Visible Light‐Mediated Metal‐Free Chlorodifluoromethylation of Arenes and Heteroarenes by a Hypervalent Iodine EDA Complex

Abstract

Anovel EDA complex comprised of a bis(chlorodifluoroacetoxy)iodoarene and 1,3,5-trimethoxybenzene is described, which enables the direct radical C(sp 2 )À H chlorodifluoromethylation of arenes and heteroarenes under monochromatic visible-light irradiation. The procedure is mild, operationally simple, and utilizes commercially available reagents. The developed conditions demonstrate compatibility with a host of commonly encountered functionalities and biologically relevant scaffolds, whilst showcasing the postfunctionalization capabilities of the À CF 2 Cl moiety. Various mechanistic studies were performed to explore the EDA complex and radical generation pathway.

Review and Theoretical Analysis of Fluorinated Radicals in Direct CAr−H Functionalization of (Hetero)arenes

“…Prakash and co‐workers adopted an EDA complex approach ( L ) involving a bis(chlorodifluoroacetoxy)iodoarene 42 and 1,3,5‐trimethoxybenzene for the production of ⋅CF 2 Cl radicals under visible light irradiation [165] . Alternatively, Hu and co‐workers relied on iron catalyzed oxidation ( G ) of the chlorodifluoromethyl sulfinate ClCF 2 SO 2 Na 43‐Cl for the efficient generation of ⋅CF 2 Cl [112] .…”

Review and Theoretical Analysis of Fluorinated Radicals in Direct CAr−H Functionalization of (Hetero)arenes

“…Prakash and co-workers adopted an EDA complex approach (L) involving a bis(chlorodifluoroacetoxy)iodoarene 42 and 1,3,5-trimethoxybenzene for the production of * CF 2 Cl radicals under visible light irradiation. [165] Alternatively, Hu and co-workers relied on iron catalyzed oxidation (G) of the chlorodifluoromethyl sulfinate ClCF 2 SO 2 Na 43-Cl for the efficient generation of * CF 2 Cl. [112] Similarly, * CF 2 Br could be accessed from the analogous brominated sulfinate BrCF 2 SO 2 Na 43-Br.…”

Transformations based on direct excitation of hypervalent iodine(iii) reagents

“…Recently, Prakash reported a similar system (Scheme 3B) in which chlorodifluoromethyl radicals are reacted with different nitrogen heterocycles. 34 In this case the hypervalent iodine reagent was prepared in situ from the corresponding carboxylic acid and HIR-2. Interestingly, the yield of some substrates is significantly higher upon the addition of a catalytic amount of 1,3,5-trimethoxybenzene.…”