Diazo transfer reaction sulfonyl azides

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... 

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 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 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... 

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 HCl generated in this reaction destroys one equivalent of diazomethane. This can be avoided by including a base, such as triethylamine, to neutralize the acid. " Cyclic a-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 Various arenesulfonyl azides and methanesulfonyl azide are used most frequently. Several types of compounds can act as the carbon nucleophile. These include the anion of the hydroxymethylene derivative of the ketone or the dialkylaminomethylene derivative of... 

Scheme 3.25 Aikyi azides via the diazo transfer reaction using imidazole-1-sulfonyl azide hydrochloride ...

Preparative Methods diazomalonates are generally prepared by diazo transfer reaction of malonates and sulfonyl azides. A recent modification employs polystyrene-supported trialkylam-monium azide (generated in situ) under phase-transfer catalysis conditions and allows for facile isolation. ... 

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]. 

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... 

Numerous methods to prepare individual classes of aliphatic diazo compounds have been extensively developed. The major strategies for their synthesis involve the alkaline cleavage of N-alkyl-N-nitroso-ureas, -carboxamides and -sulfonamides, dehydrogenation of hydrazones, as well as diazo group transfer from sulfonyl and related azides to active methylene compounds, and electrophilic diazoalkane substitution reactions. These synthetic methods have been comprehensively reviewed (15,16). Useful information on the preparation of selected diazo compounds can be found elsewhere (6,17). 

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... 

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. ... 

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. 

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. ... 

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. 

A study of reactions of benzocyclic jS-keto esters with sulfonyl azides has provided further indication, from results for a benzosuberone, that the electronic features of the azide can profoundly influence the distribution of azidation, diazo transfer, and ring contraction products. 

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... 

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