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Chemo- and Diastereoselective Synthesis of Pyrrolidines from Aroylformates and δ-Tosylamino Enones via P(NMe<sub>2</sub>)<sub>3</sub>-Mediated Reductive Amination/Base-Catalyzed Michael Addition Cascade

Rongfang Liu, Jialin Liu, Jilei Cao, Ruifeng Li, Rong Zhou, Yan Qiao, Wen‐Chao Gao

2020Organic Letters29 citationsDOI

Abstract

A novel P(NMe2)3-mediated tandem (1 + 4) annulation between aroylformates and δ-tosylamino enones has been developed that affords a facile synthesis of functionalized pyrrolidines in moderate to excellent yields with exclusive chemoselectivity and high diastereoselectivity. Mechanistic investigation reveals that the reaction proceeds through an unprecedented P(NMe2)3-mediated reductive amination/base-catalyzed Michael addition cascade. The reaction herein also represents the first study of the reactivity patterns of the Kukhtin–Ramirez adducts toward ambiphilic nucleophile–electrophiles.

Topics & Concepts

ChemoselectivityChemistryAnnulationMichael reactionNucleophileCascade reactionCatalysisReductive aminationAdductAminationElectrophileBase (topology)TandemReactivity (psychology)Combinatorial chemistryCascadeOrganic chemistryMathematicsMedicineAlternative medicineMathematical analysisMaterials sciencePathologyChromatographyComposite materialAsymmetric Synthesis and CatalysisAsymmetric Hydrogenation and CatalysisSynthesis and Catalytic Reactions
Chemo- and Diastereoselective Synthesis of Pyrrolidines from Aroylformates and δ-Tosylamino Enones via P(NMe<sub>2</sub>)<sub>3</sub>-Mediated Reductive Amination/Base-Catalyzed Michael Addition Cascade | Litcius