Fluorine-containing moieties, especially trifluoromethyl group, have a wide range of applications in agricultural chemistry, medicine and materials science owing to its profound effect on properties such as lipophilicity and metabolic stability. Thus, the introduction of trifluoromethyl groups into organic molecules has attracted considerable attention, and significant progress has been achieved in this field in the past few decades. The trifluoromethylation reaction of C(sp2)-H bond has been extensively studied. However, direct trifluoromethylation of C(sp3)–H bonds, especially late stages modification, remains a formidable challenge due to high C-H bond energy. We have recently developed a direct C(sp3)-H trifluoromethylation of heteroarene adjacent carbons by triflate transfer strategy. The reaction proceeds under mild, catalyst-free conditions, promoted by irradiation with visible light. The key to this reaction was imidazolium sulfonamide reagents, which enabled the formation of triflate transfer intermediate using the electron-deficient nitrogen of heterocycles. This functional imidazolium sulfonamide reagent is applicable to the synthesis of various fluorine-bearing heterocycles, providing opportunities for the development of new C(sp3)-H bond activation methods.

Trifluoromethylation of heteroarene adjacent C(sp3)-H

ACS Spring 2022

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