Bamford-Stevens reaction aprotic

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. 

Finally, hindered arenesulfonylhydrazones can undergo addition of the alkyllithium rather than deprotonation, and, in fact, the normal Shapiro conditions generally do not give any alkene if an a-methine proton must be removed in the initial deprotonation step. Shapiro reported that the use of LDA overcomes the problem,but there are later examples in which this modification is ineffective. In one such case, lithium t-butylamide proved to be superior (Scheme 72) and in another it proved necessary to re-son to the aforementioned N-aminoaziridine derivative in an aprotic Bamford-Stevens reaction, when the normal Shapiro and Bamford-Stevens conditions failed (Scheme 73). ... 

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. 

A structurally intriguing dimethyl[6]ditriaxane (84) has been synthesized from the polycyclic diketone tosylhydrazone (83) by the aprotic Bamford-Stevens reaction via a carbenic interm iate (equation 49). ... 

The aprotic Bamford-Stevens reaction has been utilized for the development of a methodology towards 1,2-carbonyl transposition in natural product synthesis. The example in Scheme 8 illustrates the regiocontrolled alkene formation for the synthesis of hirsutic acid. ... 

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. ... 

Using this type of evaluation, Nickon (1993) calculated the bystander assistance factors B[X] given in Table 8-1 for aprotic Bamford-Stevens reactions at 150 10°C (experimental data from various sources). 

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... 

Alternatively, for the Bamford-Stevens reaction, a sulfonylhydrazone, formed in the same way, can be treated either with sodium metal (Na) in the presence of a proton source (typically, 1,2-dihydroxyethane [ethylene glycol, HOCH2CH2OH] is used and only enough sodium metal is added to react with one of the two hydroxyl groups) and a carbocation is generated or with sodium metal (Na) in the absence of a proton source in an aprotic solvent such as methylbenzene [toluene, CeHsCHs] where a carbene forms (Scheme 9.70). 

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 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 ... 

Bamford-Stevens and Shapiro Reactions. Thermal decomposition of the monoanions of arenesulfonylhydrazones in aprotic... 

---