540-36-3Relevant academic research and scientific papers
Radical Decarboxylative Carbometalation of Benzoic Acids: A Solution to Aromatic Decarboxylative Fluorination
Xu, Peng,López-Rojas, Priscila,Ritter, Tobias
supporting information, p. 5349 - 5354 (2021/05/05)
Abundant aromatic carboxylic acids exist in great structural diversity from nature and synthesis. To date, the synthetically valuable decarboxylative functionalization of benzoic acids is realized mainly by transition-metal-catalyzed decarboxylative cross couplings. However, the high activation barrier for thermal decarboxylative carbometalation that often requires 140 °C reaction temperature limits both the substrate scope as well as the scope of suitable reactions that can sustain such conditions. Numerous reactions, for example, decarboxylative fluorination that is well developed for aliphatic carboxylic acids, are out of reach for the aromatic counterparts with current reaction chemistry. Here, we report a conceptually different approach through a low-barrier photoinduced ligand to metal charge transfer (LMCT)-enabled radical decarboxylative carbometalation strategy, which generates a putative high-valent arylcopper(III) complex, from which versatile facile reductive eliminations can occur. We demonstrate the suitability of our new approach to address previously unrealized general decarboxylative fluorination of benzoic acids.
Nucleophilic Fluorination of Heteroaryl Chlorides and Aryl Triflates Enabled by Cooperative Catalysis
Hong, Cynthia M.,Whittaker, Aaron M.,Schultz, Danielle M.
, p. 3999 - 4006 (2021/03/09)
Aryl and heteroaryl fluorides are growing to be dominant motifs in pharmaceuticals and agrochemicals, yet they are rare in both nature and commodity chemicals. As a consequence, there is an increasingly urgent need to develop mild, cost-effective, and scalable methods for fluorination. The most straightforward route to synthesize aryl fluorides is through the halide exchange "halex"reaction, but conditions, cost, and atom economy preclude most available methods from large-scale manufacturing processes. We report a new approach that leverages the cooperative action of 18-crown-6 ether and tetramethylammonium chloride to catalytically access the reactivity of tetramethylammonium fluoride and achieve halex fluorinations under mild conditions with operational ease. The described methodology readily converts both heteroaryl chlorides and aryl triflates to their corresponding (hetero)aryl fluorides in high yields and purities.
Metal-Free Photoredox-Catalyzed Hydrodefluorination of Fluoroarenes Utilizing Amide Solvent as Reductant
Toriumi, Naoyuki,Yamashita, Kazuya,Iwasawa, Nobuharu
supporting information, p. 12635 - 12641 (2021/08/03)
A metal-free photoredox-catalyzed hydrodefluorination of fluoroarenes was achieved by using N,N,N’,N’-tetramethyl-para-phenylenediamine (1) as a strong photoreduction catalyst. This reaction was applicable not only to electron-rich monofluoroarenes but also to polyfluoroarenes to afford non-fluorinated arenes. The experimental mechanistic studies indicated that the amide solvent NMP plays an important role for regeneration of the photocatalyst, enabling additive-free photoreduction catalysis.
Novel manufacturing method of fluoro-aryl compounds and derivatives thereof
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Paragraph 0225-0228; 0229-0230, (2020/01/25)
The invention relates to a novel method of manufacturing fluoro-aryl compounds and derivatives thereof, in particular, fluorobenzene and derivatives thereof. The production environment of the manufacturing method is environmentally friendly. The shortages of a conventional method are overcome through a simple and beneficial mode. Compared with the prior art, the provided method is more effective,more environmentally friendly, and more energy saving. The method is used to produce core fluorinated aromatic compounds, preferably, core fluorinated fluorobenzene. On one aspect, the invention provides a method, which is advantages in industry and uses HF and a halogenated benzene precursor to prepare fluorobenzene and hydrogen halide. Moreover, the invention provides chlorobenzene as the primary raw material to prepare fluorobenzene, which is an important material in industry, and a beneficial, unexpected and simple application of chlorobenzene. In the prior art, the provided application ofchlorobenzene is unknown.
Fluorination of arylboronic esters enabled by bismuth redox catalysis
Planas, Oriol,Wang, Feng,Leutzsch, Markus,Cornella, Josep
, p. 313 - 317 (2020/01/28)
Bismuth catalysis has traditionally relied on the Lewis acidic properties of the element in a fixed oxidation state. In this paper, we report a series of bismuth complexes that can undergo oxidative addition, reductive elimination, and transmetallation in a manner akin to transition metals. Rational ligand optimization featuring a sulfoximine moiety produced an active catalyst for the fluorination of aryl boronic esters through a bismuth (III)/bismuth (V) redox cycle. Crystallographic characterization of the different bismuth species involved, together with a mechanistic investigation of the carbonfluorine bond-forming event, identified the crucial features that were combined to implement the full catalytic cycle.
Base-Catalyzed Aryl-B(OH)2 Protodeboronation Revisited: From Concerted Proton Transfer to Liberation of a Transient Aryl Anion
Cox, Paul A.,Reid, Marc,Leach, Andrew G.,Campbell, Andrew D.,King, Edward J.,Lloyd-Jones, Guy C.
supporting information, p. 13156 - 13165 (2017/09/26)
Pioneering studies by Kuivila, published more than 50 years ago, suggested ipso protonation of the boronate as the mechanism for base-catalyzed protodeboronation of arylboronic acids. However, the study was limited to UV spectrophotometric analysis under acidic conditions, and the aqueous association constants (Ka) were estimated. By means of NMR, stopped-flow IR, and quenched-flow techniques, the kinetics of base-catalyzed protodeboronation of 30 different arylboronic acids has now been determined at pH > 13 in aqueous dioxane at 70 °C. Included in the study are all 20 isomers of C6HnF(5-n)B(OH)2 with half-lives spanning 9 orders of magnitude: a and Sδ values, kinetic isotope effects (2H, 10B, 13C), linear free-energy relationships, and density functional theory calculations, we have identified a mechanistic regime involving unimolecular heterolysis of the boronate competing with concerted ipso protonation/C-B cleavage. The relative Lewis acidities of arylboronic acids do not correlate with their protodeboronation rates, especially when ortho substituents are present. Notably, 3,5-dinitrophenylboronic acid is orders of magnitude more stable than tetra-and pentafluorophenylboronic acids but has a similar pKa.
Catalytic Hydrodefluorination of Fluoroarenes Using Ru(IMe4)2L2H2 (IMe4 = 1,3,4,5-Tetramethylimidazol-2-ylidene; L2 = (PPh3)2, dppe, dppp, dppm) Complexes
Cybulski, Mateusz K.,Nicholls, Jessica E.,Lowe, John P.,Mahon, Mary F.,Whittlesey, Michael K.
, p. 2308 - 2316 (2017/06/30)
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.
Room Temperature Regioselective Catalytic Hydrodefluorination of Fluoroarenes with trans-[Ru(NHC)4H2] through a Concerted Nucleophilic Ru?H Attack Pathway
Cybulski, Mateusz K.,McKay, David,Macgregor, Stuart A.,Mahon, Mary F.,Whittlesey, Michael K.
, p. 1515 - 1519 (2017/02/05)
The efficient and highly selective room temperature hydrodefluorination (HDF) of fluoroarenes by the trans-[Ru(IMe4)4H2] catalyst, 3, is reported. Mechanistic studies show 3 acts directly in catalysis without any ligand dissociation and DFT calculations indicate a concerted nucleophilic attack mechanism. The calculations fully account for the observed selectivities which corroborate earlier predictions regarding the selectivity of HDF.
Reactions of aromatic compounds with xenon difluoride
Bardin,Adonin, N. Yu.
, p. 1400 - 1407 (2016/11/29)
Reactions of substituted benzenes C6H5R (R = Me, F, Cl, Br, CF3, NO2) with xenon difluoride in the presence of boron trifluoride–diethyl ether complex in weakly acidic (1,1,1,3,3-pentafluorobutane) and weakly basic media (acetonitrile) have been studied. These reactions lead to the formation of fluorobenzene derivatives FC6H4R (isomer mixture) together with isomeric difluorobenzenes and fluorinated and non-fluorinated biphenyls. The results have been compared with previously reported data obtained in other solvents using other catalysts.
Copper-Mediated Radiofluorination of Arylstannanes with [18F]KF
Makaravage, Katarina J.,Brooks, Allen F.,Mossine, Andrew V.,Sanford, Melanie S.,Scott, Peter J. H.
supporting information, p. 5440 - 5443 (2016/11/04)
A copper-mediated nucleophilic radiofluorination of aryl- and vinylstannanes with [18F]KF is described. This method is fast, uses commercially available reagents, and is compatible with both electron-rich and electron-deficient arene substrates. This method has been applied to the manual synthesis of a variety of clinically relevant radiotracers including protected [18F]F-phenylalanine and [18F]F-DOPA. In addition, an automated synthesis of [18F]MPPF is demonstrated that delivers a clinically validated dose of 200 ± 20 mCi with a high specific activity of 2400 ± 900 Ci/mmol.
