Ozonolysis rearrangement

Nickel(O) forms a n-complex with three butadiene molecules at low temperature. This complex rearranges spontaneously at 0 °C to afford a bisallylic system, from which a large number of interesting olefins can be obtained. The scheme given below and the example of the synthesis of the odorous compound muscone (R. Baker, 1972, 1974 A.P. Kozikowski, 1976) indicate the variability of such rearrangements (P. Heimbach, 1970). Nowadays many rather complicated cycloolefins are synthesized on a large scale by such reactions and should be kept in mind as possible starting materials, e.g. after ozonolysis. 

The pyrazole ring is resistant to oxidation and reduction. Only ozonolysis, electrolytic oxidations, or strong base can cause ring fission. On photolysis, pyrazoles undergo an unusual rearrangement to yield imidazoles via cleavage of the N —N2 bond, followed by cyclization of the radical iatermediate to azirine (27). 

The most recent, and probably most elegant, process for the asymmetric synthesis of (+)-estrone appHes a tandem Claisen rearrangement and intramolecular ene-reaction (Eig. 23). StereochemicaHy pure (185) is synthesized from (2R)-l,2-0-isopropyhdene-3-butanone in an overall yield of 86% in four chemical steps. Heating a toluene solution of (185), enol ether (187), and 2,6-dimethylphenol to 180°C in a sealed tube for 60 h produces (190) in 76% yield after purification. Ozonolysis of (190) followed by base-catalyzed epimerization of the C8a-hydrogen to a C8P-hydrogen (again similar to conversion of (175) to (176)) produces (184) in 46% yield from (190). Aldehyde (184) was converted to 9,11-dehydroestrone methyl ether (177) as discussed above. The overall yield of 9,11-dehydroestrone methyl ether (177) was 17% in five steps from 6-methoxy-l-tetralone (186) and (185) (201). 

The molozonide was unstable and would either rearrange into the isozonide or form polymers. While Staudinger s theory explained the formation of the major products, some of the by-products could not be accounted for. The greatest step toward complete elucidation of the ozonolysis reaction was made by Criegee (Ref 3) In the 1950s. From a study of ozonolysis in various solvents and the constitution of the products, Criegee proposed these reactions ... 

Ozonolysis of alkene 446 in the presence of acetaldehyde afforded diketone 448 through the intermediacy of 447. Ring expansion through Beckmann rearrangement took place when bis-oxime 449 was mesylated and warmed in aqueous tetrahydrofuran (THF). The bis-lactam so formed gave piperidinediol 450 on reduction with lithium aluminium hydride, and this compound was transformed into ( )-sparteine by treatment with triphenylphosphine, CCI4, and triethylamine (Scheme 105) <20050BC1557>. 

In order to establish the correct absolute stereochemistry in cyclopentanoid 123 (Scheme 10.11), a chirality transfer strategy was employed with aldehyde 117, obtained from (S)-(-)-limonene (Scheme 10.11). A modified procedure for the conversion of (S)-(-)-limonene to cyclopentene 117 (58 % from limonene) was used [58], and aldehyde 117 was reduced with diisobutylaluminium hydride (DIBAL) (quant.) and alkylated to provide tributylstannane ether 118. This compound underwent a Still-Wittig rearrangement upon treatment with n-butyl lithium (n-BuLi) to yield 119 (75 %, two steps) [59]. The extent to which the chirality transfer was successful was deemed quantitative on the basis of conversion of alcohol 119 to its (+)-(9-methyI mande I ic acid ester and subsequent analysis of optical purity. The ozonolysis (70 %) of 119, protection of the free alcohol as the silyl ether (85 %), and reduction of the ketone with DIBAL (quant.) gave alcohol 120. Elimination of the alcohol in 120 with phosphorus oxychloride-pyridine... 

The abnormal ozonolysis is chiefly observed when the group R is one that shows a high migration aptitude in carbonium ion rearrangements. 

Trioxolane (1) has only been prepared by the ozonolysis of ethylene. The rearrangement of the primary ozonide occurs above — 100°C to give 1,2,4-trioxolane as a colorless, explosive liquid <42LA(553)187>. 1,2,4-Trithiolane (2) is still best prepared by a classical reaction of Na2S2.5 with excess dichloromethane. Some 1,2,4,5-tetrathiolane is also produced, but (2) can be isolated as a pale-yellow distillable liquid. It is best kept stored under inert atmosphere below 0°C to avoid polymerization <67CPB988>. Parent compounds (3)-(6) are not known and the 1- and 4-5-oxides for 1,2,4-trithiolane have been mentioned previously (see Section 4.16.5.2.3). 

A synthesis of a dimethyl derivative of 501 has also recently been announced by Hirao, et al. Following conversion of 513 to its dimesylate, Lewis acid-catalyzed rearrangement gave dienedione 514 as the major product. Heating of the disemi-carbazone of 514 with powdered KOH furnished the diolefin which was transformed into 515 by ozonolysis. When the ditosylhydrazone of 515 was heated with potassium... 

Capnellane is the generic name applied to a group of sesquiterpene alcohols and the hydrocarbon isolated from the soft coral Capnella imbricata A < >-Capnellene (667), the presumed biosynthetic precursor of the capnellenols, was first synthesized in 1981 by Stevens and Paquette Their synthetic plan called for the construction of bicyclic ketone 668 and its appropriate annulation. The latter event was achieved by application of the Rupe rearrangement to 668, conjugate addition of a vinyl group to 669, ozonolysis, and cyclization (Scheme LXVIII). Hydrogenation and olefination completed the sequence. 

Much effort this year has been expended on chrysanthemic acid syntheses. Aratani et al. have extended earlier work on asymmetric synthesis (Vol. 6, p. 21) by decomposing various alkyl diazoacetates in 2,5-dimethylhexa-2,4-diene in the presence of chiral copper complexes to yield up to 92% of rrans-chrysanthemic acid in 88% dextrorotatory enantiomeric excess. Mitra has used ozonolysis of (+)-a-pinene to obtain, stereospecifically, the bromo-ketone (104) which undergoes Favorskii rearrangement to yield the anticipated ester (105) from which (+)-trans-chrysanthemic acid is readily obtained a second paper reports another route from (+)-car-3-ene initially to methyl (—)-c/s-chrysanthemate or to (—)-dihydro-chrysanthemolactone (106), both of which are convertible into (+)-rra s-chrysan-... 

Finally, a series of novel hydroperoxy-l,2-dioxanes 233a, b (Scheme 65) were synthesized by hydroperoxide rearrangement and ozonolysis <2006EJ02174> all the products showed weak antimalarial acitivity. Also the epoxy-endoperoxides 234a,b were designed which proved to have inhibitory acitivity against Candida albicans (Scheme 65) <2007BMC36>. 

Sha et al. (45) reported an intramolecular cycloaddition of an alkyl azide with an enone in an approach to a cephalotaxine analogue (Scheme 9.45). Treatment of the bromide 205 with NaN3 in refluxing methanol enabled the isolation of compounds 213 and 214 in 24 and 63% yields, respectively. The azide intermediate 206 underwent 1,3-dipolar cycloaddition to produce the unstable triazoline 207. On thermolysis of 207 coupled with rearrangement and extrusion of nitrogen, compounds 213 and 214 were formed. The lactam 214 was subsequently converted to the tert-butoxycarbonyl (t-Boc)-protected sprrocyclic amine 215. The exocyclic double bond in compound 215 was cleaved by ozonolysis to give the spirocyclic ketone 216, which was used for the synthesis of the cephalotaxine analogue 217. 

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