Alcohols, general reduction

This procedure illustrates a general method for the stereoselective synthesis of ( P)-disubstitnted alkenyl alcohols. The reductive elimination of cyclic /3-halo-ethers with metals was first introduced by Paul3 and one example, the conversion of tetrahydrofurfuryl chloride [2-(chloromethyl)tetrahydrofuran] to 4-penten-l-ol, is described in an earlier volume of this series.4 In 1947 Paul and Riobe5 prepared 4-nonen-l-ol by this method, and the general method has subsequently been applied to obtain alkenyl alcohols with other substitution patterns.2,6-8 (I )-4-Hexen-l-ol has been prepared by this method9 and in lower yield by an analogous reaction with 3-bromo-2-methyltetra-hydropyran.10... 

In general, reduction of amides to alcohols is difficult. More commonly the amide is reduced to an amine. An exception uses LiH2NBH3 to give the alcohol. Reduction with sodium metal in propanol also gives the alcohol.Acyl imidazoles are also reduced to the corresponding alcohol with NaBH4 in aqueous HC1. °... 

Tertiary Alkyl Alcohols. Tertiary alkyl alcohols generally undergo facile reduction when treated with acids in the presence of organosilicon hydrides.127,136 This comparative ease of reduction reflects the enhanced stability and ease of formation of tertiary alkyl carbenium ions compared with primary and secondary carbenium ions. Thus, treatment of 1-methylcyclohexanol with mixtures of triethylsilane and aluminum chloride in dichloromethane produces near quantitative yields of methylcyclohexane with or without added hydrogen chloride in as little as 30 minutes at room temperature, in contrast to the more vigorous conditions needed for the reduction of the secondary alcohol cyclohex-anol.136... 

Diaryl and triaryl benzylic alcohols generally undergo smooth reduction to the corresponding hydrocarbons. Thus, both diphenyl- and triphenylcarbinol quickly give good to excellent yields of the corresponding substituted methanes when... 

Na-Protected a-amino aldehydes 4 are mainly obtained from their corresponding a-amino acid derivatives. Generally the synthetic route proceeds via acid halides, esters, or active amides of a-amino acids that are then reduced. The reduction of N -protected acid halides and esters is often accompanied by some overreduction to the respective alcohols. However, reduction of active amides is apparently free from overreduction. The different procedures described in this review are listed in Table 3. 

Preparation of a (1-Amino Alcohol by Reduction of a N"-Protected a-Amino Acid General Proce-... 

Generally, carboxylic acids are difficult to reduce either by catalytic hydrogenation or by sodium and alcohol. Nonetheless, reduction to primary alcohols proceeds smoothly with lithium aluminum hydride, LiAlH4 ... 

In general, the dissolving metal or electrochemical reductions of acyl halides or acyclic anhydrides are not useful for the preparation of primary alcohols. Such reductions invariably provide acyloin esters, ene-diolate diesters or related species. Cyclic anhydrides may be reduced to give lactones. For example, the reduction of phthalic anhydride at a mercury cathode has been used in the synthesis of phthalide (90%). In general, however, such reduction are not widely employed in synthesis. 

Alcohols, such as methanol and ethanol, lead to the sole formation of saturated alcohols from unsaturated ketones when the former are present in excess during the reduction. Mixtures of ketones and alcohols are generally formed when 1 equiv. of these proton donors is employed. These alcohols have an acidity comparable to that of saturated ketones, and when they are present, an equilibrium can be established between the initially formed metal enolate and the saturated ketone. The latter is then reduced to the saturated alcohol. Such reductions generally do not occur to a very significant extent when 1 equiv. of r-butyl alcohoP or some less acidic proton donor, such as triphenylcarbinol, is employed. The acidity of the ketone involved, as well as the solubility of the metal enolate in the reaction medium, are important in determining whether alcohols are formed. 

The majority of aliphatic ketones give the secondary alcohol on reduction at electrodes of carbon, mercury, lead, or platinum. The usual choice of electrolyte has been dilute sulfuric acid, acetate buffer, or a neutral salt solution, which will become alkaline during the course of reaction that consumes protons. Relatively few studies have been recorded of the isomer ratio obtained by reduction of open chain ketones with a prochiral center adjacent to the carbonyl function [32,33]. Results are collected in Table 2, and one aromatic carbonyl compound is included here for convenience. In general, the erythro-alcohol is favored and in an excess over that present in the equilibrium mixture [32,33]. These results are explained in terms of adsorption of intermediates at the electrode surface. For many of the examples in Table 2, the total yield of alcohol is low and this result is not generally typical of aliphatic carbonyl compounds, as can be seen from Table 3. 

Amides of aliphatic acids are converted into alcohols in methylamine [325]. It appears that this is the only general reduction of all kinds of amides to alcohols. 

The reduction of -codeine is complicated by the presence in the same molecule of an allylic ether and an allylic alcohol. Catalytic reduction generally proceeds with opening of the cyclic ether system and production of phenolic bases, but this can be suppressed by hydrogenating the hydrochloride over platinum oxide. 

Secondary Alcohols by Reduction with Aged Darvon Alcohol/Lithium Aluminum Hydride General Procedure 59 ... 

Reduction of acids or esters to aldehydes. Diaminoaluminum hydrides, particularly those derived from secondary cyclic amines such as N-methyl-piperazine or morpholine, are useful for reduction of carboxylic acids or esters to aldehydes, without contamination by the corresponding alcohols. The reduction is carried out in refluxing THF (6-20 hr.). In general, 2 moles of reagent are used for each mole of substrate. The reduction is applicable to both aromatic and aliphatic esters. Yields are in the range of 50-85%,... 

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