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.
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(N)2 adducts, whereas encumbered anions lead primarily to SN2' adducts. Mechanistic studies demonstrate that the SN2' 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.
Smith
Amos B
AB
Department of Chemistry, Monell Chemical Senses Center and Laboratory for Research on the Structure of Matter, University of Pennsylvania, Philadelphia, PA 19104, USA. smithab@sas.upenn.edu
Pitram
Suresh M
SM
Boldi
Armen M
AM
Gaunt
Matthew J
MJ
Sfouggatakis
Chris
C
Moser
William H
WH
D000478:Alkylation; D000838:Anions; D001685:Biological Factors / Q000138:chemical synthesis; D004811:Epichlorohydrin / Q000737:chemistry*; D004852:Epoxy Compounds / Q000737:chemistry*; D011807:Quinolizines / Q000737:chemistry*; D013237:Stereoisomerism; D013457:Sulfur Compounds / Q000737:chemistry*; D014753:Vinyl Compounds / Q000737:chemistry*
D000838:Anions; D001685:Biological Factors; D004852:Epoxy Compounds; D011807:Quinolizines; D013457:Sulfur Compounds; D014753:Vinyl Compounds; C438055:dithiane; D004811:Epichlorohydrin