Tosylhydra zones

Regioselective alkylative opening of a,(1-epoxy ketone oxime [40] and tosylhydra-zones [41] with organocopper reagents is initiated by the generation of unsaturated azo compounds which undergo conjugate addition. 

Despite efficient conversions, a major drawback from practical and safety considerations is the use of (potentially) explosive diazo compounds. Consequently, the application was limited to small (mmol)-scale. Thus, replacement of the direct use of the diazo compound by suitable precursors which form the desired diazo compound in situ would be much more favorable. A remarkable improvement addressing this issue was recently achieved by the Aggarwal group [223, 224]. The key step was in-situ formation of the diazo compound starting from the tosylhydra-zone salt 222 under conditions (phase-transfer catalysis at 40 °C) compatible with the sulfur-ylide type epoxidation [223], The concept of this improved method is shown in Scheme 6.100. 

The reaction starts with formation of the tosylhydrazone from the epoxy-ketone. The tosylhydra-zone is unstable with respect to opening of the epoxide in an elimination reaction, and it is this elimination that sets up the familiar 1, 2, 3, 4 system ready for fragmentation. The push comes from the newly created hydroxyl group, and the pull from the irresistible concerted loss of a good leaving group (Ts ) and an even better one (N2). Notice how all the (green) bonds that break are parallel to one another, held anti-periplanar by two double bonds. Perfect ... 

Miscellaneous derivatives are hydrolyzed back to the starting carbonyl compounds. Hienylhydtazones of ketones are converted into the parent ketones tqion treatment with manganese dioxide.Tosylhydra-zones react with molybdenyl chloride or tungsten tetrafluoride to give both aldehydes and ketones. Sodium peroxide converts aldoximes into carboxylic acids. 

Oxidative cleavage of hydrazones. Carbonyl compounds can be regenerated from 2,4-dinitrophenylhydrazones, tosylhydrazones, or N-methyl-N-tosylhydra-zones in 80-95% yield by oxidation with sodium nitrite in TFA or HOAc (0-5°, 1-2 hours). In the case of tosylhydrazones, the other product of cleavage has been identified as tosyl azide, the product of reaction of tosylhydrazine with nitrous acid. 

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... 

The thietane ring contraction with bicyclic ylide intermediacy is the basis of the synthesis of thiiradialene 413 by vacuum pyrolysis of tosylhydra-zone lithium salt 414 (81TL4815). 

Although boron trifluoride catalyzed intramolecular addition reactions of suitable tosylhydra-zones can yield 2,3-diazabicyclo[2.2.1 ]hept-2-enes (e.g. the tosylhydrazone of 5-methylhex-5-en-2-one generates 2,3-diaza-l,4-dimethylbicyclo[2.2.1]hept-2-ene) - and from these the corresponding bicyclo[2.1.0]pentanes, a much better and more general route was discovered by Criegee and Rimmelin. Based on work by Diels,they showed that 2,3-diazabicy-... 

Loev and co-workers152 prepared the unsubstituted lH-2,l-benzothia-zine 2,2-dioxide (239) by the route of Scheme 11. Methyl chlorosulfonyl-acetate was converted into the sulfonanilide (235) by reaction with aniline. Hydrolysis of the ester group in 235 gave 236 which, with polyphosphoric acid, cyclized to 1 H-2,l-benzothiazin-4-one (237). Spectral data indicated that 237 existed in the keto form. Ketone 237 was converted to the tosylhydra-zone 238 which, by a Bamford-Stevens reaction, afforded 239 in good overall yield. The iV-methyl analog of 239 was also prepared by the above reaction sequence using N-methylaniline. 

Studies of deprotonation regioselectivity in mono-A-substituted ketone hydrazones have mainly dealt with the regiochemistry of ketone tosylhydrazone deprdtonations. Deprotonation of these tosylhydra-zones, as well as deprotonation of mono-A-alkyl- or mono-A-aryl-hydrazones, proceeds predominantly syn to the starting —NHR group. This regioselectivity is plausibly similar to that reported for oxime and imine deprotonations. ... 

Benzyl alcohols. The preparation involves reaction of araldehyde tosylhydra-zones with RjB in the presence of an amine base (e.g., DBU) followed by oxidation [yielding ArCH(OH)R]. As a variation of this method, the use of BU4NOH as base and addition of H2O prior to workup gives ArCHjR. 

Among other dehydrogenation reagents, we should mention triphenylbismuth carbonate (97 7o yield of diphenyldiazomethane, Barton et al., 1979), and sodium hydride in THF, which was used by Padwa et al. (1983 a) to prepare (E)-l,4-di-phenyl-4-diazobut-l-ene (2.74) from (E)-l,4-diphenylbut-3-en-l-one A -tosylhydra-zone (2.73) (2-29). It was also used by Krebs et al. (1984) for the synthesis of diazocyclopentane, -hexane and -heptane derivatives with two methyl groups at the two C-atoms in the positions a- and a - to the diazo C-atom. At the same time, Cullen et al. (1984) published the synthesis (2-30) of the corresponding diazocy-clopentene, 4-diazo-3,3,5,5-tetramethylcyclopentene (2.78). They added first an equivalent of bromine and afterwards triphenylphosphine to the corresponding hydrazone 2.76. The triphenylphosphanylidene derivative 2.77 was isolated and heated for two hours without solvent at 185 °C. 

Alkyl hydroperoxides. N-alkyl-N -tosylhydrazines are oxidized by H2O2 and NaaOa in THF at 20° to give hydroperoxides in 90-957o yield. Tosylhydra-zones are not intermediates, since these compounds are oxidized in low yields to... 

With a, -unsaturated carbonyl compounds, reduction of the tosyl hydrazone is accompanied by migration of the double bond. Thus, cinnamaldehyde tosylhydra-zone gives 3-phenyl-1-propene in 98% yield and the a, -unsaturated ketone 99 gives the alkene 100 (7.90). The mechanism for this reaction involves reduction of the iminium ion to the tosylhydrazine 101, elimination of p-toluenesulfinic acid... 

Syntheses of 4,5- and Other Unsaturated Cyclic Compounds - Tosylhydra-zones of a-oxycarbonyl compounds are readily converted into vinyl ethers with sodium in ethylene glycol (Bamford-Stevens elimination) as illustrated by the conversion of 47 to 48. ... 

For these stepwise carbon-carbon bond-forming reactions a tosylhydra-zone was employed as an auxiliary function [23], The tosylhydrazine is directly removed from the product by acidic hydrolysis, after it has done its job in enabling skeletal bond formation. 

O-Isopropylidene, 5-Ac, tosylhydra-zone 5-0-Acetyl-l,2-0-isopropylidene-a-D-etythto-pentofuranos-3-ulose tosyl-hydrazone... 

To several known methods for the conversion of aldehydes into nitriles two convenient new ones have been added Cyanic acid esters, believed to be inaccessible, have been prepared in more than one way and excellent yields Their reactions have now been investigated extensively Simple methods for the preparation of diazo compounds by pyrolysis of salts of tosylhydra-zones have been found. The tosylhydrazones as well as the diazo... 

Mannich bases in aq. solution N-Methylnorazaadamantane could be easily prepared by cyclization of pseudopelletierine tosylhydra-zone . Isothiazoles previously difficult to obtain can be readily prepared from isoxazoles via reduction to enaminoketones... 

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