Carboxylic acid esters, reduction using

On the other hand, it has been found that the electrochemical reduction is a very unique and useful tool in synthetic organic chemistry when magnesium is used as the material of the electrode. The cathodic reduction of 1,3-dienes with magnesium electrode gives very unique products, i.e. 3-cyclopentenol derivatives when it is carried out in the presence of a carboxylic acid ester (equation 23)17. 

As described previously, carboxylic acids may be used as solvents for halide or Lewis base-promoted CO reduction. However, these solvents have the disadvantage of forming the usually less desirable carboxylate esters rather than free alcohol products. Rate or selectivity advantages are not apparent in these solvents. 

Chiral 2,2-disubstituted cyclobutanones have been obtained by asymmetric rearrangement of chiral sulfinyl- 177,178 and sulfanylcyclopropanes.179 Using readily available cyclopropyl 4-tolyl (/ )-sulfoxide (l),180 the requisite sulfinylcyclopropanes 3 and 3 were obtained by a sequence of lithiation, reaction with carboxylic acid esters and stereoselective addition of Grignard reagents to the ketones 2 thus formed.178 The corresponding sulfanylcyclopropanes 4 and 4 resulted from a sequence of protection, reduction and deprotection.179... 

A practicable strategy to provide access to chiral pyrazolidine-3-carboxylic acid (16) makes use of asymmetric dipolar cycloaddition of diazoalkanes to u,p-unsaturated carboxylic acid derivatives. For this purpose a chiral auxiliary of the alkene component is used, e.g. Op-polzer s1166 1671 (lf )-2,10-camphorsultam.t164l As shown in Scheme 7, by reaction of (tri-methylsilyl)diazomethane (41) with /V-( aery I oy I )cam p h ors u 11 am (42), the AL(4,5-dihy-dropyrazoline-5-carbonyl)camphorsultam (43) is obtained. Reduction of 44 with sodium cyanoborohydride leads to A-(pyrazolidine-3-carbonyl)camphorsultam (45) as the 35-dia-stereoisomer (ee 9 1) in 65 to 80% yields.[164] The camphorsultam 45 is then converted into the methyl ester 46 by reaction with magnesium methylate without racemizationj1641... 

This ring closure takes place readily whenever the carbonyl and amino groups occur in the relative positions shown above. Reduction of o-nitro-phenylacetonitrile by stannous chloride produces indole rather than the corresponding amino aldehyde. The synthesis is most useful for the preparation of indole-2-carboxylic acid by reduction of o-nitrophenyl-pyruvic acid with ferrous sulfate and ammonia or with sodium hydrosulfite. The ethyl ester is obtained by a similar reduction with zinc and acetic acid or by catalytic hydrogenation of ethyl o-nitrophenyl-pyruvate over platinum oxide catalyst. ... 

There is no generally useful nonhydride method for the direct reduction of carboxylic acid esters to aldehydes. There are, however, procedures which are valuable under particular circumstances. An important example is the one-electron reduction of aldonolactones to aldoses. Two factors presumably contribute to the success of these reactions firstly the presence of electron-withdrawing substituents in the substrates, raising the reactivity of the carbonyl group, and secondly the ability of the products to form cyclic hemiacetals stable to further reduction. 

The use of carboxylic acid esters as protective groups for alcohols is limited since they may undergo acyl substitution, hydrolysis or reduction. Reagents used for the preparation of esters in the presence of EtgN or pyridine are AcjO, AC2O-DMAP (note that DMAP increases the rate of acylation of alcohols with AcjO by a factor of 10" ), PhCOCl, (PhC0)20, and r-BuCOCl (pivaloyl chloride)." Deprotection of esters is usually done under basic conditions. ... 

Reduction. The reagent is useful for reduction of carboxylic acid esters to primary alcohols. For example, the following esters have been reduced to the corresponding carbinols ethyl p-nitrobenzoate (96% yield), ethyl phenylacetate (90% yield), ethyl gly-cinate (70% yield). The reaction has some useful features Hydroxylic solvents (ethanol, water) can be used, the selectivity is higher than in the case of lithium aluminum hydride, and the reagent is nearly neutral. The reagent was found to be satisfactory for reduction of the dimethyl ester of 4,4 -dinitro-2,2 -diphenic acid (la) to the corresponding alcohol (lb, 51%yield).2... 

Enders has used these asymmetric Michael additions as the key steps in the enantioselective synthesis of various esters and alcohols (69-73) which are chiral volatile ant pheromones. In these syntheses, asymmetric Michael additions of the lithio salt of the SAMP hydrazone of propanal to methyl 2-but-enoate and methyl 2-pentenoate were used to establish the chiral centers. Subsequent hydrolysis and reduction of the aldehyde or carboxylic acid ester by conventional procedures afforded the pheromones. ... 

Reduction. Carboxylic acids, esters, amides, and nitriles are reduced very rapidly by Sm and hydrochloric acid. Ytterbium may be used instead of samarium. The reduction of a-halocarbonyl compounds and the pinacol coupling with Sm in an aprotic system (MejSiCl-Nai/MeCN) are as efficient as those mediated by Sml2. 

Some simple esters of proline have found applications as auxiliaries. Thus, the methyl ester 2 was used to form chiral amides for hydride reductions (Section D.2.3.3.). Methyl and benzyl esters 2 and 3 form amides with various types of carboxylic acids which are used in the addition of zinc or titanium species to carbonyl groups (Section D. 1.3.3.3 ). The amide of (S)-proline [(S)-4] has been used in enantioselective Michael additions (Section D.I.5.8.), and (5 )-Ar-tri-fluoroacetylproline [(.S)-5] is the only simple A-acyl derivative used as an auxiliary (Section D.l.1.2.2,). 

An alternative procedure for reductive decarboxylation without the use of trialkyltin hydrides as hydrogen atom donors has been developed Alkane carboxylic acid esters derived from AT-hydroxypyridine-2-thione decomposed to alkyl radical, which can readily accept a hydrogen atom from t-BuSH (equation 74) to give alkanes. This reaction can be conveniently performed as a one-pot experiment wherein the acid chloride of an alkane carboxylic acid, the sodium salt of thiohydroxamic acid, t-BuSH and 4-dimethyl-aminopyridine (DMAP) in benzene solution are heated to reflux. This procedure works well for COOH groups attached to primary and secondary carbon atoms. Instead of AT-hydroxypyridine-2-thione, one can use other thiohydroxamic acids, viz. iV-hydroxy-AT-methylthiobenzamide, 3-hydroxy-4-methylthiazole-2(3if)-thione (equation 75) and l-iV-hydroxy-3-AT-methylbenzoylenethiourea for decarboxylation reactions. 

Alcohols from oxo compds. 20 eqs. NaBH4 added to a soln. of 5 eqs. ZrC in THF at room temp, under N2, a soln. of 4 eqs. acetophenone in the same solvent added, and the mixture stirred at room temp, for 5 h - 1-phenylethanol. Y 96%. ZrCl4 is inexpensive, easy to use, and does not affect ar. nitro compds. and bromides. F.e., also reduction of carboxylic acids, esters and halides to prim, alcohols, and amides, oximes, alkoximes, nitriles, and imines to amines, s. S. Itsuno et al.. Synthesis 1988, 995-6. 

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