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Palladium and Lewis-Acid-Catalyzed Intramolecular Aminocyanation of Alkenes: Scope, Mechanism, and Stereoselective Alkene Difunctionalizations
journal contribution
posted on 2018-02-20, 21:18 authored by Zhongda Pan, Shengyang Wang, Jason T. Brethorst, Christopher J. DouglasAn 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
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