A-Tropolone methyl ether

Upon exposure to UV light, a-tropolone methyl ether (142), included within chirally modified Y zeolite, has been found to undergo 4 7r-electron disrotatory electrocyclic ring closure to afford " the bicyclic photo-isomer (143). 

Irradiation of a-tropolone methyl ether (Formula 8a) first gives the valence tautomer 9a, then the rearranged bicyclic product 18a, and finally the ester 19a (12). The reactions occur in sequence, and each stage requires light (the final transformation of Formula 18 to Formula 19 can also be achieved by acid). The initial reaction has ample precedent (11). The final transformation simply involves addition of water to the enol ether followed by a reverse aldol reaction. 

Dauben, W.G., Koch, K., Smith, S.L., and Chapman, O.L. (1963) Photo-isomerizahons in the a-Tropolone Series The mechanistic path of the a-tropolone methyl ether to methyl 4-Oxo-2-cyclo-pentenylactetate conversion. Journal of the American Chemical Society, 85, 2616-2621. 

The inclusion complex 26, shown in Scheme 11, has been used as a host by Toda and coworkers to carry out a number of enantioselective reactions [231]. For example, irradiation of a 1 1 host-guest assembly of a-tropolone methyl ether 27 and (S,S)-( — )-26, in the solid state gave (lS,5R)-( — )-28 of 100% ee. The authors state that the high stereoselectivity is a result of the steric hindrance to disrotatory ring closure from one direction due to the structure of the host. This leads to the formation of only one enantiomer of the product. More details on this topic are available in Chap. 13. 

Decarboalkoxylation (5, 323). Greene and Crabbe have reported a novel prostanoid synthesis that employs a-tropolone methyl ether (1) as starting material. Irradiation of (1) leads to the bicycloheptadienone (2),which is con-... 

The methoxy bicycloheptadienone (135) was obtained [142] by irradiation of a-tropolone methyl ether which, after hydrogenation of the conjugated double bond, underwent cleavage by ozonolysis of the enol ether double bond to give the dimethyl acetal (136). The latter was then alkylated with ethyl 7-... 

Tlie synthesis concludes by the route pioneered by Eschenmoser. Itromination of 47 proceeds at the position a to the tropolone I ing to give 48. Displacement of halogen by ammonia followed by liase hydrolysis of the tropolone methyl ether gives trimethyl-lolchicinic acid. Acetylation of the amine followed by reesteri-... 

The photochemical reactions of three a/3-unsaturated cyclic ketones have been reported. In these cases, it appears that the reaction is that of the olefinic group although the wavelength of the incident radiation is at the ultraviolet absorption of the carbonyl group. Photolysis of 2-cyclo-pentenone (16), carvone (XXXV) (7,12) and y-tropolone methyl ether... 

Simple tropolones also photoisomerize. 7-Tropolone methyl ether (Formula 6) gives the bicyclic photoisomer (Formula 7) on irradiation in aqueous solution (11). In similar fashion the simple a-tropolone methyl... 

The photochemical transformations of simple tropolone methyl ethers can be more complex than simple valence tautomerization. Irradiation of a-tropolone or its methyl ether (Formulas 16a,b) in aqueous solution in quartz vessels gives 4-oxo-2-cyclopentenylacetic acid (Formula 17a) or the methyl ester (Formula 17b) (15,16). 

In principle, a similar tautomerism is possible in fused tropolones. Thus, O-methylation can lead either to one tropolone methyl ether (62BCJ808) or to two isomers, as in the case of anhydrosepedonin derivatives 418b and c (Scheme 112 69MI3). The yield of isomer 418c is very low, as expected. 

The tropolone carbonyl group does not give ketonic derivatives unless the aromaticity of the ring is much decreased, as in some benzo-fused tropolones (68MI2, p. 370). Pyridotropolones like 373 (65MI3), apparently having a 1,2-diketone structure (eventually 389), afford dioximes, dihydra-zones, osazones, and quinoxalines (Section IV,A,6,a). Their methyl ethers show the normal tropone reactivity. 

Schroder and co-workers studied the addition of formaldehyde-O-oxide, generated in situ at low temperature by ozonolysis of ketene diethylacetal, to the tropolonic ring of various colchicine analogues, Fig. (4) [80]. The intermediate ozonide E formed from 4 decomposed upon warming to give A-acetylcolchinol methyl ether 32 via the presumed intermediate F, in 81% yield. 

Figure 14 A cartoon representation of tropolone methyl ether and norephedrine included within a supercage under wet and dry conditions. The model helps to rationalize the difference in ee obtained under the two conditions. Dark circles represent the cations. Hydrogen bonding between the chiral inductor and interaction between the cation and TME are disturbed by water molecules.

The hydrolysis of the tropolone methyl ether 360 with concentrated HCl in boiling EtOH results in the hydroxyfluorenone 361 (equation 172) °. Thermal rearrangement with loss of sulfur dioxide occurs on heating the y-sultones 362 in dioxane, DMSO, dioxane-water or THE at 90 °C for 6-10 h to give 90% of the styrene derivatives 363 in a highly stereospecific manner (equation 173). ... 

For a mechanistic interpretation of the photoinduced valence isomerization of tropolone methyl ethers, Mukai and Miyashi have assumed that two excited state species 112 and 114 need to be considered. If 772 is stabilized by substituents in the tropolone ring, cyclization will give the product 113, but if 114 is more stable, product 115 will be favored. In the... 

Tropolones form chelate complexes with many metals and similarly, colchiceine, but not colchicine, affords a crystalline copper salt (324a, 324b). Like tropolone methyl ether, which is more soluble in water than is tropolone, colchicine is more water-soluble than the free tropolone, colchiceine. 

The transformation of 7,7-diMeO-CHT to a-, and y-tropolones is also achievable by using anodic oxidation in the key step (equation 18), namely the electrochemical oxidation of an isomeric mixture of diMeO-CHTs prepared by the thermal rearrangement of 7,7-diMeO-CHT yields a mixture of methyl ethers of ji- and y-tropolones. On the other hand, the thermal rearrangement of the ethylene acetal of tropone gives 3,4-dioxyethylene-CHT as a single product due to the difficulty of formation of other isomers, and it yields the ether of a-tropolone upon anodic oxidation. 

Azidotropolone and its methyl ether and tosylate react with active methylene compounds to yield tropolones and azulenes bearing the triazole ring as a substituent (Scheme 137).419... 

Cyclopropanation.1 The key step in a biomimctic synthesis of (i)-colchicine (4) is a regio- and stereoselective reaction of the tricyclic I, prepared in several steps from 5-bromo-2-methoxyphenol, with dimethylsulfoxonium methylide to give a single product (2) in 75% yield. When treated with trifluoroacclic acid at 25°, this product rearranges in 89% yield to the a-tropolone O-methyl ether 3. This product is converted into ( )-co chicine (4) in four known steps. 

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