Carbenes tosylhydrazones

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 ... 

The reaction mechanism has been confirmed by trapping of intermediates 13, 14 and 15. Because of the fact that neither a carbene nor a carbenium ion species is involved, generally good yields of non-rearranged alkenes 2 are obtained. Together with the easy preparation and use of tosylhydrazones, this explains well the importance of the Shapiro reaction as a synthetic method. 

The l,3-dithian-2-ylidene substituted carbene (54), accessible from the tosylhydrazone (53) by a Bamford - Stevens reaction, not only participates in cycloaddition reactions but is also a source of 4,8-dithiaspiro[2.5]oct-l-ene 6JCS(P1)2773>. 

The most common rearrangement reaction of alkyl carbenes is the shift of hydrogen, generating an alkene. This mode of stabilization predominates to the exclusion of most intermolecular reactions of aliphatic carbenes and often competes with intramolecular insertion reactions. For example, the carbene generated by decomposition of the tosylhydrazone of 2-methylcyclohexanone gives mainly 1- and 3-methylcyclohexene rather than the intramolecular insertion product. 

As shown in Table 1, however, the product distribution depends on the method of carbene generation. Whereas thermolysis of either tosylhydrazone salt (7) or methylethyldiazirine (8) affords essentially the same product distribution (in which 95% of the products are the 2-butenes), photolysis of diazirine 8 is quite different. 

Scheme 6.114, a carbene-carbene rearrangement transforms diphenylcarbene to o-phenylphenylcarbene, which is the progenitor of 565. Two phenylbicydo[4.1.0]-hepta-2,4,6-trienes and l-phenyl-l,2,4,6-cycloheptatetraene (562) have to be assumed as further intermediates. The participation of 562 is supported by the structure of the products 563 and 564, which should result from the addition of 562 to diphenylcarbene and the dimerization of 562, respectively. By thermolysis of the sodium salt of 2-phenyltropone tosylhydrazone, 562 was generated directly. At 100 °C in diglyme as solvent, 564 was identified as the only product and at 340°C/4Torr in the gas... 

The formation of the bridged product 191 was investigated using the cyclopentadiene system as a model. Thus, the salt of the tosylhydrazone 198 was prepared and thermolyzed in order to examine three possible variants of rearrangements (equation 62)75. Analysis of the reaction products 200-202 and their transformations [e.g. the pyrolysis of bicyclic triene 202 to cA-8,9-dihydroindene 203 (equation 63) rather than to product 200 or 201] allows one to conclude that the mechanism involves a transformation of carbene 188 into diradical 204 which can be the precursor of all the products observed (equation 64)75. An analogous conversion takes place via radical 205 in the case of carbene 199 (equation 65). 

The reactivity of cage-annulated carbene (53) was found to depend markedly on the method of its formation." Pyrolysis of the corresponding tosylhydrazone sodium salt gave products of intramolecular CH insertion or H-abstraction. Photolysis of a diazirine precursor gave only azine products by reaction of the carbene with the precursor or diazo compound. Treatment of the m-dibromoalkane with BuLi gave products due to intermolecular insertion of the carbene into CH bonds of the solvent. 

Photolysis of the tosylhydrazone sodium salt (94) in diglyme gave, as the major product, 1,3-diene (95) by [l,2]-vinyl shift in the intermediate carbene. Vinyl migration occurs with retention of configuration and is postulated to occur in the singlet manifold. 

Throughout this chapter, we have almost always ignored the role of the carbene precursor. Carbenes are generally made from diazo compounds, or from a variety of surrogate diazo compounds including diazirines, tosylhydrazone salts, and aziridyl imines, all of which probably decompose through nonisolable diazo compounds. Not surprisingly, it turns out that diazo compounds have a rich chemistry of their own, especially when irradiated. Moreover, that chemistry often closely resembles the reactions of carbenes. Much of intramolecular carbene chemistry is, in fact, diazo compound chemistry. 

Still another type of an intramolecular reaction is the ring enlargement by the insertion of a carbene. When 1-formylhexahelicene tosylhydrazone (105a) is heated in benzene, especially in the presence of sodium hydride, product (106) can be isolated 168). Presumably, the reaction proceeds via the intermediates (105b) and (105c) (Scheme 29). 

This is a major route of decomposition of ethyl 2-furyldiazoacetate (%) (R = H, = C02Et) when heated in dichloromethane or methanol (74JOC2939). The same type of decomposition has been observed with other 2-furylcarbenes which were generated by decomposition of the sodium salts of tosylhydrazones at 3(X)°C (78JA7927). Thermolysis of the diazo compound 96 (R = R = H) in cyclooctane or styrene gave, besides the open-chain acetylene 97, products of intermolecular carbene insertion. This led the authors to favor the carbene mechanism of ring-opening (path A in Scheme 7). 

Carbenes are known intermediates in the thermolytic or photolytic decomposition of the lithium or sodium salts of tosylhydrazones, which, for endocyclic carbenes, results in ring contraction when the elimination of / - or y-hydrogens is impeded. Simple cyclobutanes generally cannot be prepared by this route from monocyclic cyclopentanone tosylhydrazones. However, the lithium salt of bicyclo[2.2.1]heptan-7-one tosylhydrazone gave bicyclo[3.2.0]hept-l-ene (4) as the major product (74%) by vacuum pyrolysis at 185 JC/20 Torr, together with bicyclo[2.2.1]heptane (14%) and tricyclo[2.2.1.02,7]heptane (12%) in 80% overall yield.67... 

Carbenes of type (367), generated by thermal decomposition of the appropriate tosylhydrazone salts, undergo ring opening more readily when the ring heteroatom is oxygen than when it is sulfur... 

Diazomethane and its simple analogs undergo cycloaddition to unsaturated compounds both directly and after conversion to carbenes. The direct cycloadditions are 1,3-dipolar for the most part and provide access to pyrazolines and pyrazoles. Intramolecular cyclizations were recognized as early as 1965 95 The two main methods used in generation of diazo compounds for subsequent intramolecular cycloaddition include thermolysis of tosylhydrazone salts and thermolysis of iminoaziridines. Decomposition of nitros-amines has also been employed. 

Phenyl(trimethylsilyl)carbene (21) has been generated from phenyl(trimethylsilyl)diazo-methane (20) by gas-phase pyrolysis39,40 as well as by thermolysis97 or photolysis33,40,98,99 in solution, by flash thermolysis of the tosylhydrazone lithium salt 18040, and by pyrolysis... 

Dehydroadamantanes are most readily obtained from either carbene insertion reactions or from 1,3-reductive eliminations. Pyrolysis of the dry sodium salt of the tosylhydrazone of adamantanone gives good yields of 2,4-dehydroada-mantane 133>. The unstable 1,3-dehydroadamantane is obtained from the treatment of 1,3-dibromoadamantane with sodium (Eq. (43)) 134>. 

C6o reacts with diazomethane to yield fulleroids [97,99,100,234], Carbene generated from the thermolysis of precursors such as diazirines, sodium trichloroac-etate, cyclopropene, oxadiazole, and tosylhydrazone [60,235] adds onto C6o leading to methanofullerenes [12,15,236], Recently, Akasaka et al. described the photochemical reaction of diazirine with C6o [237], Irradiation of a benzene solution of 2-adamantane-2,3 -[3H]-diazirine 58 and C6o with a high pressure mercury lamp (cutoff <300 nm) at 15°C in a Pyrex tube resulted in the formation of mixture of the isomers 59a and 59b in a ratio of 51/49 (Scheme 24). 

Diazo-l, 8-, 3,6-, and 4,5-diazafluorenes are obtained by alkaline decomposition of the respective 9-tosylhydrazones. Photolysis of these diazo compounds yields reactive carbenes whose properties and reactions were investigated by Schuster and Li <86JOC3806, 87JOC3975) and by Durr and coworkers <89TL1935>. 

Two interesting synthetic applications of carbene chemistry should be cited here. The first, due to Sasaki and his co-workers, takes advantage of the steric situation present in pseudopelletierine tosylhydrazone (98).147 Pyrolytic decomposition of the sodium salt of 98 in diglyme gave 99 in 80 % yield. 

The thermal decomposition of monoanions of tosylhydrazone (Ar = p-tolyl) in a protic solvent like diglyme at 130°C or higher temperature generates dialkyl carbenes. Dialkyl carbenes can also be generated photochemically from salts of tosylhydrazones, but it is difficult to perform the reaction on a large scale. 

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