Decarboxylative N-Alkylation of Azoles through Visible-Light-Mediated Organophotoredox Catalysis
Rino Kobayashi, Shotaro Shibutani, Kazunori Nagao, Zenichi Ikeda, Junsi Wang, Ignacio Ibáñez, Matthew Reynolds, Yusuke Sasaki, Hirohisa Ohmiya
Abstract
An organophotoredox-catalyzed decarboxylative cross-coupling between azole nucleophiles and aliphatic carboxylic acid-derived redox-active esters is demonstrated. This protocol efficiently installs various tertiary or secondary alkyl fragments onto the nitrogen atom of azole nucleophiles under mild and transition-metal-free conditions. The pyridinium additive successfully inhibits the formation of elimination byproducts from the carbocation intermediate. This reaction is applicable to the synthesis of a protein-degrader-like molecule containing an azole and a thalidomide.
Topics & Concepts
ChemistryAzoleNucleophilePyridiniumAlkylationCatalysisAlkylCombinatorial chemistrySulfonamideCarbocationMoleculeOrganic chemistryAntifungalDermatologyMedicineOxidative Organic Chemistry ReactionsRadical Photochemical ReactionsCatalytic C–H Functionalization Methods