Journal of the American Chemical Society · 2005 · 182 citations · 2 references
Natural SciencesChemistryMedicinal ChemistryCatalysisOrganic ChemistryReaction EngineeringCatalytic MechanismsCross-coupling ReactionsOrganic SynthesisAmine BasesAsymmetric Cross-couplingCatalytic Reaction MechanismsEnantioselective CatalysisEnantioselective Cross-couplingEnantioselective SynthesisMechanistic Studies Of Cross-couplingRecrystallization
Catalytic asymmetric cross-coupling reactions between aldehydes and N-acylimines have been discovered that employ thiazolylalanine derivatives as catalysts. Alkylation of the thiazolyl moiety, followed by in situ generation of the derived thiazolium ylide using a tertiary amine base, leads to the active catalyst. alpha-Amidoketone products are isolated in up to 90% yield with up to 87% enantiomeric excess (>98% ee after a single recrystallization). The use of a hindered base to suppress product racemization was stimulated by a mechanistic study that revealed an isotope effect on the racemization rate of the product.
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