Rearrangement to Electron-Deficient Nitrogen

In contrast to the somewhat limited synthetic utility of nitrenes, there is an important group of reactions in which migration occurs to electron-deficient nitrogen. One of the most useful of these reactions is the Curtius rearrangement 16 This reaction has the same relationship to acylnitrene intermediates that the Wolff rearrangement does to acylcar-benes. The initial product is an isocyanate, which can be isolated or trapped by a nucleophilic solvent. 

This reaction is considered to be a concerted process in which migration accompanies loss of nitrogen.176 177 The migrating group retains its stereochemical configuration. The temperature required for reaction is in the vicinity of 100°C. 

The acyl azide intermediates are prepared either by reaction of sodium azide with a reactive acylating agent or by diazotization of an acyl hydrazide. An especially convenient version of the former process is to treat the carboxylic acid with ethyl chloroformate to form a mixed anhydride, which then reacts with azide ion.178 

The reaction can also be carried out on the acid using diphenyl phosphoryl azide.179 

Another reaction that can be used for conversion of carboxylic acids to the corresponding amines with loss of carbon dioxide is the Hofmann rearrangement. The reagent is hypobromite ion, which reacts to form an A-bromoamide intermediate. Like the 

In contrast to the somewhat limited synthetic utility of nitrenes, there is an important group of reactions in which migration occurs to electron-deficient nitrogen. 

Reactions Involving Carbocations, Carbenes, and Radicals as Reactive Intermediates 

This version of the Curtius rearrangement has been applied to the synthesis of amino acid analogs and structures containing amino acids. Several m-2-aminocyclopropane carboxylate esters were prepared by selective hydrolysis of cyclopropane-1,2-dicarboxylates, followed by reaction with DPPA.267 

The Curtius reaction has occasionally been used in formation of medium268 and large269 rings, usually in modest yield. 

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Gassman and Cryberg solvolyzed 125 in a number of solvents containing methanol.170 The predominant products were 126, 127, and 128. The first two, 126 and 127, are solvolysis products derived from rearrangement to electron-deficient nitrogen. But 128 almost surely results from hydrogen abstraction from the solvent. The proposed mechanisms for their formation are shown in Scheme 11. 

Rearrangements to Electron-Deficient Nitrogen and Oxygen Centers Migration of an alkyl group was discussed in Section 6.2.1.2. The well-known... 

Structure and Reactivity of Carbenes Generation of Carbenes Addition Reactions Insertion Reactions Rearrangement Reactions Related Reactions Nitrenes and Related Intermediates Rearrangements to Electron-Deficient Nitrogen... 

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