Redox‐Neutral TEMPO Catalysis: Direct Radical (Hetero)Aryl C−H Di‐ and Trifluoromethoxylation

Abstract

Applications of TEMPOC catalysis for the development of redox-neutral transformations are rare. Reported here is the first TEMPOC-catalyzed, redox-neutral CÀH di-and trifluoromethoxylation of (hetero)arenes. The reaction exhibits a broad substrate scope, has high functional-group tolerance, and can be employed for the late-stage functionalization of complex druglike molecules. Kinetic measurements, isolation and resubjection of catalytic intermediates, UV/Vis studies, and DFT calculations support the proposed oxidative TEMPOC/ TEMPO + redox catalytic cycle. Mechanistic studies also suggest that Li 2 CO 3 plays an important role in preventing catalyst deactivation. These findings will provide new insights into the design and development of novel reactions through redox-neutral TEMPOC catalysis. Figure 1. TEMPOC-catalyzed redox-neutral aryl CÀH functionalization.

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

“…Through intermolecular competition experiments employing two electronically diverse arenes, it was found that the * OCF 2 H reacts approximately 3 times faster with toluene than with acetophenone, thereby confirming its electrophilic nature. In a subsequent study, the same group disclosed an innovative redox-neutral process catalyzed by TEMPO, allowing the generation of * OCF 2 H through a redox pathway D. [95] Afterwards, the Prakash group outlined the photoredox-catalyzed (B) difluoromethoxylation of (hetero)arenes using a stable pyridinium reagent 7. [96] Substrate scope: The * OCF 2 H radical is highly electrophilic (ω = 3.39 eV).…”

Recent Applications of TEMPO in Organic Synthesis and Catalysis

“…12 The first TEMPO • -catalyzed, redox-neutral C–H di- and trifluoromethoxylation of (hetero)arenes is reported by Ngai and his research team (Table 1 , J). 13 The oxidation of alcohols to carbonyl compounds with dioxygen was discovered to be facilitated by a new mixture of FeCl 3 , l -valine, and TEMPO. The production of aldehydes and ketones from a variety of primary/secondary benzyl, allylic, and heterocyclic alcohols was accomplished with good to exceptional isolated yields (Table 1 , K).…”

Electrochemical C−H/C−C Bond Oxygenation: A Potential Technology for Plastic Depolymerization

“…To produce product 8 in a 70 % isolated yield, the electrochemical trifluoromethoxylation reaction could be stepped up to 3.0 mmol. [119] On the basis of relevant data from earlier research, [120][121][122][123] a possible reaction mechanism was suggested in scheme 7. To Scheme 6.…”

“…On the basis of relevant data from earlier research, [120–123] a possible reaction mechanism was suggested in scheme 7. To create A , HFIP 9 must first bind to the nitrogen atom in 7 .…”