Aldehydes to carboxylic acids

A completely different dipolar cycloaddition model has been proposed39 in order to rationalize the stereochemical outcome of the addition of doubly deprotonated carboxylic acids to aldehydes, which is known as the Ivanov reaction. In the irreversible reaction of phenylacetic acid with 2,2-dimethylpropanal, metal chelation is completely unfavorable. Thus simple diastereoselectivity in favor of u f/-adducts is extremely low when chelating cations, e.g., Zn2 + or Mg- +, are used. Amazingly, the most naked dianions provide the highest anti/syn ratios as indicated by the results obtained with the potassium salt in the presence of a crown ether. 

Horner has applied the same reaction (55) to the continuing problem of converting carboxylic acids to aldehydes, the overall yield varying from 40—90% depending on R. 

White H, G Strobl, R Feicht, H Simon (1989) Carboxylic acid reductase a new tungsten enzyme catalyses the reduction of non-activated carboxylic acids to aldehydes. Eur J Biochem 184 89-96. 

Thiol esters undergo smooth reduction to give aldehydes by the Fukuyama hydrosilylation procedure, which is an alternative way to transform carboxylic acids to aldehydes. Upon treatment with Et3SiH and 10% Pd/C, a thioester underwent smooth reduction to give an aldehyde.409,410 For example, to a stirred mixture of thioester and Pd/C in acetone may be added Et3SiH at room temperature under an Ar atmosphere. Stirring is continued until the hydrogenolysis is complete (0.5-1 h) (Scheme 4.117). 

Reductions. Silicon hydrides such as 1, which can achieve intramolecular pentacoordination, show enhanced reducing properties. Thus they can reduce aldehydes or ketones to alcohols,1 and reduce carboxylic acids to aldehydes via thermal decomposition of a silyl carboxylate (equation I).2 Reaction of acid chlo-... 

Scheme 25 Cathodic reduction of activated aliphatic carboxylic acids to aldehydes (R alkyl, yields 70-82%) and ketones (R benzyl, yields 66- 72%).

RAMP (R)-l-Amino-2-methoxyraethylpyrrolidine 1-Pyrrolidinamine, 2-(methoxyraethyl)-, (R)- 65, 173, 183 REDUCTION OF CARBOXYLIC ACIDS TO ALDEHYDES. 66, 121 RING EXPANSION, 65, 17... 

REDUCTION OF CARBOXYLIC ACIDS TO ALDEHYDES 6-OXODECANAL (Decanal, 6-oxo-)... 

Dehydroxylation (see Deoxygenation, Reduction of carboxylic acids to aldehydes)... 

Arene(tricarbonyl)chromium complexes, 19 Nickel boride, 197 to trans-alkenes Chromium(II) sulfate, 84 of anhydrides to lactones Tetrachlorotris[bis(l,4-diphenyl-phosphine)butane]diruthenium, 288 of aromatic rings Palladium catalysts, 230 Raney nickel, 265 Sodium borohydride-1,3-Dicyano-benzene, 279 of aryl halides to arenes Palladium on carbon, 230 of benzyl ethers to alcohols Palladium catalysts, 230 of carboxylic acids to aldehydes Vilsmeier reagent, 341 of epoxides to alcohols Samarium(II) iodide, 270 Sodium hydride-Sodium /-amyloxide-Nickel(II) chloride, 281 Sodium hydride-Sodium /-amyloxide-Zinc chloride, 281 of esters to alcohols Sodium borohydride, 278 of imines and related compounds Arene(tricarbonyl)chromium complexes, 19... 

In the McFadyen-Stevens reaction, microwave irradiation has also been employed to convert carboxylic acids to aldehydes via the p-toluenesulphonyl hydrazides65. The p-toluenesulphonyl hydrazide is mixed with sodium carbonate, glass powder and ethylene glycol, and pre-irradiated at 150 W for a few minutes before the actual reaction conditions were applied. The reaction was successfully used in the synthesis of the alkaloid Nauclefidine (Scheme 4.40). 

An excellent, broad review of the last 60 years of hydride reductions has been published,235 and the use of selectrides, Li and K tri-.v-butylborohydridcs or trisiamylborohydrides, has also been reviewed.236 A review of sodium borohydride-carboxylic acid as a reagent with novel selectivity in reductions has been written in particular, this reagent is useful for the A -alkylation of primary and secondary amines, through a sequence that is believed to involve sequential carboxylic acid to aldehyde reduction followed by reductive animation.237... 

A most convenient procedure for the conversion of carboxylic acids to aldehydes results from their initial treatment with borane-dimethyl sulphide to give first, the triacyloxyborane (9), which is then reduced further to the intermediate (10) the trimer of (10) is the trialkyloxyboroxine (11). Oxidation of (11) with PCC then yields the aldehyde.110 The method is illustrated for the preparation of octanal (Expt 5.81), but it has been applied to cyclohexanecarboxylic acid and to various aromatic carboxylic acids (X-C6H4C02H, X = p-Cl, NOz, OMe, ni-CN). 

Reduction of carboxylic acids to aldehydes. 2 3-Acyllhiazolidine-2-thiones (2) can be prepared by reaction of l,3-thiazolidine-2-thione (1) with carboxylic acids directly (using 2-chloro-l-methylpyridinium iodide, 8, 95-96) or with acid chlorides (triethylamine or DCC). They can also be prepared from reaction of the thallium salt of 1 with an acid chloride. Yields by all four methods are 70-95%. The amides are reduced to aldehydes by either DIBAH or, generally in higher yield, by NaBH4 (90-98% yield). 

The conversion of carboxylic acids to aldehydes is normally conducted in two steps by reduction of the acids or their derivatives to the corresponding alcohols followed by mild oxidation. 

R. A. W. Johnstone, Reduction of Carboxylic Acids to Aldehydes by Metal Hydrides, in Comprehensive Organic Synthesis (B. M. Trost, I. Fleming, Eds.), Vol. 8, 259, Pergamon Press, Oxford, 1991. 

Fig. 6.34. Chemoselective reduction of free carboxylic acids to aldehydes. Intermediate B yields, upon hydrolysis, initially an aldehyde hydrate, which dehydrates to the aldehyde spontaneously (mechanism Section 7.2.1).

Reduction to Aldehydes Reduction of carboxylic acids to aldehydes is difficult because aldehydes are more reactive than carboxylic acids toward most reducing agents. Almost any reagent that reduces acids to aldehydes also reduces aldehydes to primary alcohols. In Section 18-10, we saw that lithium tri-ferf-butoxyaluminum hydride, LiAlH(0-f-Bu)3 is a weaker reducing agent than lithium aluminum hydride. It reduces acid chlorides to aldehydes because acid chlorides are strongly activated toward nucleophilic addition of a hydride ion. Under these conditions, the aldehyde reduces more slowly and can be isolated. Therefore, reduction of an acid to an aldehyde is a two-step process Convert the acid to the acid chloride, then reduce using lithium tri-ferf-butoxyaluminum hydride. 

RCOOH RCHO. This borane reduces aliphatic carboxylic acids to aldehydes in >90% yield within minutes at 25°. Aromatic acids are reduced slowly and in significantly lower yields. 

Reduction of Carboxylic Acids to Aldehydes by Metal Hydrides... 

Direct reduction of carboxylic acids to aldehydes has been a long-sought transformation since acids are usually relatively easy to obtain. The number of hydride reagents which effect this transformation is limited. 

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