Bamford-Stevens reaction protic

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 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. 

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,... 

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. 

BAMFORD-STEVENS REACTION 4.3.2.1 Protic Banford-Stevens Process 43.2.2 Aprotic Banford-Stevens Process... 

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. 

Interesting stereochemical aspects of the protic Bamford-Stevens reactions of the epimeric 7-oxohexa-hydrocannabinol tosylhydrazone acetates (70) and (72) have been recently demonstrated. When the axial epimer (70) was added to sodium ethylene glycol, the ring expansion product (71) was obtained in 38% yield. On the other hand, reaction of the equatorial epimer (72) under the same conditions yielded (73) in 56% yield (equations 45 and 46). Notably, the aprotic Bamford-Stevens reaction of the axial epimer (70) gave rise to (73) (30-40% yield) after acetylation. 

The protic Bamford-Stevens reaction has been successfully utilized in the asymmetric synthesis of the naturally occurring sesquiterpenes (+)-a-eudesmol and (-)-a-selinene. Here, the more-substituted alkene was formed preferentially (equation 4,1). ... 

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. ... 

Most commonly, photolytic, thermal, or transition metal catalyzed decomposition of diazoalkanes is used to create carbene molecules. A variation on catalyzed decomposition of diazoalkanes is the Bamford-Stevens reaction, which gives carbenes in aprotic solvents and carbenium ions in protic solvents. Another method is induced elimination of halogen from gem-dihalides or HX from a CHXj moiety, employing organoHthium reagents (or another strong base). It is not certain that in these reactions actual free carbenes are formed. In some cases there is evidence that completely free carbene is never present instead, it is likely that a metal-carbene complex forms. Nevertheless, these metallocarbenes (or carbenoids) give the expected products. 

Bamford-Stevens and Shapiro Reactions. The Bamford-Stevens reaction is used to obtain unsaturated compounds from tosylhydrazones. A base is required to generate its monoanion, which thermally decomposes to yield the corresponding di-azo derivatives. These reactive species evolve to give an aUcene through carbenium ions in protic solvents or carbenes in aprotic solvents. The thermal decomposition of the monoanions of trisyl-hydrazones is commonly used to obtain diazoalkanes for different applications such as functionalization of solid supports, epox-idation and alkenylation of aldehydes, or the study of radicals and carbenes The functionalization of a Merrifield resin with... 

Scheme 9.70. A representation of the Bamford-Stevens reaction. Both pathways, a protic and an aprotic, are shown. The same product is formed in both, althongh the intermediates are different. See Bamford, W. R. Stevens, T. S. /. Chem. Soc., 1952, 4735, and Caglioti, R. Tetrahedron Lett., 1962,1261, as well as Shapiro, R. H., ibid, 1968,345.

The problem of distinguishing between carbenoid and carbonium ion mechanisms of decomposition of diazoalkanes in protic media arises also in interpreting the base-induced decomposition of tosylhydrazones. In the original procedure for this widely-used reaction (W. R. Bamford and Stevens, 1952), the tosylhydrazone of a carbonyl compound is treated with the sodium salt of ethylene glycol in refluxing glycol. A mixture of olefins and alkoxyethanol is produced (equation 6). Many... 

In the early 1950s Bamford and Stevens reported a thermally induced reaction of ketone tosylhydra-zone monosodium salts that gives products derived either from carbene intermediates (aptotic conditions) or carbocations (protic conditions). Both reactions, which are illustrated in Scheme 51, can give alkenes as the major product, although the protic reaction is of marginal synthetic value because mixtures of alkene regioisomers and rearrangement products are normally obtained. On the other hand, the... 

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