Synthesis of Nitrile Bearing Acyclic Quaternary Centers through Co(III)-Catalyzed Sequential C-H Bond Addition to Dienes and N-Cyanosuccinimide.

ABSTRACT: Herein we disclose a three-component strategy to access quaternary centers bearing nitriles by cobalt-catalyzed C-H bond activation and sequential addition to internally substituted 1,3-dienes and an electrophilic cyanating reagent with high regio and stereocontrol. 2-Aryl and alkyl monosubstituted dienes provide α-aryl and α-alkyl α-methyl-substituted nitriles, respectively. An even wider variety of functionality can be installed at the quaternary carbon by using 1,2-disubstituted dienes. The synthetic utility of the nitrile products was successfully demonstrated by various transformations, including conversions to γ-lactones and tetrazoles. The observed connectivity in the products along with studies with deuterium labeled reactants provide insight into the mechanism. Formation of a 7-membered cobaltacycle by C-H activation and migratory insertion of the diene is followed by β-hydride elimination and hydride reinsertion to give a 6-membered cobaltacycle that then reacts with the cyanating agent.

SUBMITTER: Dongbang S 

PROVIDER: S-EPMC7855836 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature