Thioketals, oxidative cleavage

The C18-C28 segment 502 was synthesized starting from epoxide 497 as shown in Scheme 71. The thioketal 500 was synthesized by coupling of 498 and 499, which were derived from epoxide 497. The thioketal 500 was converted into hemiketal 501 via adjustment of the silyl protective group, deprotection of thioketal, oxidative cleavage of the double bond, and acetylene formation. Hydrostannylation/iodination of acetylene 501 gave vinyliodide, and protective group manipulation afforded 502. 

Cyelobutanone has been prepared by (1) reaction of diazomethane with ketene,4 (2) treatment of methylenecyclobutane with performic acid, followed by cleavage of the resulting glycol with lead tetraacetate,s (3) ozonolysis of methylenecyclobutane, (4) epoxidation of methylene-cyclopropane followed by acid-catalyzed ring expansion,7 and (5) oxidative cleavage of cyclobutane trimethylene thioketal, which in turn is prepared from 2-(co-chloropropyl)-l,3-dithiane.8... 

Oxidative cleavage of ethylene tUoketals. Steroidal ketones can be regenerated from ethylene thioketals by oxidation with I1I04. The reaction is rapid, and yields are almost quantitative. 

In order to achieve better selectivity in a future oxidative cleavage of ring A, e. g. by ozone after transformation to a quinone system (5), 7-0-methyleucomol (11) has been transformed to its 8-hydroxy derivative (74) by potassium peroxodisulfate and potassium hydroxide in pyridine (47). Treatment of (74) with benzyl bromide and potassium carbonate in aceton gave the dibenzyl product (76) which on thioketalization yielded... 

Completion of the monomeric unit was achieved via Swem oxidation and Arbuzov reaction with trimethylphosphite to give the phosphonate 75 in 31% overall yield from the resolved amino alcohol. Dimeric olefination was effected upon deprotonation to yield the macrocycle 76, which could be converted in 81% yield to optically active vermiculine (56) via sequential cleavage of the thioketal and ketal protecting groups. 

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