Diazo transfer sulfonyl azides

A reaction known as diazo group transfer produces diazo barbituric acid from barbituric acid and p-toluene sulfonyl azide. Additional barbituric acid affords azo barbituric acid [7]. Subsequent complexation with a nickel (II) salt yields a greenish yellow pigment. 

Bis-acceptor-substituted diazomethanes are most conveniently prepared by diazo group transfer to CH acidic compounds either with sulfonyl azides under basic conditions [949,950] or with l-alkyl-2-azidopyridinium salts [951] under neutral or acidic conditions [952-954]. Diazo group transfer with both types of reagents usually proceeds in high yield with malonic acid derivatives, 3-keto esters and amides, 1,3-diketones, or p, y-unsaturated carbonyl compounds [955,956]. Cyano-, sulfonyl, or nitrodiazomethanes, which can be unstable or sensitive to bases, can often only be prepared with 2-azidopyridinium salts, which accomplish diazo group transfer under neutral or slightly acidic reaction conditions. Other problematic substrates include amides of the type Z-CHj-CONHR and P-imino esters or the tautomeric 3-amino-2-propenoic esters, which upon diazo group transfer cyclize to 1,2,3-triazoles [957-959]. 

The HC1 generated in this reaction destroys one equivalent of diazomethane. This can be avoided by including a base, such as triethylamine, to neutralize the acid.74 Cyclic z-diazoketones, which are not available from acyl chlorides, can be prepared by reaction of an enolate equivalent with a sulfonyl azide. This reaction is called diazo transfer 5 Various arenesulfonyl azides76 and methanesulfonyl azide77 are used most frequently. Several types of compounds can act as the carbon nucleophile. These include the anion of the hydroxymethylene derivative of the ketone78 or the dialkylaminomethylene derivative of... 

In addition to previously described syntheses4-5 by diazo group transfer with deformylation,6 2-diazocyclohexanone has been prepared by two variants of this method. In one, the reaction of 2-(hydroxymethylene)cyclohexanone with -toluene-sulfonyl azide is carried out in ether/diethylamine, and an enamine is assumed to be formed as an intermediate 7 in the other, the sodium salt of the hydroxymethylene compound was treated with the lithium salt of p-carboxybenzenesulfonyl azide... 

Diazocarbonyl compounds can be prepared on insoluble supports by diazo group transfer with sulfonyl azides or by diazotization of primary amines. Diazo group transfer from sulfonyl azides to 1,3-dicarbonyl compounds proceeds on cross-linked polystyrene as smoothly as in solution (Table 10.19). When 3-keto esters or amides are... 

With a range of methods available for the formation of 1,3-dicarbonyl compounds, the dicarbonyl diazomethanes can be readily prepared via a simple diazo transfer reaction with sulfonyl azide. This has made a vast array of dicarbonyl diazomethanes available, which enhances the versatility in organic synthesis. A selection of examples from recent literature to illustrate the versatility of the cyclopropanation using dicarbonyl diazomethane in the construction of natural products as well as other biologically active compounds is described below. 

The diazo transfer reaction with sulfonyl azides has been extensively used for the preparation of diazo compounds with two electron-withdrawing groups (equation 1 ).28 Toluenesulfonyl azide (13a)29 is the standard reagent used, but due to problems of safety and ease of product separation, several alternative reagents have been developed recently. n-DodecylbenzenesuIfonyl azide (13b)30 is very effective for the preparation of crystalline diazo compounds, while p-acetamidobenzenesulfonyl azide (13c)31 or naph-thalenesulfonyl azide (13d)30 are particularly useful with fairly nonpolar compounds. Other useful reagents are methanesulfonyl azide (13e)32 and p-carboxybenzenesulfonyl azide (13f).33... 

The importance of a-diazo ketones as synthetic intermediates has led to the development of a number of general methods for their preparation.5 Particularly popular approaches include the acylation of diazo alkanes and the base-catalyzed "diazo group transfer" reaction of sulfonyl azides with 8-dicarbonyl compounds.6-7 While direct diazo transfer to ketone enolates is usually not a feasible process,8-9 diazo transfer to simple ketones can be achieved in two steps by employing an indirect deformylative diazo transfer strategy in which the ketone is first formylated under Claisen condensation conditions, and then treated with a sulfonyl azide reagent such as p-toluenesulfonyl azide.6a,6c,9,i0,11... 

The transformation of an active CH compound into the corresponding diazo derivative with -toluenesulfonyl azide has been designated a diazo transfer reaction and possesses a variety of preparative uses. The method has been useful for the syntheses of diazo derivatives of cyclopentadiene, 1,3-dicar-bonyl compounds, 1,3-disulfonyl compounds,1,3-keto-sulfonyl compounds, ketones, " carboxylic acid esters, and /3-keto imines. Further reaction of these diazo intermediates can lead to azo compounds,"- " 1,2,3-triazoles, and pyrazolinones. ... 

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 most widely used application of sulfonyl azides is in the azidation of enolates and other stabilized carbanions. The main challenge here is the avoidance of the diazo transfer reaction, which leads to diazo compounds and thus makes a diastereoselective animation impossible. Addition of the enolates to the sulfonyl azide proceeds rapidly at low temperatures (—78° or lower) to give the mesomeric ion 42 (Eq. 30).318 Reagents 41, the counter ion M+, the solvent, and the quenching reagent all influence the subsequent partition between azide and diazo compound. For enolates of esters (39) and N-acyloxazolidinoncs (40) the preferred reagent is trisyl azide (41a) 4-nitrobenzenesulfonyl azide (41c) promotes diazo transfer, and tosyl azide (41b) usually leads to mixtures of the two types of products. For ester enolates 39, either lithium or potassium as the... 

Other useful syntheses of 1,2,3-triazoles include diazo-transfer to enamino-ketones from either sulfonyl azides or S-diazo-oxindole, " and reaction of dichloroacetaldehyde tosylhydrazone with amines, and each of these is illustrated below. ... 

The possible mechanism for diazo transfer from p-toluenesulfonyl azide to active methylene compound 3 (flanked by carbonyl groups) is depicted below.1,3 Deprotonation of a-keto ester 3 with NEt3 leads to enolate 4 which attacks at the electrophilic N of the sulfonyl azide 5 to give intermediate tosyl derivative 6. Proton transfer occurs within intermediate 6 followed by elimination of p-toluenesulfonamide, leading to diazo compound 7 and the by-product -toluene sulfonamide 8.1,3... 

Diazo transfer to pyrazolidone (39) using azidinium salt (38) affords diazo pyrazolidone (41) and imine 40 this method has proved superior to the aryl sulfonyl azide reactions in cases where azo coupling occurs. 

Tricyclodecanone (85) is formylated to 86, then converted to the diazoketone (87) via deformylation diazo transfer reaction using p-toluene sulfonyl azide in the presence of... 

Dimedone provides diazo dimedone (135) with -benzoic acid sulfonylazide (84%) and with p-tolyl sulfonylazide (96%). Weak nucleophilic base such as 1,8-diazabicyclo[5.4.0]undecen-7-ene (DBU) has been used as catalyst for the diazo transfer reactions of 1,3-diketones (136 -139).55 A highly efficient methodology in solid state has been developed for the synthesis of a-diazo carbonyl/sulfonyl compounds from 1,3-diketones using tosyl azide. This method avoids any aqueous workup and diazo compounds are obtained via a column filtration over silica gel. 0... 

IX. SULFONYL AZIDES AS SYNTHONS A. Diazo Transfer Reaction... 

In diazo transfer reactions both N-atoms, i. e., the entire diazo group, are introduced into a suitable substrate from a diazo donor (2-46). In most cases this transfer reagent is a sulfonyl azide (Y=N2 = Ar-S02N=N2 or R-S02-N=N2), from which the N(yff)- and N(y)-atoms will form the diazo group in the product. There are, however, also cases in which the diazo group of an aromatic diazonium ion or of a diazoalkene is transferred. Such examples are of minor importance. 

The two principal and most general synthetic routes to a-diazocarbonyl conpounds are (1) acylation of diazoalkanes and (2) diazo-transfer reactions to carbonyl conpounds with sulfonyl azide reagents. Caution Diazo conpounds and azide reagents are presumed to be toxic and potentially explosive, and appropriate safety measures should be deployed when handling these conpounds. 

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... 

Polymer-supported Reagents. Polymer-supported toluene-sulfonyl azide I3I was prepared by reaction of a macroreticular p-toluenesulfonyl chloride resin (prepared, in turn, by chlorosul-fonation of Amberlite XE 305) with excess sodium azide. Resin 13, a solid-phase equivalent of />-toluenesulfonyl azide, can be used for diazo transfer to /3-dicarbonyl compounds (eq 14). Unlike tosyl azide, resin 13 does not detonate on shock treatment and is stable at room temperature. Recently, an analogous benzenesul-fonyl azide resin has been prepared from PS-TsCl. ... 

Introduction. TfNs acts both as diazo- and as triflylamino-transfer reagent. Unlike other sulfonyl azides, it does not act as azido-transfer reagent, but readily undergoes cycloaddition to electron-rich alkenes at room temperature. 

General Considerations. The reactions of arylsulfonyl azides with enolates have been reported to give a range of products, depending on the fragmentation of the initial adduct. This may differ according to the nature of the enolate, the particular sulfonyl azide, and the quenching procedure. Net diazo transfer is usually observed for stabilized enolates, while azide transfer is more common with more reactive enolates. 

Another advantage of sterically demanding trisyl azide is the selective azidation of cyclic 8-ketoesters (eq 32). Thus, the desired azidation product A was slowly formed as a single product in either THF or MeCN. In contrast, more reactive sulfonyl azides such as 4-methoxybenzenesulfonyl azide, 4-nitrobenzenesulfonyl azide, mesyl azide, triflyl azide, and tosyl azide provided not only the azidation product A but also a ring-contraction product B, a ring-opened diazo-transfer product C, and a mixture of ring-opened olefins D. The amounts of by-products B, C, and D were dependent upon the azide reagent. 

Related Reagents, p-toluenesulfonyl azide and methane-sulfonyl azide have been used widely for diazo transfer to stabilized enolates. The latter reagent simplifies isolation of the desired product, but is potentially explosive and must be handled with care. Relative to other aryl analogs, the electron-deficient p-nitrobenzenesulfonyl analog favors diazo transfer to imide enolates. ... 

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