Cyclobutanone tosylhydrazone

Since the first report in 1960 of the observation that sodium methoxide induced carbenoid decomposition of cyclobutanone tosylhydrazone (1) at 180 °C in either bis(2-ethoxyethyl) ether or /V-methylpyrrolidone results in an intriguing ring contraction to produce methylenecyclopropane (3),1 many experimental results have been presented invoking cyclobutylidene (2) as a key intermediate in this rearrangement. 

Ring contraction of cyclobutylidenes is known, but not so widely explored. Thus, pyrolysis (200°C) or irradiation of the lithium or sodium salt of cyclobutanone tosylhydrazone (262) gave the 2-vinylcyclobutylidene (263) which then rearranged mainly to ring contraction products (equation 181). 

Cyclobutanone tosylhydrazone has been reported to react with sodium methoxide in diethylene glycol or l-methylpyrrolidin-2-one to give methylenecyclopropane 40 (79-80%) from ring contraction, cyclobutene (18-20%) from hydrogen migration and buta-1,3-diene (1-2%) from ring opening. 

This result contrasts with that from cyclopentanone tosylhydrazone, which yielded cyclopentane (94%) as the major product,and with the cationic decomposition of the sodium salt of cyclobutanone tosylhydrazone in ethylene glycol which gave an 86% yield of a mixture of bicyclo[1.1.0]butane 41 (60%), cyclobutene (12%) and methylenecyclopropane (6%). Likewise, deamination of cyclobutylamine hydrochloride with amyl nitrite leads in low yield (13%) to methylenecyclopropane (56%) along with cyclobutene (40%). ... 

A general synthesis of fused methylenecyclopropanes employs the carbenoid ring contraction of bicyclic cyclobutanone tosylhydrazones, available from [2-1-2] cycloaddition of dichloro-ketene to alkenes. ... 

Donor-substituted 1-aminomethylcyclopropanes 108 110 and tosylhydrazones of 1-donor-substituted cyclopropyl ketones 111 can undergo ring enlargement to cyclobutanones through deamination. To this purpose, aminomethylcyclopropanes were diazotized with sodium nitrite 108-110 or isopentyl nitrite 109 in acidic medium and tosylhydrazones were decomposed in basic medium.111 The rearrangements proceed via diazonium ions and are especially useful for the construction of bicyclic systems. For examples of these rearrangements see 1,108 2,109 3,109 4,110 5,111 6 and 7.1 1... 

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... 

Both tosylhydrazones95-287-288 and oximes289 292- 336 were formed in good yields from the corresponding cyclobutanones under standard conditions. The tosylhydrazone of 4-isopropyli-dene-7,7-dimethylbicyclo[3.2.0]hept-2-en-6-one was reported288 to first crystallize at — 20 °C as a thermally labile stereoisomer which isomerized to a 1 5 mixture of the two possible stereoisomeric hydrazones 1 at room temperature. In deuteriochloroform at room temperature, the half life of the least stable isomer was approximately 8 hours. The exact configuration of each stereoisomer was not stated. 

The key step in the stereocontrolled total synthesis of the tricyclic (+)-kelsoene by M. Koreeda et al. was a base-catalyzed homo-Favorskii rearrangement of a y-keto tosylate to elaborate the 4-5 fused ring portion of the target molecule. The bicyclic 5-6 fused y-keto tosylate was treated with excess potassium fert-butoxide, which effected the desired rearrangement in less than 2 minutes at room temperature. The nucleophilic solvent was too bulky to effect the opening of the cyclobutanone intermediates, making their isolation possible. The mixture of isomeric cyclobutanones was converted to a separable 1 1 mixture of cyclobutanones with p-TsOH, and the ketone functionality was then removed via the corresponding tosylhydrazone. 

Thus, addition of dichloroketene to cyclohexene gave 8,8-dichlorobicyclo[4.2.0]octan-7-one in 39% yield which underwent dehalogenation upon treatment with zinc in acetic acid at room temperature for 24 hours to give the corresponding cyclobutanone. Pyrolysis of the dry lithium salt of its tosylhydrazone at 120-180°Cat0.1 Torr produced a 2 1 mixture of isomeric methylenecyclopropanes 42 and 43 in 50% yield. 

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. ... 

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