Reduction, acid chlorides

The mechanism of ester (and lactone) reduction is similar to that of acid chloride reduction in that a hydride ion first adds to the carbonyl group, followed by elimination of alkoxide ion to yield an aldehyde. Further reduction of the aldehyde gives the primary alcohol. 

Acid chlorides, reduction to aldehydes, 53, 55 Acid chlorides, aromatic, diazoketones from, 53, 37... 

The mechanism for acid chloride reduction proceeds via a hydride-ion transfer from the reducing agent to the acid chloride. The following steps summarize this mechanism. 

Access to the aldehyde function has always been very important in organic chemistry. The two main transformations to introduce this function are oxidation of a primary alcohol to the aldehyde or reduction of an acid derivatives to the aldehyde. This second reaction has not found any general simple solution. If some progress has been made, the main methods used today are either the Rosenmund10 reaction on the acid chloride, reduction of the ester using a sophisticated hydride, or reduction of the ester to the alcohol followed by reoxidation of the alcohol function to the aldehyde. 

RCOCl — RH,4 This reaction can be effected with this silane in combination with AIBN in dodccane or toluene at 80° in high yield, particularly in reactions of sec-or tert-acid chlorides. Reduction of primary acid chlorides leads also lo aldehydes as coproducts. 

RCOCl -> RH. This reactwo. AIBN in dodecane or toluene at or tert-acid chlorides. Reduction of pn coproducts. 

Carboxylic acids, their esters, and amides are usually resistant to sodium borohydride reduction, whereas carboxylic acid chlorides may be reduced in inert solvents to give alcohols. Where this proves unsatisfactory a new alternative procedure for acid chloride reduction in ether solution involves sodium borohydride adsorbed on alumina. Other recently published borohydride reductions of acid derivatives to primary alcohols include those of the 1-succinimidyl esters (8)" and the N-nitroso-amides (9). 2-Methoxyethoxymethyl (MEM) esters have the possibility of co-ordinating the metal cation of complex hydrides at the MEM group, and hence of activating the carbonyl group towards reduction by intramolecular hydride delivery. The selective reduction of the less hindered ester group in the bis-MEM ester (10) to give (11) illustrates this idea. 

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