A Proline and 4‐Hydroxyproline Based Approach to Enantiopure Pyrrolidin‐2‐yl‐Substituted Pyridine and Pyrimidine Derivatives

The optimized coupling of N-protected (S)-proline and (2S,4R)-4-hydroxyproline derivatives with (Z)-4-aminopent-3-en-2-one provided the expected β-ketoenamides in good to excellent yields. subsequent intramolecular cyclizations afforded enantiopure pyridin-4-one pyrrolidin-2-yl substituents. nonaflates generated from these intermediates were precursors for typical palladium-catalyzed reactions. Oxidation m-chloroperbenzoic acid gave pyrrolidine N-oxides whose reactions investigated. condensation hydroxylamine hydrochloride furnished corresponding pyrimidine Boekelheide rearrangement hydroxymethyl-substituted together minor components. Overall, this study nicely demonstrates potential (S)-proline- or (2S,4R)-4-hydroxyproline-derived approach a library novel chiral pool-derived functionalized pyridine derivatives.