Visible‐Light Photoredox‐Catalyzed Radical Fluoromethoxylation of Olefins

Abstract

Fluoroalkyl ethers have attracted considerable research interest in the fields of pharmaceutical, agrochemical, nuclear imaging and material sciences, forging the development of new synthetic methods to access this class of compounds. Radical fluoroalkoxylation has recently emerged as a promising approach for synthesizing fluoroalkyl ethers. Herein, a solid, easy‐to‐access redox‐active N−O reagent, 1‐(fluoromethoxy)‐3‐methyl‐benzotriazolium triflate (FMBT), serving as a radical source of (mono)fluoromethoxy group under photocatalytic conditions, was introduced. The synthetic potential of FMBT was demonstrated in the functionalization of olefins to access amino and keto‐monofluoromethyl ethers, benefiting the related study in the context of chemical biology and drug discovery.

Fluoroalkoxylating Reagents in Organic Synthesis: Recent Advances

“…In 2023, Veliks group [27] also disclosed the redox-active N-(monofluoromethoxy)benzotriazole salts 2.3 for the functionalization of alkenes 2.1-2.2 under photoredox conditions (Scheme 2). A variety of amino-monofluoromethoxylation products 2.4 of vinylarenes and α-monofluoromethoxylated ketones 2.5 were efficiently assembled through visible light catalysis.…”

Recent Advances in Visible Light‐Mediated Radical Fluoro‐alkylation, ‐alkoxylation, ‐alkylthiolation, ‐alkylselenolation, and ‐alkylamination

“…Much like other (per)fluoroalkoxy radicals, the monofluoromethoxy radical (⋅OCH 2 F) is an electrophilic species and preferentially functionalizes electron‐rich sites. Recently, Veliks and coworkers presented the monofluoromethoxylation of olefins and Boc‐protected enols utilizing benzotriazolium salt 44 [169] . Under irradiated ruthenium catalyzed conditions with unactivated alkenes in acetonitrile, the monofluoromethoxylation was paired with Ritter‐amination to form 1,2‐difunctionalized alkenes.…”

Recent Uses of Photogenerated Oxygen-Centered Radicals in Intermolecular C–O Bond Formation

“…A few months later, Veliks and co-workers also reported their efforts towards the synthesis of new precursors of monofluoromethoxy radical under photoredox catalysis. 27…”

“…A few months later, Veliks and co-workers also reported their efforts towards the synthesis of new precursors of monofluoromethoxy radical under photoredox catalysis. 27 Although some monofluoromethoxy pyridinium salts could be efficiently prepared, they displayed inferior reactivity for the monofluoromethoxylation of olefins compared with benzotriale-based reagent 39. From a mechanistic point of view, the first SET step is similar to previously, with the generation of the O-centered fluorinated radical via the reduction of 39 by the excited state of Ru(II) photocatalyst.…”