible redox couples.2 The homocoupling of aldehydes is effected by vanadium or titanium catalysts in the presence of Me3SiCl and Zn or A1 to give the 1,2-diol derivatives high selectivity for the /-isomer is observed in the case of secondary aliphatic or aromatic aldehydes. 

Besides direct reduction, a one-pot reductive amination of aldehydes and ketones with a-picoline-borane in methanol, in water, and in neat conditions gives the corresponding amine products (Scheme 8.2).40 The synthesis of primary amines can be performed via the reductive amination of the corresponding carbonyl compounds with aqueous ammonia with soluble Rh-catalyst (Eq. 8.17).41 Up to an 86% yield and a 97% selectivity for benzylamines were obtained for the reaction of various benzaldehydes. The use of a bimetallic catalyst based on Rh/Ir is preferable for aliphatic aldehydes. 

The carbon dioxide anion-radical was used for one-electron reductions of nitrobenzene diazo-nium cations, nitrobenzene itself, quinones, aliphatic nitro compounds, acetaldehyde, acetone and other carbonyl compounds, maleimide, riboflavin, and certain dyes (Morkovnik and Okhlobystin 1979). The double bonds in maleate and fumarate are reduced by CO2. The reduced products, on being protonated, give rise to succinate (Schutz and Meyerstein 2006). The carbon dioxide anion-radical reduces organic complexes of Co and Ru into appropriate complexes of the metals(II) (Morkovnik and Okhlobystin 1979). In particular, after the electron transfer from this anion radical to the pentammino-p-nitrobenzoato-cobalt(III) complex, the Co(III) complex with thep-nitrophenyl anion-radical fragment is initially formed. The intermediate complex transforms into the final Co(II) complex with the p-nitrobenzoate ligand. 

Reduction of aldehydes and ketones. Earlier work on amine borane reagents was conducted mainly with tertiary amines and led to the conclusion that these borane complexes reduced carbonyl compounds very slowly, at least under neutral conditions, and that the yield of alcohols is low. Actually complexes of borane with primary amines, NHj or (CH3)3CNH2, reduce carbonyl compounds rapidly and with utilization of the three hydride equivalents. BH3 NH3 is less subject to steric effects than traditional complex hydrides. A particular advantage is that NH3 BH3 and (CH3)3CNH2 BH3 reduce aldehyde groups much more rapidly than keto groups, but cyclohexanone can be reduced selectively in the presence of aliphatic and aromatic acyclic ketones. 

Lower aliphatic amines are widely used as intermediates for the synthesis of herbicides, insecticides and drugs or can be applied as rubber accelerators, corrosion inhibitors, surface active agents etc. [l]. The most widespread method for the preparation of lower aliphatic amines involves the reaction of ammonia with an alcohol or a carbonyl compound in the presence of hydrogen. The most common catalysts used for reductive amination of alcohols, aldehydes and ketones contain nickel, platinum, palladium or copper as active component [ I — 3 ]. One of the most important issues in the reductive amination is the selectivity control as the product distribution, i.e. the ratio of primary to secondary or tertiary amines, is strongly affected by thermodynamics. 

Electroenzymatic reactions are not only important in the development of ampero-metric biosensors. They can also be very valuable for organic synthesis. The enantio- and diasteroselectivity of the redox enzymes can be used effectively for the synthesis of enantiomerically pure compounds, as, for example, in the enantioselective reduction of prochiral carbonyl compounds, or in the enantio-selective, distereoselective, or enantiomer differentiating oxidation of chiral, achiral, or mes< -polyols. The introduction of hydroxy groups into aliphatic and aromatic compounds can be just as interesting. In addition, the regioselectivity of the oxidation of a certain hydroxy function in a polyol by an enzymatic oxidation can be extremely valuable, thus avoiding a sometimes complicated protection-deprotection strategy. 

The first report on a successful microwave-assisted one-step reduction of ketones to their respective hydrocarbons via the hydrazones appeared in 20 0 265. This so called Huang-Minlon variant of the Wolff-Kishner reduction was successfully applied to some aromatic and aliphatic aldehydes and ketones, including intermediates in the synthesis of the alkaloid flavopereirine. The reactions were performed by mixing the carbonyl compound with 2 equiv of hydrazine hydrate and an excess of powdered KOH in a commercial microwave oven. The mixtures were irradiated at 150 W for a few minutes before 250-350 W irradiations were applied (Scheme 4.39). The reaction was shown... 

Many aliphatic aldehydes exist primarily as hemiacetals in alcoholic solvents. It has been well understood for many years47 that the actual reducible species, or electrophore , in such media is not the hemiacetal but rather the small amount of the carbonyl compound itself (actually a hydrogen-bonded complex see above) present at equilibrium. Thus reduction is kinetically controlled that is, the overall rate of reduction is governed by the rate of conversion of the hemiacetal to the aldehyde. More recently, this has been confirmed and studied for formaldehyde and acetaldehyde in water at different pH levels48 and the kinetics of the reduction process have been studied for glucose, galactose and lactose49. 

The reduction is usually effected catalytically in ethanol solution using hydrogen under pressure in the presence of Raney nickel. As in the reduction of nitriles (Section 5.16.1, p. 771), which also involves the intermediate imine, ammonia or the amines should be present in considerable excess to minimise the occurrence of undesirable side reactions leading to the formation of secondary and tertiary amines. These arise from the further reaction of the carbonyl compound with the initially formed amine product. Selected experimental conditions for these reductive alkylation procedures have been well reviewed.210 Sodium borohydride has also been used as an in situ reducing agent and is particularly effective with mixtures of primary amines and aliphatic aldehydes and ketones.211... 

Reduction of carbonyl compounds.2 The reagent reduces aromatic and aliphatic ketones, aldehydes, and acid chlorides to alcohols in moderate to excellent yield in chloroform solution. The order of substrate reactivity is RCOCl>RCHO>R2CO. Only three of the eight hydrogens are transferred under the reaction conditions. 

The reduction of aliphatic carbonyl compounds is most simply expressed by assuming the addition of HCo(CO)4 to the carbonyl group in the manner of other HA addenda, followed by reaction of the adduct with additional hydrocarbonyl ... 

Reductive amination of carbonyl compounds. This reagent effects reductive ami-nation of aldehydes or ketones with amines (equation 1). Yields tend to be only moderate with anilines, but are high with aliphatic amines. 

Aromatic ketones represent a rather special case in dissolving metal reductions. Under many conditions pinacol formation is the predominent reaction path (see Volume 3, Chapter 2.6). Also, the reduction potentials of aromatic carbonyl compounds are approximately 1 V less negative than their aliphatic counterparts. The reductions of aromatic ketones by metals in ammonia are further complicated by the fact that hydrogenolysis of the carbon-oxygen bond can take place (Chapter 1.13, this volume) and Birch reduction may intervene (Chapter 3.4, this volume). 

Detailed discussion of the preparation of a variety of alkyl- and arylpyrazines by primary syntheses, principally from aliphatic components, appears in Chapter II. These include, for example, the preparation of 2,5-disubstituted and 2,3,5,6-tetrasubstituted alkyl- and arylpyrazines from a-amino carbonyl compounds, which may be produced by many methods such as reduction of a-hydroxyimino carbonyl compounds, aminolysis of a-halogeno carbonyl compounds, oxidation of a-amino... 

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