Cascade reactions of unsaturated xanthates and related reactions: Computer-assisted molecular design and analysis of reaction mechanisms

Abstract

Chugaev reaction provides access to olefins from alcohols without rearrangement through pyrolysis of O-alkyl S-alkyl dithiocarbonates (xanthates) via cis elimination. Xanthates having no β-hydrogens undergo thione-to-thiol rearrangement to give S,S-dialkyl dithiocarbonates (thiolcarbonates). Based on these backgrounds, we intended to use the dithiolcarbonates as precursors of thiols. Xanthates could be converted to the corresponding dithiolcarbonates by Lewis-acid catalysis. Pyridine N-oxides and 4-dimethylaminopyridine also catalyzed the rearrangement reaction. On the other hand, O-(2-alkenyl) S-alkyl dithiocarbonates undergo [3,3]-sigmatropic rearrangement to give the allylically rearranged S- (2-alkenyl) S-alkyl dithiocarbonates. The homoallylic xanthates gave the corresponding dithiolcarbonates on heating with phenols. Pyrolysis of allylic dithiolcarbonates caused retro-ene type reaction to give the allylic sulfides in which allylic rearrangement also occurs. Coupling of these pericyclic reactions with intramolecular Diels-Alder reaction affords a one-pot synthetic method for the construction of hydroisobenzothiophenes. The mechanisms of the cascade and related reactions are demonstrated by location of the transition states using molecular orbital calculation method at various levels of theory involving density functional theory (DFT). © 2005 The Pharmaceutical Society of Japan.