Regitz diazo group transfer

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.

Quinone diazides can also be obtained by the diazo group transfer reaction of 4-tosyl azide. For example, 9-diazo-10-anthrone (2.55) is formed from anthrone (2.54) if the reaction is carried out in an ethanol-piperidine mixture. On the other hand, if ethanol is replaced by pyridine, dimerization with loss of molecular nitrogen takes place and the azine 2.56 is isolated (Scheme 2-32 Regitz, 1964 Cauquis et al., 1965). In the preceding discussion tosyl azide was shown to be an electrophilic reagent. It therefore seems likely that it is not the anthrone 2.54 but its conjugate base which reacts with tosyl azide. 

Fig. 15.42. Preparation of diazomalonic ester via diazo group transfer via the Regitz procedure.

Diazomalonic ester is another important 1,3-dipole for synthesis. We saw the kinetics of 1,3-dipolar cycloadditions of diazomalonic ester earlier, in the discussion of Figure 12.36. The preparation of this 1,3-dipole is accomplished most conveniently with the procedure shown in Figure 12.39 diazo group transfer according to Regitz. 

Regitz, M. Reactions of carbon-hydrogen active compounds with azides. XIII. Diazo group transfer. Neuere Method. Praep. Org. Chem. 

Regitz, M., Rueter, J. Reactions of CH-active compounds with azides. XVIII. Synthesis of 2-oxo-1-diazo cycloalkanes by deformylative diazo-group transfer. Chem. Ber. 1968, 101, 1263-1270. 

Regitz, M., Menz, F., Lledhegener, A. Reactions of CH-actIve compounds with azides. XXVIII. Synthesis of a, 3-unsaturated dIazoketones by deformylating diazo group transfer. Liebigs Ann. Chem. 1970, 739, 174-184. 

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... 

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. 

Regitz, M. Transfer of diazo groups. Angew. Chem., Int. Ed. Engl. 1967, 6, 733-749. 

The Regitz reaction involves the transfer of a diazo group from the tosyl azide or mesyl azide to active methylene compounds such as 1,3-diketones and their derivatives (1) in the presence of a base leading to 2-diazo-l,3-diketones (2). 

Regitz, M., Transfer of Diazo Groups, Newer Methods of Preparative Organic Chemistry, Vol. VI, Academic Press, New York, 1971. 

Pathway A has already been discussed (2-23). In the reaction sequence C, introduction of the formyl group by a Claisen ester condensation with a formic acid ester is followed by treatment with 4-toluenesulfonyl azide, i. e., by a diazo transfer reaction (Regitz and Menz, 1968 see Sect. 2.6). Mn04 is also frequently used for the synthesis of bis- and tetradiazo compounds from the corresponding bis- and tetrahydrazones (Teki et al., 1986 Hannemann et al., 1988 and references therein). 

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