Uniting Amide Synthesis and Activation by P<sup>III</sup>/P<sup>V</sup>–Catalyzed Serial Condensation: Three-Component Assembly of 2-Amidopyridines
Jeffrey M. Lipshultz, Alexander T. Radosevich
Abstract
An organophosphorus (PIII/PV redox) catalyzed method for the three-component condensation of amines, carboxylic acids, and pyridine N-oxides to generate 2-amidopyridines via serial dehydration is reported. Whereas amide synthesis and functionalization usually occur under divergent reaction conditions, here a phosphetane catalyst (together with a mild bromenium oxidant and terminal hydrosilane reductant) is shown to drive both steps chemoselectively in an auto-tandem catalytic cascade. The ability to both prepare and functionalize amides under the action of a single organocatalytic reactive intermediate enables new possibilities for the efficient and modular preparation of medicinal targets.
Topics & Concepts
ChemistryCatalysisAmideTandemCondensationSurface modificationCombinatorial chemistryCascade reactionPyridineCondensation reactionOrganic chemistryPhysical chemistryComposite materialThermodynamicsMaterials sciencePhysicsAdvanced Synthetic Organic ChemistryChemical Synthesis and AnalysisChemical synthesis and alkaloids