REDUCTION, OF CARBOXYLIC ACIDS TO ALDEHYDES

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)... 

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). 

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. 

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. 

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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