The reduction of aldehydes, ketones and esters

Primary and secondary alcohols may be synthesised by the reduction of the corresponding carbonyl compounds by a great variety of reagents. 

Two reductive systems for ketones, which have the merit of being economic for large-scale preparations, are sodium and absolute ethanol (Expt 5.29), and zinc dust and aqueous sodium hydroxide (Expt 5.30). 

PTC procedures using tetrabutylammonium borohydride have been described.47 

Aldehydes and ketones can be selectively reduced to the corresponding alcohols by aluminium alkoxides. The most satisfactory alkoxide for general use is aluminium isopropoxide. 

The mechanism of the reaction involves the coordination of the carbonyl compound with the aluminium atom in aluminium isopropoxide followed by an intramolecular transfer of a hydride ion  

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Some alkah metal and trialkylaimnonium salts also work as efficient catalysts for the reduction of aldehydes, ketones and esters with monohydrosUanes. Among those salts CsF was foimd most effective. Esters are reduced to the alcohols... 

Louis Bouveault (Nevers, ii February 1864-Paris, 6 September 1909), assistant professor in the Paris Faculty of Sciences, worked out methods for the conversion of nitriles or amides to acids, the synthesis of aromatic aldehydes and acids by the use of aluminium chloride, the synthesis of aldehydes from nitro-olefins, and the reduction of aldehydes, ketones, and esters to alcohols by boiling with alcohol and sodium. ... 

In this section primarily reductions of aldehydes, ketones, and esters with sodium, lithium, and potassium in the presence of TCS 14 are discussed closely related reductions with metals such as Zn, Mg, Mn, Sm, Ti, etc., in the presence of TCS 14 are described in Section 13.2. Treatment of ethyl isobutyrate with sodium in the presence of TCS 14 in toluene affords the O-silylated Riihlmann-acyloin-condensation product 1915, which can be readily desilylated to the free acyloin 1916 [119]. Further reactions of methyl or ethyl 1,2- or 1,4-dicarboxylates are discussed elsewhere [120-122]. The same reaction with trimethylsilyl isobutyrate affords the C,0-silylated alcohol 1917, in 72% yield, which is desilylated to 1918 [123] (Scheme 12.34). Likewise, reduction of the diesters 1919 affords the cyclized O-silylated acyloin products 1920 in high yields, which give on saponification the acyloins 1921 [119]. Whereas electroreduction on a Mg-electrode in the presence of MesSiCl 14 converts esters such as ethyl cyclohexane-carboxylate via 1922 and subsequent saponification into acyloins such as 1923 [124], electroreduction of esters such as ethyl cyclohexylcarboxylate using a Mg-electrode without Me3SiCl 14 yields 1,2-ketones such as 1924 [125] (Scheme 12.34). 

Meerwein-Pondorf-Verley reduction is the hydrogenation in which alcohols are used as a source of hydrogen, and one of the hydrogen transfer reactions. M-P-V reduction of aldehydes, ketones and esters are efficiently catalyzed by hydrous Zr02 catalyst[18]. In these reactions, 2-propanol is the best for hydrogen source. 

Alcohols can be prepared by the hydration of alkenes or by the reduction of aldehydes, ketones, acids, and esters. 

Anionic activation of Si—H bonds " by fluorides, such as KF or CsF, or by potassium phthalate, KHCO3, KSCN, etc., yields powerful hydridic reagents that reduce the carbonyl group of aldehydes, ketones and esters, " and 1,2-reductions of a,p-unsaturated aldehydes and ketones occur with high selectivity. " The analogous activation of hydridosllanes by fluoride ions is also achieved under acidic conditions with boron trifluoride etherate, in which the latter compound is consumed and fluorosilanes are formed. ... 

The reagent is used for the reduction of aldehydes, ketones, acid anhydrides, and acid chlorides. Esters and nitriles are reduced only slowly at elevated temperatures. H. C. Brown, H. I. Schlesinger, I. Sheft, and D. M. Ritter, Am. Sac., 75, 192 (1953)... 

Bp3-OEt2 followed hy DiisobutyUduminum Hydride is used for the 1,2-reduction of y-aimno-Q, -unsaturated esters to give unsaturated amino alcohols, which are chiral building blocks for a -amino acids. Q , -Unsaturated nitroalkenes can be reduced to hydroxylamines by Sodium Borohydride and BF3-OEt2 in THF extended reaction times result in the reduction of the hydroxylamines to alkylamines. Diphenylamine-borane is prepared from sodium borohydride, BF3-OEt2, and diphenylamine in THF at 0 °C. This solid is more stable in air than BF3-THF and is almost as reactive in the reduction of aldehydes, ketones, carboxyhc acids, esters, and anhydrides, as well as in the hydrob-oration of alkenes. 

Transition metal-free hydrosilylation of carbonyl compounds can be realized with the use of Brpnsted or Lewis acids as well as Lewis bases. Alkali or ammonium fiuorides (CsF, KF, TBAF, and TSAF) are highly effective catalysts for the reduction of aldehydes, ketones, esters, and carboxylic acids with H2SiPh2 or PMHS. Lithium methoxide promotes reduction of esters and ketones with trimethoxysilane. A generally accepted mechanism of Lewis base-catalyzed hydrosilylation of carbonyl compovmds involves the coordination of the nucleophile to the silicon atom to give a more reactive pentacoordinate species that is attacked by the carbonyl compound giving hexacoordinate silicon intermediates (or transition states), in which the hydride transfer takes place (Scheme 30) (235). 

Although it is mechanistically different from the Tsuji-Trost allylation, indirect allyla-tions of ketones, aldehydes, and esters via their enolates are briefly summarized here. Related reactions are treated in Sect V.2.1.4. Pd-catalyzed allylation of aldehydes, ketones, and esters with aUyhc carbonates is possible via the Tr-allylpaUadium enolates of these carbonyl compounds. Tr-AUylpalladium enolates can be generated by the treatment of silyl and stannyl enol ethers of carbonyl compounds with allyl carbonates, and the allylated products are obtained by the reductive elimination of the Tr-allylpalladium enolates. 

Lithium aluminium hydride modified with some chiral 1,2-aminodiols, for example (106), gives enantiomeric excesses of up to 82% in the reduction of aromatic ketones," and lithium tris[(3-ethyl-3-pentyl)oxy]aluminium hydride has been introduced as a chemoselective reagent (98—100%) for the reduction of aldehydes in the presence of ketones." Finally, the reagents AlCL-EtSH and AlBrs-EtSH have found further application in the cleavage of esters and lactones. 

Identify the target alcohol as primary, secondary, or tertiary. A primary alcohol can be prepared by reduction of an aldehyde, an ester, or a carboxylic acid a secondary alcohol can be prepared by reduction of a ketone and a tertiary alcohol can t be prepared by reduction. 

Reduction of conjugated carbonyl compounds using stoichiometric amounts of the ammonium salt shows little advantage over the sodium salt in acidic methanol [11] with both reagents producing allylic alcohols (58-88% for acyclic compounds and 15-64% for cyclic compounds) by selective 1,2-reduction of the conjugated systems. Aldehydes, ketones and conjugated enones are also reduced by tetra-n-butylammonium cyanoborohydride in HMPA [11, 12], whereas haloalkanes and alkanesulphonic esters are cleaved reductively under similar conditions [13]. 

Catalysts suitable specifically for reduction of carbon-oxygen bonds are based on oxides of copper, zinc and chromium Adkins catalysts). The so-called copper chromite (which is not necessarily a stoichiometric compound) is prepared by thermal decomposition of ammonium chromate and copper nitrate [50]. Its activity and stability is improved if barium nitrate is added before the thermal decomposition [57]. Similarly prepared zinc chromite is suitable for reductions of unsaturated acids and esters to unsaturated alcohols [52]. These catalysts are used specifically for reduction of carbonyl- and carboxyl-containing compounds to alcohols. Aldehydes and ketones are reduced at 150-200° and 100-150 atm, whereas esters and acids require temperatures up to 300° and pressures up to 350 atm. Because such conditions require special equipment and because all reductions achievable with copper chromite catalysts can be accomplished by hydrides and complex hydrides the use of Adkins catalyst in the laboratory is very limited. 

The reduction of carboxylic acids or esters requires very powerful reducing agents such as lithium aluminum hydride (LiAlH,) or sodium (Na) metal. Aldehydes and ketones are easier to reduce, so they can use sodium borohy-dride (NaBH,j). Examples of these reductions are shown in Figure 3-13. 

However, the most important methods for preparing alcohols are catalytic hydrogenation (H2/Pd-C) or metal hydride (NaBH4 or LiAlH4) reduction of aldehydes, ketones, carboxylic acids, acid chlorides and esters (see Sections 5.7.15 and 5.7.16), and nucleophilic addition of organometalhc reagents (RLi and RMgX) to aldehydes, ketones, acid chlorides and esters (see Sections 5.3.2 and 5.5.5). 

Alcohols are easily accessible by reduction of carbonyl compounds, such as aldehydes, ketones or carboxylic acid derivatives. While aldehydes, ketones and esters have been frequently used in microwave-assisted reductions, there have been no reports about the use of microwave technology in the reduction of nitriles or amides. 

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