A-Tosylhydrazones

Shapiro and Related Reactions Organic Reactions 1990, 39, 1 1976, 23, 405 - Reaction of a tosylhydrazone with a strong base to give an olefin. 

Bam ford-Stevens Reaction- initial conversion of a tosylhydrazone to a diazo intermediate... 

The aminoketone 1, required as starting material, can be obtained by a Neber rearrangement from a A -tosylhydrazone. Another route to a-aminoketones starts with the nitrosation of an a-methylene carbonyl compound—often in situ—to give the more stable tautomeric oxime 7, which is then reduced in a subsequent step to yield 1 ... 

The Hurd-Mori reaction,where a tosylhydrazone is converted by thionyl chloride to the corresponding thiadiazole, involves the formation of a 1,2,3-thiadiazole-3,3-dioxide. In one example, this type of compound was isolated and subsequently deoxygenated with thiourea <1991PS175>. There have been no further reports of S-linked sulfoxide or sulfone derivatives of 1,2,3-thiadiazoles since the publication of CHEC-II(1996). 

Thus, the 1,2-C pathway dominates when 84 is generated by the thermolysis of a tosylhydrazone salt, but a 1,2-H shift to cyclopropylethene is the major pathway when 84 is generated from either a hydrocarbon precursor or via the atomic carbon abstraction of oxygen from cyclopropylmethylketone at —196°C.U1... 

A disadvantage of the traditional synthesis of A -alkyl-A -tosylhydrazones, particularly in the reaction of the tosylhydrazine with weakly electrophilic carbonyl compounds, is the instability of the hydrazine under the reaction conditions. However, A -alkylation of the tosylhydrazone (Table 5.23) under weakly basic condi-... 

The Shapiro reaction occurs when a tosylhydrazone 86, easily prepared from a ketone and tosylhydrazine, is treated with 2 equivalents of an ethereal solution of n-butyllithium 87, resulting first in the removal of the N—H proton to give the anion 88 and then of a one proton from the less-substituted a position to give the dianion 89. Elimination of lithium p-toluenesulfinate in the rate-limiting step gives the lithium aUtenyldiazenide 90, which suffers loss of nitrogen to afford the alkenyllithium 91 (equation 31) ° . ... 

Normally following the Hurd and Mori procedure a tosylhydrazone is converted with thionyl chloride to the corresponding thiadiazole. In one case under these conditions, the dioxide (30) was isolated <91PS(60)175> and subsequently deoxygenated with thiourea (Scheme 7). 

A 2-cyclohexenone derivative can be transformed into the corresponding epoxy tosyl-hydrazone by sequential treatment with peracid and tosylhydrazine. The elimination of nitrogen and p-toluenesulfinate and fragmentation after rearrangement to the 3-tosylazo allylic alcohol may occur under mild conditions. Carbonyl compounds with 5,6-triple bonds are formed in high yields (J. Schreiber, 1967 M. Tanabe, 1967). If one applies this reaction to a 9,10-epoxy-1-decalone, a ten-membered 5-cyclodecyn-l-one ring is formed (D. Felix, 1971). This product is an important intermediate in the perfume industry and has been used on a large scale. For this purpose Eschenmoser developed a synthesis in which the readily removed styrene was split off instead of a sulfmic acid. Thus a l-amino-2-phenylaziridine hydrazone was used instead of a tosylhydrazone (D. Felix, 1968). ... 

Ruthenium porphyrins are effective catalysts for the cyclization of A-tosylhydrazones via intramolecular carbenoid C-H insertion to afford azetidin-2-ones <2003OL2535, 2003TL1445>. A non-porphyrin-based ruthenium catalyst, [RuCl2(/>-cymene)]2, has been developed recently for catalytic carbenoid transformation <20050L1081>. A [RuCl2(/>-cymene)]2-catalyzed stereoselective cyclization of a-diazoacetamides 418 by intramolecular C-H insertion produced azetidin-2-ones 419 in excellent yields and excellent (>99%) air-stereoselectivity (Equation 168). 

Fig. 17.70. Alternative II to the Wolff-Kishner reduction reduction of a tosylhydrazone. Due to the lack of a sufficiently strong base, the diazene intermediate D does not react further via a diazene anion, which was encountered in the reactions of the Figures 17.67-17.69, but undergoes a radical reaction. "Non" refers to a nonyl group.

Fig. 14.60. Alternative II to the Wolff-Kishner reduction reduction of a tosylhydrazone Non refers to a nonyl group.

The Bamford-Stevens reaction is a tosylhydrazones, 4.106, decomposition with a base to form alkenes. 

The same authors have proposed a similar approach for the total syntheses of serofendic acids [90] using tin-free conditions with the NaBH3CN/ZnCl2 reduction of a tosylhydrazone [91]. 

A two-step method to reduce a 0=0 to a CH2 group involves the conversion of a carbonyl group to a tosylhydrazone, followed by reduction with NaBH4. Draw a mechanism for the conversion of cyclohexanone to its tosylhydrazone, which is illustrated in the following equation. 

Mechanistic information on the photolytic Bamford-Stevens reaction is provided by the successful isolation of a diazo hydrocarbon as a reaction intermediate from the direct photolysis of a tosylhydrazone sodium salt (90 Scheme 10). This study also clarifies that the carbene derived thermally and that derived photolytically behave differently with respect to the stereoselectivity of the 1,2-hydrogen shift that produces the alkene. 

The reaction of a tosylhydrazone with at least 2 equiv. of an alkyllithium reagent in ether or hexane generates the dianion (Shapiro reaction) this gives, after loss of Ts" and N2, the vinyllithium compound, which can be trapped by a variety of electrophiles, e.g. H", CO2, DMF (Scheme 27). The less-substituted alkene is formed predominantly under these conditions. 

Thermal decomposition of a tosylhydrazone salt has also been demonstrated as one of only few examples of methods for the generation of 1-substituted 1-vinylcyclopropanes from diazoalkenes. Heating the dilithiotosylhydrazone 26 in xylene in the presence of dimethyl fumarate generates the pentacyclic carbon skeleton 27 via two stereospecific cyclopropanations. ... 

The Shapiro reaction is the conversion of ketone to an alkene via a tosylhydrazone. The tosylhydrazone is treated with two equivalents of strong base, typically n-BuLi or MeLi, to afford an alkenyllithium species which is quenched with an electrophile to form an alkene (see also chapter 5, 5.1.25 Shapiro reaction). Reviews (a) Chamberlin, A. R. Bloom, S. H. Org. React. 1990, 39,1-83. (b) Shapiro, R.H. Org. React. 1976,23,405. 

Ketones are converted to the corresponding nitrile by a sequence that begins with conversion of the ketone to a tosylhydrazone, followed by HCN addition across the C = N bond. Thermolysis of the intermediate 1-cyanohydrazine affords the cyanide in acceptable yields (Buehler and Pearson, 1976). 

An elegant route to pyrazoles, involves forming a ring closure precursor by Homer-Emmons condensation of a tosylhydrazone-phosphonate with an aldehyde, which becomes the 5-substituent intramolecular Michael addition and then loss of toluenesulfinate as the final aromatising step, completes the sequence. ... 

In most cases the regiochemistry of the Shapiro reaction is controlled by steric factors, with the second metalation occurring at the less-substituted a-carbon atom of the hydrazone.2 For example, a-methyl ketone 10 was transformed to disubstituted alkene 11 in 69% yield as a single regioisomer via conversion to a tosylhydrazone followed by treatment with -BuLi. However, the regiochemical outcome of Shapiro reactions involving a,p-unsaturated hydrazones is difficult to predict in the absence of data obtained from reactions of structurally related substrates, as the second metalation can occur at either the a - or y-position. 

In summary, the known preparative methods for the synthesis of [l,2,3]triazolo[l,5-a]pyridines prior to 1983 have been extensively reviewed in a number of different reviews <61CHE749,83AHC(34)80, 84CHEC-I(5)847>. These reviews reveal that the most straightforward methods involves an oxidation of the hydrazone of a pyridine-2-carbaldehyde or ketone, treatment of a tosylhydrazone with a base, cyclization of Af-aminopyridinium oxime mesylates, pyrolysis of pyridyldiazoalkanes, and diazo group (tosyl azide as source of the diazo group) transfer to an active methylene group (e.g., 2-methylpyridines) under basic conditions. 

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