Metal hydrides carboxyl derivatives

A less powerful complex metal hydride is Na BH4 which will reduce aldehydes and ketones only, and does not attack carboxylic acid derivatives nor does it—as Li AlH4 does—attack NO2 or C=N present in the same compound. It has the great advantage of being usable in hydroxylic solvents. A wide variety of other reagents of the MH4 , MH3OR , MHjfORlj type have been developed their relative effectiveness is related to both the nucleophilicity and size of MH4 , etc. 

Acid chlorides are easy to reduce than carboxylic acids and other carboxylic acid derivatives. They are reduced conveniently all the way to 1° alcohols by metal hydride reagents (NaBH4 or LiAlH4), as well as by catalytic hydrogenation (H2/Pd—C). 

Amides, azides and nitriles are reduced to amines by catalytic hydrogenation (H2/Pd—C or H2/Pt—C) as well as metal hydride reduction (LiAlH4). They are less reactive towards the metal hydride reduction, and cannot be reduced by NaBITj. Unlike the LiAlIU reduction of all other carboxylic acid derivatives, which affords 1° alcohols, the LiAlIU reduction of amides, azides and nitriles yields amines. Acid is not used in the work-up step, since amines are basic. Thus, hydrolytic work-up is employed to afford amines. When the nitrile group is reduced, an NH2 and an extra CH2 are introduced into the molecule. 

Metal hydrides, such as lithium aluminum hydride, also can be used to reduce derivatives of carboxylic acids (such as amides and nitriles see Table 16-6) to aldehydes. An example follows ... 

The following discussion deals not only with this reaction, but related reactions in which a transition metal complex achieves the addition of carbon monoxide to an alkene or alkyne to yield carboxylic acids and their derivatives. These reactions take place either by the insertion of an alkene (or alkyne) into a metal-hydride bond (equation 1) or into a metal-carboxylate bond (equation 2) as the initial key step. Subsequent steps include carbonyl insertion reactions, metal-acyl hydrogenolysis or solvolysis and metal-carbon bond protonolysis. 

J. S. Cha, Recent Developments in the Synthesis of Aldehydes by Reduction of Carboxylic Acids and their Derivatives with Metal Hydrides, Org. Prep. Proced. Int. 1989, 21, 451- 477. 

Complex or soluble neutral metal hydrides are usually employed for the reduction of carboxylic acid derivatives to alcohols or amines. The standard reagents for the most important transformations are shown in Table 17.6. For completeness, various reagents also are listed for the reduction of carboxylic acid derivatives to aldehydes. The latter mode of reduction was discussed in Section 6.5.2. 

Sodium/ammonia" treatment also causes disruption of the ring in thiophene and simple thiophenes, however thiophene-2-carboxylic acid and 2-acyl-thiophenes can be converted into the 2,5-dihydro derivatives using lithium in ammonia, followed by protonation or trapping with an alkyl halide."" Side-chain reductions can be carried out with metal hydrides, which do not affect the ring. 

An attractive feature of tartaric acid is the potential for treating each of the two carboxylic moieties as distinct functional groups. Most metal hydride reductions of tartaric acid derivatives afford polyhydroxy compounds. The chemoselective reduction of malic acid (for details see Chapter 3) suggests that tartaric acid, under favorable conditions, might also be susceptible to such a transformation. 

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