1,3-Ketones, Regitz diazo reactions

One popular method in the synthesis of a-diazo ketones is in the base-catalyzed diazo group transfer reaction of sulfonyl azides with activated dicarbonyl compounds The Regitz Diazo Reaction) While direct diazo transfer to ketone enolates is usually not feasible, a two step deformylative diazo transfer strategy has been employed, whereby a ketone is first... 

Fig. 14.29. Preparation of an a-diazoketone (compound E) from a ketone (A) and subsequent Wolff rearrangement of the a-diazoketone. Initially, A is transformed to give the enolate B of its a-formyl derivative. In a Regitz diazo group transfer reaction, this will then be converted into the a-diazoketone E. Ring contraction via Wolff rearrangement occurs and the 10-membered cyclic diazoketone C rearranges in aqueous media to give the nine-membered ring carboxylic acid E via the ketene D.

The reaction sequence is called the Regitz diazo transfer and requires active methylene compounds as substrates/ Hence it is common to use formic esters to create P-carbonyl compounds from ketones or aldehydes in an aldol reaction. These are used as substrates for deformy-lative diazo transfer reactions in which the diazo group is transferred and the formyl group is removed in one concerted step. The mechanism of the deformylative diazo transfer is shown below. In this case the bulky base NaHMDS ensures deprotonation at the less-hindered a-position of 3, forming the so-called kinetic enolate 13. This enolate is formylated by ethyl formate yielding the P-formyl ketone 14, which is used as substrate in the deformylative diazo transfer. 

The Regitz reaction provides a gateway for the synthesis of the following diazo derivatives cyclopentadienes, cyclohexadienes, ketones, 1,2-, and 1,3-diketones and their derivatives, (3-keto esters, a-iminoketones, a-ketohydrazones, amino-1,3-diketones, nitro-1,3-diketones and 1,3,5-triketones. Secondary reactions of diazo compounds lead to heterocycles such as 1,3,5-triazoles, 1,2,3-thiadiiazoles, and pyrazolines. 

The direct diazo transfer from sulfonyl azides to methyl ketones is usually not a practicable process, with the exception of the a-diazotization of ketones with 2,4,6-triisopropylbenzenesulfonyl azide under phase-transfer conditions. However, diazomethyl ketones amenable to the Arndt-Eistert reaction can be easily prepared in two steps by a formylation-deformylation diazo-transfer sequence (Regitz procedure ). A related practical method advantageously applies the detrifluoroacetylation of a-trifluoroacetyl ketones tScheme 3 a). The preparation of 2-diazo-1,3-dicarbonyl compounds is commonly best performed with p-toluenesulfonyl azide (TsNg) as the diazo-transfer reagent tScheme 3.9h). > An issue... 

P-Enamino ketones or esters 30, readily accessible from 1,3-diketones or P-ketoesters, are susceptible to diazo transfer (Regitz reaction [499]) with mesyl or tosyl azide in basic medium at room temperature and subsequent cyclization to give 4-acyl-(or 4-carbalkoxy-) 1,5-substituted 1,2,3-triazoles 32 [500] ... 

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