Nitromethane-Enabled Fluorination of Styrenes and Arenes

Abstract

The electrophilic fluorination of unsaturated compounds provides a reliable approach to the generation of organofluorides, which are used widely in agrochemicals, pharmaceuticals, and other materials. Numerous active electrophilic fluorine reagents, such as the fluorine molecule (F 2 ) or xenon difluoride (XeF 2 ), have been applied in fluorination. However, these reagents suffer from their hazardous, toxic, corrosive, and poor selective properties, and the relatively weak electrophilicity of Selectfluor or N-fluorobenzenesulfonimide (NFSI) usually limits their broad applications. Herein, we disclose nitromethane (MeNO 2 ) as an efficient activator of Selectfluor and NFSI, as well as a stabilizer of carbocations.Therefore, the fluoro-azidation, fluoroamination, fluoroesterification of styrenes, and C-H fluorination of (hetero)arenes were well realized just by the facilitation of MeNO 2 . The mild reaction conditions and practicability made our current method a versatile protocol for accessing organofluorides.

Fluorination of 2H-Indazoles Using N-Fluorobenzenesulfonimide

“…A plausible mechanism of this reaction has been presented based on the above experimental results and previous reports ,, in Scheme . The BDE of NFSI in H2O is 63.5 kcal/mol .…”

Ring Expansion Fluorination of Unactivated Cyclopropanes Mediated by a New Monofluoroiodane(III) Reagent

“…The formation of elimination product 4 a suggested that the reaction might proceed via a carbocation intermediate. Considering that nitromethane can stabilize carbocations because of its high dielectric constant ( ϵ =36.16), [22] we carried out a reaction with nitromethane as a cosolvent. Specifically, reaction of 2 a and 1 (1.5 equiv) in the presence of BF 3 ⋅Et 2 O (0.4 equiv) in 9:1 (v/v) DCM/MeNO 2 (3 mL) for 2 h afforded 89 % yield of 3 a with only a trace of 4 a (Table 1, entry 3); moreover, the addition of nitromethane markedly shortened the reaction time.…”

“…In this reaction, we did not detect fivemembered fluorinated product and 4-exo-cyclization fluorinated product, indicating that the reagent 1 has excellent regioselectivity for the intramolecular ring expansion fluorination reaction of unactivated cyclopropane.E ncouraged by this result, we carried out some experiments aimed at optimizing the chemical yield of 3a.I ncreasing the amount of 1 from 1.2 to 1.5 equiv increased the yield of 3a to 81 % (Table 1, entry 2). Thef ormation of elimination product 4a suggested that the reaction might proceed via ac arbocation intermediate.C onsidering that nitromethane can stabilize carbocations because of its high dielectric constant (e = 36.16), [22] we carried out ar eaction with nitromethane as ac osolvent. Specifically,r eaction of 2a and 1 (1.5 equiv) in the presence of BF 3 •Et 2 O( 0.4 equiv) in 9:1( v/v) DCM/ MeNO 2 (3 mL) for 2h afforded 89 %y ield of 3a with only at race of 4a (Table 1, entry 3);m oreover,t he addition of nitromethane markedly shortened the reaction time.D ecreasing the amount of 1 to 1.3 equiv and the amount of BF 3 •Et 2 Ot o0.3 equiv did not affect the yield of 3a (Table 1, entry 4).…”

New Strategies for the Synthesis of Aliphatic Azides

“…In 2020, the Jiao group described the nitromethane promoted azidofluorination of styrenes using NaN 3 and selectfluor as the azide and fluoro sources, respectively. 205 In this reaction, the nitromethane does not only act as a Lewis base to activate the electrophilic fluorinating reagents but also as a stabilizer of carbocations and solvent. The mechanistic studies revealed that the reaction proceeds via the initial electrophilic fluorine addition followed by the nucleophilic azide addition to the resulting nitromethane-stabilized cationic intermediate 171−1 (Scheme 44b).…”

“…The reaction proceeded well in aqueous media at room temperature and furnished the desired β-fluorinated alkyl azides 172 in good yields with excellent functional group compatibility and good stereoselectivity. In 2020, the Jiao group described the nitromethane promoted azidofluorination of styrenes using NaN 3 and selectfluor as the azide and fluoro sources, respectively . In this reaction, the nitromethane does not only act as a Lewis base to activate the electrophilic fluorinating reagents but also as a stabilizer of carbocations and solvent.…”