Functionalization to Form Carboxyl Groups

Just as there are several methods for incorporating an amino group into a molecule, there are several strategies for incorporating a carboxyl moiety (-COOH) into the molecule. Certain acid chlorides (such as ethyl chloroformate) may be the best direct method for introducing a carboxyl group. There are also several reagents such as cyanide and carbon dioxide that can be used to insert a carboxyl into a putative amino acid. 

One of the most common methods for incorporating an acid moiety into a molecule involves the reaction of cyanide with a suitable leaving group to give a nitrile. Subsequent hydrolysis of that cyano group leads to an acid moiety. An 

A variation in this approach is the reduction of conjugated nitriles such as 1.159. which gave 2-ethyl-3-aminopropanoic acid (1.160) after hydrolysis of the cyano group to COOH and removal of the phthalimido protecting group. This route was also used to prepare 3-amino-2-methylpropanoic acid, in 65% yield. 

Nitriles can be used in reactions other than displacement The Boc-protected aldehyde derived from alanine (known as N-Boc alinal, 1.161) was condensed with potassium cyanide to give a cyanohydrin. Hydrolysis of the cyano group to give an acid and removal of the N-Boc group gave 3-amino-2-hydroxybutanoic acid, 1.162.9  

Specialized variations are also possible. Treatment of his-cyano-ester 1.163 with 

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