Japp-Klingemann reaction, enol

As in the Japp-Klingemann reaction, when Z is an acyl or carboxyl group (in the case of R2CH—Z), it can be cleaved. Since oximes and nitroso compounds can be reduced to primary amines, this reaction often provides a route to amino acids. As in the case of 12-4, the silyl enol ether of a ketone can be used instead of the ketone itself. Good yields of a-oximinoketones (20) can be obtained by treating ketones with fert-butyl thionitrate. ... 

In addition to preparation of arylhydrazones from the carbonyl compounds and an arylhydrazine, the Japp-Klingemann reaction of arenediazonium ions with enolates and enamines is an important method for preparation of arylhydrazones. This method provides a route to monoarylhydrazones of a-dicarbonyl compounds from /3-keto acids and to the hydrazones of pyruvate esters from / -keto esters. Enamines also give rise to monoarylhydrazones of a-diketones. Indolization of these arylhydrazones provides the expected 2-acyI-or 2-alkoxycarbonyl-indoles (equations 95-97). 

The initial intent to cover the subject exhaustively had to be abandoned because of the overwhelming amount of relevant literature. The following reactions are not covered but are briefly discussed, with references to reviews and seminal papers, in the section on Comparison with Other Methods reactions of carbanions and enolates and their surrogates with nitrogen oxides, nitrite and nitrate esters, and nitroso and nitro compounds reactions of enolates with diazonium salts, including the Japp-Klingemann reaction the diazo transfer reaction except as it interferes with the synthesis of azides the animation of boranes and the Neber rearrangement. 

Serotonin has been synthesised by several routes the method shown relies on a Fischer indole synthesis, the requisite aryl-hydrazone being constructed by a process known as the Japp-Klingemann reaction in which the enol of a 1,3-dicarbonyl compound is reacted with an aryl-diazonium salt, with subsequent cleavage of the 1,3-dicarbonyl unit. 

In addition to direct formation from an arylhydrazine and a carbonyl compound, iV-aryl-hydrazones can be prepared from aryldiazonium ions by coupling with enolates or enamines (Japp-Klingemann reaction). This reaction has most frequently been applied to j -ketoesters. The coupling product undergoes deacylation so that the ultimate product of Fischer cycUzation is an indole-2-carboxylate ester (Scheme 58) <92JMC4823>. 

Reaction of an aqueous ethanol solution of the sodium enolate of 1-adamantyl-malonic aldehyde with benzenediazonium chloride gave (680 67%), which was hydrolysed to (681 86%). This is the first instance that the postulated intermediate (680) has been isolated in the Japp-Klingemann reaction of a l,3-dialdehyde. ° ... 

SCHEME 9 Japp-Klingemann reaction of the enol from 24. 

It should be mentioned that O-methylation of the ketone in 24 was necessary to avoid competition between the Heck-Matsuda arylation and the nucleophilic addition of the enol to the aryldiazonium salt, a process known as the Japp-Klingemann reaction. Indeed, when 24 was submitted to the standard Heck-Matsuda reacticm conditions, the azo compound 25 was obtained in quantitative yield (Scheme 9). Azo compounds are easily detected due to the formation of highly colored products via this reaction. 

The Japp-Klingemann coupling of aryldiazonium ions with enolates and other nucleophilic alkenes provides an alternative route to arylhydrazones. The reaction has most frequently been applied to (Vketoesters, in which deacylation follows coupling and the indolization affords an indole-2-carboxylate ester. 

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