Tungstate-Catalyzed Biomimetic Oxidative Halogenation of (Hetero)Arene under Mild Condition-论文阅读讨论-ReadPaper - 轻松读论文 | 专业翻译 | 一键引文

DOI: 10.1016/j.isci.2020.101072

JCR-Q1 SCIE

Zhuang MaHe-Lin LuKe LiaoZhilong Chen

iScience

May 2020

6被引用

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摘要原文

•Tungstate-catalyzed halogenation of (hetero)arenes under mild condition•Robust in 100-g-scale synthesis; good functional group tolerance•Late-stage halogenation of complex molecules; good application in drug synthesis Aryl halide (Br, Cl, I) is among the most important compounds in pharmaceutical industry, material science, and agrochemistry, broadly utilized in diverse transformations. Tremendous approaches have been established to prepare this scaffold; however, many of them suffer from atom economy, harsh condition, inability to be scaled up, or cost-unfriendly reagents and catalysts. Inspired by vanadium haloperoxidases herein we presented a biomimetic approach for halogenation (Br, Cl, I) of (hetero)arene catalyzed by tungstate under mild pH in a cost-efficient and environment- and operation-friendly manner. Broad substrates, diverse functional group tolerance, and good chemo- and regioselectivities were observed, even in late-stage halogenation of complex molecules. Moreover, this approach can be scaled up to over 100 g without time-consuming and costly column purification. Several drugs and key precursors for drugs bearing aryl halides (Br, Cl, I) have been conveniently prepared based on our approach. Aryl halide (Br, Cl, I) is among the most important compounds in pharmaceutical industry, material science, and agrochemistry, broadly utilized in diverse transformations. Tremendous approaches have been established to prepare this scaffold; however, many of them suffer from atom economy, harsh condition, inability to be scaled up, or cost-unfriendly reagents and catalysts. Inspired by vanadium haloperoxidases herein we presented a biomimetic approach for halogenation (Br, Cl, I) of (hetero)arene catalyzed by tungstate under mild pH in a cost-efficient and environment- and operation-friendly manner. Broad substrates, diverse functional group tolerance, and good chemo- and regioselectivities were observed, even in late-stage halogenation of complex molecules. Moreover, this approach can be scaled up to over 100 g without time-consuming and costly column purification. Several drugs and key precursors for drugs bearing aryl halides (Br, Cl, I) have been conveniently prepared based on our approach. (Hetero)aryl halides (Br, Cl, I) are embodied in many biologically important molecules, like natural products, drugs, and drug leads (Hernandes et al., 2010Hernandes Z.M. Cavalcanti S.M.T. Moreira D.R.M. Azevedo Jr., Lima W.F.D. Halogen atoms in the modern medicinal chemistry: hints for the drug design.Curr. Drug Targets. 2010; 11: 303-314Crossref PubMed Scopus (465) Google Scholar). In organic molecules, replacing a proton by a halide can significantly improve their properties, including solubility, polarity, melting point, stability, binding affinity, selectivity to biological targets, and metabolism. Recently, halogen bonding emerges as a useful tool in both catalyst and drug design (Wilcken et al., 2013Wilcken R. Zimmermann M.O. Lange A. Joerger A.C. Boeckler F.M. Principles and applications of halogen Bonding in medicinal chemistry and chemical biology.J. Med. Chem. 2013; 56: 1363-1388Crossref PubMed Scopus (855) Google Scholar). For example, chloride is normally used as bioisostere of methyl and hydroxyl groups, whereas bromide is frequently used as bioisostere of isopropyl and trifluoromethyl groups. The isotopes of iodide, like 123I and 131I, are widely used in medical setting for imaging, such as iopanoic acid. Meanwhile, as one of the most useful building blocks in organic synthesis, (hetero)aryl halides are broadly utilized in countless transformations like cross-couplings (e.g., Suzuki coupling, Buchwald-Hartwig coupling, Ullman coupling) (Johansson et al., 2012Johansson S.C. Kitching M.O.T.J. Colacot S.V. Palladium-catalyzed cross-coupling: a historical contextual perspective to the 2010 Nobel Prize.Angew. Chem. Int. Ed. 2012; 51: 5062-5085Crossref PubMed Scopus (2063) Google Scholar) (Figure 1A). Conventional approach to introduce halides (Br, Cl, I) on (hetero)arenes heavily relies on electrophilic halogenation with various of reagents, like chlorine, bromine, iodine, NCS, NBS, tBuOCl, and Palau'chlor4 (Rodriguez et al., 2014Rodriguez R.A. Pan C.-M. Yabe Y. Kawamata Y. Eastgate M.D. Baran P.S. Palaúchlor: a practical and reactive chlorinating reagent.J. Am. Chem. Soc. 2014; 136: 6908-6911Crossref PubMed Scopus (125) Google Scholar). Such electrophilic halogenation process, unavoidably, generates another part of molecule as waste, like HBr and succinimide from bromine and NBS, respectively. Besides, they also suffer from being erosive, explosive, or toxic. The Sandmeyer reaction (Kumar et al., 2012Kumar L. Mahajan T. Agarwal D.D. Aqueous bromination method for the synthesis of industrially important intermediates catalyzed by micellar solution of sodium dodecyl sulfate (SDS).Ind. Eng. Chem. Res. 2012; 51: 2227-2234Crossref Scopus (14) Google Scholar) is another commonly used approach to prepare (hetero)aryl halides. However, multiple steps, lots of chemical wastes, and harsh reaction conditions are necessary. Oxidative halogenation serves as an important alternative (Podgoršek et al., 2009Podgoršek A. Zupan M. Iskra J. Oxidative halogenation with “green” oxidants: oxygen and hydrogen peroxide.Angew. Chem. Int. 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The large-scale synthesis (>100g) is also quite challenging for these methods, due to cost-unfriendly reagents, harsh conditions, or difficulties in purification. Halogenation in nature, on the other hand, can be achieved in high selectivity even with complex molecules under mild conditions via utilizing nucleophilic halides by enzymes, like metalloenzymes and flavoenzymes (Latham et al., 2018Latham J. Brandenburger E. Shepherd S.A. Menon B.R.K. Micklefield J. Development of halogenase enzymes for use in synthesis.Chem. Rev. 2018; 118: 232-236Crossref PubMed Scopus (175) Google Scholar, Butler and Sandy, 2009Butler A. Sandy M. Mechanistic considerations of halogenating enzymes.Nature. 2009; 460: 848-854Crossref PubMed Scopus (242) Google Scholar, Gkotsi et al., 2018Gkotsi D.S. Dhaliwal J. McLachlan M.M. Mulholand K.R. Goss R.J.M. Halogenases: powerful tools for biocatalysis (mechanisms application and scope).Curr. Open Chem. 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Exploring the chemistry and biology of vanadium-dependent haloperoxidases.J. Bio. Chem. 2009; 284: 18577-18581Crossref PubMed Scopus (165) Google Scholar), vanadium-catalyzed biomimetic halogenation (de la Rosa et al., 1992de la Rosa R.I. Clague M.J. Butler A. A functional mimic of vanadium bromoperoxidase.J. Am. Chem. Soc. 1992; 114: 760-761Crossref Scopus (109) Google Scholar) has attracted lots of attention. According to the mechanism, a V-η2-peroxy intermediate (V-II) was formed first in the presence of H2O2 and then opened by halide assisted by H-bonding from proximate lysine, yielding an electrophilic hypohalite (OX−, HOX or V-OX, X = Br, Cl, I) captured by (hetero)arenes (Winter and Moore, 2009Winter J.M. Moore B.S. Exploring the chemistry and biology of vanadium-dependent haloperoxidases.J. Bio. Chem. 2009; 284: 18577-18581Crossref PubMed Scopus (165) Google Scholar) (Figure 1C, I). 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However, low pH condition was normally required to maintain the activity of catalysts, and many acid-sensitive functional groups cannot be tolerated. Actually, development of biomimetic halogenation under mild pH is a long-time challenge. Among them, tungsten (W) (Beinker et al., 1998Beinker P. Hanson J.R. Meindl N. Medina I.C.R. Oxidative iodination of aromatic amides using sodium perborate or hydrogen peroxide with sodium tungstate.J. Chem. Res. 1998; 1998: 204-205Crossref Scopus (18) Google Scholar, Sels et al., 1999Sels B. Vos D.D. Buntinx M. Pierard F. Mesmaeker K.-D. Jacobs P. Layered double hydroxides exchanged with tungstate as biomimetic catalysts for mild oxidative bromination.Nature. 1999; 400: 855-857Crossref Scopus (478) Google Scholar, Badetti et al., 2015Badetti E. Romano F. Marchiò L. Taşkesenlioğlu S. Daştan A. Zonta C. Licini G. Effective bromo and chloro peroxidation catalyzed by tungsten(VI) amino triphenolate complexes.Dalton. 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Crystal structure of tripotassium oxodiperoxooxalatovanadate(V) monohydrate.Inorg. Chem. 1975; 14: 1785-1790Crossref Scopus (65) Google Scholar), it is supposed to be a better peroxy electrophile as observed in oxidation of (thiolato)-cobalt (III) complexes (Ghiron and Thompson, 1988Ghiron A.F. Thompson R.C. Kinetic study of the oxygen-transfer reactions from the oxo diperoxo complexes of molybdenum (VI) and tungsten(VI) to (thiolato)- and (sulfenato) cobalt (III) complexes.Inorg. Chem. 1988; 26: 4766-4771Crossref Scopus (56) Google Scholar). Meanwhile, the electrophilicity of W-η2-peroxy, we believe, can be further enhanced by Brønsted or Lewis acid (Kikushima et al., 2010Kikushima K. Moriuchi T. Hirao T. Vanadium-catalyzed oxidative bromination promoted by brønsted acid or Lewis acid.Tetrahedron. 2010; 66: 6906-6911Crossref Scopus (51) Google Scholar), promoting the formation of hypohalous species (W-III, HOX) (Roy and Bhar, 2010Roy S. Bhar S. Sodium tungstate-catalyzed “On-water” synthesis of β-arylvinyl bromides.Green. Chem. Lett. Rev. 2010; 3: 341-347Crossref Scopus (12) Google Scholar). From this perspective, biomimetic W-catalyzed halogenation under mild pH could be possible (Figure 1C, II). Herein, we present such a tungstate-catalyzed, biomimetic oxidative halogenation (Br, Cl, I) of (hetero)arene in a scalable (>100 g), inexpensive, environment- and operation-friendly manner, along with broad substrate scope, diverse functional group tolerance, and good chemo- and regioselectivity (Figure 1D). Initially, aniline 1-1 was selected as model substrate for our hypothesis. After lots of efforts in condition screening, ultimately the desired product 2-1 can be obtained in good yield in the presence of 5 mol % sodium tungstate, 1.1 equivalents of NaBr, and 6.0 equivalents of H2O2 (30% aq.) in EtOH assisted by adding 1.1 equivalents of HOAc (Table 1, entry 1). The reaction still moved on but at a much slower rate without adding HOAc (Table 1, entry 2). Only trace amount of the product can be detected by thin-layer chromatography without catalyst in background reaction (Table 1, entry 3). Polyoxotungstate also worked well in this reaction, with a little bit lower yield (Table 1, entry 4 and 5). Other bromides, like LiBr and KBr, afforded the product 2-1 as well in eroded efficiency (Table 1, entry 6 and 7). Sodium perborate failed to afford any product (Table 1, entry 8). Other protonic solvents, like MeOH, also worked smoothly (Table 1, entry 9). Notably, the reaction went on well even in H2O, although both starting material and product were not well dissolved (Table 1, entry 10). Decreasing the loading of either catalyst or H2O2 evidently reduced the reaction efficiency (Table 1, entry 11-12). Only trace ortho-bromination (2-1B), dibromination (2-1C), and nitroso products (2-1D) were observed in all condition screenings. In addition, no azo or azoxy products were observed (Ke et al., 2019Ke L. Zhu G. Qian H. Xiang G. Chen Q. Chen Z. Catalytic selective oxidative coupling of secondary N-alkylanilines: an approach to azoxyarene.Org. Lett. 2019; 21: 4008-4013Crossref PubMed Scopus (12) Google Scholar), demonstrating good chemo- and regioselectivity of this transformation (Tables 1, see also S1 and S2 and Figure S6).Table 1Condition OptimizationEntryVary from Optimized ConditionYieldaAll the reactions were conducted in 1.0-mmol scale (1-1) for 12 h, isolated yield.Major By-products1None78%–83%2Without HOAc<50% conversion for 3 days3Without Na2WO4-2H2OTraceb2.0 equivalents of HOAc was utilized.4H3O40PW12-xH2O instead of Na2WO4-2H2O64%c1.5 equivalents NaBr and 2.0 equiv. HOAc were utilized.5(NH4)10(H2W12O42)-xH2O instead of Na2WO4-2H2O77%c1.5 equivalents NaBr and 2.0 equiv. HOAc were utilized.6LiBr instead of NaBr66%d1.5 equivalents of NaBr and 2.0 equivalents of HOAc were utilized, and the reactions were conducted at 50°C7KBr instead of NaBr75%d1.5 equivalents of NaBr and 2.0 equivalents of HOAc were utilized, and the reactions were conducted at 50°C8SPB instead of H2O2N.R9MeOH instead of EtOH67%10H2O instead of EtOH67%11Na2WO4-2H2O, 1 mol % instead of 5 mol %67%122.0 equiv H2O2 instead of 6.0 equiv57%N.R, no reactiona All the reactions were conducted in 1.0-mmol scale (1-1) for 12 h, isolated yield.b 2.0 equivalents of HOAc was utilized.c 1.5 equivalents NaBr and 2.0 equiv. HOAc were utilized.d 1.5 equivalents of NaBr and 2.0 equivalents of HOAc were utilized, and the reactions were conducted at 50°C Open table in a new tab N.R, no reaction With the optimized reaction condition at hand, the substrate scope for bromination was investigated as summarized in Table 2. Overall, anilines, phenols, other electronically rich (hetero)arenes, and carbonyl compounds can all afford the bromination products smoothly in moderate to excellent yield. Diverse functional groups were well tolerated, including ester (2-1, 2-3, 2-11, 2-16, 2-20), amide (2-2, 2-12), hydroxy (2-7 to 2-12), nitrone (2-4, 2-10), halogens (2-7, 2-22), morpholine (2-6), methoxy (2-13, 2-14), carboxylic acid (2-9), and ketone (2-15). Good to excellent chemo- and regioselectivity were observed as well. The para-product was favored over ortho-product (e.g., 2-1, 2-2, and 2-6). The unprotected amine groups in anilines remained untouched, even though the azoxy formation could dominate the reaction (Ke et al., 2019Ke L. Zhu G. Qian H. Xiang G. Chen Q. Chen Z. Catalytic selective oxidative coupling of secondary N-alkylanilines: an approach to azoxyarene.Org. Lett. 2019; 21: 4008-4013Crossref PubMed Scopus (12) Google Scholar). Unlike the dimerization and dearomatization frequently encountered under similar conditions (Dewar and Nakaya, 1968Dewar M.J.S. Nakaya T. Oxidaive coupling of phenols.J. Am. Chem. Soc. 1968; 90: 7134-7135Crossref Scopus (140) Google Scholar), the oxidative bromination of phenol still worked smoothly in this reaction. Adding 2.2 equiv NaBr and HOAc, the dibromination products can be easily prepared as well (2-10, 2-11, 2-12) (Figure 2B). Interestingly, only monobromination of 1,3,5-trimethoxy benzene (2-14) was observed without any dibromination product and 1,3-dicarbonyl compounds afforded the α-bromination product.Table 2Substrate Scope of Tungstate-Catalyzed Oxidative Bromination of (Hetero)Arene2-1, 91% (p: o: d = 21:1:1)2-2, 52%2-3, 85% (89%aThe reactions were conducted in H2O with Na2WO4-2H2O (2.5 mol %), NaBr (1.1 equivalent), H2O2 (30 % aq., 1.1 equivalent) and HOAc (1.1 equivalent) (see also Figure S2). in H2O)2-4, 75% (90% brsm)2-5, 69%b5.0-mmol scale.2-6, 57%2-7, 65% (76%aThe reactions were conducted in H2O with Na2WO4-2H2O (2.5 mol %), NaBr (1.1 equivalent), H2O2 (30 % aq., 1.1 equivalent) and HOAc (1.1 equivalent) (see also Figure S2). in H2O)2-8, 54%2-9, 70%2-10, 93%c2.2 mmol NaBr (2.2 equivalents) and HOAc (2.2 equivalents) were utilized.2-11, 86%c2.2 mmol NaBr (2.2 equivalents) and HOAc (2.2 equivalents) were utilized.2-12, 83%c2.2 mmol NaBr (2.2 equivalents) and HOAc (2.2 equivalents) were utilized.2-13, 86%2-14, 98% (92%aThe reactions were conducted in H2O with Na2WO4-2H2O (2.5 mol %), NaBr (1.1 equivalent), H2O2 (30 % aq., 1.1 equivalent) and HOAc (1.1 equivalent) (see also Figure S2). in H2O)2-15, 62% yield2-16, 81%2-17, 74%2-18, 73%2-19, 72%2-2052% (m: d = 5:1)2-21, 38% (79% brsm)2-22, 92%2-23, 79%2-24, 61% (m: d = 2:1)2-25, 33%2-26, 97% (tolfenamic acid)2-27, 74% (sulfapyridine)2-28, 34% (98% brsm)(derived from tyrosine)2-29, 31% (45% brsm)(indole-2-one)2-30, 48% (56% brsm, m: d = 11:1)(estrone)2-31, 83% (by HNMR)(cytidine)2-32, 75% (by NMR, 2:1 rr)(naringin)p, para-bromination product; o, ortho-bromination product; m, mono-bromination; d, dibromination product; rr, regioselective ration; brsm, based on recovered starting material.Unless noted, all the reactions were conducted in 1.0-mmol scale (1) with Na2WO4-2H2O (5 mol %), NaBr (1.1 equivalents), H2O2 (30 % aq., 6.0 equivalents.), HOAc (1.1 equiv.) in EtOH (5.0 mL) at 30°C isolated yield (see also Figure S1).a The reactions were conducted in H2O with Na2WO4-2H2O (2.5 mol %), NaBr (1.1 equivalent), H2O2 (30 % aq., 1.1 equivalent) and HOAc (1.1 equivalent) (see also Figure S2).b 5.0-mmol scale.c 2.2 mmol NaBr (2.2 equivalents) and HOAc (2.2 equivalents) were utilized. Open table in a new tab p, para-bromination product; o, ortho-bromination product; m, mono-bromination; d, dibromination product; rr, regioselective ration; brsm, based on recovered starting material. Unless noted, all the reactions were conducted in 1.0-mmol scale (1) with Na2WO4-2H2O (5 mol %), NaBr (1.1 equivalents), H2O2 (30 % aq., 6.0 equivalents.), HOAc (1.1 equiv.) in EtOH (5.0 mL) at 30°C isolated yield (see also Figure S1). As it is well known, the Lewis basicity of nitrogen (N) could hamper the reaction by coordinating to transition metals as observed in halogenation catalyzed by Pd, Cu, Rh, and Ru (Petrone et al., 2016Petrone D.A. Ye J. Lautens M. Modern transition-metal-catalyzed carbon–halogen bond formation.Chem. Rev. 2016; 116: 8003-8104Crossref PubMed Scopus (399) Google Scholar, Wan et al., 2006Wan X. Ma Z. Li B. Zhang K. Cao S. Zhang S. Shi Z. Highly selective C-H functionalization/halogenation of acetanilide.J. Am. Chem. Soc. 2006; 128: 7416-7417Crossref PubMed Scopus (381) Google Scholar). In addition, heteroarenes bearing strong basic nitrogen (e.g., pyridine, isoquinoline, and quinolone) can form salts with HOAc, leading to a decrease in their nucleophilicity and enhancement of the pH value in the reaction. Surprisingly, the bromination of N-containing heteroarenes still proceeded smoothly in our reaction, including indole (2-16), indole analogs (2-17, 2-18, 2-19), pyrroles (2-20, see also Figure S7), carbazone (2-21), imidazo[1,2-a]pyridine (2-22), pyridine (2-23), isoquinoline (2-24, see also Figure S8), and quinoline (2-25). Actually, the reactions were conducted in neutral condition to some extent for those basic heteroarenes. Of note, no N-oxide products were observed in all tested heteroarenes, indicating excellent chemoselectivity in this reaction. Late-stage bromination of complex molecules, like drug leads and bioactive natural products, is highly appealing, facilitating quick structure-activity relationship studies given the diverse transformations based on aryl bromides. It is reasonable to hypothesize that the selective late-stage bromination of complex molecules can be achieved, considering the good functional group tolerance as observed in previous studies. However, it can be challenging to obtain good chemo- and regioselectivities for substrates bearing multiple reaction sites with slightly different chemical surroundings. Nonetheless, the late-stage bromination of complex molecules was proved to be successful in our reaction. For instance, the slight difference of multiple reactive positions in olfenamic acid (2-26) and sulfapyridine (2-27) could be distinguished, affording the single monobromination products in high yield. Tyrosine (2-28), indole-2-one (2-29), and estrone (2-30, see also Figure S9) also yielded the monobromination products in good chemo- and regioselectivity. It is worth pointing out that the acid-sensitive tert-butylcarbamate group was well tolerated in our reaction, demonstrating that our approach has better functional group tolerance than that of reported HX/oxidant system. Notably, saccharide scaffolds are maintained untouched, as shown in cytidine (2-31, see also Figure S10) and naringin (2–32, see also Figure S11), albeit many oxidant transformations could occur with such multiple unprotected hydroxyl groups. Water is the ideal reaction solvent, from the perspective of cost and environmental concerns. Delightfully, our reaction worked in water as well (see also Table S3), giving comparable results as those in EtOH (2-2, 2-3, 2-7, 2-14). The oxidative chlorination and iodination were also investigated as summarized in Table 3. Noticing that the redox potential of chloride is higher than that of bromide, oxidative chlorination was more challenging. Indeed, unlike the fact that the bromination worked smoothly with NaBr and KBr, no chlorination product was observed in the presence of NaCl or KCl. After tedious efforts in condition optimization, ultimately it was found that BaCl2 could afford the chlorination products in best yield with model substrate 1-1 (see also Tables S4 and S5). Aniline, phenol, other electronically rich (hetero)arenes, and carbonyl compounds all worked well. Good functional group tolerance was observed as well, including ester (2-33, see also Figure S12; 2-40), free aniline (2-33, 2-34), morpholine (2-35, see also Figure S13), halide (2-36, 2-42), alkoxyl (2-37), carboxylic acid (2-38), and ketone (2-39). Compared with bromination, chlorination generally required longer reaction time and higher reaction temperature. Although iodide is easier to be oxidized than bromide, such biomimetic oxidative iodination of (hetero)arenes is scarcely reported (Sels et al., 2005Sels B. Levecque P. Brosius R. De Vos D. Jacobs P. Gammon D.W. Kinfe H.H. A new catalytic route for the oxidative halogenation of cyclic enol ethers using tungstate exchanged on takovite.Adv. Synth. Catal. 2005; 347: 93-104Crossref Scopus (24) Google Scholar). Moreover, the aryl iodide product can potentially be further oxidized into hyperiodide species (Banik et al., 2016Banik S.M. Medley J.W. Jacobsen E.N. Catalytic, asymmetric difluorination of alkenes to generate difluoromethylated stereocenters.Science. 2016; 353: 51-54Crossref PubMed Scopus (201) Google Scholar), leading to undesired by-products. To our delight, such overoxidation was not observed in this reaction (Emmanuvel et al., 2006Emmanuvel L. Shukla R.K. Sudalai A. Gurunath S. Sivaram S. NaIO4/KI/NaCl: a new reagent system for iodination of activated aromatics through in situ generation of iodine monochloride.Tetra. Lett. 2006; 47: 4793-4796Crossref Scopus (53) Google Scholar). Selected substrates were investigated, and all afforded the products in moderate to excellent yield, including aniline (2-43, 2-45), phenol (2-44), and heteroarene (2-46, 2-47). It should be pointed out that the background of iodination worked as well without catalyst. However, the catalyst acceleration was also evident as observed in some substrates, and longer reaction time is required without catalyst (2-45, 2-47).Table 3Substrate Scope of Tungstate-Catalyzed Oxidative Chlorination and Iodination2-33aUnless noted, the chlorination reactions were carried out in 1.0-mmol scale (1) in MeCN (5.0 mL) at 50°C with Na2WO4-2H2O (5 mol %), H2O2 (30% aq. 4.0 equiv.), BaCl2·2H2O (1.2 equiv), and HOAc (1.0 equiv) (see also Figure S3)., 81% (p: o = 2.2: 1)2-34aUnless noted, the chlorination reactions were carried out in 1.0-mmol scale (1) in MeCN (5.0 mL) at 50°C with Na2WO4-2H2O (5 mol %), H2O2 (30% aq. 4.0 equiv.), BaCl2·2H2O (1.2 equiv), and HOAc (1.0 equiv) (see also Figure S3)., 49% (64% brsm)2-35aUnless noted, the chlorination reactions were carried out in 1.0-mmol scale (1) in MeCN (5.0 mL) at 50°C with Na2WO4-2H2O (5 mol %), H2O2 (30% aq. 4.

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· Biochemistry· Organic chemistry· Photochemistry· Combinatorial chemistry· Tungstate· Hydrogen peroxide· Oxidative phosphorylation· Catalysis· Halogenation· Chemistry

Tungstate-Catalyzed Biomimetic Oxidative Halogenation of (Hetero)Arene under Mild Condition-论文阅读讨论-ReadPaper - 轻松读论文 | 专业翻译 | 一键引文 | 图表同屏 (2024)