Bamford-Stevens conditions

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). ... 

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). 

The Mann group demonstrated a new approach to the skeleton of the aphidicolin diterpenoid 54. Treatment of tosylhydrazone 52 with aprotic Bamford-Stevens conditions afforded the required alkene 53. 

However, protic Bamford-Stevens conditions gave the unusual mixed acetal 58, presumably via the mechanism shown. 

A novel carbene-insertion reaction at the 3-position of the benzothiophen group was postulated for the formation of (47) from the tosylhydrazone of 2-(2 -benzo-thienylthiq)-5-nitrobenzaldehyde under Bamford-Stevens conditions. The new... 

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 ... 

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 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,... 

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 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. 

Chandrasekhar, S., Rajaiah, G., Chandraiah, L., Swamy, D. N. Direct conversion of tosyihydrazones to tort-butyl ethers under Bamford-Stevens reaction conditions. Syn/etf 2001,1779-1780. 

No increased C H insertion into methyl group. In contrast to all other reaction conditions, trace amounts of insertion product 30 are produced only by the thermal Bamford-Stevens method in high-boiling NMP.111 Formation of bis (2-methylcyclohexanylidene)hydrazine (31) is inhibited in MeOH, due to the short... 

Under more vigorous conditions, the Bamford-Stevens reaction yields diazoalkanes only as unobservable, metastable intermediates. The carbene formed is also metastable. This procedure is used, however, for the synthesis of compounds that are carbene products. 

No drastic reaction conditions are required for Bamford-Stevens reactions of a-diketone mono-4-toluenesulfonyl hydrazones. The conditions are similar to those of quinone mono-4-toluenesufonyl hydrazones discussed in Section 2.6. 

Ketone 4-toluenesulfonylhydrazone salts can be used for carbene formation. The mild thermolysis and the photolysis of these salts leading to diazoalkanes are known as the Bamford-Stevens reaction. If run under more energetic conditions, the metastable diazoalkanes form carbenes and their subsequent products (e.g., alkenes), or, in the presence of mild acids, products of carbocations (see Subsect. 2.5.2). 

Carbenes produced by photolysis of diazoalkanes are highly energetic species and often react indiscriminately. Thermal decomposition of diazoalkanes can be catalysed by certain transition metal (particularly copper or rhodium) salts, to produce less energetic and more selective carbenes. The active species in such a reaction is thought to be the metallocarbene rather than the free carbene. Another convenient and widely used route to alkylcarbenes is the thermal or photolytic decomposition of the lithium or sodium salts of toluene-p-sulfonylhydrazones. The diazoalkane is first formed (by elimination of the toluenesulfinate anion) and decomposes imder the reaction conditions to give the carbene (4.76). This process is often referred to as the Bamford-Stevens reaction. 

When cyclobutanone is subjected to the conditions for the Bamford-Stevens reaction, the major products are cyclobutene and methylenecyclopropane. Propose a mechanism to account for their formation. 

Nickon investigated the 1,2-hydrogen shifts in thermal and photic Bamford-Stevens reactions of cyclohexanones. Under eonditions known to favor the Shapiro reaction, tosylhydrazone 18a afforded the two expected alkenes 19 and 20 as well as an unexpected product (identified as 21) in a ratio of 15 60 25. Under conditions known to favor the Bamford-Stevens reaction, lithium salt 18b was subjected to thermolysis (neat, 170 °C) and also to photolysis (pentane suspension, -70 °C). Under both sets of conditions the three products 19, 20 and 21 were formed in approximately the same ratio (84 4 12 and 83 6 11), thus demonstrating the switching of major alkene product from 19 to 20 on moving from the Shapiro reaction to the Bamford-Stevens reaction. 

Direct conversion of tosylhydrazones to tert-butyl ethers under Bamford-Stevens reaction conditions was recently demonstrated by... 

As in the Corey synthesis, an intramolecular Mannich reaction converted 29 to 31. Mercuric acetate oxidation of 31 to the corresponding iminium ion, followed by basification, gave enaminoketone 32. This intermediate does not have the proper stereochemistry for an intramolecular Mannich reaction, but under acidic conditions, epimerization is followed by cyclization to provide 2. The synthesis of porantherine (1) was completed using a Bamford-Stevens reaction to introduce the olefin. ... 

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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