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    Synthesis of Functionalized Arylacetamido-2-pyridones through ortho-C(sp2)–H-Activated Installation of Olefins and Alkynes

    Synthesis of Functionalized Arylacetamido-2-pyridones through ortho-C(sp2)–H-Activated Installation of Olefins and Alkynes

    Authors: Tanmay K. Pati (TCGLS Member), Sk Ajarul, Mrinalkanti Kundu (TCGLS Member), Deepak Tayde, Uttam Khamrai (TCGLS Member),* and Dilip K. Maiti*

    DOI: https://doi.org/10.1021/acs.joc.0c00941

    We have identified different N-substituted 2-pyridones as inbuilt directing groups for selective C–H-activated functionalization instead of deprotecting and/or throwing away the directing groups. A robust general method for external ligand-free PdII-catalyzed C¬(sp2)–H olefination and alkynylation is established to access valuable phenylacetamido-2-pyridones. Diverse substrate scope has been demonstrated with 48 different examples with high yield and gram-scale synthesis. Adequate tolerance of valuable functional groups was also observed, such as olefins possessing esters, sulfone, amide, cyanide, and ketones, aromatic residues containing fluorine, chlorine, bromine, NO2, methyl, dimethyl, and methoxy, as well as 2-pyridone-N-bearing methyl, cyclopropyl methyl, cyclopentyl methyl, benzyl, phenyl, acetate, and acetamide groups, which smoothly produced the respective desired products. We used triisopropyl silane-substituted alkynes for the alkynylation reaction, which can easily be converted to several functional groups including terminal alkyne, heterocycle through click reaction, and others. Implementing our protocol, we have also demonstrated late-stage olefination and alkynylation of 2-pyridone, containing the CB2 agonist-type molecule with excellent yield. Considering N-substituted 2-pyridone acts as a biologically-active structural unit, this general method has the significance in terms of late-stage functionalization to access new molecular entities which can be employed in medicinal chemistry research through diverse C–H activation.