Cyclopropanes from tosylhydrazones

Tosylhydrazones of aliphatic aldehydes and ketones react with a base in an aprotic solvent at 90-180 C to give diazo compounds which undergo thermal decomposition with loss of nitrogen to yield alkenes derived from hydrogen migration and cyclopropanes from intramolecular insertion. In proton donor solvents decomposition of y-tosylhydrazones by base occurs primarily by a cationic mechanism involving diazonium and/or carbenium ion intermediates. 

The generation of carbenes from tosylhydrazones of thiophene aldehydes, and their reactivity have been discussed in CHEC-I, <84CHEC-I(4)74i>. A few further reactions of such carbenes have been reported. In presence of acrylonitrile, the product could be either the cyclopropane (484) (from the carbene) or the pyrazoline (485) (by cycloaddition of the diazo intermediate) <88H(27)ll4i>. The carbene can similarly be trapped by cis and trans stilbene, dimethyl fumarate or maleate to form the respective cyclopropanes <87BCJ4317>. 

This chapter focuses on the generation of carbenes by extrusion of nitrogen (Tables 91.1 through 91.8). Several other methods are possible, such as the formation from tosylhydrazone salts, oxiranes, aziridines, dioxolanes, and pyrazolenines from cyclopropanes by photocydoehmination, from transition-metal carbene complexes or by a-elimination, from ot,a-dihalogen compounds, or from base treatment of N-nitrosocarbamate. ... 

Scheme 7.43 Catalytic epoxide (X=0), aziridine (X=AZ-Ts or AZ-SES), and cyclopropane (X=CH-COY) formation mediated by chalcogen-ylides generated from metal carbenes using diazo compounds generated in situ from tosylhydrazones (start at lower right)...

The same type of reaction occurs in the work of Hauptman (76T1293), who, studying the chemistry of diethynylcarbenes, found that the pyrolysis of the lithium salts of diethynylketone tosylhydrazones 5 (140-150°C) in the presence of olefins leads to cyclopropanes. This process results in the formation of the corresponding 3-ethynylpyrazoles. The formation of l-p-tolylsulfonyl-3-alkynylpyrazoles from hydrazone runs in milder conditions (50°C, 14 h) (Scheme 24). 

Thermal decomposition of y-lactone tosylhydrazone sodium salts are reported to yield cyclobu-tanones, which can be accounted for by rearrangement of an intermediate oxycarbene. In this manner, the sodium salts of dihydrofuran-2(37/)-one tosylhydrazones 1 were decomposed as a loose powder, at 310 C in a bulb-to-bulb distillation apparatus at an initial pressure of 0.1 Torr, to give the corresponding cyclobutanones 2 in addition to enol ethers, cyclopropanes and open-chain alkenes. Condensable products (74-76%) were collected at — 78 °C, weighed and the ratio of components was determined from their relative GC peak areas.63... 

In support of the above mechanism, spiro[cyclopropane-l,2 -(6 -methyienebicycIo[3.1.0]hexane)] (10) is indeed isolated from thermolysis of the sodium salt of 7-oxospiro[bicyclo[3.2.0]hept-3-ene-2,1 -cyclopropane] tosylhydrazone (9), presumably due to the fact that the corresponding homofulvene would be too strained to form.8 Additional support of the proposed mechanism is also provided by the pyrolysis of the sodium salt of [7,7-2H2]bicyclo[3.2.1]hept-2-en-6-one tosylhydrazone (11), which gives [7,7-2H2]-4-methylenebicyclo[3.1.0]hex-2-ene (12).8... 

The pyrolysis and photolysis of this diazirine yield 1,1,2-trimethyl-cyclopropane, teri-butylethylene, and tetramethylethylene. The pyrolysis results are very similar to those obtained by the methanolysis of the analogous tosylhydrazone in an aprotic solvent, but differ appreciably from the photolytic data. These results are shown in Table V. Once again the results are consistent with the production of a hot carbene in the photochemical experiments. No details are at present available for the photolysis of this diazirine at low pressures, where, by analogy with other work, the isomerization of the trimethylcyclopropane would be expected to occur. 

Treatment of a,p-unsaturated tosylhydrazones with NaBH4 in MeOH affords principally allylic ethers from cyclic derivatives and pyrazoles with most noncyclic examples. This divergent behavior compared to saturated tosylhydrazones has been attributedto a lessening of the electrophilicity of conjugated imine ir-bonds, which allows initial abstraction of the acidic N—H proton by BH4 to compete with reduction, and gives alternative reactions related to the Bamford-Stevens process as depicted in Scheme 4. An exception to this may be the deoxygenation of conjugated vinyl triflates (entry 11, Table 6). The cyclopropanation and elimination products produced in entry 4, Table 6 also probably arise from similar, alternative reaction paths. ... 

Norbornyldiazomethane (1) was prepared by gentle heating (90-100 °C) of the corresponding tosylhydrazone salt, obtained from bicyclo[2.2.1]heptane-l-carbaldehyde, in a Kugelrohr apparatus. 1-Norbornyldiazomethane (1) is an unstable orange-yellow liquid and was immediately dissolved in a solvent prior to use. Irradiation of a benzene solution of 1-norbor-nyldiazomethane (1) in the presence of ( )- or (Z)-but-2-ene for 2 hours at 25 C led to cyclopropanated products 2 and 3/4 in addition to dimeric products of the precursor carbene. The addition of the monoalkylcarbene is stereospecific with a singlet reaction state. 

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 Wolff rearrangement of six- and five-membered a-diazocycloalkanones has been extensively applied to the synthesis of highly strained frameworks. The rearrangement of an (x-diazo-cyclobutanone was reported from 2-diazo-3,4-bis(diphenylmethylene)cyclobutanone (1). The diazo ketone (1) was prepared by treatment of the 3,4-bis(diphenylmethyl-ene)cyclobutane-l,2-dione tosylhydrazone with alumina in 95% overall yield from the corresponding cyclobutanedione. Irradiation in the presence of water, alcohols and aniline afforded 1-carboxy-, 1-alkoxycarbonyl- and 1-phenylcarbamoyl-substituted 2,3-bis(diphenyl-methylene)cyclopropanes 2, respectively, in 13-87% yields. Thermal decomposition in aqueous dioxane afforded the cyclopropanecarboxylic acid 2 (X = OH) in 52% yield. ... 

Another transannular reaction, which likewise proceeds via carbene insertion, is the base-catalyzed decomposition of the tosylhydrazone of cyclooctanone. In general these carbenes react with a- and -C—H bonds to give alkenes and cyclopropanes. However, when the carbene carbon can approach distant C —H bonds, such as in the cyclooctane conformation, then bicyclo[3.3.0]octane derivatives are also formed from transannular insertion.Thus, cyclooctanone- and 5-phenylcyclooctanone tosylhydrazones reacted with sodium methoxide to give a mixture of mono- and bicyclic products 4-6 and 7-10, respectively, in the stated proportions. 

This effect is even more pronounced in the phenanthryl series where, starting from the tosylhydrazone salt of 54, the cyclopropane 55 was trapped in up to 73% yield using cyclopentadiene [Eq. (15)]. 

Deprotonation of TosyIhyd razones. The deprotonation of to-sylhydrazones with LHMDS provides the corresponding lithium salts, which can be further decomposed into the diazo intermediates. The addition of late transition metal complexes leads to the formation of metal carbenoid species which undergo various reactions, such as cyclopropanation, aziridination, epoxidation, and C-H insertion. For instance, the lithium salt of tosylhydrazone 2, prepared from LHMDS, is reacted with an imine or an alkene in the presence of rhodium(II) acetate and a chiral sulfide to give respectively, the corresponding aziridine or cyclopropane derivatives (eqs 36 and 37). Under similar reaction conditions, the sodium salt prepared from NHMDS works equally well. 

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