Arene Amination Instead of Fluorination: Substitution Pattern Governs the Reactivity of Dialkoxybenzenes with Selectfluor

Abstract

Arene substitution patterns are well-known to affect the regioselectivity of a given transformation but not necessarily the type of reactivity. Herein, we report that the substitution pattern of alkoxyarenes dictates whether a putative one-electron or two-electron reaction predominates in reactions with Selectfluor. A series of amination products is presented, resulting from the single-electron oxidation of electron-rich arenes followed by direct C−H to C−N bond formation. We demonstrate the ability of this transformation to synthesize medicinally and biologically relevant nitrogen heterocycles. Lastly, this unusual "mechanistic switch" is probed with computational chemistry and competition experiments.

I(III)-Mediated Arene C–H Amination Using (Hetero)Aryl Nucleophiles

“…31,32 Furthermore, a recent report by Lectka discussed the effect of dialkoxy arene substitution patterns on the reaction pathway upon treatment with Selectfluor; 1,2-and 1,4-substitution favored amination via initial SET, while 1,3-substition gave predominantly the expected electrophilic fluorination. 33 Thus, to begin, we benchmarked the reactivity of in situ Py-HVI (5) against anisole and all three regioisomers of dimethoxybenzene and found that both electronics and substitution pattern played a significant role in determining the reaction outcome (Scheme 2). Under our conditions, anisole gave quantitative conversion to a ∼1:1 ratio of both ortho and para pyridinium salts to diaryliodonium.…”

Selectfluor Mediated Difunctionalization of Olefins towards the Synthesis of Fluoromethylated Morpholines

“…However, the use of À OMe substituent afforded diminished yield (Scheme 2, product 2 c), presumably because Selectfluor may have caused oxidation of the electron rich aryl ring as a side-reaction. [21] A survey of sulphonyl groups revealed that the phenylsulphonyl and tosyl derivatives afforded products in good yields (80 and 88 % respectively) but the nosyl group led to a slight decrease in the yield (Scheme 2, products 2 g-2 i). At this stage, we explored the effect of replacing the aryl ring with a methyl group (R 4 substituent) and observed that yields were significantly reduced (Scheme 2, products 2 j and 2 k).…”

“…The first set of precursors explored various electronically distinct substituents on the aryl ring (Scheme 2, products 2 a – 2 f ) and it was observed that the yields were generally high for alkyl and halogen substituents. However, the use of −OMe substituent afforded diminished yield (Scheme 2, product 2 c ), presumably because Selectfluor may have caused oxidation of the electron rich aryl ring as a side‐reaction [21] . A survey of sulphonyl groups revealed that the phenylsulphonyl and tosyl derivatives afforded products in good yields (80 and 88 % respectively) but the nosyl group led to a slight decrease in the yield (Scheme 2, products 2 g – 2 i ).…”

I(III)-Mediated Arene C-H Amination using (Hetero)Aryl Nucleophiles

“…29 Furthermore, a recent report by Lectka discussed the effect of dialkoxy arene substitution patterns on reaction pathway when treated with Selectfluor; 1,2-and 1,4substitution favored amination via initial SET, while 1,3substition gave predominantly the expected electrophilic fluorination. 30 Thus to begin, we benchmarked the reactivity of in situ Py-HVI (5) against anisole, and all three regioisomers of dimethoxybenzene and found that both electronics and substitution pattern played a significant role in determining reaction outcome (Scheme 2). Under our conditions, anisole gave quantitative conversion to an ~1:1 ratio of both ortho and para pyridinium salts to diaryliodonium.…”