Photocatalytic Hydrodefluorination Research Articles

Copper-catalyzed pentafluoroethylation of aryl/alkenyl iodides with pentafluoroethylsilane

A copper-catalyzed pentafluoroethylation of aryl/alkenyl iodides is described using Et3SiCF2CF3 as a direct CF2CF3 source. An intriguing selective photocatalytic hydrodefluorination of pentafluoroethylarenes is also discovered.

A general photocatalytic hydrodefluorination and defluoroalkylation of electronically-variable ArCF3 by changing commercially-available arenethiolates

The selection of electronically-different thiolate-based photosensitizers is employed to achieve a precise and specific C–F bond defluorination of a broad range of trifluoromethylarenes, enabling the synthesis of 88 α,α-difluoromethyl compounds.

Molecular Sculpting: A Multipurpose Tool for Expedited Access to Various Fluorinated Arenes via Photocatalytic Hydrodefluorination of Benzoates.

Starting with highly fluorinated benzoates, we develop the directed photocatalytic hydrodefluorination (HDF) of fluorinated aryl benzoates and demonstrate its synergistic use with other HDF strategies, along with C-H arylation, decarboxylative coupling, and decarboxylative protonation, to access most fluorination patterns found in benzoate derivatives and by extension benzene derivatives via a molecular sculpting approach. Mild reaction conditions and excellent regioselectivity make the approach ideal for synthesis. This approach provides access to 16 benzoate derivatives with different fluorination patterns from just a couple of highly fluorinated, commercially available benzoic acids. We synthesize key intermediates or the active pharmaceutical ingredient for sitagliptin, diflunisal, and other pharmaceutically important molecules. Importantly, we provide key insights into relative rates of defluorination and strategies to alter these rates. We provide demonstrations of the synergistic use of HDF and related technologies to rapidly enhance the synthetic complexity of these simple commercially available perfluoroarenes to form complex partially fluorinated molecules.

Retraction of "Hydrogen Bond Directed Photocatalytic Hydrodefluorination: Overcoming Electronic Control".

The photocatalytic C–F functionalization of highly fluorinated arenes is a powerful method for accessing functionalized multifluorinated arenes. The decisive step in the determining regioselectivity in fluorine functionalization is fluoride fragmentation from the radical anion of the multifluorinated arene. To date, the availability of regioisomers has been dictated by the innate electronics of the fluorinated arene, limiting the synthetic utility of the chemistry. This study investigates the remarkable ability of a strategically located hydrogen bond to transcend the normal regioselectivity of the C–F functionalization event. A significant rate acceleration is additionally observed for hydrodefluorination of fluorines that can undergo intramolecular hydrogen bonds that form 5–8-membered cycles with moderately acidic N–H’s. The hydrogen bond is expected to facilitate the fragmentation not only by bending the C–F bond of the radical anion out of planarity but also by increasing the exothermicity of the flu...

Plasmon-driven carbon–fluorine (C(sp3)–F) bond activation with mechanistic insights into hot-carrier-mediated pathways

The activation of carbon–fluorine bonds is an industrially and environmentally critical, but energetically challenging, transformation. Here we demonstrate a plasmonic photocatalysis approach to visible-light-driven hydrodefluorination that utilizes aluminium–palladium antenna–reactor heterostructures. Photocatalytic hydrodefluorination of aliphatic carbon–fluorine (C(sp3)–F) bonds in fluoromethane as a model molecule, in the presence of deuterium, results in the selective production of monodeuterated methane with a remarkable photocatalytic efficiency and stability. Analysis of the reaction kinetics reveals a reduction in the apparent reaction barrier and changes to the deuterium reaction order under illumination, which suggests a non-thermal contribution from photogenerated hot carriers to the reaction pathway. Using embedded correlated wavefunction methods, the ground- and excited-state energetics and the role of plasmon excitation in lowering the reaction barrier and modifying the kinetics under illumination are determined. Plasmon-mediated carbon–fluorine bond activation represents a promising potential for applications in high-value chemical transformations, as well as in abatement technologies for the mitigation of anthropogenic polyfluoroorganic compounds. The cleavage of C–F bonds through hydrodefluorination is challenging and has been traditionally limited to unsaturated fluorocarbons. Now, a simple plasmonic approach based on the use of aluminium nanocrystal-supported palladium nanoparticles is introduced to effectively upgrade fluoromethane under visible light.

Expression of Concern for "Hydrogen Bond Directed Photocatalytic Hydrodefluorination: Overcoming Electronic Control".

Expression of Concern for "Hydrogen Bond Directed Photocatalytic Hydrodefluorination: Overcoming Electronic Control".

Modulating Electron Transfer in an Organic Reaction via Chemical Group Modification of the Photocatalyst.

Tuning electron-transfer (ET) rates from catalysts to substrates is important for modulating photocatalytic organic reactions. In this work, we have taken pyrene-based photocatalysts (Py's) for photocatalytic hydrodefluorination of polyfluoroarenes (FAs) as model systems and conducted a first-principles study on modulating ET rates from Py to FA via the chemical modification of Py with different electron-donating/withdrawing groups (EDGs/EWGs). The computed spatial distributions of frontier Kohn-Sham orbitals suggest that ET is energetically more favorable for Py-EDGs than for Py-EWGs. The estimated ET rates by a simplified Marcus model show that they are appreciably enhanced by EDG substitution and weakened by EWG substitution. Noticeably, the associated Gibbs free-energy change plays a dominant role. Our findings of tuning ET rates for Py-FA complexes via chemical group modifications cast new insight into the rational design of metal-free photocatalysts for organic transformations.

Hydrogen Bond Directed Photocatalytic Hydrodefluorination: Overcoming Electronic Control.

The photocatalytic C-F functionalization of highly fluorinated arenes is a powerful method for accessing functionalized multifluorinated arenes. The decisive step in the determining regioselectivity in fluorine functionalization is fluoride fragmentation from the radical anion of the multifluorinated arene. To date, the availability of regioisomers has been dictated by the innate electronics of the fluorinated arene, limiting the synthetic utility of the chemistry. This study investigates the remarkable ability of a strategically located hydrogen bond to transcend the normal regioselectivity of the C-F functionalization event. A significant rate acceleration is additionally observed for hydrodefluorination of fluorines that can undergo intramolecular hydrogen bonds that form 5-8-membered cycles with moderately acidic N-H's. The hydrogen bond is expected to facilitate the fragmentation not only by bending the C-F bond of the radical anion out of planarity but also by increasing the exothermicity of the fluoride extrusion step through protonation of the naked fluoride. Finally, the synthetic utility of the method is demonstrated in an expedited synthesis of the trifluorinated α-phenyl acetic acid derivative required for the commercial synthesis of Januvia, an antidiabetic drug. This represents the first synthesis of a commercially important multifluorinated arene via a defluorination strategy and is significantly shorter than the current strategy.

Photocatalytic Hydrodefluorination Promoted by π-Hole–π Interactions

Key words pyrenes - photocatalysis - hydrodefluorination - polyfluoroarenes

“π-Hole−π” Interaction Promoted Photocatalytic Hydrodefluorination via Inner-Sphere Electron Transfer

We describe a metal-free, photocatalytic hydrodefluorination (HDF) of polyfluoroarenes (FA) using pyrene-based photocatalysts (Py). The weak "π-hole-π" interaction between Py and FA promotes the electron transfer against unfavorable energetics (ΔGET up to 0.63 eV) and initiates the subsequent HDF. The steric hindrance of Py and FA largely dictates the HDF reaction rate, pointing to an inner-sphere electron transfer pathway. This work highlights the importance of the size and shape of the photocatalyst and the substrate in controlling the electron transfer mechanism and rates as well as the overall photocatalytic processes.

Light induced catalytic hydrodefluorination of perfluoroarenes by porphyrin rhodium

Photocatalytic hydrodefluorination of a series of perfluoroarenes by rhodium porphyrin complexes was described. The key intermediate (por)Rh-C6F4R underwent fast photo-cleavage of Rh–C bonds to produce hydrodefluorination products.

ChemInform Abstract: Selective Perfluoro‐ and Polyfluoroarylation of Meldrum′s Acid.

This work describes the facile and mono-selective per- and polyfluoroarylation of Meldrum’s acid to generate a versatile synthon for highly fluorinated α-phenyl acetic acid derivatives, which provide straightforward access to fluorinated building blocks. The reaction takes place quickly, and most products were isolated without the need for chromatography. Importantly, this method provides an alternative strategy to access α-arylated Meldrum’s acids, which avoids the need for aryl-Pb(IV) salts or diaryliodonium salts. Furthermore, we demonstrate the synthetic versatility and utility of the Meldrum’s acid products by subjecting our products to several derivatizations of the Meldrum’s acid products as well as photocatalytic hydrodefluorination.

Selective perfluoro- and polyfluoroarylation of Meldrum's acid.

This work describes the facile and mono-selective per- and polyfluoroarylation of Meldrum's acid to generate a versatile synthon for highly fluorinated α-phenyl acetic acid derivatives, which provide straightforward access to fluorinated building blocks. The reaction takes place quickly, and most products were isolated without the need for chromatography. Importantly, this method provides an alternative strategy to access α-arylated Meldrum's acids, which avoids the need for aryl-Pb(IV) salts or diaryliodonium salts. Furthermore, we demonstrate the synthetic versatility and utility of the Meldrum's acid products by subjecting our products to several derivatizations of the Meldrum's acid products as well as photocatalytic hydrodefluorination.

ChemInform Abstract: Photocatalytic Hydrodefluorination: Facile Access to Partially Fluorinated Aromatics.

Polyfluorinated aromatics are essential to materials science as well as the pharmaceutical and agrochemical industries and yet are often difficult to access. This Communication describes a photocatalytic hydrodefluorination approach which begins with easily accessible perfluoroarenes and selectively reduces the C–F bonds. The method allows facile access to a number of partially fluorinated arenes and takes place with unprecedented catalytic activity using a safe and inexpensive amine as the reductant.

Photocatalytic Hydrodefluorination: Facile Access to Partially Fluorinated Aromatics

Polyfluorinated aromatics are essential to materials science as well as the pharmaceutical and agrochemical industries and yet are often difficult to access. This Communication describes a photocatalytic hydrodefluorination approach which begins with easily accessible perfluoroarenes and selectively reduces the C-F bonds. The method allows facile access to a number of partially fluorinated arenes and takes place with unprecedented catalytic activity using a safe and inexpensive amine as the reductant.