Regioselective Difluoroalkylation of 2-Pyridones with Fluoroalkyl Bromides Enabled by a Nickel(II) Catalyst
Chandini Pradhan1,2, Disha Khandelwal1,3, Benudhar Punji1,2
1Organometallic Synthesis and Catalysis Lab, Organic Chemistry Division, CSIR - National Chemical Laboratory (CSIR-NCL), Dr. Homi Bhabha Road, Pune, 411 008, India.
Abstract:
Regioselective C-H difluoroalkylation of diverse 2-pyridones with ethyl bromodifluoroacetates and bromodifluoroacetamides is accomplished by using a (dppf)NiCl2 catalyst under mild conditions. This efficient protocol could deliver a variety of C-3 difluoroalkylated pyridones with the tolerance of a range of highly susceptible functionalities, such as -Cl, -Br, -I, -COMe, -CN, -NMe2 and -NO2, including heteroarenes like pyridinyl, furanyl, thiophenyl and carbazolyl moieties. A preliminary mechanistic study suggests the radical pathway for the reaction involving fluoroalkyl radical intermediate.
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