Multicomponent Linchpin Couplings. Reaction of Dithiane Anions with Terminal Epoxides, Epichlorohydrin, and Vinyl Epoxides: Efficient, Rapid, and Stereocontrolled Assembly of Advanced Fragments for Complex Molecule Synthesis

Article abstract of DOI:10.1021/ja0376238

The development, application, and advantages of a one-flask multicomponent dithiane linchpin coupling protocol, over the more conventional stepwise addition of dithiane anions to electrophiles leading to the rapid, efficient, and stereocontrolled assembly of highly functionalized intermediates for complex molecule synthesis, are described. Competent electrophiles include terminal epoxides, epichlorohydrin, and vinyl epoxides. High chemoselectivity can be achieved with epichlorohydrin and vinyl epoxides. For vinyl epoxides, the steric nature of the dithiane anion is critical; sterically unencumbered dithiane anions afford S_N2 adducts, whereas encumbered anions lead primarily to S_N2′ adducts. Mechanistic studies demonstrate that the S_N2′ process occurs via syn addition to the vinyl epoxide. Integration of the multicomponent tactic with epichlorohydrin and vinyl epoxides permits the higher-order union of four and five components.