Reduction of carboxylic acid derivatives

The aldehyde intermediate can be isolated if 1 equivalent of diisobutvl-aluminum hydride (D1BAH) is used as the reducing agent instead of LiAlH4. The reaction has to be carried out at -78 °C to avoid further reduction to the alcohol. Such partial reductions of carboxylic acid derivatives to aldehydes also occur in numerous biological pathways, although the substrate is either a thioester or acyl phosphate rather than an ester. 

Hydride as a nucleophile reduction of carboxylic acid derivatives... 

Of the several methods now available for the reduction of carboxylic acid derivatives to aldehydes, all require careful control of conditions to avoid ovorreduetion or underreduetion. The procedure described here is particularly convenient in that... 

The Reimer-Tiemann reaction is not an effective route to formyl-pyrroles or -indoles (see Section 3.05.1.6) and the oxidation of alkyl and hydroxyalkyl derivatives of the heterocycles and the reduction of carboxylic acid derivatives are discussed in Sections 3.05.2.2 and 3.05.2.4, respectively. 

Aldehydes are intermediate ill oxidation level, and thus the aldehyde functional group can be installed by either reduction of carboxylic acid derivatives or oxidation of alcohols. Aldehydes are rarely installed without a change of oxidation level. One difficulty is that they undergo both oxidation and reduction readily. Special methods are required to stop at the aldehyde stage rather than proceeding by further reduction or oxidation. 

Acylation of Hydride Donors Reduction of Carboxylic Acid Derivatives to Aldehydes... 

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. 

A. G. M. Barrett, Reduction of Carboxylic Acid Derivatives to Alcohols, Ethers and Amines, in Comprehensive Organic Synthesis (B. M. Trost, I. Fleming, Eds.), Vol. 8, 235, Pergamon Press, Oxford, U. K., 1991. 

In summary, reductions of carboxylic acid derivatives to primary alcohols are usually accomplished by reaction of esters or acids with lithium aluminum hydride. The following equations provide several examples ... 

The mechanism, illustrated in Mechanism 20.5 with RCONH2 as starting material, is somewhat different than the previous reductions of carboxylic acid derivatives. Amide reduction proceeds with formation of an intermediate imine, a compound containii a C-N double bond, which is then further reduced to an amine. 

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