A nickel-catalyzed three-component carboamination of unactivated alkenes with organoboronic acids and anthranils has been achieved for the expedient synthesis of δ-aryl and γ-amino acid derivatives. The 8-aminoquinoline (AQ) directing group is crucial for the success of the reaction, and anthranil serves as an arylnitrene precursor in this conversion. This method features mild reaction conditions, good chemo- and regioselectivity, and a broad substrate scope with good functional group tolerance.
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http://dx.doi.org/10.1021/acs.joc.4c01536 | DOI Listing |
J Org Chem
October 2024
School of Chemical Engineering and Light Industry, Guangdong University of Technology, Guangzhou 510006, China.
A nickel-catalyzed three-component carboamination of unactivated alkenes with organoboronic acids and anthranils has been achieved for the expedient synthesis of δ-aryl and γ-amino acid derivatives. The 8-aminoquinoline (AQ) directing group is crucial for the success of the reaction, and anthranil serves as an arylnitrene precursor in this conversion. This method features mild reaction conditions, good chemo- and regioselectivity, and a broad substrate scope with good functional group tolerance.
View Article and Find Full Text PDFJ Am Chem Soc
September 2024
Department of Chemistry, University of Texas at Austin, 100 East 24th Street, Austin, Texas, 78712, United States.
Herein, we report mechanistic investigations into the Cu-catalyzed three-component carboamination of alkenes with α-halo carbonyls and aryl amines via an oxocarbenium intermediate. Monitoring the reaction reveals the formation of transient atom transfer radical addition (ATRA) intermediates with both electron-neutral and deficient vinyl arenes as well as unactivated alkenes. Based on our experimental studies and density functional theory calculations, the oxocarbenium is generated through atom transfer and subsequent intramolecular substitution.
View Article and Find Full Text PDFOrg Lett
July 2024
School of Chemistry and Molecular Engineering, Nanjing Tech University, Nanjing 211816, China.
A general intermolecular polarity-mismatched carboamination reaction of unactivated alkenes with unactivated alkyl halides has been developed. A series of nonactivated alkyl-substituted aziridines were constructed in exclusive regioselectivity. The dual polarity-mismatched mechanism might be involved.
View Article and Find Full Text PDFJ Am Chem Soc
November 2023
Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, United States.
Catalytic carboamination of alkenes is a powerful synthetic tool to access valuable amine scaffolds from abundant and readily available alkenes. Although a number of synthetic approaches have been developed to achieve the rapid buildup of molecular complexity in this realm, the installation of diverse carbon and nitrogen functionalities onto unactivated alkenes remains underdeveloped. Here we present a ligand design approach to enable nickel-catalyzed three-component carboamidation that is applicable to a wide range of alkenyl amine derivatives via a tandem process involving alkyl migratory insertion and inner-sphere metal-nitrenoid transfer.
View Article and Find Full Text PDFJ Org Chem
October 2023
College of Chemistry, Beijing Normal University, Beijing 100875, China.
Density functional theory (DFT) calculations have been employed to investigate the mechanism of carboamination and diamination of unactivated alkenes mediated by Pd(IV) intermediates. Both reactions share a common Pd(IV) intermediate, serving as the starting point for either the carboamination or the diamination pathway. The formation of this Pd(IV) intermediate encompasses a transition state that substantially impacts the turnover frequency (TOF) of catalytic cycles, with an apparent activation free-energy barrier of 26.
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