Dithianes, acylation rearrangement

Williams and McClymont have observed that acylation reactions of the dianion of 2-(5-oxazolyl)-l,3-dithiane (15) lead to formation of 4,5-disubstituted oxazole products through a Comforth rearrangement pathway under base-induced, low-temperature conditions. For example, deprotonation of 15 with LiHMDS (3.0 equivalents) at -78°C, followed by addition of benzoyl chloride or p-chlorobenzoyl chloride and warming to 0°C, provided 16 in 74% and 47% yield, respectively. 

In the laboratory of D.R. Williams, a carbanion methodology for the alkylations and acylations of substituted oxazoles was investigated. The study showed that the monoalkylation of the dianion generated from 2-(5-oxazolyl)-1,3-dithiane exclusively led to the substitution of the carbon adjacent to sulfur. However, acylation reactions of the dianion afforded 4,5-disubstituted oxazoles. These new products presumably arose from carbonyinitrile ylide intermediates, which were generated by the selective C-acylation of a ring-opened dianion tautomer. This is the first example of a base-induced, low-temperature Cornforth rearrangement. 

Lithiated dithiane 35 is another example of a formyl anion equivalent. Acylation would provide 36 and thioacetal hydrolysis would provide 29. The thioacetal hydrolysis is the FGT that establishes the equivalency. Acylation of dimsyl anion 37 (from metallation of DMSO) would afford )8-ketosulfoxide 38. Once again an oxidation is needed to establish the desired equivalency. This can be accomplished using a Pummerer rearrangement wherein oxidation occurs at carbon with reduction at sulfur. Hydrolysis of the resulting S,0-acetal would complete the required FGT. 

---