Regitz procedure

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

The original Regitz procedure for diazo transfer to a -keto ester (131) used p-toluenesulfonyl azide (132 equation 54). This reagent works well, and is easy to prepare from the corresponding sulfonyl chloride. A disadvantage of this reagent is that the p-toluenesulfonylamide coproduct (134), as well as any excess p-toluenesulfonyl azide, have to be removed from the product diazo ketone (133) before it can be used. 

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... 

For a review, sec Regitz Maas Diazo Compounds-, Academic Press New York. 1986, pp. 257-295. For an improved procedure, see Wulfman Youscfian White Synth. Commun. 1988, IS, 2349. 

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. 

The diazo transfer method offers a route to terminal diazo derivatives, as a-diazo ketones are smoothly cleaved by treatment with alkali ethoxide. An Organic Syntheses procedure is described by Regitz et al. (1973) for obtaining tert-hwtyX diazoacetate (2.114). The diazo transfer from 4-toluenesulfonyl azide to tert-huiy acetoacetate (2.113) in anhydrous acetonitrile and one equivalent of triethylamine yields tert-h xty a-diazoacetate (94-98%) after cleavage of the central C —C bond of the primarily formed a-diazo ketone with sodium methoxide (2-52). With ethyl acetoacetate instead of the tert-h xiy ester 2.113, the yield is, however, only 65% (Regitz, 1965 b). 

Reports of fully unsaturated monocyclic 1,3-diazepines are rare but the formation of 5/f-1,3-diazepine is reported by Regitz and co-workers <88CB357>. A [4ti -t- 27t] cycloaddition of 3-alkyl diazarines with t-butyl 2,3,4-tri-/-butyl-cyclobutadiene-l-carboxylate is the key step in this procedure, which affords the 1,3-diazepine (39). Clearly the initial step is the formation of the... 

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