Photocatalytic Trifluoromethylation Research Articles

Easy to make highly efficient FG@ACC stable platform for sp3C-CF3 bond generation and NADH regeneration under sun light

The conversion of sun light energy into sustainble greener chemicals are a major obstacle due to the use of expensive and toxic materials. Sun light induced trifluoromethylation emerges as a highly efficient procedure to insert trifluoromethyl groups into the organic compounds. Yet, the expensive and toxic properties of the metal-based photocatalysts creates a major obstacle for the insertion of trifluoromethyl groups. Metal free activated carbon cloth (ACC) emerged as a highly efficient pillar in the area of material science. In this work, we have successfully synthesized self-assembled metal free fast green with activated carbon cloth (FG@ACC) photocatalyst for photocatalytic trifluoromethylation and reduced nicotinamide adenine dinucleotide (NADH) cofactor regeneration (85.89 %, 2 h) under sun light. The sun light induced organic transformation promotes the use of low-cost CF3SO2Na as the CF3 radical source to produce highly selective products with 97% yield.

Trifluoromethylative Bifunctionalization of Alkenes via a Bibenzothiazole-Derived Photocatalyst under Both Visible- and Near-Infrared-Light Irradiation

The incorporation of trifluoromethyl groups into organic molecules such as agrochemicals and pharmaceuticals has attracted a significant amount of interest because they will impact the binding ability, lipophilicity, metabolic stability, and chemical stability of the resulting molecules. Over the past few years, photocatalytic trifluoromethylation of aryl alkenes has been reported, which typically requires precious Ru/Ir-containing photocatalytic systems. Herein, we report a metal-free organic photocatalyst composed of a bibenzothiazole core and two imine-bridged methoxyphenyl substituents (dBIP–OMe), which is able to drive trifluoromethylative bifunctionalization of alkenes photocatalytically without the use of any sacrificial reagents. Mechanistic studies reveal two consecutive single-electron-transfer steps between the excited dBIP–OMe*, the CF3 precursor (Umemoto’s reagent), and the alkene substrate. Substrate scope studies demonstrated that our trifluoromethylative bifunctionalization strategy using dBIP–OMe is applicable for both aryl and aliphatic alkenes. Furthermore, a variety of nucleophiles, such as H2O, acetate, cyanide, azide, etc., can be readily incorporated into the carbocation intermediate once the foremost trifluoromethylation step is accomplished, substantially broadening the application scope of this photocatalytic method. Finally, taking advantage of the two-photon absorption capability of dBIP–OMe in the near-infrared region, we demonstrated that the hydroxytrifluoromethylation of styrene could be achieved using an inexpensive 740 nm LED as the sole light source.

Visible-Light-Induced Photocatalytic Trifluoromethylation of Bunte Salts: Easy Access to Trifluoromethylthiolated Synthons.

A metal-free visible-light-induced trifluoromethylation of Bunte salts of α-bromoketones/alkyl bromide/benzyl bromides/functionalized allyl (Baylis-Hillman) bromides has been accomplished using Langlois' reagent in the presence of inexpensive eosin Y as a photocatalyst to form the privileged trifluoromethylthiolated synthons. The method is straightforward, operationally simple, and endowed with broad substrate scope and good functional group tolerance.

Cadmium–Chalcogenide Photocatalytic Selective Trifluoromethylation

Cadmium–Chalcogenide Photocatalytic Selective Trifluoromethylation

Visible Light Photocatalytic Trifluoromethylation/SET Oxidation/Cycloaddition Sequences of 2‐Vinyl Phenols: Multicomponent Synthesis of 4H‐Chromenes

AbstractVisible light‐mediated photocatalytic trifluoromethylation, single electron transfer (SET) oxidation, and cycloaddition cascades of 2‐vinyl phenols with Umemoto's reagent and malononitrile were developed. This approach provided the multicomponent synthesis of trifluoromethylated 4H‐chromenes via the in situ generation of o‐quinone methides, followed by sequential cyclization.

Frontispiece: New Visible‐Light‐Triggered Photocatalytic Trifluoromethylation Reactions of Carbon–Carbon Multiple Bonds and (Hetero)Aromatic Compounds

Frontispiece: New Visible‐Light‐Triggered Photocatalytic Trifluoromethylation Reactions of Carbon–Carbon Multiple Bonds and (Hetero)Aromatic Compounds

New Visible‐Light‐Triggered Photocatalytic Trifluoromethylation Reactions of Carbon–Carbon Multiple Bonds and (Hetero)Aromatic Compounds

Visible-light-photocatalyzed methods employed in synthetic transformations present attractive properties such as environmentally friendly, safety, availability and excellent functional group tolerance. In this regard, research on the visible-light photocatalytic incorporation of the trifluoromethyl CF3 moiety into organic substrates, in particular, has contributed to a clear evolution of the field of photocatalysis. Although this particular area is constantly evolving and has been reviewed, the last five years have experienced an outburst of seminal and significant photocatalytic trifluoromethylation examples that are leading the way and opening new synthetic avenues. Recent review articles on Ru- and Ir-based photocatalytic trifluoromethylation reactions have borne witness of this evolution. Although this account will show the new Ru- and Ir-based photocatalytic trifluoromethylations, Sections 2 and 3 will also illustrate other photocatalytic systems, such as organic dyes, organic semiconductors and newly-developed all-organic photocatalysts. All the known and reviewed strategies for photocatalytic trifluoromethylation reactions of olefins and (hetero)aromatic compounds will not be discussed but will be summarized in two figures (Figures 4 and 5), and new examples (2015-present) will be presented and discussed.

Au@ZnO Nanoparticles for Photocatalytic Trifluoromethylation of Aromatic Compounds

Key words gold catalysis - nanoparticles - zinc oxide - photocatalysis - trifluoromethylation - aromatic compounds

Au@ZnO Core–Shell: Scalable Photocatalytic Trifluoromethylation Using CF3CO2Na as an Inexpensive Reagent under Visible Light Irradiation

Trifluoromethylation is of significant importance for the synthesis of many small molecules vital for medicinal and agrochemical research. The importance of the CF3 group as well as the related syn...

Energy‐Efficient Solar Photochemistry with Luminescent Solar Concentrator Based Photomicroreactors

AbstractThe sun is the most sustainable light source available on our planet, therefore the direct use of sunlight for photochemistry is extremely appealing. Demonstrated here, for the first time, is that a diverse set of photon‐driven transformations can be efficiently powered by solar irradiation with the use of solvent‐resistant and cheap luminescent solar concentrator based photomicroreactors. Blue, green, and red reactors can accommodate both homogeneous and multiphase reaction conditions, including photochemical oxidations, photocatalytic trifluoromethylation chemistry, and metallaphotoredox transformations, thus spanning applications over the entire visible‐light spectrum. To further illustrate the efficacy of these novel solar reactors, medicinally relevant molecules, such as ascaridole and an intermediate of artemisinin, were prepared as well.

Visible-light photocatalytic trifluoromethylation of arenes using graphene oxide as a metal-free photocatalyst

Graphene oxide sheets can function as a kind of metal-free photocatalyst for the trifluoromethylation of arenes under visible light irradiation.

Dye-incorporated coordination polymers for direct photocatalytic trifluoromethylation of aromatics at metabolically susceptible positions

Direct trifluoromethylation of unactivated aromatic rings at metabolically susceptible positions is highly desirable in pharmaceutical applications. By incorporating thiophenes into the backbone of triphenylamine to enlarge its π-system, a new approach for constructing coordination polymers is reported for direct trifluoromethylation without prefunctionalization of the aryl precursors. The improved light-harvesting ability and well-modulated excited state redox potential of the designed polymers endow the generated CF3 radicals with suitable reactivity and enhance radical adduct oxidation in pores. The well-configurated interactions between the organic ligands distort the coordination geometry to create active interaction sites within the coordination polymer; thus, the substrates could be docked near the photoredox-active centres. The synergistic electronic and spatial effects in the confined pores balance the contradictory demands of electronic effects and reaction dynamics, achieving regio- and diastereoselective discrimination among reaction sites with unremarkable electronic/steric differences.

Blue‐Emissive Cobalt(III) Complexes and Their Use in the Photocatalytic Trifluoromethylation of Polycyclic Aromatic Hydrocarbons

AbstractRoom‐temperature luminescent CoIII complexes (1 and 2) are presented that exhibit intense ligand‐to‐metal and ligand‐to‐ligand charge transfer absorption in the low‐energy UV region (λabs≈360–400 nm) and low‐negative quasi‐reversible reduction events (E1/2(red)=−0.58 V and −0.39 V vs. SCE for 1 and 2, respectively). The blue emission of 1 and 2 at RT is due to the large bite angles and strong σ‐donation of the ligands, the combined effect of which helps to separate the emissive 3LMCT (triplet ligand‐to‐metal charge transfer) and the non‐emissive 3MC (triplet metal‐centered) states. 1 and 2 were found to be powerful photo‐oxidants (E =2.26 V and 2.75 V vs. SCE of 1 and 2, respectively) and were used as inexpensive photoredox catalysts for the regioselective mono(trifluoromethylation) of polycyclic aromatic hydrocarbons (PAHs) in good yields (ca. 40–58 %).

Blue-Emissive Cobalt(III) Complexes and Their Use in the Photocatalytic Trifluoromethylation of Polycyclic Aromatic Hydrocarbons.

Room-temperature luminescent CoIII complexes (1 and 2) are presented that exhibit intense ligand-to-metal and ligand-to-ligand charge transfer absorption in the low-energy UV region (λabs ≈360-400 nm) and low-negative quasi-reversible reduction events (E1/2(red) =-0.58 V and -0.39 V vs. SCE for 1 and 2, respectively). The blue emission of 1 and 2 at RT is due to the large bite angles and strong σ-donation of the ligands, the combined effect of which helps to separate the emissive 3 LMCT (triplet ligand-to-metal charge transfer) and the non-emissive 3 MC (triplet metal-centered) states. 1 and 2 were found to be powerful photo-oxidants (ECoIII*/CoII =2.26 V and 2.75 V vs. SCE of 1 and 2, respectively) and were used as inexpensive photoredox catalysts for the regioselective mono(trifluoromethylation) of polycyclic aromatic hydrocarbons (PAHs) in good yields (ca. 40-58 %).

Synthesis of oxindoles through trifluoromethylation of N-aryl acrylamides by photoredox catalysis

Mild and direct intramolecular oxidative aryltrifluoromethylations of activated alkenes have been established through visible light photocatalysis, affording a range of CF3-containing oxindoles or isoquinolinediones in the presence of an organic fluorophore-type photocatalyst 4CzIPN, oxygen and visible light irradiation under strong oxidant and transition metal free conditions. A variety of frequently encountered functional groups are well tolerated in this transformation.

Metal-free di- and tri-fluoromethylation of alkenes realized by visible-light-induced perylene photoredox catalysis.

Regioselective amino-difluoromethylation of aromatic alkenes via C(sp3)-CF2H and C(sp3)-N bond formation with the C[double bond, length as m-dash]C moiety has been achieved in a single operation by visible-light photoredox catalysis. The combination of a shelf-stable and easy-to-handle sulfonium salt, S-difluoromethyl-S-di(p-xylyl)sulfonium tetrafluoroborate, and perylene catalysis is the key to the successful transformation. Furthermore, this noble metal-free protocol allows for the photocatalytic trifluoromethylation of alkenes.

Practical Photocatalytic Trifluoromethylation and Hydrotrifluoromethylation of Styrenes in Batch and Flow

AbstractStyrenes represent a challenging class of substrates for current radical trifluoromethylation and hydrotrifluoromethylation methods due to a myriad of potential side reactions. Herein, we describe the development of mild, selective and broadly applicable photocatalytic trifluoromethylation and hydrotrifluoromethylation protocols for these challenging substrates. The methods use fac‐Ir(ppy)3, visible light and inexpensive CF3I and can be applied to a diverse set of vinylarene substrates. The use of continuous‐flow photochemical reaction conditions allowed to reduce the reaction time and increase the reaction selectivity.

Practical Photocatalytic Trifluoromethylation and Hydrotrifluoromethylation of Styrenes in Batch and Flow.

Styrenes represent a challenging class of substrates for current radical trifluoromethylation and hydrotrifluoromethylation methods due to a myriad of potential side reactions. Herein, we describe the development of mild, selective and broadly applicable photocatalytic trifluoromethylation and hydrotrifluoromethylation protocols for these challenging substrates. The methods use fac-Ir(ppy)3 , visible light and inexpensive CF3 I and can be applied to a diverse set of vinylarene substrates. The use of continuous-flow photochemical reaction conditions allowed to reduce the reaction time and increase the reaction selectivity.

Fine Design of Photoredox Systems for Catalytic Fluoromethylation of Carbon-Carbon Multiple Bonds.

Trifluoromethyl (CF3) and difluoromethyl (CF2H) groups are versatile structural motifs, especially in the fields of pharmaceuticals and agrochemicals. Thus, the development of new protocols for tri- and difluoromethylation of various skeletons has become a vital subject to be studied in the field of synthetic organic chemistry. For the past decades, a variety of fluoromethylating reagents have been developed. In particular, bench-stable and easy-to-use electrophilic fluoromethylating reagents such as the Umemoto, Yagupolskii-Umemoto, Togni, and Hu reagents serve as excellent fluoromethyl sources for ionic and carbenoid reactions. Importantly, the action of catalysis has become a promising strategy for developing new fluoromethylations. For the past several years, photoredox catalysis has emerged as a useful tool for radical reactions through visible-light-induced single-electron-transfer (SET) processes. Commonly used photocatalysts such as [Ru(bpy)3](2+) and fac-[Ir(ppy)3] (bpy = 2,2'-bipyridine; ppy = 2-pyridylphenyl) have potential as one-electron reductants strong enough to reduce those fluoromethylating reagents, resulting in facile generation of the corresponding fluoromethyl radicals. Therefore, if we can design proper reaction systems, efficient and selective radical fluoromethylation would proceed without any sacrificial redox agents, i.e., via a redox-neutral process under mild reaction conditions: irradiation with visible light, including sunlight, below room temperature. It should be noted that examples of catalytic fluoromethylation of compounds with carbon-carbon multiple bonds have been limited until recent years. In this Account, we will focus on our recent research on photoredox-catalyzed fluoromethylation of carbon-carbon multiple bonds. First, choices of the photocatalyst and the fluoromethylating reagent and the basic concept involving a redox-neutral oxidative quenching cycle are explained. Then photocatalytic trifluoromethylation of olefins is discussed mainly. Trifluoromethylative difunctionalization reactions, i.e., simultaneous introduction of the CF3 group and a different functional group across carbon-carbon double bonds, are in the middle of the discussion. Oxy-, amino-, and ketotrifluoromethylation allow us to synthesize various organofluorine compounds bearing C(sp(3))-CF3 bonds. In addition, the synthesis of valuable trifluoromethylated alkenes is also viable when the olefins have an appropriate leaving group or undergo deprotonation. The present reaction system features high functional group compatibility and high regioselectivity. Furthermore, future prospects, especially trifluoromethylative difunctionalization of alkynes and difluoromethylation of alkenes, are also discussed.

A Mechanistic Investigation of the Visible-Light Photocatalytic Trifluoromethylation of Heterocycles Using CF3 I in Flow.

Photocatalytic radical trifluoromethylation strategies have impacted the synthesis of trifluoromethyl-containing molecules. However, mechanistic aspects concerning such transformations remain poorly understood. Here, we describe in detail the mechanism of the visible-light photocatalytic trifluoromethylation of N-methylpyrrole with gaseous CF3 I in flow. The use of continuous-flow microreactor technology allowed for the determination of different important parameters with high precision (e.g., photon flux, quantum yield, reaction rate constants) and for the handling of CF3 I in a convenient manner. Our data indicates that the reaction occurs through a reductive quenching mechanism and that there is no radical chain process present.