- Mechanistic study of Ru-NHC-catalyzed hydrodefluorination of fluoropyridines: The influence of the NHC on the regioselectivity of C-F activation and chemoselectivity of C-F versus C-H bond cleavage
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We describe a combined experimental and computational study into the scope, regioselectivity, and mechanism of the catalytic hydrodefluorination (HDF) of fluoropyridines, C5F5-xHxN (x = 0-2), at two Ru(NHC)(PPh3)2(CO)H2 catalysts (NHC = IPr, 1, and IMes, 2). The regioselectivity and extent of HDF is significantly dependent on the nature of the NHC: with 1 HDF of C5F5N is favored at the ortho-position and gives 2,3,4,5-C5F4HN as the major product. This reacts on to 3,4,5-C5F3H2N and 2,3,5-C5F3H2N, and the latter can also undergo further HDF to 3,5-C5F2H3N and 2,5-C5F2H3N. para-HDF of C5F5N is also seen and gives 2,3,5,6-C5F4HN as a minor product, which is then inert to further reaction. In contrast, with 2, para-HDF of C5F5N is preferred, and moreover, the 2,3,5,6-C5F4HN regioisomer undergoes C-H bond activation to form the catalytically inactive 16e Ru-fluoropyridyl complex Ru(IMes)(PPh3)(CO)(4-C5F4N)H, 3. Density functional theory calculations rationalize the different regioselectivity of HDF of C5F5N at 1 and 2 in terms of a change in the pathway that is operating with these two catalysts. With 1, a stepwise mechanism is favored in which a N → Ru σ-interaction stabilizes the key C-F bond cleavage along the ortho-HDF pathway. With 2, a concerted pathway favoring para-HDF is more accessible. The calculations show the barriers increase for the subsequent HDF of the lower fluorinated substrates, and they also correctly identify the most reactive C-F bonds. A mechanism for the formation of 3 is also defined, but the competition between C-H bond activation and HDF of 2,3,5,6-C5F4HN at 2 (which favors C-H activation experimentally) is not reproduced. In general, the calculations appear to overestimate the HDF reactivity of 2,3,5,6-C5F4HN at both catalysts 1 and 2. (Chemical Equation Presented).
- McKay, David,Riddlestone, Ian M.,Macgregor, Stuart A.,Mahon, Mary F.,Whittlesey, Michael K.
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- Dual C-F, C-H Functionalization via Photocatalysis: Access to Multifluorinated Biaryls
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Multifluorinated biaryls are challenging to synthesize and yet are an important class of molecules. Because of the difficulty associated with selective fluorination, this class of molecules represent a formidable synthetic challenge. An alternative approach to selective fluorination of biaryls is to couple an arene that already possesses C-F bonds in the desired location. This strategy has been regularly utilized and relies heavily on traditional cross-coupling strategies that employ organometallics and halides (or pseudohalides) in order to achieve the coupling. Herein we report conditions for the photocatalytic coupling via direct functionalization of the C-F bond of a perfluoroarene and C-H bond of the other arene to provide an expedient route to multifluorinated biaryls. The mild conditions and good functional group tolerance enable a broad scope, including access to the anti-Minisci product of basic heterocycles. Finally, we demonstrate the value of the C-F functionalization approach by utilizing the high fluorine content to systematically build complex biaryls containing between two and five Caryl-F bonds via the synergistic use of photocatalysis and SNAr chemistry.
- Senaweera, Sameera,Weaver, Jimmie D.
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- Dual Photoredox-/Palladium-Catalyzed Cross-Electrophile Couplings of Polyfluoroarenes with Aryl Halides and Triflates
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A visible-light photoredox-/Pd-catalyzed cross-electrophile arylation of polyfluoroarenes with aryl halides and triflates in the presence of dialkylamines is reported for the first time. This synergistic protocol affords access to a series of fluorodiaryls from easily available starting materials under mild and operationally simple conditions. A series of mechanistic experiments, including the stoichiometric reactions of a ligated (aryl)Pd complex, Stern-Volmer fluorescence quenching studies, cyclic voltammetry studies, and UV-vis spectroscopy, were performed to elucidate the potential catalytic pathway in this synergistic process.
- Qin, Jian,Zhu, Shengqing,Chu, Lingling
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supporting information
p. 2246 - 2252
(2021/04/02)
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- Photoredox/Nickel Dual-Catalyzed Reductive Cross Coupling of Aryl Halides Using an Organic Reducing Agent
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A successful protocol for the reductive aryl-Aryl cross-coupling of polyfluorinated arenes with a broad range of aryl halides has been developed. Sequential carbon-fluorine bond cleavage and carbon-carbon bond formation are two of the important features of the reaction. Addition of an aryl radical anion to a nickel intermediate was achieved for the first time using polyfluoroarenes as radical precursors. This, in combination with the excellent para selectivity, paves the way for the synthesis of various new multifluorinated biaryl compounds.
- Bülow, Raoul F.,Dewanji, Abhishek,Rueping, Magnus
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supporting information
p. 1611 - 1617
(2020/03/13)
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- Dihydridoboranes: Selective Reagents for Hydroboration and Hydrodefluorination
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The preparation of a new series of dihydridoboranes supported by N,N-chelating ligands, [R2NCH2CH2NAr]- (R = alkyl, Ar = aryl), is reported. These new boranes react selectively with carbonyls, imines, and a series of electron-deficient fluoroarenes. The reactivity is complementary to recognized reagents such as pinacolborane, catecholborane, NHC-BH3, and borane (BH3) itself. Selectivities are rationalized by invoking both open- A nd closed-chain forms of the reagents as part of equilibrium mixtures.
- Phillips, Nicholas A.,O'hanlon, James,Hooper, Thomas N.,White, Andrew J. P.,Crimmin, Mark R.
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supporting information
p. 7289 - 7293
(2019/10/08)
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- Hydrodefluorination of fluoroaromatics by isopropyl alcohol catalyzed by a ruthenium NHC complex. An unusual role of the carbene ligand
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The NHC (NHC = N-heterocyclic carbene) complex Cp*(IPr)RuH3 catalyzes hydrodefluorination of aromatic fluorides at 70 °C with isopropyl alcohol as the reducing reagent. The reaction is selective for aromatic fluorides, as almost negligible C(sp3)?F bond reduction takes place. The activity decreases from more to less fluorinated substrates, but polyaromatic monofluorides, such as 1-fluoronaphthalene and 6-fluoro-2-methylquinoline, can also be reduced in moderate to good yields. Kinetic studies are consistent with a mechanism based on elimination of NHC and reversible substrate coordination, followed by coordination of the alcohol.
- Mai, Van Hung,Nikonov, Georgii I.
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p. 7956 - 7961
(2018/05/23)
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- Photocatalytic C-F alkylation; Facile access to multifluorinated arenes
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C-F functionalizations that provide C-C bonds are challenging synthetic transformations, due in part to the large C-F bond strength, short bond length, nonpolarizable nature, the production of fluoride, and the regioselectivity-in the case of multifluorinated substrates. However, commercially available highly fluorinated arenes possess great synthetic potential because they already possess the C-F bonds in the desired locations that would be difficult to selectively fluorinate. In order to take advantage of this potential, selective C-F functionalizations must be developed. Herein, we disclose conditions for the photocatalytic reductive alkylation of highly fluorinated arenes with ubiquitous and unactivated alkenes. The mild reaction conditions provide for a broad functional group scope, and the reaction is remarkably efficient using just 0.25 mol% catalyst. Finally, we demonstrate the utility of the strategy by converting highly fluorinated arenes to elaborate (hetero)arenes that contain 2-5 Caryl-F bonds via synergistic use of photocatalysis and SNAr chemistry.
- Singh,Kubik,Weaver
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p. 7206 - 7212
(2015/11/24)
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- Rhodium catalyzed, carbon-hydrogen bond directed hydrodefluorination of fluoroarenes
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[CpRhCl(μ-Cl)]2 is reported as a highly efficient and selective precatalyst for the hydrodefluorination of perfluoroarenes using a hydrocarbon-soluble aluminum dihydride as the terminal reductant. Reactions are directed to cleave a C-F bond adjacent to an existing C-H bond with high regioselectivity (98.5-99%). A heterobimetallic complex containing an extremely rare Al-H-Rh functional group has been isolated and shown to be catalytically competent.
- Ekkert, Olga,Strudley, Sebastian D. A.,Rozenfeld, Alisa,White, Andrew J. P.,Crimmin, Mark R.
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supporting information
p. 7027 - 7030
(2015/05/19)
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- Hydrodeboration of potassium polyfluoroaryl(fluoro)borates with alcohols
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Potassium polyfluoroaryltrifluoroborates, K[ArFBF3] (ArF = C6F5, HC6F4, MeC6F4, 4-MeOC6F4, 4-indol-1-ylC6F4, 4-i
- Adonin, Nicolay Yu.,Shabalin, Anton Yu.,Bardin, Vadim V.
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p. 111 - 120
(2015/03/05)
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- π-π Interaction assisted hydrodefluorination of perfluoroarenes by gold hydride: A case of synergistic effect on C-F bond activation
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Synergistic effect is prevalent in natural metalloenzymes in activating small molecules, and the success has inspired the development of artificial catalysts capable of unprecedented organic transformations. In this work, we found that the attractive π-π interaction between organic additives (as electron-donors) and the perfluorinated arenes (as electron acceptors) is effective in gold hydride catalyzed activation of C-F bonds, specifically hydrodefluorination (HDF) of perfluoroarenes catalyzed by the Sadighi's gold hydrides [(NHC)AuH] (NHC = N-heterocyclic carbene). Although a weak interaction between [(NHC)AuH] and perfluoroarenes was observed from 1H NMR and UV-vis spectroscopies, low reactivity of [(NHC)AuH] toward HDF was found. In contrast, in the presence of p-N,N-dimethylaminopyridine (DMAP), the HDF of perfluoroarenes with silanes can be efficiently catalyzed by [(NHC)AuH], resulting in mainly the para-hydrodefluorinated products with up to 90% yield and 9 turnovers. The yield of the reaction increases with the more electron-withdrawing groups and degree of fluorination on the arenes, and the HDF reaction also tolerates different function groups (such as formyl, alkynyl, ketone, ester, and carboxylate groups), without reduction or hydrogenation of these function groups. To reveal the role of DMAP in the reactions, the possible π-π interaction between DMAP and perfluoroarenes was suggested by UV-vis spectral titrations, 1H NMR spectroscopic studies, and DFT calculations. Moreover, 1H and 19F-NMR studies show that this π-π interaction promotes hydrogen transfer from [(NHC)AuH] to pyridyl N atom, resulting in C-F bond cleavage. The interpretation of π-π interaction assisted C-F activation is supported by the reduced activation barriers in the presence of DMAP (31.6 kcal/mol) than that in the absence of DMAP (40.8 kcal/mol) for this reaction. An analysis of the charge distribution and transition state geometries indicate that this HDF process is controlled by the π-π interaction between DMAP and perfluoroarenes, accompanied with the changes of partial atomic charges.
- Lv, Hongbin,Zhan, Jin-Hui,Cai, Yuan-Bo,Yu, Yi,Wang, Bingwu,Zhang, Jun-Long
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supporting information
p. 16216 - 16227,12
(2020/09/09)
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- The ionic liquid [bmim]Br as an alternative medium for the catalytic cleavage of aromatic C-F and C-Cl bonds
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The potential of [bmim]Br as an alternative to aprotic dipolar solvents in nickel-catalyzed hydrodehalogenation reactions is demonstrated. Hydrodechlorination of pentafluorochlorobenzene proceeds under the action of zinc in aqueous [bmim]Br. Under the above conditions aromatic C-F bonds also undergo slow cleavage. The reaction is significantly accelerated in the presence of nickel complexes with 2,2′-bipyridine or 1,10-phenanthroline. In the case of pentafluoroacetanilide highly regioselective ortho-hydrodefluorination leading to the formation of 3,4,5-trifluoroacetanilide is observed.
- Prikhod'ko, Sergey A.,Adonin, Nicolay Yu.,Parmon, Valentin N.
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scheme or table
p. 2265 - 2268
(2010/05/18)
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- From hypervalent xenon difluoride and aryliodine(III) difluorides to onium salts: Scope and limitation of acidic fluoroorganic reagents in the synthesis of fluoroorgano xenon(II) and iodine(III) onium salts
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Fluorinated organodifluoroboranes RfBF2 are in general suitable reagents to transform XeF2 and RIF2 into the corresponding onium tetrafluoroborate salts [RfXe][BF4] and [R(Rf)I][BF4], respectively. (4-C5F4N)BF2 and trans-CF3CF{double bond, long}CFBF2 which represent boranes of high acidity form no Xe-C onium salts in reactions with XeF2 but give the desired iodonium salts with RIF2 (R = C6F5, o-, m-, p-C6FH4). The reaction of (4-C5F4N)BF2 with XeF2 ends with a XeF2-borane adduct. C6F5Xe(4-C5F4N), the first Xe-(4-C5F4N) compound, was obtained when C6F5XeF was reacted with Cd(4-C5F4N)2. We describe the synthesis of (4-C5F4N)IF2 and reactions of (4-C5F4N)IF2 and C6F5IF2 with (4-C5F4N)BF2. Analogous to [(4-C5F4N)2I][BF4] and [C6F5(4-C5F4N)I][BF4] aryl(perfluoroalkenyl)iodonium salts [R(R′)I][BF4] were obtained from RIF2 (R = C6F5, o-, m-, p-C6FH4) and R′BF2 (R′ = trans-CF3CF{double bond, long}CF, CF2{double bond, long}CF). The gas phase fluoride affinities pF- of selected fluoroorganodifluoroboranes RfBF2 and their hydrocarbon analogs are calculated (B3LYP/6-31+G*) and discussed with respect to their potential to introduce Rf-groups into hypervalent EF2 bonds. Four aspects which influence the transformation of hypervalent EF2 bonds (E = Xe, R′I) under the action of Lewis acidic reagents RAFn-1 (A = B, P; n = 3, 5) into the corresponding [RE][AFn+1] salts are presented and the important role of the acidity is emphasized. Fluoride affinities may help to plan the introduction of organo groups into EF2 moieties and to expand the types of acidic reagents. Thus C6H5PF4 with a pF- value comparable to that of RfBF2 compounds is able to introduce the C6H5 group into RIF2 (R = C6F5, p-C6FH4).
- Abo-Amer, Anwar,Frohn, Hermann-Josef,Steinberg, Christoph,Westphal, Ulrich
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p. 1311 - 1323
(2008/12/21)
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- Reductive transformations of organofluorine compounds: II. Hydrodechlorination of chloropolyfluoroarenes by the action of zinc
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Polyfluoroarenes containing chlorine atoms in the aromatic ring and/or in the benzylic position undergo hydrodechlorination by the action of zinc in aqueous dimethylformamide. The use of Zn/Cu and addition of salts (NaCl, Na2SO4, NH4Cl) favor reductive dechlorination of the Carom - Cl bond. Polyfluorobenzotrichlorides react with excess zinc to give the corresponding CH3-substituted derivatives, otherwise CH2Cl- and CHCl2-containing compounds are formed. The reduction of C6F5CCl3 and C6F5CH2Cl with zinc in the presence of copper provides lower yields of the hydrodechlorination products and leads to formation of 1,2-bis(pentafluorophenyl)ethane.
- Krasnov,Platonov
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p. 1488 - 1499
(2007/10/03)
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- Polyhalogenated heterocyclic compounds. Part 42. Fluorinated nitrogen heterocycles with unusual substitution patterns
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Reductive replacement of fluorine in 3,5-dichloro-2,4,6-trifluoropyridine 2a and pentafluoropyridine 2 using DIBAL and LAH leads to useful syntheses of fluoro and chlorofluoro pyridine derivatives. Replacement of fluorine by bromine using a mixture of HBr and AlBr3 is extremely efficient, giving excellent routes to 2,4,6-tribromo-3,5-difluoropyridine 3. Bromofluoro-pyrimidine and -quinoxaline derivatives have also been efficiently synthesised from perfluorinated precursors. Catalytic hydrogenation of bromofluoro heterocycles gives high yields of the corresponding fluorinated heterocycles. Reactions of nucleophiles with 3 gives surprising results. Soft nucleophiles, e.g. PhSNa displace bromine whereas hard nucleophiles, e.g. MeONa, displace fluorine. British Crown Copyright 1998, Defence Evaluation and Research Agency. Published by the Royal Society of Chemistry with the permission of the controller of Her Britannic Majesty's Stationery Office.
- Chambers, Richard D.,Hall, Christopher W.,Hutchinson, John,Millar, Ross W.
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p. 1705 - 1713
(2007/10/03)
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- Reductive defluorination of polyfluoroarenes by zinc in aqueous ammonia
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Aqueous ammonia has been found to be a good and versatile medium for the reductive defluorination of polyfluoroarenes by zinc. Upon the reduction of pentafluorobenzoic acid, 2,3,4,5,6-pentafluorobenzyl alcohol, pentafluoropyridine and heptafluoro-2-naphthoic acid individual products derived from the removal of one fluorine atom have been obtained.
- Laev, Sergey S.,Shteingarts, Vitalij D.
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p. 3765 - 3768
(2007/10/03)
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- THE MONO-ALKYLDECYANATION OF TETRAFLUOROTEREPHTHALONITRILE BY REACTION WITH GRIGNARD REAGENTS
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Treatment of tetrafluoroterephthalonitrile in THF with alkyl Grignard reagents gives the corresponding 4-alkyltetrafluorobenzonitrile in about 60percent yield.The scope and limitations of this transformation are reported.
- Milner, David J.
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p. 147 - 152
(2007/10/02)
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