Full-Spectrum Fluoromethyl Sulfonation via Modularized Multicomponent Coupling

Abstract

Open AccessCCS ChemistryCOMMUNICATION1 May 2022Full-Spectrum Fluoromethyl Sulfonation via Modularized Multicomponent Coupling Kejie Li, Ming Wang and Xuefeng Jiang Kejie Li Shanghai Key Laboratory of Green Chemistry and Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062 , Ming Wang *Corresponding authors: E-mail Address: [email protected] E-mail Address: [email protected] Shanghai Key Laboratory of Green Chemistry and Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062 and Xuefeng Jiang *Corresponding authors: E-mail Address: [email protected] E-mail Address: [email protected] Shanghai Key Laboratory of Green Chemistry and Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062 State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071 https://doi.org/10.31635/ccschem.021.202100980 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Modular free-assembly construction of mono-, di-, and tri-fluoromethyl sulfones was comprehensively achieved by a combination of halides, a sulfur dioxide surrogate, and halofluorocarbons. The industrial raw material thiourea dioxide served as the sulfur dioxide source, combined with readily available fluorocarbon sources such as 2-bromo-2-fluoroacetate and chlorodifluoromethane (ClCF2H, Freon) employed as fluoromethyl reagents. Notably, four methyl sulfone-containing pharmaceuticals were modified into three types of fluoromethyl sulfones, displaying their great potential for drug discovery via the current strategy. Mechanistic studies further demonstrated that C–F···H–N interactions between thiourea dioxide and halofluorocarbons play a key role in stabilizing monofluoromethyl electrophiles and difluorocarbene species. Download figure Download PowerPoint Introduction Methyl sulfone has been extensively introduced into pharmaceuticals, such as firocoxib, rofecoxib, etoricoxib, and vismodegib, as a key motif for drug function improvement. Fluoromethyl sulfone noticeably improves the lipophilicity, metabolic stability, and biological potency of target drug molecules.1–4 For example, PT2385, which was the first HIF-2α antagonist in clinical trials with a luciferase EC50 of 27 nM, acquired different activities and metabolism via mono-, di-, and tri-fluoromethyl modifications (Scheme 1a).5–8 Therefore, quantity-controlled fluorinated methyl sulfone is in great demand for drug optimization. Conventionally, fluoromethyl sulfones are prepared via oxidation of the corresponding sulfides, originating from odorous and non-ecofriendly thiols.9 Moreover, strong oxidants give rise to low functional group compatibility. Shekhar et al.,10,11 Qing et al.,12 and Hu et al.13,14 pioneered the transition-metal-catalyzed synthesis of mono-, di-, and tri-fluoromethyl sulfone from sodium fluoromethylsulfinates. Although sodium trifluoromethylsulfinate can be easily obtained via a sulfonatodehalogation process from halotrifluoromethanes, and trifluoromethylsulfonyl can be synthesized via chlorideelectrochemical fluorination,15–17 sodium monofluoromethylsulfinate and sodium difluoromethylsulfinate are prepared via the oxidation of fluorinated sulfides and the reduction of functional sulfones18 (Scheme 1b). Strategies for introduction of the same oxygenation state of SO2 into two coupling partners have been intensively studied to improve the step economy and oxidative economy for sulfone synthesis.19–29 Based on the observed effect of sulfur introduction from inorganic salts,30–36 sulfur dioxide surrogates possessing diverse masking groups with disparate properties have been explored for the construction of sulfones.37–45 Thiourea dioxide, an industrial raw material containing urea units as a masking group, is able to release sulfur dioxide anions in the presence of a base. We envisioned the use of thiourea dioxide as both a sulfur dioxide source and a hydrogen bond donor due to the properties of the urea motif. C–F···H–N interactions46–50 between the N–H of thiourea dioxide and the C–F of halofluorocarbons enable fluorinated reagent activation. Herein, we disclose a general construction method for full-spectrum fluoromethyl sulfones via multicomponent cross-coupling of halides, thiourea dioxide, and halofluorocarbons (Scheme 1c). Scheme 1 | (a–c) Construction of full-spectrum fluorinated methyl sulfone. Download figure Download PowerPoint Results and Discussion We commenced multicomponent cross-coupling with 4-iodo-biphenyl 1a, thiourea dioxide, and bromofluoroacetic acid ethyl ester 2 for the construction of monofluoromethyl sulfone 3a. To increase the solubility of sulfur dioxide salts, the phase transfer catalyst tetrabutylammonium hexafluorophosphate was applied. Distinct sulfur dioxide sources were tested, among which only thiourea dioxide led to desired product 3a (Table 1, entries 1–4). This result indicated that the unique masking effect of thiourea dioxide played an important role in this transformation. Due to the release rate of SO2 from thiourea dioxide affected by bases, pH control studies found that cesium carbonate is the optimal choice (entries 5–8). A mixed solvent consisting of N,N-dimethylformamide and dichloroethane was found to improve the conversion (entry 9). Further screening of phase transfer catalysts showed that tetrabutylammonium iodide (TBAI) promoted this transformation (entries 10–13, the optimal conditions were bold values in entry 12). In the absence of a palladium catalyst, no product (NP) was detected (entry 14) (See Supporting Information Tables S1–S2 for details). Table 1 | Conditions Optimizationa Entry "SO2" Source Base Additive Yield (%) 1 DABSO Cs2CO3 nBu4NPF6 Trace 2 Na2S2O5 Cs2CO3 nBu4NPF6 Trace 3 Rongalite Cs2CO3 nBu4NPF6 Trace 4 Thiourea dioxide Cs2CO3 nBu4NPF6 69 5 Thiourea dioxide K2CO3 nBu4NPF6 41 6 Thiourea dioxide Na2CO3 nBu4NPF6 49 7 Thiourea dioxide DIPEA nBu4NPF6 61 8 Thiourea dioxide DABCO nBu4NPF6 27 9b Thiourea dioxide Cs2CO3 nBu4NPF6 78 10b Thiourea dioxide Cs2CO3 TBAB 40 11b Thiourea dioxide Cs2CO3 TBAI 83 (79)c 12b,d Thiourea dioxide Cs2CO3 TBAI 80 (78) c 13b Thiourea dioxide Cs2CO3 — 72 14b,e Thiourea dioxide Cs2CO3 TBAI NP aConditions: 1a (0.2 mmol), thiourea dioxide (0.3 mmol), 2 (0.3 mmol), base (0.4 mmol), additive (0.2 mmol), solvent (1.0 mL), 90 °C, 15 h. bThe solution of 2 in 1 mL of DCE was added. cIsolated yields. dAdditive (0.1 mmol). eIn the absence of PdCl2dppf. DABSO: 1,4-diazabicyclo[2.2.2]octane·bis(sulfur dioxide); DIPEA: N,N-diisopropylethylamine; DABCO: 1,4-diazabicyclo[2.2.2]octane; TBAB: tetrabutylammonium bromide. With the optimized conditions in hand, full-spectrum fluoromethyl sulfonation was systemically studied (Scheme 2), with a comprehensive library of mono-, di-, and tri-fluoromethyl sulfones achieved. A broad range of aryl halides bearing electron-donating or -withdrawing substituents at the para- ( 3a– 3f), meta- ( 3g and 3h), and even ortho- ( 3i) positions was successfully employed in the multicomponent coupling reaction of thiourea dioxide and bromofluoroacetic acid ethyl ester 2a to afford monofluoromethyl sulfone derivatives with good to excellent yields. A gram-scale reaction of 4-iodobiphenyl ( 1a) afforded the desired product 3a with a moderate yield. Benzo[d][1,3]dioxole ( 3j), fluorenyl ( 3k) and naphthyl ( 3l) were well tolerated. This protocol was generally efficient for heteroaryliodide substrates, such as dibenzothiophenyl-, thienyl-, 2-pyridinyl-, 3-pyridinyl-, and quinolyl-derived substrates ( 3m– 3q). Amino acid-derived aryl halides were also compatible with the current transformation ( 3r). Remarkably, 4,4′-diiodo-1,1′-biphenyl underwent double-site monofluoromethyl sulfonation via the current strategy ( 3s), and the structure of 3s was further confirmed via X-ray diffraction analysis.a It should be noted that a decarboxylative process can be readily achieved for accessing monofluoromethyl sulfones with excellent yields ( 3a′, 3k′, and 3j′). Gram-scale decarboxylation of 3a afforded the desired product 3a′ with excellent yield by recrystallization. ClCF2H (Freon), as an abundant industrial raw material,51,52 was considered an ideal difluoromethyl source in this process. A wide range of aryl halides bearing electron-donating or -withdrawing substituents afforded the corresponding difluoromethyl sulfones via this transformation ( 4a– 4i). Fluorenyl, 2-thienyl, 3-thienyl, and quinolyl were compatible in the difluoromethyl sulfonation protocol ( 4j– 4m). Even cholesterol derivatives were amenable to difluoromethyl sulfonation through the current strategy ( 4n). Subsequently, the trifluoromethyl sulfonation process was realized using a Togni reagent.53 Diversified trifluoromethyl sulfones can be accessed with excellent yields, regardless of the presence of electron-donating or -withdrawing substituents ( 5a– 5f). The structure of 5e was further confirmed through X-ray diffraction analysis. Fused rings were proven to be entirely compatible, furnishing the corresponding conjugated trifluoromethyl sulfones ( 5g– 5j). Furthermore, heteroaryl halides, including imidazo[1,2-a]pyridine-, quinolone-, dibenzothiazole-, and pyridine-containing substrates, were applicable to this transformation ( 5k– 5n). Notably, herbicidal motif quinazoline-2,4-diones were compatible, providing the corresponding trifluoromethyl sulfone derivative ( 5o). Scheme 2 | Divergent mono-, di-, and tri-fluoromethyl sulfone construction with a modular strategy. Conditions for –SO2CHFCO2Et: 1 (0.2 mmol), thiourea dioxide (0.3 mmol), BrCFHCO2Et (0.3 mmol), Cs2CO3 (0.4 mmol), PdCl2dppf (10 mol %), TBAI (0.1 mmol), dimethylformamide (DMF) (1 mL)/dichloroethane (DCE) (1 mL), 90 °C for 2 h, and room temperature for 15 h, isolated yields. Conditions for SO2CHF2: 1 (0.2 mmol), thiourea dioxide (0.3 mmol), Cs2CO3 (0.8 mmol), PdCl2dppf (7.5 mol %), DMF (2 mL), H2O (0.3 mL), ClCF2H (3 mL, 2.4 M in DMF), 90 °C, 17.5 h, isolated yields. Conditions for –SO2CF3: 1 (0.2 mmol), thiourea dioxide (0.3 mmol), Togni reagent (0.22 mmol), PdCl2dppf (7.5 mol %), nBu4NPF6 (0.1 mmol), Cs2CO3 (0.4 mmol), TBAI (0.1 mmol), DMF (2 mL), 90 °C for 2.5 h, and room temperature for 1 h, isolated yields. Download figure Download PowerPoint To further demonstrate the practicality and applicability of the full-spectrum fluoromethyl sulfonation protocol, clinically applied methyl-sulfone-containing pharmaceuticals were isostered via the current cross-coupling strategy with fluoromethyl sulfone installation at the final stage, highlighting the attractiveness of this protocol for drug discovery (Scheme 3). The anticancer drug vismodegib with naked amide and pyridine groups was efficiently derivatized to mono-, di-, and tri-fluoromethyl sulfones under the conditions of full-spectrum fluoromethyl sulfonation ( 3aa, 4aa, and 5aa). Late-stage modification of the antiinflammatory drug rofecoxib was conducted through the current transformation method to afford three kinds of fluorinated rofecoxib analogs ( 3ab, 4ab, and 5ab). The SO2 motif was successfully incorporated into a series of pharmaceuticals bearing multiple heteroatom-containing functional groups. The fluorinated derivatives of the antiinflammatory drug firocoxib and the Duchenne muscular dystrophy drug ezutromid were indubitably obtained from the corresponding halides through the current strategy ( 3ac– 5ad). The structures of 4aa and 3ac were further confirmed through X-ray diffraction analysis.a Scheme 3 | Late-stage mono-, di-, and tri-fluoromethyl sulfonation of clinically pharmaceuticals. Download figure Download PowerPoint To reveal the mechanism and excellent compatibility of the multicomponent fluoromethyl sulfonation, control experiments were conducted under the standard conditions (Scheme 4a). First, the reaction of sulfinate salt 6 and bromofluoroacetic acid ethyl ester 2a was conducted under standard conditions. It was found that thiourea dioxide is necessary for the reaction of 6 and 2a (Scheme 4a). A control experiment with sulfinate salt 6 and ClCF2H was conducted in the presence of deuterated water. The difluoromethyl sulfone products were obtained with 76% yield with D/H = 91∶9, which illustrated that ClCF2H may possibly undergo a difluorocarbene intermediate to cooperate with sulfinate salt for difluoromethyl coupling with a quenching process from water (Scheme 4b). The control experiment with sulfinate salt 6 and the Togni reagent afforded trifluoromethyl sulfone product 5a with 81% yield without the addition of thiourea dioxide, which indicated that the nucleophilic substitution process of trifluoromethyl sulfonation was not associated with thiourea dioxide (Scheme 4c). 19F NMR studies found that the addition of thiourea dioxide slightly altered the chemical shift of bromofluoroacetic acid ethyl ester 2a and HCF2Cl but not of the Togni reagent, which further indicated the C–F···H–N interactions between thiourea dioxide and mono- and di-fluoromethyl reagents (Scheme 4d). Thus, the postulated reaction pathway is depicted in Scheme 5. Initially, intermediate 9 was formed via the oxidative addition of an aryl halide with Pd0. Coupling of a sulfur dioxide anion, formed from thiourea dioxide under the control of a base, with intermediate 9 led to intermediate 10, which underwent reductive elimination to afford sulfinate salt intermediate 11. C–F···H–N interactions between thiourea dioxide and bromofluoroacetic acid ethyl ester 2a enhanced the leaving ability of bromide, assisting monofluoromethyl sulfonation of sulfinate salt 11 with 2a to generate the desired monofluoromethyl sulfone 3. Sulfinate salt 11 reacted with the difluorocarbene intermediate stabilized by thiourea dioxide, followed by a protonation process with water to provide difluoromethyl sulfone 4. The direct nucleophilic substitution of sulfinate salt 11 and the Togni reagent furnished trifluoromethyl sulfone 5. Scheme 4 | (a–d) Mechanistic study. Download figure Download PowerPoint Conclusion Modular construction of full-spectrum fluoromethyl sulfones was achieved by facile combination of halides, thiourea dioxide, and halofluorocarbons. Thiourea dioxide served as not only a sulfur dioxide source but also a hydrogen bond donor for the activation of halofluorocarbon substrates. Notably, diverse methyl sulfone-containing drugs can be transformed to the corresponding mono-, di-, and tri-fluoromethyl sulfones via the current multicomponent cross-coupling. Mechanistic studies further demonstrated that the weak C–F⋯H–N interactions between thiourea dioxide and halofluorocarbons play a key role in activation and stabilization. Further drug discovery studies with this protocol are in progress in our laboratory. Scheme 5 | Proposed mechanism. Download figure Download PowerPoint Footnote a CCDC 2056340 ( 3s), 2056343 ( 4a), 2056345 ( 5e), 2056349 ( 4aa) and 2056346 ( 3ac) (see Supporting Information Tables S3–S7) can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif Supporting Information Supplemental Information is available and includes all data supporting the findings of this study. Supplemental Information is also available from the corresponding author upon reasonable request. Conflict of Interest The authors declare no competing financial or nonfinancial interests. Acknowledgments The authors are grateful for financial support provided by the NSFC (nos. 22071057, 21971065, and 21871089), STCSM (nos. 20XD1421500, 20JC1416800, and 18JC1415600), the Innovative Research Team of High-Level Local Universities in Shanghai (no. SSMU-ZLCX20180501), and the Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning. References 1. Ilardi E. A.; Vitaku E.; Njardarson J. T.Data-Mining for Sulfur and Fluorine: An Evaluation of Pharmaceuticals to Reveal Opportunities for Drug Design and Discovery.J. Med. Chem.2014, 57, 2832–2842. Google Scholar 2. Feng M.; Tang B.; Liang S.; Jiang X.Sulfur Containing Scaffolds in Drugs: Synthesis and Application in Medicinal Chemistry.Curr. Top. Med. Chem.2016, 16, 1200–1216. Google Scholar 3. Scott K. A.; Njardarson J. T.Analysis of US FDA-Approved Drugs Containing Sulfur Atoms.Top. Med. Chem.2018, 376, 5. Google Scholar 4. Jiang X."Sulfur Chemistry": Topics in Current Chemistry; Springer: Berlin, 2018. Google Scholar 5. Cho H.; Du X.; Rizzi J. P.; Liberzon E.; Chakraborty A. A.; Gao W.; Carvo I.; Signoretti S.; Bruick R. K.; Josey J. A.; Wallace E. M.; Kaelin W. G.On-Target Efficacy of a HIF-2α Antagonist in Preclinical Kidney Cancer Models.Nature2016, 539, 107–111. Google Scholar 6. Chen W.; Hill H.; Christie A.; Kim M. S.; Holloman E.; Pavia-Jimenez A.; Homayoun F.; Ma Y.; Patel N.; Yell P.; Hao G.; Yousuf Q.; Joyce A.; Pedrosa I.; Geiger H.; Zhang H.; Chang J.; Gardner K. H.; Bruick R. K.; Reeves C.; Hwang T. H.; Courtney K.; Frenkel E.; Sun X.; Zojwalla N.; Wong T.; Rizzi J. P.; Wallace E. M.; Josey J. A.; Xie Y.; Xie X.-J.; Kapur P.; McKay R. M.; Brugarolas J.Targeting Renal Cell Carcinoma with a HIF-2 Antagonist.Nature2016, 539, 112–117. Google Scholar 7. Wallace E. M.; Rizzi J. P.; Han G.; Wehn P. M.; Cao Z.; Du X.; Cheng T.; Czerwinski R. M.; Dixon D. D.; Goggin B. S.; Grina J. A.; Halfmann M. M.; Maddie M. A.; Olive S. R.; Schlachter S. T.; Tan H.; Wang B.; Wang K.; Xie S.; Xu R.; Yang H.; Josey J. A.A Small-Molecule Antagonist of HIF2α Is Efficacious in Preclinical Models of Renal Cell Carcinoma.Cancer Res.2016, 76, 5491–5500. Google Scholar 8. Wehn P. M.; Rizzi J. P.; Dixon D. D.; Grina J. A.; Schlachter S. T.; Wang B.; Xu R.; Yang H.; Du X.; Han G.; Wang K.; Cao Z.; Cheng T.; Czerwinski R. M.; Goggin B. S.; Huang H.; Halfmann M. M.; Maddie M. A.; Morton E. L.; Olive S. R.; Tan H.; Xie S.; Wong T.; Josey J. A.; Wallace E. M.Design and Activity of Specific Hypoxia-Inducible Factor-2α (HIF-2α) Inhibitors for the Treatment of Clear Cell Renal Cell Carcinoma: Discovery of Clinical Candidate (S)-3-((2,2-Difluoro-1-hydroxy-7-(methylsulfonyl)-2,3-dihydro-1H-inden-4-yl)oxy)-5-fluorobenzonitrile (PT2385).J. Med. Chem.2018, 61, 9691–9721. Google Scholar 9. González-Núňez M. E.; Mello R.; Royo J.; Ríos J. V.; Asensio G.Mechanism of the Oxidation of Sulfides by Dioxiranes. 1. Intermediacy of a 10-S-4 Hypervalent Sulfur Adduct.J. Am. Chem. Soc.2002, 124, 9154–9163. Google Scholar 10. Cullen S. C.; Shekhar S.; Nere N. K.Cu-Catalyzed Couplings of Aryl Iodonium Salts with Sodium Trifluoromethanesulfinate.J. Org. Chem.2013, 78, 12194–12201. Google Scholar 11. Smyth L. A.; Phillips E. M.; Chan V. S.; Napolitano J. G.; Henry R.; Shekhar S.Pd-Catalyzed Synthesis of Aryl and Heteroaryl Triflones from Reactions of Sodium Triflinate with Aryl (Heteroaryl) Triflates.J. Org. Chem.2016, 81, 1285–1294. Google Scholar 12. Zhang K.; Xu X.-H.; Qing F.-L.Copper-Promoted Trifluoromethanesulfonylation and Trifluoromethylation of Arenediazonium Tetrafluoroborates with NaSO2CF3.J. Org. Chem.2015, 80, 7658–7665. Google Scholar 13. Xing B.; Ni C.; Hu J.Copper-Mediated Di- and Monofluoromethanesulfonylation of Arenediazonium Tetrafluoroborates: Probing the Fluorine Effect.Chin. J. Chem.2018, 36, 206–212. Google Scholar 14. He Z.; Tan P.; Ni C.; Hu J.Fluoroalkylative Aryl Migration of Conjugated N-Arylsulfonylated Amides Using Easily Accessible Sodium Di- and Monofluoroalkanesulfinates.Org. Lett.2015, 17, 1838–1841. Google Scholar 15. Liao D.; Liao D.; Sun B.Simple and Green Production Process of Sodium Trifluoromethyl Sulfinate with High Yield. CN 106748916, 2017. Google Scholar 16. Liu L. K.; Chi Y.; Jen K.-Y.Copper-Catalyzed Additions of Sulfonyl Iodides to Simple and Cyclic Alkenes.J. Org. Chem.1980, 45, 406–410. Google Scholar 17. Sakai S.; Morinaka T.; Nanmei T.; Kume K.Purification of Trifluoromethanesulfonyl Fluoride. JP 5169880, 2010. Google Scholar 18. Tordeux M.; Langlois B.; Wakselman C.Reactions of Bromotrifluoromethane and Related Halides. 8. Condensations with Dithionite and Hydroxymethanesulfinate Salts.J. Org. Chem.1989, 54, 2452–2453. Google Scholar 19. Aziz J.; Messaoudi S.; Alami M.; Hamze A.Sulfinate Derivatives: Dual and Versatile Partners in Organic Synthesis.Org. Biomol. Chem.2014, 12, 9743–9759. Google Scholar 20. Emmett E. J.; Willis M. C.The Development and Application of Sulfur Dioxide Surrogates in Synthetic Organic Chemistry.Asian J. Org. Chem.2015, 4, 602–611. Google Scholar 21. Qiu G.; Zhou K.; Gao L.; Wu J.Insertion of Sulfur Dioxide via a Radical Process: An Efficient Route to Sulfonyl Compounds.Org. Chem. Front.2018, 5, 691–705. Google Scholar 22. Hofman K.; Liu N.-W.; Manolikakes G.Radicals and Sulfur Dioxide: A Versatile Combination for the Construction of Sulfonyl-Containing Molecules.Chem. Eur. J.2018, 24, 11852–11863. Google Scholar 23. Qiu G.; Zhou K.; Wu J.Recent Advances in the Sulfonylation of C-H Bonds with the Insertion of Sulfur Dioxide.Chem. Commun.2018, 54, 12561–12569. Google Scholar 24. Ye S.; Qiu G.; Wu J.Inorganic Sulfites as the Sulfur Dioxide Surrogates in Sulfonylation Reactions.Chem. Commun.2019, 55, 1013–1019. Google Scholar 25. Ye S.; Yang M.; Wu J.Recent Advances in Sulfonylation Reactions Using Potassium/Sodium Metabisulfite.Chem. Commun.2020, 56, 4145–4155. Google Scholar 26. Zeng D.; Wang M.; Deng W.-P.; Jiang X.The Same Oxygenation-State Introduction of Hypervalent Sulfur under Transition-Metal-Free Conditions.Org. Chem. Front.2020, 7, Google Scholar Wang M.; Jiang X.The Same Introduction of Hypervalent Sulfur via 21. Google Scholar A.; S. B.; A. C.; of Aryl and Heteroaryl to and Google Scholar Emmett E. J.; B. R.; Willis M. Synthesis of from Aryl and a Sulfur Dioxide A and Chem. Google Scholar J.; Jiang via Commun.2020, Google Scholar Wang M.; Z.; Jiang and Application of as Commun.2019, 10, Google Scholar Li Y.; S. A.; Hu D.; Sun D.; Gao A.; Zhou Y.; Li J.; Jiang with Based on Sulfides by Chem. Google Scholar X.; J.; Jiang Design for Commun.2018, Google Scholar Li Y.; Wang M.; Jiang and with Organic Salts via Dual and 7, Google Scholar X.; Feng M.; Jiang Design of a and to by Chem. 55, Google Scholar Liu H.; Jiang of Simple to Google Scholar Y.; Wang M.; Jiang as a Construction of Google Scholar Li Y.; Chen S.; Wang M.; Jiang to Chem. Google Scholar Y.; Wang M.; Jiang of an Sulfur Dioxide Construction of Chem. Google Scholar Zhang Wang M. Jiang to from and Thiourea Dioxide with Google Scholar Chen S.; Li Y.; Wang M.; Jiang Construction via Sulfur Dioxide Google Scholar Li Y.; Wang M.; Jiang via Coupling of and under Transition-Metal-Free J. Google Scholar Wang M.; J.; Jiang Methyl Construction from Sulfur Dioxide and Methyl 12, Google Scholar Wang M.; Q.; Jiang Construction of through Chem.2018, Google Scholar Wang M.; Chen S.; Jiang of via of Cyclic Google Scholar L.; J. of in Organic 5, Google Scholar V. R.; H.; D.; R.; A.; in the of Am. Chem. Google Scholar M. Y.; J. K.; N. R.; A. W.; M. in and Application to Design of with High Am. Chem. Google Scholar Liu Zhou F.; Wang X.; Zhou of Di- and Trifluoromethyl Fluorine Google Scholar P. A.; J.; J. Fluorine as a and Google Scholar J.; J. as in in the of with Sodium Am. Chem. Google Scholar Feng Z.; An L.; Zhang of by Google Scholar P.; N.; Togni Trifluoromethylation of and and Using Hypervalent Google Scholar Information Chemical authors are grateful for financial support provided by the NSFC (nos. 22071057, 21971065, and 21871089), STCSM (nos. 20XD1421500, 20JC1416800, and 18JC1415600), the Innovative Research Team of High-Level Local Universities in Shanghai (no. SSMU-ZLCX20180501), and the Professor of Special Appointment (Eastern Scholar) at Shanghai Institutions of Higher Learning.

Topics & Concepts