Esters enol ether ozonolysis

The most common procedure is ozonolysis at -78 °C (P.S. Bailey, 1978) in methanol or methylene chloride in the presence of dimethyl sulfide or pyridine, which reduce the intermediate ozonides to aldehydes. Unsubstituted cydohexene derivatives give 1,6-dialdehydes, enol ethers or esters yield carboxylic acid derivatives. Oxygen-substituted C—C bonds in cyclohexene derivatives, which may also be obtained by Birch reduction of alkoxyarenes (see p. 103f.), are often more rapidly oxidized than non-substituted bonds (E.J. Corey, 1968 D G. Stork, 1968 A,B). Catechol derivatives may also be directly cleaved to afford conjugated hexa-dienedioic acid derivatives (R.B. Woodward, 1963). Highly regioselective cleavage of the more electron-rich double bond is achieved in the ozonization of dienes (W. KnOll, 1975). 

The same year, Gerlach described a synthesis of optically active 1 from (/ )- ,3-butanediol (7) (Scheme 1.2). The diastereomeric esters produced from (-) camphorsulfonyl chloride and racemic 1,3-butanediol were fractionally recrystallized and then hydrolized to afford enantiomerically pure 7. Tosylation of the primary alcohol, displacement with sodium iodide, and conversion to the phosphonium salt 8 proceeded in 58% yield. Methyl-8-oxo-octanoate (10), the ozonolysis product of the enol ether of cyclooctanone (9), was subjected to Wittig condensation with the dilithio anion of 8 to give 11 as a mixture of olefin isomers in 32% yield. The ratio, initially 68 32 (E-.Z), was easily enriched further to 83 17 (E Z) by photolysis in the presence of diphenyl disulfide. The synthesis was then completed by hydrolysis of the ester to the seco acid, conversion to the 2-thiopyridyl ester, and silver-mediated ring closure to afford 1 (70%). Gerlach s synthesis, while producing the optically active natural product, still did not address the problem posed by the olefin geometry. 

Ozonolysis of an enol ether provides a carboxylic ester, as one of the two carbonyl products. For example, the enol ether 103 (formed by Birch reduction - see Section 7.2) was converted to the ester-alcohol 104, used in a synthesis of the Cecropia moth juvenile hormone (5.103). This example illustrates the preferential oxidation of the more electron-rich alkene by the electrophilic ozone. 

The proposed synthetic route to TM 2.8 starts with anisole, which on methy-lation and Birch reduction affords a derivative of non-conjugated cyclohexadiene TM 2.8g. The importance and mechanism of this reaction are discussed in Sect.5.4. Chemoselective hydrogenation of one C=C bond is possible since the double bond in enol ether C=C-OMe is less reactive. TM 2.8f affords ester-aldehyde TM 2. 8e on ozonolysis (Scheme 2.20). 

Another interesting way to construct 8-lactones is the Baeyer-Villiger oxidation [72] of cyclopentanones. For example, Hacini and Santelli have reported an efficient synthesis of the Prelog-Djerassi lactone methyl ester using Baeyer-Villiger oxidation [73] (Scheme 30). Hydrolysis of enol ether 162 derived from —)-trans-pulegenic acid furnished an inseparable diastereomeric mixture of the corresponding dimethylacetals. Ozonolysis of the olefin and subsequent... 

The tricyclic lactone, 163, was also transformed to a yohimbine precursor by Polniaszek and Stevens (Scheme 3.26). Treatment of 163 with methoxide induced a double bond migration which was followed by Michael addition of methoxide. Subsequent oxidation and thermolysis effected selenoxide elimination to provide 166. Ozonolysis of the double bond followed by reduction yielded a mixture of bis-hemiacetals which were reduced with triethylsilane in trifluoroacetic acid to provide the tricyclic pyran 167. Reduction of the lactone and tritylation of the primary alcohol function afforded 168 which was subjected to xanthate ester elimination to give the enol ether 169. Oxymercuration-reduction and detritylation afforded the methylpyranoside... 

L-dihydroxy-succinic acid (L(dexiro)-tartaric acid, CXIII). This result establishes the position of the double bond between C4 and C5 and demonstrates that C4 carries only one hydrogen atom while C5 has attached to it the enolic hydroxyl group. Treatment of the enol CXI with ethereal diazomethane gives 5-methyl-A4-D-glucosaccharo-3,6-lactone methyl ester (CXIY) which upon further methylation with silver oxide and methyl iodide yields 2,5-dimethyl-A4-D-glucosaccharo-3,6-lactone methyl ester (CXV). When the latter is subjected to ozonolysis there is formed oxalic acid and 3-methyl-L-threuronic acid (CXVI). Oxidation of this aldehydic acid (CXYI) with bromine gives rise to a monomethyl derivative (CXVII) of L-ilireo-dihydroxy-succinic acid. 

Nitrosolysis of camphor ethyl acetal with ethanolic ethyl nitrite in sulphur dioxide yields the orthoester oxime (205) which is rapidly dehydrated by excess acetal to the orthoester nitrile which then reacts with sulphur dioxide to form the ester nitrile and diethyl sulphite.Further papers in this section include the full paper on ozonolysis of silyl ethers (Vol. 5, p. 33), another synthesis of camphor-enol trimethylsilyl ether (cf. Vol. 6, p. 41)/°° the conversion of camphor oxime with Grignard reagents into the corresponding imine with no aziridine formation/° the preparation of (206) by treating bornylene with trichloroacetyl isocyanate/ the oxidation of thiocam-phor to the 5-oxide and alkylation in the presence of thallium(i) ethoxide to a/S-unsaturated sulphoxides/ and the free-radical C-3 alkylation of camphor with alkenes. " ... 

---