Abstract Dehydrochlorination (DHC) is of importance for modulating the physical properties of halogenated polymers. In this work, the DHC of commercial VDF‐CTFE (vinylidene fluoride‐co‐chlorotrifluoroethylene) (10 mol % CTFE) copolymer to VDF‐DB (vinylidene fluoride with unsaturated moieties‐ D ouble B ond) was achieved in mild reaction conditions (150 °C and 3 bar hydrogen) using different supported nickel catalysts. A complete DHC was observed within four hours of the reaction. Additionally, a certain extent (8–35 %) of hydrodefluorination (HDF) of the polymer, a challenging transformation, can also be achieved after 72 hours. A plausible mechanism based on the nuclear magnetic resonance (NMR) spectroscopy study of DHC and HDF of VDF‐CTFE was proposed. The catalyst was recyclable and stable against leaching after at least three cycles.

This study explores the synergistic effect between the Rh and Pd of bimetallic Rh-Pd/C catalysts for the catalytic hydro-defluorination (HDF) of 4-fluorophenol (4-FP). It was found that 4-FP could not be efficiently hydro-defluorinated over 6% Pd/C and 6% Rh/C due to the inherent properties of Pd and Rh species in the dissociation of H2 and the activation of C-F bonds. Compared with 6% Pd/C and 6% Rh/C, bimetallic Rh-Pd/C catalysts, especially 1% Rh-5% Pd/C, exhibited much higher catalytic activity in the HDF of 4-FP, suggesting that the synergistic effect between the Rh and Pd of the catalyst was much more positive. Catalyst characterizations (BET, XRD, TEM, and XPS) were introduced to clarify the mechanism for the synergistic effect between the Rh and Pd of the catalyst in the HDF reaction and revealed that it was mainly attributed to the bifunctional mechanism: Pd species were favorable for the dissociation of H2, and Rh species were beneficial to the activation of C-F bonds in the HDF reaction. Meanwhile, the interaction between Rh and Pd species enabled Rh and Pd to exhibit a more positive synergistic effect, which promoted the migration of atomic H* from Pd to Rh species and thus enhanced the HDF of 4-FP. Furthermore, 1% Rh-5% Pd/C prepared using 20-40 equiv NaBH4 exhibited the best performance in the catalytic HDF of 4-FP. Catalysis characterizations suggested that appropriate Rh3+/Rh0 and Pd2+/Pd0 ratios were beneficial to the dissociation of H2 and the activation of C-F bonds, which caused the more positive synergistic effect between the Rh and Pd of Rh-Pd/C in the HDF reaction. This work offers a valuable strategy for enhancing the performance of catalytic HDF catalysts via promoting synergistic effects.

Promoted Raney Ni catalyzed hydrodefluorination of fluorophenols under mild conditions via controlling solvents and bases

The selective activation of C-F bonds under mild reaction conditions remains an ongoing challenge of bond activation. Here, we present a cooperative [Rh/P(O)nBu2 ] template for catalytic hydrodefluorination (HDF) of perfluoroarenes. In addition to substrates presenting electron-withdrawing functional groups, the system showed an exceedingly rare tolerance for electron-donating functionalities and heterocycles. The high chemoselectivity of the catalyst and its readiness to be deployed at a preparative scale illustrate its practicality. Empirical mechanistic studies and a density functional theory (DFT) study have identified a rhodium(I) dihydride complex as a catalytically relevant species and the determining role of phosphine oxide as a cooperative fragment. Altogether, we demonstrate that molecular templates based on these design elements can be assembled to create catalysts with increased reactivity for challenging bond activations.

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.

An efficient and direct hydrodefluorination (HDF) of ortho-fluoro aromatic amides using Ni(cod)2 as the catalyst, 2-propanol as a green reductant, and potassium tert-butoxide as a base is described. The reaction proceeds via the use of an amidate anion directing group. The reaction does not require any external ligands and the reaction proceeds at low temperatures.

The catalytic hydrodefluorination (HDF) with a bifunctional azairidacycle using HCOOK was examined for cyano- and chloro-substituted fluoroarenes, including penta- and tetrafluorobenzonitriles, tetrafluoroterephthalonitrile, tetrafluorophthalonitrile, 3-chloro-2,4,5,6-tetrafluoropyridine, and 4-cyano-2,3,5,6-tetrafluoropyridine. The reaction was performed in the presence of a controlled amount of HCOOK with a substrate/catalyst ratio (S/C) of 100 in a 1:1 mixture of 1,2-dimethoxyethane (DME) and H2O at an ambient temperature of 30 °C to obtain partially fluorinated compounds with satisfactory regioselectivities. The C–F bond cleavage proceeded favorably at the para position of substituents other than fluorine, which is in consonance with the nucleophilic aromatic substitution mechanism. In the HDF of tetrafluoroterephthalonitrile and 4-cyano-2,3,5,6-tetrafluoropyridine, which do not contain a fluorine atom at the para position of the cyano group, the double defluorination occurred solely at the 2- and 5-positions, as confirmed by X-ray crystallography. The HDF of 3-chloro-2,4,5,6-tetrafluoropyridine gave preference to the C–F bond cleavage over the C–Cl bond cleavage, unlike the dehalogenation pathway via electron-transfer radical anion fragmentation. In addition, new azairidacycles with an electron-donating methoxy substituent on the C–N chelating ligand were synthesized and served as a catalyst precursor (0.2 mol%) for the transfer hydrogenative defluorination of pentafluoropyridine, leading to 2,3,5,6-tetrafluoropyridine with up to a turnover number (TON) of 418.

Hydrodefluorination (HDF) is a very important fundamental transformation for conversion of the C-F bond into the C-H bond in organic synthesis. In the past decade, much progress has been achieved with HDF through the utility of low-valent metals, transition-metal complexes and main-group Lewis acids. Recently, novel methods have been introduced for this purpose through photo- and electrochemical pathways, which are of great significance, due to their considerable environmental and economical advantages. This Review highlights the HDF of fluorinated organic compounds (FOCs) through photo- and electrochemical strategies, along with mechanistic insights.

The development of novel Lewis acids derived from bipyridinium and phenanthrolinium dications is reported. Calculations of Hydride Ion Affinity (HIA) values indicate high carbon-based Lewis acidity at the ortho and para positions. This arises in part from extensive LUMO delocalization across the aromatic backbones. Species [C10 H6 R2 N2 CH2 CH2 ]2+ (R=H [1 a]2+ , Me [1 f]2+ , tBu [1 g]2+ ), and [C12 H4 R4 N2 CH2 CH2 ]2+ (R=H [2 a]2+ , Me [2 b]2+ ) were prepared and evaluated for use in the initiation of hydrodefluorination (HDF) catalysis. Compound [2 a]2+ proved highly effective towards generating catalytically active silylium cations via Lewis acid-mediated hydride abstraction from silane. This enabled the HDF of a range of aryl- and alkyl- substituted sp3 (C-F) bonds under mild conditions. The protocol was also adapted to effect the deuterodefluorination of cis-2,4,6-(CF3 )3 C6 H9 . The dications are shown to act as hydride acceptors with the isolation of neutral species C16 H14 N2 (3 a) and C16 H10 Me4 N2 (3 b) and monocationic species [C14 H13 N2 ]+ ([4 a]+ ) and [C18 H21 N2 ]+ ([4 b]+ ). Experimental and computational data provide further support that the dications are initiators in the generation of silylium cations.

Palladium-Catalyzed Hydrodefluorination of Fluoroarenes

A highly stereoselective palladium(0)-catalyzed hydrodefluorination (HDF) of tetrasubstituted gem-difluoroalkenes is developed. By using catalytic Pd(PPh3)4 (2.5-5 mol %) and hydrosilane Me2PhSiH, various trisubstituted terminal (E)-monofluoroalkenes can be synthesized with excellent E/Z selectivity (>99:1) and good functional group tolerability. The key stereocontrol should be exerted by an ester-directed C-F bond oxidative addition step in the catalytic cycle.

The transition to more economically friendly small-chain fluorinated groups is leading to a resurgence in the synthesis and reactivity of fluoroalkenes. One versatile method to obtain a variety of commercially relevant hydrofluoroalkenes involves the catalytic hydrodefluorination (HDF) of fluoroalkenes using silanes. In this work it is shown that copper hydride complexes of tertiary phosphorus ligands (L) can be tuned to achieve selective multiple HDF of fluoroalkenes. In one example, HDF of the hexafluoropropene dimer affords a single isomer of heptafluoro-2-methylpentene in which five fluorines have been selectively replaced with hydrogens. DFT computational studies suggest a distinct HDF mechanisms for L2CuH (bidentate or bulky monodentate phosphines) and L3CuH (small cone angle monodentate phosphines) catalysts, allowing for stereocontrol of the HDF of trifluoroethylene.

The gallium hydrides (iBu)2 GaH (1 a), LiGaH4 (1 b) and Me3 N⋅GaH3 (1 c) hydrodefluorinate vinylic and aromatic C-F bonds when O and N donor molecules are present. 1 b exhibits the highest reactivity. Quantitative conversion to the hydrodefluorination (HDF) products could be observed for hexafluoropropene and 1,1,3,3,3-pentafluoropropene, 94 % conversion of pentafluoropyridine and 49 % of octafluorotoluene. Whereas for the HDF with 1 b high conversions are observed when catalytic amounts of O donor molecules are added, for 1 a, the addition of N donor molecules lead to higher conversions. The E/Z selectivity of the HDF of 1,1,3,3,3-pentafluoropropene is donor-dependent. DFT studies show that HDF proceeds in this case via the gallium hydride dimer-donor species and a hydrometallation/elimination sequence. Selectivities are sensitive to the choice of donor, as the right donor can lead to an on/off switching during catalysis, that is, the hydrometallation step is accelerated by the presence of a donor, but the donor dissociates prior to elimination, allowing the inherently more selective donorless gallium systems to determine the selectivity.

We present herein the utilization of NHC‐stabilized alane adducts of the type (NHC)·AlH3 [NHC = Me2Im (1), Me2ImMe (2), iPr2Im (3), iPr2ImMe (4), Dipp2Im (5)] and (NHC)·AliBu2H [NHC = iPr2Im (6), Dipp2Im (7)] as novel hydride transfer reagents in the hydrodefluorination (HDF) of different fluoroaromatics and hexafluoropropene. Depending on the alane adduct used, HDF of pentafluoropyridine to 2,3,5,6‐tetrafluoropyridine in yields of 15–99 % was observed. The adducts 1, 2, and 5 achieved a quantitative conversion into 2,3,5,6‐tetrafluoropyridine at room temperature immediately after mixing the reactants. Studies on the HDF of fluorobenzenes with the (NHC)·AlH3 adducts 1, 3, and 5 and (Dipp2Im)·AliBu2H (7) showed the decisive influence of the reaction temperature on the H/F exchange and that 135 °C in xylene afforded the best product distribution. Although the HDF of hexafluorobenzene yielded 1,2,4,5‐tetrafluorobenzene in moderate yields with traces of 1,2,3,4‐tetrafluorobenzene and 1,2,4‐trifluorobenzene, pentafluorobenzene was converted quantitatively into 1,2,4,5‐tetrafluorobenzene, with (Dipp2Im)·AliBu2H (7) showing the highest activity and reaching complete conversion after 12 h at 135 °C in xylene. The HDF of hexafluoropropene with (Me2Im)·AlH3 (1) occurred even at low temperatures and preferably at the CF2 group with the formation of 1,2,3,3,3‐pentafluoropropene (with 0.4 equiv. of 1) or 2,3,3,3‐tetra‐fluoropropene (with 0.9 equiv. of 1) as the main product.

In connection with the mechanism of the catalytic reduction of fluoroarenes, the intramolecular defluorinative transformation of a family of iridium hydrides utilized as a hydrogen transfer catalyst is studied. Hydridoiridium(III) complexes bearing fluorinated phenylsulfonyl-1,2-diphenylethylenediamine ligands are spontaneously converted into iridacycles via selective C–F bond cleavage at the ortho position. NMR spectroscopic studies and synthesis of intermediate model compounds verify the stepwise pathway involving intramolecular substitution of the ortho-fluorine atom by the hydrido ligand, i.e., hydrodefluorination (HDF), and the following fluoride-assisted cyclometalation at the transiently formed C–H bond. A hydridoiridium complex with a 2,3,4,5,6-pentafluorophenylsulfonyl (Fs) substituent is more susceptible to HDF than its analog with a 2,3,4,5-tetrafluorophenylsulfonyl (FsH) group. The FsH-derivative clearly shows that C–F bond cleavage occurs in preference to C–H activation. These experimental re...

Catalytic hydrodefluorination (HDF) of unactivated fluoroalkanes or CF3 -substituted aryl species is performed using the PIII Lewis acids, [(bipy)PPh]2+ (12+ ) and [(terpy)PPh]2+ (22+ ) under mild conditions (25 or 50 °C). Mechanistic studies indicate that activation of C-F bond by the PIII center is key. Particularly noteworthy is that the catalyst 2[B(C6 F5 )4 ]2 is air-stable and readily accessible from bench-stable, commercially available reagents in one-step and can be used without isolation.

Rh-Pd-alloy catalyzed electrochemical hydrodefluorination of 4-fluorophenol in aqueous solutions

Abstract A transition‐metal‐free catalytic hydrodefluorination (HDF) reaction of polyfluoroarenes is described. The reaction involves direct hydride transfer from a hydrosilicate as the key intermediate, which is generated from a hydrosilane and a fluoride salt. The eliminated fluoride regenerates the hydrosilicate to complete the catalytic cycle. Dispersion‐corrected DFT calculations indicated that the HDF reaction proceeds through a concerted nucleophilic aromatic substitution (CSNAr) process.

A transition-metal-free catalytic hydrodefluorination (HDF) reaction of polyfluoroarenes is described. The reaction involves direct hydride transfer from a hydrosilicate as the key intermediate, which is generated from a hydrosilane and a fluoride salt. The eliminated fluoride regenerates the hydrosilicate to complete the catalytic cycle. Dispersion-corrected DFT calculations indicated that the HDF reaction proceeds through a concerted nucleophilic aromatic substitution (CSN Ar) process.

The all-trans isomer of Ru(IMe4)2(PPh3)2H2 (ttt-4; IMe4 = 1,3,4,5-tetramethylimidazol-2-ylidene) reacts with C6F6 at 70 °C to afford the hydride fluoride complex Ru(IMe4)2(PPh3)2HF (ttt-6). At room temperature, ttt-6 reacts with Et3SiH to give a mixture of products, one of which is assigned as the silyl trihydride complex Ru(IMe4)2(PPh3)(SiEt3)H3 (8) by comparison to the isolated and structurally characterized analogue Ru(IMe4)2(PPh3)(SiPh3)H3 (9). As ttt-4 was re-formed cleanly upon heating ttt-6 with Et3SiH, it was tested in the catalytic hydrodefluorination (HDF) of C6F6 (10 mol %, 90 °C), along with 9, Ru(IMe4)2(P-P)HF (P-P = Ph2P(CH2)2PPh2 (dppe, cct-13), Ph2P(CH2)3PPh2 (dppp, cct-14), Ph2PCH2PPh2 (dppm, cct-15)), Ru(IEt2Me2)2(PPh3)2HF (cct-7; IEt2Me2 = 1,3-diethyl-4,5-dimethylimidazol-2-ylidene)), and Ru(IEt2Me2)2(dppe)2HF (cct-16) for comparison. Both cct-13 and cct-14 brought about near-quantitative conversion to C6FH5 in 24 h, in comparison to ca. 50% conversion with ttt-4 in 144 h.