Redox‐Active Reagents for Photocatalytic Generation of the OCF₃ Radical and (Hetero)Aryl C−H Trifluoromethoxylation

Abstract

The trifluoromethoxy (OCF3) radical is of great importance in organic chemistry. Yet, catalytic and selective generation of this radical at room temperature and pressure remains a longstanding challenge. Herein, we report the design and development of a redox- active cationic reagent 1 that enables the formation of the OCF3 radical in a controllable, selective, and catalytic fashion under visible light photocatalytic conditions. More importantly, the reagent allows catalytic, intermolecular C-H trifluoromethoxylation of a broad array of (hetero)arenes and biorelevant compounds. Experimental and computational studies suggest single electron transfer (SET) from excited photoredox catalysts to 1 resulting in exclusive liberation of the OCF3 radical. Addition of this radical to (hetero)arenes gives trifluoromethoxylated cyclohexadienyl radicals that are oxidized and deprotonated to afford the products of trifluoromethoxylation.

Direct Trifluoromethylation of Alcohols Using a Hypervalent Iodosulfoximine Reagent

“…[15] Unfortunately, these compounds have intrinsic limitations,i ncluding:1 )degradationo ft he OCF 3 fragment to fluorophosgene, 2) reagent synthesis from toxic, gaseous, or expensive chemicals, 3) often low yields, 4) the requirement of several additives (including transition-metal catalysts), and 5) need for pre-functionalized materials. In 2018 three radical trifluoromethoxylatingr eagents were reported; Ngai and co-workersr eportedt he use of benzimidazole [2] and benzotriazole [3] based compounds, while one of our groupsr eported ap yridine N-oxide reagent. [1] The major advantage of these radical-based reagentsi st he ability to functionalize unactivated arenes under photoredox conditions.…”

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

“…The mechanistic hypothesis of the proposed transformation is outlined in Scheme 1. We envisioned that the reaction proceeds through an oxidative redox cycle beginning SET between di‐ or trifluoromethoxylating reagent 1 a ( E p =+0.11 V vs. SCE) [18g] or 1 b ( E p =+0.14 V vs. SCE) [18e] and TEMPO . ( E 1/2 =+0.62 V vs. SCE), [12b] generating 2,2,6,6‐tetramethyl‐1‐oxo‐1λ 4 ‐piperidine (TEMPO + ) and the di‐ or trifluoromethoxy radical ( .…”

Synthesis of Tri‐ and Difluoromethoxylated Compounds by Visible‐Light Photoredox Catalysis

“…To overcome these limitations, Liu and Ngai reported a second‐generation, redox‐active, cationic trifluoromethoxylating reagent II that can liberate . OCF 3 in a controllable, catalytic, and selective manner under visible‐light‐mediated photocatalytic conditions at room temperature (Scheme ) . The reagent II showed a broader substrate scope than their first‐generation trifluoromethoxylating reagent.…”