{"id":7014,"date":"2026-04-01T14:23:28","date_gmt":"2026-04-01T14:23:28","guid":{"rendered":"https:\/\/www.proefschriftmaken.nl\/portfolio\/gabriele-laudadio\/"},"modified":"2026-04-01T14:23:34","modified_gmt":"2026-04-01T14:23:34","slug":"gabriele-laudadio","status":"publish","type":"us_portfolio","link":"https:\/\/www.proefschriftmaken.nl\/en\/portfolio\/gabriele-laudadio\/","title":{"rendered":"Gabriele Laudadio"},"content":{"rendered":"","protected":false},"excerpt":{"rendered":"","protected":false},"author":8,"featured_media":7017,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"footnotes":""},"us_portfolio_category":[45],"class_list":["post-7014","us_portfolio","type-us_portfolio","status-publish","has-post-thumbnail","hentry","us_portfolio_category-new-template"],"acf":{"naam_van_het_proefschift":"New synthetic methods enabled by photochemistry and electrochemistry in flow","samenvatting":"Er is geen Nederlandse samenvatting beschikbaar. De Engelse samenvatting vind je <a href=\"https:\/\/www.proefschriftmaken.nl\/en\/portfolio\/gabriele-laudadio\/\">hier<\/a>.","summary":"The research presented in this thesis focused on the development of new synthetic methods enabled by photochemistry and electrochemistry. The employment of traceless reagents like photons or electrons allows more selective and effective transformations. Furthermore, combining these approaches with continuous-flow technology, acceleration of reaction kinetics and improved selectivity can be achieved.\n\nThe work described in this dissertation can be divided in two main research lines. Firstly, photochemical hydrogen atom transfer (HAT) reactions were discussed. Owing to the powerful combination of decatungstate catalysis with continuous flow technology, methods suitable for C(sp3)\u2013H oxidation reactions and alkylation of Michael acceptors with volatile gases were presented.\n\nIn Chapter 2, a continuous-flow protocol for the aerobic oxidation of both activated and unactivated C(sp3)-H bonds was described. The implementation of a continuous-flow microreactor afforded an enhanced gas-liquid mass transfer between the two immiscible phases, while allowing a safe handling of gaseous reactants, together with a uniform irradiation of the reaction mixture. With this method many natural scaffolds could be selectively oxidized, such as (-)-ambroxide, pregnenolone acetate, (+)-sclareolide and artemisinin.\n\nIn Chapter 3, an innovative and selective photochemical activation of light alkanes was presented. In this chapter, isobutane, propane, ethane and methane were efficiently incorporated to organic molecules (36 examples) via Decatungstate catalysis employing a commercially available photoreactor. High selectivity was observed in the case of isobutane and propane towards the more stabilized radicals.\n\nIn the second part of the thesis, a parallel research line focused on the development of new electrochemical reactions was presented. In this, continuous-flow technology was adopted to overcome some of the major drawbacks currently limiting the reproducibility and the scalability of electrochemical transformations.\n\nIn Chapter 4, a newly designed, undivided-cell electrochemical flow reactor was presented. In particular, the electrochemical cell could be used both in serial and parallel mode thanks to the flexible reactor volume. The continuous-flow system was subsequently assessed in two synthetic transformations, which confirms its versatility and scale-up potential.\n\nNext, in Chapter 5 a selective electrochemical synthesis of sulfoxides, sulfones and disulfides was described. The reaction was solely governed by the applied potential, exhibiting a broad scope and good functional group compatibility. The use of continuous flow allowed to rapidly assess the optimal reaction parameters (e.g. residence time, applied potential), to avoid mass-transfer limitations and to scale the electrochemistry.\n\nAfter this, an environmentally benign electrochemical method which enables the oxidative coupling between thiols and amines was reported in Chapter 6. Sulfonamides could be synthesized by commodity chemicals like thiols, disulfides and amines, and the reaction displays a broad substrate scope and functional group compatibility. In this case, the continuous-flow approach displayed higher selectivity and faster kinetics compared to the corresponding batch reaction.\n\nWith a similar approach, in Chapter 7 a novel synthesis of sulfonyl fluorides was presented. In this chapter thiols or disulfides could be employed as starting materials, and potassium fluoride was used both as fluorine source and supportive electrolyte. Even in this case, continuous-flow reactions showed faster kinetics due to high mass transfer.\n\nFinally, in Chapter 8 a versatile electrochemical synthesis of aziridines was presented. In this chapter, it was observed that a continuous-flow approach could enhance the selectivity towards the desired product compared to the corresponding batch reaction. Moreover, the hydrogen produced at the cathode was efficiently used to reduce the reactive intermediate leading to the corresponding hydroaminated product. The reaction showed a broad scope, with 26 different examples.\n\nIn conclusion, the positive combination of photochemistry and electrochemistry with continuous-flow technology resulted in the development of different methodologies. Nowadays, the chemistry community has already embraced the idea that green approaches like photochemistry and electrochemistry can be dramatically improved by carrying them out in a microenvironment. This can be demonstrated by the rising attention that both academia and fine chemical industries are giving to these important topics. Despite this interest, further improvements to ameliorate the applicability of electrochemical technology are necessary. For example, standardization of batch and flow setups might boost reaction discovery, improving the reproducibility of the results. Reactor designs for divided-cell and photoelectrochemical microreactors might also be explored to open up new chemical possibilities, further reducing the impact of old and energetically non affordable processes.\n\nFrom the chemical point of view, new gas-liquid photochemical hydrogen atom transfer reactions can be investigated, introducing selectively different functional groups starting from strong C(sp3)-H bonds. Moreover, different electrochemical transformations can be studied, from cross coupling reactions to new electrochemical C-H functionalization. In both cases, continuous-flow approaches can accelerate dramatically the discovery and the optimization of novel methodologies, thanks to the limited amount of materials needed for optimization and the improved kinetic profiles. These processes might also be significantly facilitated by the implementation of automated platforms both for photochemical and electrochemical applications in the reactor technology.\n\nList of abbreviations\n\nAc Acetyl\nBDE Bond Dissociation Energy\nBF3\u22c5OEt2 Boron Trifluoride Diethyl Etherate\nBHT 2,6-di-tert-butyl-4-methylphenol\nBu4NClO4 Tetrabutylammonium Perchlorate\nCD3CN Deuterated Acetonitrile\nCDCl3 Deuterated Chloroform\nCE Counter Electrode\nCH3CN Acetonitrile\nCrO3 Chromium Trioxide\nCsF Cesium Fluoride\nCSTR Continuous Stirring Tank Reactor\nDABSO 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide)\nDCM Dichloromethane\nDIY Do-It-Yourself\nDMSO Dimethylsulfoxide\nDT Decatungstate\nEt3N Triethylamine\nEtOAc Ethyl Acetate\nGC-FID Gas Chromatography \u2013 Flame Ionization Detector\nGC-MS Gas Chromatography \u2013 Mass Spectrometry\nH2 Hydrogen\nH2O Water\nH2O2 Water Peroxide\nHAT Hydrogen Atom Transfer\nHCl Hydrochloric Acid\nHFIP 1,1,1,3,3,3-hexafluoro-2-propanol\nHPLC High-Pressure Liquid Chromatography\nHRMS High Resolution Mass Spectrometry\nID Inner diameter\nKF Potassium Fluoride\nKMnO4 Potassium Permanganate\nLC-MS Liquid Chromatography \u2013 Mass Spectrometry\nLED Light Emitting Diode\nm-CPBA meta-chloroperbenzoic Acid\nMe4NBF4 Tetramethylammonium Tetrafluoroborate\nMeOH Methanol\nMFC Mass flow controller\nMgSO4 Magnesium Sulfate\nNaF Sodium Fluoride\nNaIO4 Sodium Periodate\nNFSI N-Fluorobenzenesulfonimide\nNH3 Ammonia\nNMR Nuclear Magnetic Resonance\nO2 Oxygen\nOD Outer diameter\nPd\/C Palladium on Carbon\nPEEK Polyether Ether Ketone\nPFA Perfluoroalkoxy alkane\npRS-SDR Photochemical Rotor-Stator Spinning Disk Reactor\nPTFE Polytetrafluoroethylene\nPy Pyridine\nRE Reference Electrode\nrt Room Temperature\nSCE Saturated Calomel Electrode\nSET Single Electron Transfer\nSI Supporting Information\nSO2 Sulfur Dioxide\nSS Stainless Steel\nSuFEx Sulfur Fluoride Exchange\nTBADT Tetrabutylammonium Decatungstate\nTBAF Tetrabutylammonium Fluoride\nTEMPO 2,2,6,6-Tetramethylpiperidine 1-oxyl\nTFA Trifluoroacetic Acid\nTFDO Methyl(trifluoromethyl) dioxirane\nTiO2 Titanium Oxide\nTLC Thin Layer Chromatography\ntR Residence Time\nTsOH para-toluenesulfonic Acid\nUV Ultraviolet light\nVIS Visible light\nWE Working Electrode\nZnO Zinc Oxide\n\nPublication list\n\nPeer-reviewed articles\n\nPublished\n\n1. No\u00ebl, T.; Cao, Y. and Laudadio, G. The Fundamentals Behind the Use of Flow Reactors in Electrochemistry, Accounts of Chemical Research, 2019, 52 (10), 2858-2869. DOI: 10.1021\/acs.accounts.9b00412 (Highlighted by OPRCD).\n\n2. Laudadio, G.; de Andrade Bartolomeu, A.; Verwijlen, L.M.H.M., Cao, Y., de Oliveira, K. and No\u00ebl, T. Sulfonyl Fluoride Synthesis through Electrochemical Oxidative Coupling of Thiols and Potassium Fluoride. Journal of American Chemical Society, 2019, 141 (30), 11832-11836. DOI: 10.1021\/jacs.9b06126 (Highlighted by Synfacts).\n\n3. Laudadio, G.; Barmptoutis E.; Schotten, C.; Struik, L.; Govaerts, S.; Browne, D.L. and No\u00ebl, T. Sulfonamide Synthesis through Electrochemical Oxidative Coupling of Amines and Thiols. Journal of American Chemical Society, 2019, 141 (14), 5664-5668. DOI: 10.1021\/jacs.9b02266 (Highlighted by OPRCD).\n\n4. Laudadio, G.; de Smet, W.; Struik, L.; Cao, Y. and No\u00ebl, T. Design and application of a modular and scalable electrochemical flow microreactor. Journal of Flow Chemistry, 2018, 8 (3-4), 157-165. DOI: 10.1007\/s41981-018-0024-3.\n\n5. Laudadio, G.; Govaerts, S.; Wang, Y.; Ravelli, D.; Koolman, H; Fagnoni, M.; Djuric, S. and No\u00ebl, T. Selective C(sp3)\u2013H Aerobic Oxidation enabled by Decatungstate Photocatalysis in Flow. Angewandte Chemie International Edition, 2018, 130 (15), 4142-4146. DOI: 10.1002\/anie.201800818.\n\n6. Laudadio, G.; Straathof, N.J.W.; Lanting, M.D.; Knoops, B.; Hessel, V. and No\u00ebl, T. An environmentally benign and selective electrochemical oxidation of sulfides and thiols in a continuous-flow microreactor. Green Chemistry, 2017, 19 (17), 4061-4066. DOI: 10.1039\/C7GC00971D (Selected as Hot Article).\n\n7. Kockmann, N.; Then\u00e9e, P.; Fleischer-Trebes, C.; Laudadio G. and No\u00ebl T. Safety assessment in development and operation of modular continuous-flow processes. Reaction and Chemical Engineering, 2017, 2, 258-280. DOI: 10.1039\/C7RE00021A (RCE Most Read Article, Q3 2017).\n\n* Combined First Authorship\n\nOut of the thesis:\n\n8. Cao, Y.; Adriaenssens, B.; de Andrade Bartolomeu, A.; Laudadio, G.; de Oliveira, K. and No\u00ebl, T. Accelerating Sulfonyl Fluoride Synthesis through Electrochemical Oxidative Coupling of Thiols and Potassium Fluoride in Flow. Journal of Flow Chemistry, 2020, 10, 191-197, 10.1007\/s41981-019-00070-9.\n\n9. Hell, S.H.; Meyer, C.F.; Laudadio, G.; Misale, A.; Willis, M.C.; No\u00ebl, T.; Trabanco, A.A. and Gouverneur, V. Silyl Radical-Mediated Activation of Sulfamoyl Chlorides Enables Direct Access to Aliphatic Sulfonamides from Alkenes. Journal of American Chemical Society, 2019, 142 (2), 720-725. DOI: 10.1021\/jacs.9b13071.\n\n10. Laudadio, G.; Fusini, G.; Casotti, G.; Evangelisti, C.; Angelici, G. and Carpita, A. Synthesis of Pterostilbene through supported-catalyst promoted Mizoroki-Heck reaction, and its transposition in continuous flow reactor. Journal of Flow Chemistry, 2019, 9 (2), 133-143. DOI: 10.1007\/s41981-019-00033-0.\n\n11. van Schie, M.M.C.H.; Pedroso de Almeida, T.; Laudadio, G.; Tieves, F.; Fern\u00e1ndez-Fueyo, E.; No\u00ebl, T.; Arends, I.W.C.E. and Hollman, F. Biocatalytic synthesis of the Green Note trans-2-hexenal in a continuous-flow microreactor. Beilstein Journal of Organic Chemistry, 2018, 14 (1), 697-703. DOI: 10.3762\/bjoc.14.58.\n\n12. Laudadio, G.; Gemoets, H.P.L.; Hessel, V. and No\u00ebl, T. Flow Synthesis of Diaryliodonium Triflates. Journal of Organic Chemistry, 2017, 82 (22), 11735-11741. DOI: 10.1021\/acs.joc.7b01346 (Highlighted by OPRCD).\n\n13. Gemoets, H.P.L.; Laudadio, G.; Verstraete, K.; Hessel, V. and No\u00ebl, T. A Modular Flow Design for the meta-Selective C\u2013H Arylation of Anilines. Angewandte Chemie International Edition, 2017, 56 (25), 7161-7165. DOI: 10.1002\/anie.201703369.\n\nSubmitted\/In Preparation:\n\n14. Laudadio, G.; Deng, Y.; van der Wal, K.; Ravelli, D.; Nuno, M.; Fagnoni, M.; Guthrie, D.; Sun, Y.; and No\u00ebl, T. C(sp3)\u2013H functionalizations of light hydrocarbons using decatungstate photocatalysis in flow. Submitted.\n\n* Combined First Authorship\n\n15. Oseka, M.; Laudadio, G.; van Leest, N. P.; Dyga, M.; de Andrade Bartolomeu, A.; Goo\u00dfen, L.J.; de Bruin, B.; de Oliveira, K. T. and No\u00ebl, T. Electrochemical Aziridination of Internal Alkenes with non-activated amines in flow. Manuscript in preparation.\n\nBook Chapters:\n\n16. Laudadio, G. and No\u00ebl, T. Flow Chemistry Perspective for C\u2013H Bond Functionalization. Strategies for Palladium-Catalyzed Non-Directed and Directed C\u2013H Bond Functionalization, 2017, 275-288. DOI: 10.1016\/B978-0-12-805254-9.00007-4.\n\n* Combined First Authorship\n\nConference presentations\n\nOral\n\n1. Laudadio, G. and No\u00ebl, T. Photochemical Activation of gaseous alkanes in continuous-flow. The Netherlands\u2019 Catalysis and Chemistry Conference (NCCC), 2nd \u2013 4th March 2020, Noordwijkerhout, The Netherlands.\n\n2. Laudadio, G. and No\u00ebl, T. Combining electrochemical methodology development with flow technology - The best of two worlds? CHemistry as INnovative Science (CHAINS), 10th \u2013 11th December 2019, Veldhoven, The Netherlands.\n\n3. Laudadio, G.; Govaerts, S. and No\u00ebl, T. Photochemical Csp3 Oxidation in a Continuous-Flow Microreactor. CHemistry as INnovative Science (CHAINS), 3rd \u2013 5th December 2018, Veldhoven, The Netherlands.\n\n4. Laudadio, G.; Govaerts, S. and No\u00ebl, T. Photochemical Csp3 Oxidation in a Continuous-Flow Microreactor. The Netherlands\u2019 Catalysis and Chemistry Conference (NCCC), 5th \u2013 7th March 2018, Noordwijkerhout, The Netherlands.\n\nPoster\n\n1. Laudadio, G. and No\u00ebl, T. Electrochemical Sulfonamide Synthesis - Oxidative Coupling of Amines and Thiols. Beilstein Organic Chemistry Symposium 2019 - Electrifying Organic Synthesis, 9th - 11th April 2019, Mainz, Germany.\n\n2. Laudadio, G.; de Smet, W.; Struik, L.; Cao, Y. and No\u00ebl, T. Electrochemical Flow Microreactor - Design and Application. #RSCPoster 2019 (Virtual Conference), 5th March 2019 (Poster Award).\n\n3. Laudadio, G.; Govaerts, S.; and No\u00ebl, T. Selective sp3 C-H Aerobic Oxidation enabled by Decatungstate Photocatalysis in Flow. Photo4Future: Final Symposium on Photochemistry, 12th - 13th November 2019, Eindhoven, The Netherlands.\n\n4. Laudadio, G.; Govaerts, S.; and No\u00ebl, T. Selective sp3 C-H Aerobic Oxidation enabled by Decatungstate Photocatalysis in Flow. Photo4Future: Final Symposium on Photochemistry, 12th - 13th November 2018, Eindhoven, The Netherlands.\n\n5. Laudadio, G.; Govaerts, S.; and No\u00ebl, T. Selective sp3 C-H Aerobic Oxidation enabled by Decatungstate Photocatalysis in Flow. Belgian Organic Synthesis Symposium 2018, 8th - 13th July 2018, Bruxelles, Belgium.\n\n6. Laudadio, G.; Govaerts, S.; and No\u00ebl, T. Selective sp3 C-H Aerobic Oxidation enabled by Decatungstate Photocatalysis in Flow. #RSCPoster 2018 (Virtual Conference), 6th March 2018.\n\n7. Laudadio, G. and No\u00ebl, T. An environmentally benign and selective electrochemical oxidation of sulfides and thiols in a continuous-flow microreactor. Flow Chemistry Europe 2018, 6th - 7th February 2018, Cambridge, United Kingdom.\n\n8. Laudadio, G. and No\u00ebl, T. An environmentally benign and selective electrochemical oxidation of sulfides and thiols in a continuous-flow microreactor. 7th German-Japanese Symposium on Electrochemistry, 14th - 15th September 2017, Mainz, Germany (Poster Award).","auteur":"Gabriele Laudadio","auteur_slug":"gabriele-laudadio","publicatiedatum":"27 mei 2020","taal":"EN","url_flipbook":"https:\/\/ebook.proefschriftmaken.nl\/ebook\/gabrielelaudadio?iframe=true","url_download_pdf":"","url_epub":"","ordernummer":"FTP-202604011420","isbn":"978-90-386-5044-9","doi_nummer":"","naam_universiteit":"Overig","afbeeldingen":7018,"naam_student:":"","binnenwerk":"","universiteit":"Overig","cover":"","afwerking":"","cover_afwerking":"","design":""},"_links":{"self":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/7014","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio"}],"about":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/types\/us_portfolio"}],"author":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/users\/8"}],"replies":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/comments?post=7014"}],"version-history":[{"count":1,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/7014\/revisions"}],"predecessor-version":[{"id":7015,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio\/7014\/revisions\/7015"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media\/7017"}],"wp:attachment":[{"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/media?parent=7014"}],"wp:term":[{"taxonomy":"us_portfolio_category","embeddable":true,"href":"https:\/\/www.proefschriftmaken.nl\/en\/wp-json\/wp\/v2\/us_portfolio_category?post=7014"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}