Diazo compounds, Bamford-Stevens reaction

Phosphoryl-substituted diazo compounds of general type 4 have recently been synthesized by amine diazotization, Bamford-Stevens reaction, and diazo group... 

The most frequent synthetic approaches, summarized in Scheme 4, are towards the primary photophores. The preparation of aryl azide derivatives follows the typical retro-synthetic pathway in the majority of the reported cases (Scheme 4 A), and, practically, diazotation is the most commonly used procedure [24 - 29]. In the case of diazirines only one major synthetic sequence is repeated ammonolysis of oximes followed by dehydrogenation (Scheme 4B) [30-32]. There are various ways of preparing diazo- or diazocarbonyl-compounds most frequently the Forster and Bamford-Stevens reactions (Scheme 4C) are employed [33-37]. 

The reaction also takes place with other bases (e.g., LiH,213 Na in ethylene glycol, NaH, NaNH2) or with smaller amounts of RLi, but in these cases side reactions are common and the orientation of the double bond is in the other direction (to give the more highly substituted olefin). The reaction with Na in ethylene glycol is called the Bamford-Stevens reaction,214 For these reactions two mechanisms are possible—a carbenoid and a carbocation mechanism.215 The side reactions found are those expected of carbenes and carbocations. In general, the carbocation mechanism is chiefly found in protic solvents and the carbenoid mechanism in aprotic solvents. Both routes involve formation of a diazo compound (34) which in some cases can be isolated. 

Phenyldiazomethane, 1, 834. A new method for preparation of this (and other aryl-diazomethanes) involves a vacuum pyrolysis of the sodium salt of benzaldehyde tosylhydrazone, a method introduced for carrying out the Bamford-Stevens reaction. The yield is 80%, the highest yield yet reported. Another advantage is that the reagent is obtained free from solvents. The pyrolysis can also be coitducted in ethylene glycol at 80° with extraction of the aryldiazomethane into hexane.1 Caution All diazo compounds arc highly toxic and potentially explosive. 

Mechanism The first step of the Bamford-Stevens reaction is the formation of the diazo compound A by the treatment of tosylhydrazone with a base. The reaction mechanism involves a carbene B in an aprotic solvent (Path A) and carbocation C in a protic solvent (Path B) (Scheme 4.53). When an aprotic solvent is used, predominantly Z-alkenes are obtained, while a protic solvent gives a mixture of E- and Z-alkenes. If there is a choice of product, the more substituted alkene is produced predominantly. 

The Bamford-Stevens reaction is particularly effective for the generation of 9-phenyl-l(9)-homo-cubene (93), the most twisted alkene yet known. Thus, thermolysis of the cubyl phenyl ketone tosylhydrazone (91) in ethanolic sodium ethoxide or photolysis of the diazo compound (92) in ethanol both give good conversions to a 3 2 mixture of the isomeric ethers (95) and (96) (Scheme 11). The formation of (96) suggests the intervention of l-phenyl-9-homocubylidene (94) via the rearrangement of (93). 

The reaction of tosylhydrazones with sodium in ethylene glycol to give alkenes had been observed before (Bamford-Stevens reaction) other bases, e.g. NaOMe, alkali metal hydrides and NaNH2 were also used. However, in these cases side reactions occur and, in contrast to the Shapiro reaction, the more highly substituted alkene is predominantly formed. Two mechanisms are discussed for these reactions a mechanism via a carbenium ion, which usually takes place in protic solvents, and a carbene mechanism in aprotic solvents (Scheme 28). In both cases diazo compounds are intermediates, which can sometimes be isolated. ... 

As masked diazo compounds the salts of tosyl hydrazones can react thermally and photochemically ( Bamford-Stevens-reaction ) to give alkenes (Scheme 3, variable... 

The first successful syntheses of phosphorus-containing diazoalkyl compounds (1) appear to have been reported independently by two groups of workers. Petzold and Henning employed a method presently described as that of diazo transfer, in which an active methylene compound, as its anion, is treated with an aromatic sulphonyl azide. Seyferth et al on the other hand, reported on a development to the Bamford-Stevens reaction, in which a carbonyl/7-toluenesulphonylhydrazone is treated with a base. Both methods thus depend on modifications to compounds with existing phosphorus-carbon bonds, as do other procedures which have since been developed. 

The Bamford-Stevens reaction is frequently used not for the isolation of aliphatic diazo compounds, but for the synthesis of the products obtained by dediazoniation either by the carbene or the carbocation mechanisms in (2-38). As 4-toluenesulfonyl-hydrazones are fairly stable under Bamford-Stevens conditions, the reactions must be carried out at higher temperature, which is, of course, a disadvantage when it is desired to stop the reaction at the diazoalkane stage. Yields above 90% can, however, be obtained in some cases, particularly for the synthesis of 9-diazofluorene (Dudman and Reese, 1982). 

Bamford-Stevens reaction. Tosylhydrazones undergo the Bamford-Stevens reaction in a two-phase system (aqueous NaOH-dioxane) to give diazo compounds. Depending on the structure, the diazo compounds can be isolated or converted into alkenes or products of cyclization or cycloaddition. ... 

Preparing the diazoalkane in situ by warming the sodium salt of the corresponding toluene-p-sulfonylhydrazone (Bamford-Stevens reaction, see Scheme 4.76) avoids isolation of the potentially explosive diazo compound. In the presence of a chiral sulfide the methodology has been applied to the asymmetric synthesis of epoxides (4.105). ... 

Much more widely used carbene precursors are tosylhydrazones, which are readily prepared from aldehydes or ketones by reaction with 4-toluenesulfonyl hydrazide. Tosylhydrazones produce transient diazo compounds by base-catalyzed elimination of toluenesulfinate. The diazo compound is not normally isolated, and decomposes to the carbene on heating. The whole process is known as the Bamford-Stevens reaction. The leaving group is not the famihar tosylate (toluene-p-sulfonate, p.CH3-C, H4S03 , TsO ), but the less famihar toluene-p-sulfinate (Ts , P.CH3-C5H4S02 ) (Scheme 5.7). 

The Bamford-Stevens reaction is the formation of an alkene 4 by the treatment of the tosylhydrazone 1, of an aldehyde or a ketone, with a base. A few diazo compounds 3 can be isolated if mild temperatures are employed however in the majority of cases, the diazo compounds thermally decompose to form alkenes. 

The mechanism was originally proposed by Powell and Whiting," with further corroboration by others soon thereafter. The first step of the Bamford-Stevens reaction is the formation of the diazo compound 3, via the tosylate salt 2. ... 

As mentioned previously, the Aggarwal group has utilized the Bamford-Stevens reaction as a method to in situ generate diazo compounds 33 and further trap out these in a subsequent reaction. This in situ concept was initially tested on the sulfur-ylide 37 mediated epoxidation of aldehydes 39. "... 

From Diazo-compounds. The Wolff rearrangement of a-diazo-ketones has been reviewed and a discussion of the Bamford-Stevens reaction and its associated mechanisms has appeared. The details of a cryochemical synthesis of cyclo-propanone from keten and diazomethane have been described, as have syntheses of cyclopropanone and cyclopropanone acetal. The photolysis of 1-diazobutane, resulting in methylcyclopropane, has been subjected to physico-chemical study. 

A liimtation of the current protocol is the use of diazo compounds, which are potentially explosive and not readily available. The inherent hazards in handling these diazo compounds severely limit the practical apphcation of this methodology. In 2001, Aggarwal and coworkers disclosed a modified Bamford-Stevens reaction [29] for the in situ generation of diazo compound from N-tosylhydrazone salts. The addition of BnEtsN CT as a phase-transfer catalyst can enable the diazo compound to be produced at 30-40°C (Scheme 20.12) [30]. 

Diazo compounds can be dediazonized by transition metal complexes to generate metallocarbenes, which are important intermediates in various transformations [45-48]. Since tosylhydrazones have been found to be readily available precursors of diazo compounds through the Bamford-Stevens reaction, a series of transition metal-catalyzed reactions of aldehyde tosylhydrazone salts in the presence of base and phase transfer catalyst (PTC) have been reported since 2000 [49-53]. It has been considered that metal carbenes generated from the in situ generated diazo compounds are involved in the catalytic cycle of these reactions -see (7). 

Similar to the Pd-catalyzed reaction of diazo compounds with benzyl halides [73], the reaction was proposed to be initiated by oxidative addition of aryl halide to Pd(0) species to form aryl palladiumfll) complex A. Then Pd carbene B is produced by decomposition of the in situ generated diazo compound from A -tosylhydrazone through Bamford-Stevens reaction with the aid of base under heating. Migratory insertion of Pd carbene to Pd-aryl bond leads to Pd(Il) intermediate C. The compound then midergoes p-hydride elimination to yield complex D with the formation of di- or trisubstituted olefins (Fig. 5). 

Weak base such as cesium carbonate has been utilized in this reaction to generate diazo compounds in situ from tosylhydrazones through the Bamford-Stevens reaction. The reaction is initiated by palladium-promoted decarboxylation of propargylic carbonate to form propargylpalladium complex A, which then tautomerizes to afford allenylpalladium intermediate B. Subsequently, the common carbene formation-migratory insertion-p-hydride elimination occurs to afford various vinylallenes (Fig. 30). 

The Bamford-Stevens decomposition of tosylhydrazones by base has been applied to steroids, although not extensively. It has been demonstrated that the reaction proceeds via a diazo compound which undergoes rapid decomposition. The course of this decomposition depends upon the conditions in proton-donating solvents the reaction has the characteristics of a process involving carbonium ions, and olefins are formed, often accompanied by Wagner-Meerwein-type rearrangement. In aprotic solvents the diazo compound appears to give carbene intermediates which form olefins and insertion products ... 

Carbenoid generation of nitrogen ylides represents a useful alternative to the widely employed base-promoted methodology.49 The reaction of aliphatic diazo compounds with tertiary amines was first investigated by Bamford and Stevens in 1952.50 The formation of a-benzyl-a-dimethyl-aminofluorene (99) from the reaction of diazofluorene (97) with ben-zyldimethylamine is consistent with a mechanism involving the generation of ammonium ylide 98 which then undergoes a [l,2]-benzyl shift. 

Because of the difficulties of purification and handling, many of the results for diazoalkanes have been obtained from reactions in which the diazo compound is not the starting material but in which it may reasonably be supposed to be an intermediate. Most popular in this respect has been the base-catalysed decomposition of arylsulphonyl-hydrazones of aliphatic aldehydes and ketones, a reaction which was first investigated by Bamford and Stevens (1952). Because the reaction... 

The base-mediated conversion of arylsulfonylhydrazones to alkenes was first observed by Bamford and Stevens in 1952.6 In a representative transformation, tosylhydrazone 3 was converted to cyclohexene (4) in quantitative yield after refluxing for 90 minutes in an alkoxide solution derived from dissolution of sodium in ethylene glycol. These reactions are believed to proceed via intermediate diazo compounds, which are transformed to alkenes by thermal elimination processes. 

---