Cyclic acetals, oxidation

Other non-traditional preparations of 1,2,3-triazoles have been reported. The rearrangement in dioxane/water of (Z)-arylhydrazones of 5-amino-3-benzoyl-l,2,4-oxadiazole into (2-aryl-5-phenyl-27/-l,2,3-triazol-4-yl)ureas was investigated mechanistically in terms of substituents on different pathways <06JOC5616>. A general and efficient method for the preparation of 2,4-diary 1-1,2,3-triazoles 140 from a-hydroxyacetophenones 139 and arylhydrazines is reported <06SC2461>. 5-Alkylamino-] //-], 2,3-triazoles were obtained by base-mediated cleavage of cycloadducts of azides to cyclic ketene acetals <06S1943>. Oxidation of N-... 

Manganese acetate-promoted oxidative addition of 1,3-dicarbonyl compounds (351) to endo-cyclic enol ethers (352) and enol lactones (353) gives 2,3,3a,6a-tetrahydrofuro[2,3-6]furan derivatives (354) and (355) <87CL223, 91TL711, 91TL7107). 

If the cyclic oxide LXXXV, on the other hand, be treated with acetic anhydride in the presence of ferric chloride or zinc chloride there is formed a heptaacetate (XCI). The same compound is obtained by acetylation of the cyclic oxide LXXXVI in the presence of ferric chloride or zinc chloride. Hydrolysis of this heptaacetate yielded XCII, an isomer of hydroxyisomytilitol. It is apparent that a Walden inversion has occurred here in the opening of both cyclic oxides XCII is therefore appropriately named hydroxym3rtilitol. 

Undeterred by this first Wessely oxidation obstacle, we set out to modify our design and give the dearomatization step the best opportunity to succeed. We postulated that an intramolecular Wessely oxidatirai approach would have a better chance of directing the oxidant to the desired site for dearomatization. The results of our investigations are presented in Scheme 4. We used the aldol addition product from the previous route (10) and instead of forming a cyclic ketal we developed a mild method to gently form the requisite ori/io-quinone methide, which we trapped in situ with ethyl vinyl ether to provide 11. Deprotection of the acetal and oxidation then afforded lactone 12, which served as precursor to the acetic acid tether (13) we needed for the dearomatization... 

The starting material for iloprost is the enantiomerically pure Corey lactone, which is treated with the lithium salt of ethyl acetate. After oxidation, treatment with l,5-diazabicyclo[4.3.0]non-5-ene (DBN) leads to an exceptionally interesting rearrangement. Presumed cleavage of the cyclic ether generates an enolate, which adds to the cyclopentenone in a Michael reaction. Decarbethoxylation is achieved with l,5-diazabicyclo[2.2.2]octane (DABCO), and the w-chain is constructed under Horner-Wadsworth-Emmons conditions. The subsequent reduction leads to a mixture of allyl alcohols, which can be purified by chromatography, and the alcohol from the less polar product then be released by trans-esterification. Both alcohol functions are then protected as THP-ethers. The... 

Similarly, the other enantiomer of the epoxide was ring-opened with the Grignard derivative of 5b to yield alcohol 20 in 76 % yield (Scheme 3.8). Subsequent ZrCLj-catalysed deprotection and cyclization generated cyclic acetal 21 in 96 % yield. Finally, as before, this acetal was oxidized to lactone 22 in an 82 % yield followed by hydrogenolysis of the benzyl group to form (H-)-5-muricatacin lb in a 75 % yield. 

Ozonolysis of a cyclic alkene leads to oxidative cleavage, but the two carbonyl fragments are connected, so there is only one product rather than the two observed from ozonolysis of 2,3-dimethyl-2-butene or 2-methyl-2-pentene. When cycloheptene, for example, is treated with ozone and then with zinc and acetic acid, oxidative cleavage leads to the a,(o-dialdehyde 146 (1,7-heptanedial or 1,7-heptanedicarboxaldehyde). 

The oxidation of the cyclic enol ether 93 in MeOH affords the methyl ester 95 by hydrolysis of the ketene acetal 94 formed initially by regioselective attack of the methoxy group at the anomeric carbon, rather than the a-alkoxy ketone[35]. Similarly, the double bond of the furan part in khellin (96) is converted ino the ester 98 via the ketene acetal 97[l23],... 

The intramolecular oxidative earbonylation has wide synthetie applieation. The 7-lactone 247 is prepared by intramolecular oxycarbonylation of the alke-nediol 244 with a stoichiometric amount of Pd(OAc)2 under atmospheric pres-sure[223]. The intermediate 245 is formed by oxypalladation, and subsequent CO insertion gives the acylpalladium 246. The oxycarbonylation of alkenols and alkanediols can be carried out with a catalytic amount of PdCl2 and a stoichiometric amount of CuCb, and has been applied to the synthesis of frenolicin(224] and frendicin B (249) from 248[225]. The carbonylation of the 4-penten-l,3-diol 250, catalyzed by PdCl2 and CuCl2, afforded in the c -3-hydroxytetrahydrofuran-2-aeetie acid lactone 251[226J. The cyclic acetal 253 is prepared from the dienone 252 in the presence of trimethyl orthoformate as an accepter of water formed by the oxidative reaction[227]. 

The reaction of a halide with 2-butene-1,4-diol (104) affords the aldehyde 105, which is converted into the 4-substituted 2-hydroxytetrahydrofuran 106, and oxidized to the 3-aryl-7-butyrolactone 107[94], Asymmetric arylation of the cyclic acetal 108 with phenyl triflate[95] using Pd-BINAP afforded 109, which was converted into the 3-phenyllactone 110 in 72% ee[96]. Addition of a molecular sieve (MS3A) shows a favorable effect on this arylation. The reaction of the 3-siloxycyclopentene 111 with an alkenyl iodide affords the. silyl... 

A carbonyl group can be protected as a sulfur derivative—for example, a dithio acetal or ketal, 1,3-dithiane, or 1,3-dithiolane—by reaction of the carbonyl compound in the presence of an acid catalyst with a thiol or dithiol. The derivatives are in general cleaved by reaction with Hg(II) salts or oxidation acidic hydrolysis is unsatisfactory. The acyclic derivatives are formed and hydrolyzed much more readily than their cyclic counterparts. Representative examples of formation and cleavage are shown below. 

The oxidation of amines by mercuric acetate is an old reaction (54) which up until recent years was employed primarily to modify alkaloid structures (55). A systemic study of the oxidizing action of mercuric acetate by Leonard and co-workers led to the development of a general method for the synthesis of enamines from cyclic tertiary amines. An observation made after a large number of compounds were oxidized, but which is worth noting at the onset, is that a tertiary hydrogen alpha to the nitrogen atom is removed preferentially to a secondary a-hydrogen. 

The most general method for synthesis of cyclic enamines is the oxidation of tertiary amines with mercuric acetate, which has been investigated primarily by Leonard 111-116) and applied in numerous examples of structural investigation and in syntheses of alkaloids 102,117-121). The requirement of a tram-coplanar arrangement of an a proton and mercury complexed on nitrogen, in the optimum transition state, confers valuable selectivity to the reaction. It may thus be used as a kinetic probe for stereochemistry as well as for the formation of specific enamine isomers. 

The key step in syntheses of if/-quebrachamine (122-127) and if/-dihydro-cleavamine (12S) is the oxidation of tertiary amines with mercuric acetate to cyclic imonium salts, which give rise to an intramolecular electrophilic attack on an indole. 

The formation of an enamine from an a,a-disubstituted cyclopentanone and its reaction with methyl acrylate was used in a synthesis of clovene (JOS). In a synthetic route to aspidospermine, a cyclic enamine reacted with methyl acrylate to form an imonium salt, which regenerated a new cyclic enamine and allowed a subsequent internal enamine acylation reaction (309,310). The required cyclic enamine could not be obtained in this instance by base isomerization of the allylic amine precursor, but was obtained by mercuric acetate oxidation of its reduction product. Condensation of a dihydronaphthalene carboxylic ester with an enamine has also been reported (311). 

X0 to hydroxy compounds. Lower temperatures favor ketone formation and sterically hindered carbonyls, such as 2-thienyl t-butyl ketone, are not reduced. The sensitivity of desulfurization to steric factors is evident by the failure to desulfurize 2,5-di-i-butyl-3-acetylthiophene. The carbonyl groups of both aldehydes and ketones can be protected by acetal formation, as particularly cyclic acetals are stable during desulfurization in methanol at room temperature. " The free aldehydes give primary alcohols on desulfurization. Another method to obtain only keto compounds is to oxidize the mixtures of ketone and secondary alcohol with CrOs after the desulfurization. - Through the desulfurization of 5,5 -diacetyl-2,2, 5, 2"-terthienyl (228), 2,15-hexadecandione (229) has been obtained, which... 

Hydrazinopyridazines such as hydralazine have a venerable history as anti hypertensive agents. It is of note that this biological activity is maintained in the face of major modifications in the heterocyclic nucleus. The key intermediate keto ester in principle can be obtained by alkylation of the anion of pi peri done 44 with ethyl bromo-acetate. The cyclic acylhydrazone formed on reaction with hydrazine (46) is then oxidized to give the aromatized compound 47. The hydroxyl group is then transformed to chloro by treatment with phosphorus oxychloride (48). Displacement of halogen with hydrazine leads to the formation of endralazine (49). ... 

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