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Pd-Catalyzed Domino Narasaka–Heck/C–H Activation/Amination Reactions: Synthesis of Bis-heterocyclic Spirocycles

Jonathan Bajohr, Aurélien Dupeux, Daniel Schenk, Clara Jans, Mark Lautens

2023Organic Letters20 citationsDOI

Abstract

The palladium-catalyzed synthesis of bis-heterocyclic spirocycles containing both pyrroline and indoline motifs is reported. Di- tert -butyldiaziridinone is used to functionalize palladacycles generated in situ via domino Narasaka–Heck/C–H activation reactions. The reaction is readily scalable, and the spirocyclic products can undergo deprotection, reduction, and (3 + 2) cycloadditions, highlighting their synthetic utility. Additionally, kinetic isotope effect experiments support a turnover-limiting C–H functionalization step in the catalytic cycle.

Topics & Concepts

ChemistryDominoCatalysisIndolineAminationHeck reactionCombinatorial chemistryCascade reactionReductive aminationOrganic synthesisOrganic chemistryPalladiumCatalytic C–H Functionalization MethodsAsymmetric Hydrogenation and CatalysisSynthesis and Catalytic Reactions
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