Stereospecific Furanosylations Catalyzed by Bis-thiourea Hydrogen-Bond Donors
Andrew B. Mayfield, Jan B. Metternich, Adam H. Trotta, Eric N. Jacobsen
Abstract
We report a new method for stereoselective O-furanosylation reactions promoted by a precisely tailored bis-thiourea hydrogen-bond-donor catalyst. Furanosyl donors outfitted with an anomeric dialkylphosphate leaving group undergo substitution with high anomeric selectivity, providing access to the challenging 1,2-cis substitution pattern with a range of alcohol acceptors. A variety of stereochemically distinct, benzyl-protected glycosyl donors were engaged successfully as substrates. Mechanistic studies support a stereospecific mechanism in which rate-determining substitution occurs from a catalyst–donor resting-state complex.
Topics & Concepts
ChemistryStereospecificityAnomerThioureaStereoselectivityCatalysisStereochemistryHydrogen bondSelectivitySubstitution reactionMedicinal chemistryOrganic chemistryMoleculeCarbohydrate Chemistry and SynthesisChemical Synthesis and AnalysisMicrobial Natural Products and Biosynthesis