Photocatalytic Palladium-Catalyzed Fluoroalkylation of Styrene Derivatives (original) (raw)
Direct photocatalytic fluorination of benzylic C-H bonds with N-fluorobenzenesulfonimide
Chemical communications (Cambridge, England), 2015
The late-stage fluorination of common synthetic building blocks and drug leads is an appealing reaction for medicinal chemistry. In particular, fluorination of benzylic C-H bonds provides a means to attenuate drug metabolism at this metabolically labile position. Here we report two complimentary strategies for the direct fluorination of benzylic C-H bonds using N-fluorobenzenesulfonimide and either a decatungstate photocatalyst or AIBN-initiation.
Journal of the American Chemical Society, 2021
This Article describes the development of a decarbonylative Pd-catalyzed aryl-fluoroalkyl bondforming reaction that couples fluoroalkylcarboxylic acid-derived electrophiles [R F C(O)X] with aryl organometallics (Ar-M'). This reaction was optimized by interrogating the individual steps of the catalytic cycle (oxidative addition, carbonyl de-insertion, transmetalation, and reductive elimination) to identify a compatible pair of coupling partners and an appropriate Pd catalyst. These stoichiometric organometallic studies revealed several critical elements for reaction design. First, uncatalyzed background reactions between R F C(O)X and Ar-M' can be avoided by using M' = boronate ester. Second, carbonyl de-insertion and Ar-R F reductive elimination are the two slowest steps of the catalytic cycle when R F = CF 3. Both steps are dramatically accelerated upon changing to R F = CHF 2. Computational studies reveal that a favorable F 2 C-H-X interaction contributes to accelerating carbonyl de-insertion in this system. Finally, transmetalation is slow with X = difluoroacetate but fast with X = F. Ultimately, these studies enabled the development of an (SPhos)Pd-catalyzed decarbonylative difluoromethylation of aryl neopentylglycol boronate esters with difluoromethyl acetyl fluoride.
Photocatalytic fluoroalkylation reactions of organic compounds
Organic & Biomolecular Chemistry, 2015
Photocatalytic methods for fluoroalkyl-radical generation provide more convenient alternatives to the classical perfluoroalkyl-radical (Rf) production through chemical initiators, such as azo or peroxide compounds or the employment of transition metals through a thermal electron transfer (ET) initiation process.
The Journal of Organic Chemistry, 2019
Visible light induced metal-free trifluoromethylation of activated, carbocyclic and unactivated vinylcyclopropanes via ring opening reaction using Langlois reagent (CF 3 SO 2 Na) is reported to synthesize allylic trifluoromethylated derivatives. Allylic trifluoromethylation was achieved by photo-oxidative single electron transfer (SET) process at ambient temperature and metal-free condition under visible-light irradiation using pyrylium salt as photoredox catalyst. The reported methodology has operational simplicity, broad substrate scope, high functional group tolerance and scalability. Trifluoromethyl group is a valuable moiety in pharmaceutical and agrochemical fields. 1 The Journal of Organic Chemistry acetophenone derivatives, which is very cost-effective. 13 Pyrylium salts absorb in the visible region and act as powerful oxidizing agents in their excited states. 11,13,14 They can enhance the formation of free radicals because of no net charge separation in electron transfer step. 14 Among the many trifluoromethylating reagents (Togni, Umemoto, TMSCF 3 , CF 3 SO 2 Na, CF 3 I, CF 3 SO 2 Cl, etc.), Langlois (CF 3 SO 2 Na) reagent has received special attention due to its easy handling, stability and cost-effectiveness. However, this reagent has high oxidation potential (E oxd = +1.05 V vs SCE) 15 making the generation of the CF 3 radical difficult. Few methods are known for trifluoromethylation from CF 3 SO 2 Na using transition metal catalysts at high temperatures 16a-c and excess of explosive peroxides as strong oxidant. 16d-f In the case of photocatalysis, generation of CF 3 radical directly from CF 3 SO 2 Na using Mes.Acr.ClO 4 17a and [Ir(dF-CF 3 -ppy) 2 (dtbpy)](PF 6 ) 17b is known (Scheme 1b). However, till date, no other photocatalysts have been explored. Here, we report for the first time, pyrylium organic salt as a photocatalyst for the generation of CF 3 radical using visible light and subsequent trifluoromethylation of vinylcyclopropanes (VCPs) using Langlois' reagent (Scheme 1b). Though vinylcyclopropanes (VCP) are well known for radical clock experiments, 4c,18 there is no detailed study of ring opening of VCPs using photoredox catalysis. Here, we are reporting trifluoromethylation of VCPs using Langlois reagent by organic photoredox catalysis. We hypothesized generation of CF 3 radical that could react with the vinyl moiety of VCPs and undergo ring opening to form long alkyl chained allylic trifluoromethylated products. First, we tried trifluoromethylation on activated VCP 1a as a model substrate using Macmillan 19a and Stephenson et al. 19b conditions (Entry 1 and 2). However, these conditions failed to yield the expected product. Next, we screened different photocatalysts as shown in Table . Initially, we screened different Ru and Ir-metal photocatalysts for the trifluoromethylation of VCP. Catalysts like Ru(bpy) 3 Cl 2 •6H 2 O (bpy = bipyridyl) {E 1/2 red = [ * Ru II /Ru I ] = +0.77 V vs SCE in MeCN}, 20a Ir(ppy) 2 (dtbbpy)PF 6 (dtbbpy = 4,4′-di-tert-butyl-2,2′-dipyridyl) {E 1/2 red [ * Ir III /Ir II ] = +0.66 V vs SCE in MeCN} 20b and fac-Ir(ppy) 3 (ppy = 2-phenylpyridine) {E 1/2 red [ * Ir III /Ir II ] = +0.31 V vs SCE in MeCN} 20c and Eosin Y {E 1/2 red = [ 3 EY * /EY •-] = +0.83 V vs SCE in MeCN} 20d have insufficient potentials to generate the CF 3 radical, hence the reaction failed to provide expected product (Entry 3-5 and 7).
Trifluoroethanol: key solvent for palladium-catalyzed polymerization reactions
2005
A series of cationic palladium complexes of general formula [Pd(CH 3 )(NCCH 3 )(N-N)][X] (N-N = phen 1, 3-sec-butyl-1,10-phenanthroline (3-sBu-phen) 2, bpy 3, (À)-(S,S)-3,3 0 -(1,2-dimethylethylenedioxy)-2,2 0 -bipyridine (bbpy) 4, (+)-(R)-3,3 0 -(1-methylethylenedioxy)-2,2 0 -bipyridine (pbpy) 5, N,N 0 -bis(2,6-diisopropylphenyl)-2,3-butanediimine (iso-DAB) 6; X ¼ PF À 6 a, OTf (OTf = triflate) b) containing different nitrogen-donor ligands were prepared from the corresponding neutral chloro derivatives [Pd(CH 3 )(Cl)(N-N)] (1c-6c). They were characterized by 1 H NMR spectroscopy and elemental analysis. Single crystals suitable for X-ray determination were obtained for complexes [Pd(CH 3 )(NCCH 3 )(bbpy)][PF 6 ] (4a), [Pd(CH 3 )(NCCH 3 )(iso-DAB)][PF 6 ] (6a) and [Pd(Cl) 2 (bbpy)] (4c 0 ). The latter is the result of an exchange reaction of the methyl group, present in complex 4c, with a chloride, that occurred after dissolution of 4c in CDCl 3 , for 1 week at 0°C. The catalytic behavior of complexes 1a-5a and 1b-5b in the CO/styrene copolymerization was studied in CH 2 Cl 2 and 2,2,2-trifluoroethanol (TFE) evidencing the positive effect of the fluorinated alcohol both in terms of productivity and molecular weight values of the polymers obtained. Influence of the nitrogen ligand, the anion and the reaction time in both solvents were investigated and is discussed in detail. Encouraging preliminary results were also obtained in the synthesis of polyethylene, in TFE, catalyzed by [Pd(CH 3 )(NCCH 3 )(iso-DAB)][PF 6 ] (6a).
Journal of the American Chemical Society, 2015
A new biaryl monophosphine ligand (AlPhos, L1) allows for the room temperature Pd-catalyzed fluorination of a variety of activated (hetero)aryl triflates. Furthermore, aryl triflates and bromides that are prone to give mixtures of regioisomer-ic aryl fluorides with Pd-catalysis can now be converted to the desired aryl fluorides with high regioselectivity. Analysis of the solid-state structures of several Pd(II) complexes, as well as density functional theory (DFT) calculations, shed light on the origin of the enhanced reactivity observed with L1.
Journal of Fluorine Chemistry, 1996
Butane-1,4-diol was fluoroalkylated by its photoaddition reactions with hexafluoropropene and perfluoro (propyl vinyl) ether under atmospheric pressure, by which monofluoroalkylated and bis-fluoroalkylated products were obtained. 1,3-Diols were completely unreactive under the conditions. 2,2,2-Trifluoroethanol, tert.butyl alcohol and methyl tert.butyl ether appeared to be inert solvents for the additions while acetonitrile quenched the reactions. The reactivity of perfluoro vinyl ethers was studied (tested) in their photoaddition reactions with alkanols that were less regioselective (up to 7% rel.of regioisomer) in comparison with hexafluoropropene. Surprisingly, photo-supportedbase-induced nucleophilic mono-and bis-addition of butane-l+diol onto hexafluoroprnpene was observed in acetonitrile.
Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology, 2017
Tetrabutylammonium decatungstate has been exploited to photoinduce the trifluoromethylation of (hetero)aromatics and electron-poor olefins. The process made use of the cheap Langlois' reagent (CF3SO2Na) and occurred under sunlight irradiation in an acetonitrile/water mixture. The trifluoromethylation of (hetero)aromatics required the use of potassium persulfate as an additive and the mono- or bis-trifluoromethylated adducts were obtained, depending on the actual reaction conditions and the chosen substrate.
Pd-Catalyzed Stereoselective Carboperfluoroalkylation of Alkynes
Journal of the American Chemical Society, 2015
A Pd-catalyzed three component reaction involving terminal alkynes, boronic acids and perfluoroalkyl iodides is presented here. Trisubstituted perfluoroalkenes can be obtained in a highly regio-and stereocontrolled manner by the simultaneous addition of both aryl and C n F m groups across the triple bond in a radical-mediated process. The reaction is operationally simple offering a broad scope and functional group tolerance.
Synthesis of Fluorinated Dienes by Palladium-Catalyzed Coupling Reactions
Chemistry – An Asian Journal, 2008
Recently, we used the Negishi coupling to prepare 1,1,4,4tetrafluorobutadiene, the key precursor in the synthesis of 1,1,4,4-tetrafluorobutatriene. [21] Since then, other groups have extended the variety of fluorinated compounds prepared by vinyl-vinyl coupling reactions. [22-26] A particularly elegant method of synthesizing symmetrical dienes by Pdcatalyzed coupling of vinyl halides by generation of vinyl stannanes in situ with (Bu 3 Sn) 2 was published recently by Xu and Burton. [22c] As a continuation of our work, we report herein the synthesis of a number of fluorine-substituted 1,3and 1,4-dienes (Schemes 1 and 2). Butadienes 1-5 have been known since the 1950s, [27] but so far there exists no convenient laboratory-scale synthesis for dienes 2-5. Hexafluorobutadiene 1 was prepared by cou
Chemical Communications, 2007
General Methods. Difluoroenol silyl ethers 1 2a-2e and monofluoro silyl enol ether 2 4 were prepared as described previously. Tri-n-butyltin fluoride and a 1M toluene solution of P(t-Bu)3, were purchased from Aldrich Chemical Co. and used as received. Toluene was distilled under nitrogen over sodium prior to use. All other chemicals were used as received from commercial sources. 1 H NMR spectra were obtained on a 300-or 500-MHz spectrometer, and chemical shifts were recorded relative to a residual protonated solvent. 13 C NMR spectra were obtained at 75.5 MHz on a 300-MHz instrument, and chemical shifts were recorded relative to the solvent resonance. Both 1 H NMR and 13 C NMR chemical shifts are reported in parts per million relative to tetramethylsilane. 19 F NMR chemical shifts are reported in parts per million from CFCl 3. The solvent was CDCl 3 unless otherwise stated. The purity of products was determined by CH&N elemental analyses. Column chromatography was carried out using ACROS silicagel (0.060-0.200 mm). Thin layer chromatography (TLC) was carried out on commercially available pre-coated plates (Whatman UV 254 silica).
The Journal of Organic Chemistry, 1988
Perfluoroalkenylzinc reagents [CF2=CFZnX (l), (2)-CF,CF=CFZnX (2), and (E)-CFSCF=CFZnX (3); X = perfluoroalkenyl group or I (Br or I for l)] coupled with aryl iodides in the presence of Pd(PPh3)4 (1-3 mol %) to give the corresponding arylalkenes. A series of substituted a,@,@-trifluorostyrenes were prepared in good yields. This method provides ready availability of these fluorinated styrenes, which were previously obtained with difficulty. For the first time, 1-arylperfluoropropenes were prepared stereoselectively. Palladium-catalyzed reactions of 2 with aryl iodides gave stereospecific (E)-1-arylperfluoropropenes, and the same procedure with 3 gave stereoselective Z / E ratios ranging from 9812 to 9218.
Palladium-Catalyzed Decarboxylative Trifluoroethylation of Aryl Alkynyl Carboxylic Acids
A trifluoroethylation of alkynes through a palladium-catalyzed decarboxylative coupling reaction was developed. When alkynyl carboxylic acids and ICH 2 CF 3 were allowed to react with [Pd(η 3 -allyl)Cl] 2 /XantPhos and Cs 2 CO 3 in N,N-dimethylformamide (DMF) at 80°C for 1 h, the desired products were formed in good yields. This catalytic system showed high functional group tolerance.
Trifluoromethylation of Allylsilanes under Photoredox Catalysis
Organic Letters, 2013
A new catalytic method to access allylic secondary CF 3 products is described. These reactions use the visible light excited Ru(bpy) 3 Cl 2 3 6H 2 O catalyst and the Togni or Umemoto reagent as the CF 3 source. The photoredox catalytic manifold delivers enantioenriched allylic trifluoromethylated products not accessible under Cu(I) catalysis.