Reductive transformations of substances that are difficult to reduce continue to pose challenges for photoredox catalysis. Promising photoreduction catalysts include flavin and deazaflavin derivatives; however, even their reductive abilities are limited for the range of substrates considered "inert". In this work, we present 5-deazaalloxazines, a new group of deazaflavin analogues that are predisposed to catalyze reductions due to their low reduction potential (down to -1.65 V vs. SCE) even in the ground state. We studied three series of 5-deazaalloxazines ([i] 5-unsubstituted, [ii] 5-aryldeazaalloxazines, and [iii] 5-trifluoromethyl-5-deazaalloxazines) to determine their photophysical and electrochemical properties and their ability to participate in model photoreduction reactions. From 31 compounds, we selected 1,3-dimethyl-7,8-dimethoxy-5-(o-tolyl)-5-deazaalloxazine [3a(o-MePh)], as it showed, among other things, the highest efficiency in photodehalogenation of p-fluoroanisole and was photostable and absorbed in the visible light region, thereby allowing photoreactions using a 400 nm LED. Practical applicability was demonstrated in the C─P coupling reaction of electron-rich aryl halides (including chloroanisoles and p-fluoroanisole) with trimethyl phosphite, providing an arylation reaction to form dimethyl arylphosphonates, and in the release/deprotection of amines from the corresponding tosyl and triflylamides.

Central Laboratories University of Chemistry and Technology Prague Technická 5 Prague 16628 Czech Republic

Department of Molecular Electrochemistry and Catalysis J Heyrovský Institute of Physical Chemistry Czech Academy of Sciences Dolejškova 3 Prague 18223 Czech Republic

Department of Organic Chemistry University of Chemistry and Technology Prague Technická 5 Prague 16628 Czech Republic

Faculty of Chemistry Adam Mickiewicz University Uniwersytetu Poznańskiego 8 Poznań 61 614 Poland

Faculty of Physics and Astronomy Adam Mickiewicz University Uniwersytetu Poznańskiego 2 Poznań 61 614 Poland

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Wang H., Tian Y.‐M., König B., Nat. Rev. Chemistry 2022, 6, 745. PubMed

Pitre S. P., Overman L. E., Chem. Rev. 2022, 122, 1717. PubMed

Holmberg‐Douglas N., Nicewicz D. A., Chem. Rev. 2022, 122, 1925. PubMed PMC

Tian X., Liu Y., Yakubov S., Schütte J., Chiba S., Barham J. P., Chem. Soc. Rev. 2024, 53, 263. PubMed

Liao L.‐L., Song L., Yan S.‐S., Ye J.‐H., Yu D.‐G., Trends in Chemistry 2022, 4, 512.

Ghosh I., Marzo L., Das A., Shaikh R., König B., Acc. Chem. Res. 2016, 49, 1566. PubMed

Das A., Justin Thomas K. R., Chem. Eur. J. 2024, 30, e202400193. PubMed

Ghosh I., Ghosh T., Bardagi J. I., König B., Science 2014, 346, 725. PubMed

MacKenzie I. A., Wang L., Onuska N. P. R., Williams O. F., Begam K., Moran A. M., Dunietz B. D., Nicewicz D. A., Nature 2020, 580, 76. PubMed PMC

Xu J., Cao J., Wu X., Wang H., Yang X., Tang X., Toh R. W., Zhou R., Yeow E. K. L., Wu J., J. Am. Chem. Soc. 2021, 143, 13266. PubMed

Chmiel A. F., Williams O. P., Chernowsky C. P., Yeung C. S., Wickens Z. K., J. Am. Chem. Soc. 2021, 143, 10882. PubMed

Cole J. P., Chen D.‐F., Kudisch M., Pearson R. M., Lim C.‐H., Miyake G. M., J. Am. Chem. Soc. 2020, 142, 13573. PubMed PMC

Glaser F., Kerzig C., Wenger O. S., Angew. Chem. Int. Ed. 2020, 59, 10266. PubMed

Kim H., Kim H., Lambert T. H., Lin S., J. Am. Chem. Soc. 2020, 142, 2087. PubMed PMC

Cowper N. G. W., Chernowsky C. P., Williams O. P., Wickens Z. K., J. Am. Chem. Soc. 2020, 142, 2093. PubMed PMC

Johnston B., Reynolds K. G., Campbell B. M., Li A., Nocera D. G., J. Am. Chem. Soc. 2025. PubMed

Nocera D. G., Zhu Q., Constentin C., Stubbe J., Chem. Sci. 2023, 14, 6876. PubMed PMC

Rieth A. J., Gonzalez M. I., Kudisch B., Nava M., Nocera D. G., J. Am. Chem. Soc. 2021, 143, 14352. PubMed

Pfund B., Wenger O. S., JACS Au 2025, 5, 426; PubMed PMC

Kerzig C., Guo X., Wenger O. S., J. Am. Chem. Soc. 2019, 141, 2122. PubMed

Horsewill S. J., Sharrock K. M. M., Fehér P. P., Woolley J. M., Pápai I., Scott D. J., Angew. Chem. Int. Ed. 2025, 64, e202506701. PubMed PMC

Jin S., Dang H. T., Haug G. C., He R., Nguyen V. D., Nguyen V. T., Arman H. D., Schanze K. S., Larionov O. V., J. Am. Chem. Soc. 2020, 142, 1603. PubMed PMC

Bortolato T., Simionato G., Vayer M., Rosso C., Paoloni L., Benetti E. M., Sartorel A., Lebœuf D., Dell'Amico L., J. Am. Chem. Soc. 2023, 145, 1835. PubMed PMC

Wu S., Schiel F., Melchiorre P., Angew. Chem. Int. Ed. 2023, 62, e202306364. PubMed

Mallik S., Wang H., Matera N., Li B.‐X., Stagni S., Melchiorre P., Angew. Chem. Int. Ed. 2025, 64, e202509770. PubMed PMC

Liu C., Zhang Y., Shang R., Chem 2025, 11, 102359.

Singh V., Singh R., Hazari A. S., Adhikari D., JACS Au 2023, 3, 1213. PubMed PMC

Shen N., Liu C., Zhang X., Shang R., ACS Catal. 2023, 13, 11753.

Halder S., Mandal S., Kundu A., Mandal B., Adhikari D., J. Am. Chem. Soc. 2023, 145, 22403. PubMed

Wang S., Wang H., König B., Chem 2021, 7, 1653.

Li H., Wenger O. S., Angew. Chem. Int. Ed. 2022, 61, e202110491. PubMed PMC

Schmalzbauer M., Marcon M., König B., Angew. Chem. Int. Ed. 2021, 60, 6270. PubMed PMC

Biswas A., Kolb S., Röttger S. H., Das A., Patalag L. J., Dey P. P., Sil S., Maji S., Chakraborty S., Wenger O. S., Bhunia A., Werz D. B., Mandal S. K., Angew. Chem. Int. Ed. 2025, 64, e202416472. PubMed

Pavlovska T., Cibulka R., in Flavin‐Based Catalysis, 2021, pp. 1–27.

Sideri I. K., Voutyritsa E., Kokotos C. G., Org. Biomol. Chem. 2018, 16, 4596. PubMed

Rehpenn A., Walter A., Storch G., Synthesis 2021, 53, 2583.

Iida H., Imada Y., in Flavin‐Based Catalysis, 2021, pp. 125–144.

Fukuda T., Miyake H., Iida H., Org. Lett. 2025, 27, 2885. PubMed

Pokluda A., Zubova E., Chudoba J., Krupička M., Cibulka R., Org. Biomol. Chem. 2023, 21, 2768. PubMed

Takeda A., Okai H., Watabe K., Iida H., J. Org. Chem. 2022, 87, 10372. PubMed

König B., Kümmel S., Svobodová E., Cibulka R., in Physical Sciences Reviews

Srivastava V., Singh P. K., Srivastava A., Singh P. P., RSC Adv. 2021, 11, 14251.

Rackl J. W., Müller A. F., Profyllidou A., Wennemers H., J. Am. Chem. Soc. 2025. PubMed PMC

Lenka B. S., Mishra R. K., Sarkar D., Org. Lett. 2025, 27, 7738. PubMed

Shiogai Y., Oka M., Miyake H., Iida H., Org. Biomol. Chem. 2024, 22, 4450. PubMed

Gary S., Woolley J., Goia S., Bloom S., Chem. Sci. 2024, 15, 11444. PubMed PMC

Walter A., Eisenreich W., Storch G., Angew. Chem. Int. Ed. 2023, 62, e202310634. PubMed

Shen D., Zhong F., Li L., Zhang H., Ren T., Sun C., Wang B., Guo M., Chao M., Fukuzumi S., Org. Chem. Front. 2023, 10, 2653.

Obertík R., Chudoba J., Šturala J., Tarábek J., Ludvíková L., Slanina T., König B., Cibulka R., Chem. Eur. J. 2022, 28, e202202487. PubMed

Cariello M., Dietrich B., Thomson L., Gauci V., Boyer A., Sproules S., Cooke G., Seddon A., Adams D. J., Chemistry 2022, 28, e202201725. PubMed PMC

Pokluda A., Anwar Z., Boguschová V., Anusiewicz I., Skurski P., Sikorski M., Cibulka R., Adv. Synth. Catal. 2021, 363, 4371.

Langschwager T., Storch G., Angew. Chem. Int. Ed. 2025, 64, e202414679. PubMed

Foja R., Walter A., Jandl C., Thyrhaug E., Hauer J., Storch G., J. Am. Chem. Soc. 2022, 144, 4721. PubMed

Prukała D., Zubova E., Svobodová E., Šimková L., Varma N., Chudoba J., Ludvík J., Burdzinski G., Gulaczyk I., Sikorski M., Cibulka R., Chem. Sci. 2025, 16, 11255. PubMed PMC

Pavlovska T., Král Lesný D., Svobodová E., Hoskovcová I., Archipowa N., Kutta R. J., Cibulka R., Chem. Eur. J. 2022, 28, e202200768. PubMed PMC

Graml A., Neveselý T., Jan Kutta R., Cibulka R., König B., Nat. Commun. 2020, 11, 3174. PubMed PMC

Rückel J., Pavlovska T., Gawron M., Cibulka R., Wolf R., Adv. Synth. Catal. 2025, 367, e70005.

Šimková L., Svobodová E., Liška A., Lušpai K, Cibulka R., Ludvík J., Electrochim. Acta 2025, 147520.

Malki W. H., Gouda A. M., Ali H. E. A., Al‐Rousan R., Samaha D., Abdalla A. N., Bustamante J., Abd Elmageed Z. Y., Ali H. I., Eur. J. Med. Chem. 2018, 152, 31. PubMed

Ali H. I., Ashida N., Nagamatsu T., Biorg. Med. Chem. 2008, 16, 922. PubMed

Mahmoud S., Samaha D., Mohamed M. S., Abou Taleb N. A., Elsawy M. A., Nagamatsu T., Ali H. I., Molecules 2020, 25, 2518. PubMed PMC

Wilson J. M., Henderson G., Black F., Sutherland A., Ludwig R. L., Vousden K. H., Robins D. J., Biorg. Med. Chem. 2007, 15, 77. PubMed

Pavlovska T., Weisheitelová I., Pramthaisong C., Sikorski M., Jahn U., Cibulka R., Adv. Synth. Catal. 2023, 365, 4662.

Insinska‐Rak M., Golczak A., Gierszewski M., Anwar Z., Cherkas V., Kwiatek D., Sikorska E., Khmelinskii I., Burdzinski G., Cibulka R., Mrowczynska L., Kolanowski J. L., Sikorski M., Photochem. Photobiol. Sci. 2023, 22, 1655. PubMed

Nishigaki S., Sato J., Shimizu K., Furukawa K., Senga K., Yoneda F., Chem. Pharm. Bull. 1980, 28, 142.

Weisheitelová I., Cibulka R., Sikorski M., Pavlovska T., Beilstein J. Org. Chem. 2024, 20, 1831. PubMed PMC

Dudkin S., Iaroshenko V. O., Sosnovskikh V. Y., Tolmachev A. A., Villinger A., Langer P., Org. Biomol. Chem. 2013, 11, 5351. PubMed

Prukala D., Gierszewski M., Karolczak J., Sikorski M., Phys. Chem. Chem. Phys. 2015, 17, 18729. PubMed

Koziołowa A., Visser N. V., Kozioł J., Szafran M. M., J. of Photochem. Photobiol. A: Chemistry 1996, 93, 157.

Prukała D., Taczkowska M., Gierszewski M., Pędziński T., Sikorski M., J. Fluorescence 2014, 24, 505. PubMed

Greening C., Ahmed F. H., Mohamed A. E., Lee B. M., Pandey G., Warden A. C., Scott C., Oakeshott J. G., Taylor M. C., Jackson C. J., Microbiol.Mol. Biol. Rev. 2016, 80, 451. PubMed PMC

Capaldo L., Ravelli D., Fagnoni M., Chem. Rev. 2022, 122, 1875. PubMed PMC

Chatgilialoglu C., Guerra M., Kaloudis P., Houée‐Lévin C., Marignier J.‐L., Swaminathan V. N., Carell T., Chem. Eur. J. 2007, 13, 8979. PubMed

Obertík R., Ludvíková L., Chudoba J., Cibulka R., ChemCatChem 2025, 17, e202401795.

Becke A. D., J. Chem. Phys. 1993, 98, 5648.

Kendall R. A., Dunning Jr T. H., Harrison R. J., J. Chem. Phys. 1992, 96, 6796.

Frisch M. J., Trucks G. W., Schlegel H. B., Scuseria G. E., Robb M. A., Cheeseman J. R., Scalmani G., Barone V., Petersson G. A., Nakatsuji H., Li X., Caricato M., Marenich A. V., Bloino J., Janesko B. G., Gomperts R., Mennucci B., Hratchian H. P., Ortiz J. V., Izmaylov A. F., Sonnenberg J. L., Williams, Ding F., Lipparini F., Egidi F., Goings J., Peng B., Petrone A., Henderson T., Ranasinghe D., Zakrzewski V. G., Gao J., Rega N., Zheng G., Liang W., Hada M., Ehara M., Toyota K., Fukuda R., Hasegawa J., Ishida M., Nakajima T., Honda Y., Kitao O., Nakai H., Vreven T., Throssell K., Montgomery Jr J. A., Peralta J. E., Ogliaro F., Bearpark M. J., Heyd J. J., Brothers E. N., Kudin K. N., Staroverov V. N., Keith T. A., Kobayashi R., Normand J., Raghavachari K., Rendell A. P., Burant J. C., Iyengar S. S., Tomasi J., Cossi M., Millam J. M., Klene M., Adamo C., Cammi R., Ochterski J. W., Martin R. L., Morokuma K., Farkas O., Foresman J. B., Fox D. J., Wallingford, CT, 2016.

Cowden W. B., Halladay P. K., Cunningham R. B., Hunt N. H., Clark I. A., J. Med. Chem. 1991, 34, 1818. PubMed

vom Stein T., Meuresch M., Limper D., Schmitz M., Hölscher M., Coetzee J., Cole‐Hamilton D. J., Klankermayer J. R., Leitner W., J. Am. Chem. Soc. 2014, 136, 13217. PubMed

Sharma U., Kumar P., Kumar N., Kumar V., Singh B., Adv. Synth. Catal. 2010, 352, 1834.

Goldschmid S. L., Soon Tay N. E., Joe C. L., Lainhart B. C., Sherwood T. C., Simmons E. M., Sezen‐Edmonds M., Rovis T., J. Am. Chem. Soc. 2022, 144, 22409. PubMed

Wei D., Bruneau‐Voisine A., Valyaev D. A., Lugan N., Sortais J.‐B., Chem. Commun. 2018, 54, 4302. PubMed

Kiely‐Collins H. J., Sechi I., Brennan P. E., McLaughlin M. G., Chem. Commun. 2018, 54, 654. PubMed

Rasheed S., Rao D. S., Subramanyam C., Basha S. T., Raju C. N., Synth. Commun. 2014, 44, 2988.