Ozonolysis/Wittig-olefination

This method was used in the stereoselective synthesis of cis- and /ran -hemicaronic aldehydes 9 which were prepared in high enantiomeric purity starting from optically active sorbic aldehyde diene tricarbonyliron complex 6 via Wittig olefination, diazo ester cyclopropanation (copper powder), and further conversion with release of the cyclopropane from the complex and ozonolysis. ... 

Ozonolysis of the mixture of 35 and 36 followed by sodium borohydride reduction afforded 39 (86%) and 40 (6%) (Scheme 3)7 Detrityladon of 39 followed by Swem oxidation and Wittig olefination of the resulting aldehyde with Ph3P=CH(CH2)9CH3 furnished the Z-olefin 41 (49%) and the fi-olefin 42 (3%). The Z-olefin was hydrogenated and the oxazolidinone ring was saponified to produce (-)-desoxoprosopinine (4). 

The first straight-chain A5,9 fatty acid to be synthesized was actually the (5Z,9Z)-5,9-hexacosadienoic acid [47]. The methodology developed by Djerassi et al. is shown in Fig. (17). This six-step synthesis started with the unusual controlled ozonolysis of one of the double bonds of (lZ,5Z)-l,5-cyclooctadiene to secure a 100% Z stereochemistry for what eventually was going to be the A9 double bond of the target molecule. Transformation of the product to the tosylated acetal, followed by Grignard coupling under dilithium tetrachlorocuprate catalysis afforded (Z)-4-heneicosenal, which after Wittig olefination with 4-carboxybutyltriphenylphosphonium bromide resulted in the desired A5,9... 

Stereospecific osmylation produces lactone 840 as a single diastereomer. This, upon treatment with sodium bicarbonate, gives bicyclic lactone 841 in high yield. Reduction of lactone 841 to a lactol followed by Wittig olefination affords allyltetrahydrofuran 842. Pal-ladium(II) isomerization of the olefin, epoxidation, ozonolysis, and reduction gives the target compound 844 with 95% optical purity. 

The asymmetric total synthesis of the natural enantiomer (—)-nakadomarin A was completed by Nishida et al. in 2004 (Scheme 8.12) [82]. Diels-Alder reaction between siloxydiene 173 and chiral dienophile 172 (prepared from L-serine in 10 steps [83]) gave the highly functionalized key intermediate hydroisoquinoline 174, which was subjected to Luche reduction, cyclization, and HCl treatment to furnish the tricyclic intermediate 175. Compound 175 was converted to 177 via ozonolysis cleavage of ring B followed by recyclization of the unstable bisaldehyde to a five-membered ring by aldol condensation. The Z-olefin 178 was obtained from Wittig reaction of 177, and was further converted to furan 180 via peroxide 179. The... 

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. 

Alkenes can be considered as a class of protected carbonyl compounds since they can be converted into carbonyls by ozonolysis. Hall [69] demonstrated a practical strategy for solid phase synthesis of peptide aldehydes using an olefinic linker, which was constructed using Wittig chemistry. After normal peptide synthesis using the alkene linker, ozonolysis of the linker and subsequent workup with... 

Intermediate (61) has also been taken forward by a new procedure whereby the ethylene ketal, by olefin cleavage, esterification, Baeyer—Villiger oxidation and lactonisation, afforded (66a), of which the formyl derivative (66b) on ozonolysis and acetylation gave (67). PGEi then followed via olefin cleavage and Wittig elaboration [65]. 

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