Palladium and Lewis-Acid-Catalyzed Intramolecular Aminocyanation of Alkenes: Scope, Mechanism, and Stereoselective Alkene Difunctionalizations
journal contributionposted on 20.02.2018, 21:18 by Zhongda Pan, Shengyang Wang, Jason T. Brethorst, Christopher J. Douglas
An expansion of methodologies aimed at the formation of versatile organonitriles, via the intramolecular aminocyanation of unactivated alkenes, is herein reported. Importantly, the need for a rigid tether in these reactions has been obviated. The ease-of-synthesis and viability of substrates bearing flexible backbones has permitted for diastereoselective variants as well. We demonstrated the utility of this methodology with the formation of pyrrolidones, piperidinones, isoindolinones, and sultams. Furthermore, subsequent transformation of these motifs into medicinally relevant molecules is also demonstrated. A double crossover 13C-labeling experiment is consistent with a fully intramolecular cyclization mechanism. Deuterium labeling experiments support a mechanism involving syn-addition across the alkene.
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motifpiperidinoneexperiments supportcrossover 13 C-labeling experimentMechanismLewis-Acid-Catalyzed Intramolecular AminocyanationisoindolinoneScopetetherutilityviabilitymethodologyImportantlyunactivated alkenesStereoselective Alkene DifunctionalizationsPalladiumintramolecular aminocyanationpyrrolidonemedicinallymoleculesynDeuteriumformationsubstratetransformationintramolecular cyclization mechanismorganonitrilesultamease-of-synthesiobviateddiastereoselective variants