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Free Radicals in Chemical Biology: from Chemical Behavior to Biomarker Development
Published on: April 15, 2013
Radical Chlorodifluoromethylation: Providing a Motif for (Hetero)arene Diversification
Rory C McAtee1, Joel W Beatty1, Christopher C McAtee1
1Willard Henry Dow Laboratory, Department of Chemistry , University of Michigan , 930 North University Avenue , Ann Arbor , Michigan 48109 , United States.
Abstract:
A method for the radical chlorodifluoromethylation of (hetero)arenes using chlorodifluoroacetic anhydride is reported. This operationally simple protocol proceeds under mild photochemical conditions with high functional group compatibility and complements the large body of literature for the trifluoromethylation of (hetero)arenes. Introduction of the chlorodifluoromethyl motif enables rapid diversification to a wide array of aromatic scaffolds. This work showcases the chlorodifluoromethyl group as an attractive entryway to otherwise synthetically challenging electron-rich difluoromethyl(hetero)arenes. Furthermore, facile conversion of the CF2Cl moiety into the corresponding aryl esters, gem-difluoroenones, and β-keto-esters is demonstrated.
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