And the Bamford-Stevens reactions

Okfm Syntheses. Conversion of aldehydes and ketones to olefins by the base-catalyzed decomposition of -toluenesulfonic (Ts) acid hydrazones (10) is known as the Bamford-Stevens reaction (54,55). 

The alkyl lithium method gives high yields of -olefins from 17-ketones via the tosylhydrazones. A -Olefins are formed from 6- and 7-ketones. (Compare with the Bamford-Stevens reaction which gives A - and A -olefins, respectively.) In the presence of an excess of alkyl lithium, alkylation may occur. 

From 5 the formation of alkene 2 is possible through loss of a proton. However, carbenium ions can easily undergo a Wagner-Meerwein rearrangement, and the corresponding rearrangement products may be thus obtained. In case of the Bamford-Stevens reaction under protic conditions, the yield of non-rearranged olefins may be low, which is why this reaction is applied only if other methods (e.g. dehydration of alcohols under acidic conditions) are not practicable. 

The Bamford-Stevens reaction and the Shapiro reaction share a similar mechanistic pathway. The former uses a base such as Na, NaOMe, LiH, NaH, NaNHa, heat, etc., whereas the latter employs bases such as alkyllithiums and Grignard reagents. As a result, the Bamford-Stevens reaction furnishes more-substituted olefins as the thermodynamic products, while the Shapiro reaction generally affords less-substituted olefins as the kinetic products. 

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. 

The intermediate bicyclo[2,2,l]heptyl cation has been written in Fig. 1 in its unbridged form by analogy with conclusions reached from studies of the Bamford-Stevens reaction of 18 stereospecifically deuteriated in either the 6-exo- or 6-endo positions (Nickon and Werstiuk, 1966). Under aprotic conditions (diglyme/sodium methoxide), the product is entirely norticyclene (19), formed without loss of deuterium in keeping with carbene formation followed by intramolecular insertion. Under standard protic conditions, 19 still constitutes more than 90% of the reaction product, but 19% of the label is lost from ea o-deuteriated starting material and 52% from the endo-deuteriated compound,... 

The reduction of a carbonyl group to an olefin has been accomplished by the Shapiro modification5 of the Bamford-Stevens reaction and by the hydride reduction of the corresponding enol ether,6 enol acetate,7 or en-amine.8 The nickel reduction of the thioketal has also been used successfully.9... 

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 the base-catalyzed decomposition of arenesulfonylhydrazones of aldehydes and ketones, leading to the formation of alkenes an or cyclopropanes. There are several important general reviews in this area of organic synthesis. Since the reactions are mostly carried out either in protic or in aprotic solvents, the reaction types are divided into the protic and aprotic Bamford-Stevens processes. This section reviews recent examples in the synthesis of alkenes and cyclopropanes from arenesulfonylhydrazones, which is closely related to the following Shapiro reaction. 

The Bamford-Stevens reaction is the key step in a convenient procedure for the conversion of aldehydes and ketones into the corresponding diazoalkanes. Here, the use of 2,4,6-triisopropylbenzenesulfo-nylhydrazone (trisylhydrazone) is far superior to the use of the more common tosylhydrazones (equation 50). This behavior is attributed to the greater release of steric compression in the decomposition of ort/io-substituted arenesulfonylhydrazones. 

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 base catalyzed decomposition of arylsulfonylhydrazones of aldehydes and ketones to provide alkenes is called the Bamford-Stevens reaction. When an organolithium compound is used as the base, the reaction is termed the Shapiro reaction. The most synthetically useful protocol involves treatment of the substrate with at least two equivalents of an organolithium compound (usually MeLi or BuLi) in ether, hexane, or tetramethylenediamine. The in s/ft formed alkenyllithium is then protonated to give the alkene. The above procedure provides good yields of alkenes without side reactions and where there is a choice, the less highly substituted alkene is predominantly formed. Under these reaction conditions tosylhydrazones of a,(3-unsaturated ketones give rise to conjugated dienes. It is also possible to trap the alkenyllithium with electrophiles other than a proton. 

Solid-state photolyses were conducted in argon-purged borosilicate flasks. After 2 h, no more diazirine 26 was present by NMR nor by gas chromatographic (GC) analysis. The results of solution photolyses of diazirine 26 are shown in Table 3. Carbene 27 can also be generated from the 2-methylcyclohexanone p-tosyl hydra-zone sodium salt (33) via the Bamford-Stevens reaction.116 The gas phase results are also included in Table 3 as are the results of Wilt and Wagner.111... 

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

In the Bamford-Stevens reaction,2 sodium methoxide is commonly used as base. Kirmse et al.m have shown that use of sodamide or sodium hydride converts tosyl-hydrazones of aliphatic ketones and cyclic ketones into 1-olefins. Thus the tosyl-hydrazone of pentanone-2 gives pentene-1 in 83% yield together with small amounts of cis- and trans-pentene-2. 

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). 

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