A Radical Revolution for Trifluoromethoxylation

Abstract

The study of OCF -substituted molecules is somewhat hampered by a lack of diverse synthetic methods to access them. By introducing a new mild and practical reaction system for accessing the OCF radical, a recent study by Liu, Ngai, and co-workers has the potential to dramatically expand the scope of direct trifluoromethoxylation. The features of this ground-breaking system are discussed and placed into context with other recent advances on nucleophilic trifluoromethoxylation.

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

“…The incorporation of the OCF 3 group into (hetero)aromatic substrates has long been known as a daunting task in synthesis, and until recently there has been a scarcity of synthetic methods for the introduction of this functional group into organic molecules . The most common approach towards trifluoromethyl ethers is based on nucleophilic trifluoromethoxylation strategies, which employ reagents capable of releasing the OCF 3 anion ( − OCF 3 ).…”

Merging Visible‐Light Catalysis for the Direct Late‐Stage Group‐16–Trifluoromethyl Bond Formation

“…The formation of C(sp 2 )−OCF 3 is still constituting a very challenging transformation in modern organofluorine chemistry. Indeed, the challenge arises from the poor nucleophilicity of trifluoromethoxide anion, its low stability since it collapses very quickly to difluorophosgene and fluoride anion as well as the quick β‐fluoride elimination when it is σ‐bonded to a transition metal (Scheme ) . Facing these challenges merging photoredox catalysis has taken the right direction in order to address this challenge and the groups of Ngai and Liu as well as Togni published recently independent breakthrough in this field based on the design of new shelf‐stable reagents for direct C(sp 2 )−H bond trifluoromethoxylation reactions.…”

“…First of all, The groups of Ngai and Liu reported a new class of neutral (heteroaryl)‐ N ‐OCF 3 I for the direct C−H trifluoromethoxylation of arenes and heteroarenes . Ru(bpy) 3 (PF 6 ) 2 was used as the photocatalyst with blue LED irradiation and the reactions were performed in MeCN at room temperature.…”

“…First of all, The groups of Ngai andL iu reported an ew class of neutral (heteroaryl)-N-OCF 3 I for the direct CÀHt rifluoromethoxylation of arenes and heteroarenes. [4] Ru(bpy) 3 (PF 6 ) 2 was used as the photocatalyst with blue LED irradiation and the reactions were performed in MeCN at room temperature. These optimized conditions allow the direct trifluoromethoxylation of aw ide range of substrates with ap articular compatibility with sensitivef unctional groups including halides( F, Cl and Br) or protic functionalities.…”

Visible‐Light‐Mediated Liberation and In Situ Conversion of Fluorophosgene

“…[11] However, the photocatalytic N-OCF 3 cleavage of complex startingm aterials was reported very recently. [12] To address the need of ah azard-and metalfree access to highly reactive C1 buildingb locks, we envisioned to cleave the CÀOCF 3 bond of as imple, commercially availablea ryl trifluoromethoxy ether by photoredox catalysis. We identified 4-(trifluoromethoxy)-benzonitrile as as uitable startingm aterial, which can be cleaved quantitativelyi nto benzonitrile and fluorophosgene by an organic photosensitizer ( Figure 1d).…”