Redox-Neutral Photocatalytic C−H Carboxylation of Arenes and Styrenes with CO2

•Redox-neutral insertion of CO2 into C─H bonds•Visible-light photoredox catalysis characterized by mild and metal-free conditions•Broad substrate scope for aromatic carboxylations including a gram-scale example•Substrate reactivity and regioselectivity can be assessed based on DFT calculations CO2 is a highly abundant and sustainable carbon source that serves as a feedstock for the biosynthesis of organisms. However, it is also considered a greenhouse gas, therefore, the fixation of CO2 in synthetic processes is of great environmental value. In the field of renewable energy storage and conversion of CO2 into solar fuels, large strides have been made into effective catalytic reductions. However, the need for a stoichiometric reductant is a significant disadvantage for the use of CO2 as a C1 synthon in synthesis, limiting its use. A mild, direct, redox-neutral, and transition-metal-free insertion of CO2 into a C─H bond, as reported here, accomplishes highest energy and atom economy, avoiding pre-functionalization. Using a new mechanistic manifold, the methodology presents a straightforward, sustainable, and atom-efficient alternative to current approaches and paves the way to develop novel applications of CO2 in chemical synthesis. Carbon dioxide (CO2) is an attractive one-carbon (C1) building block in terms of sustainability and abundance. However, its low reactivity limits applications in organic synthesis as typically high-energy reagents are required to drive transformations. Here, we present a redox-neutral C─H carboxylation of arenes and styrenes using a photocatalytic approach. Upon blue-light excitation, the anthrolate anion photocatalyst is able to reduce many aromatic compounds to their corresponding radical anions, which react with CO2 to afford carboxylic acids. High-throughput screening and computational analysis suggest that a correct balance between electron affinity and nucleophilicity of substrates is essential. This novel methodology enables the carboxylation of numerous aromatic compounds, including many that are not tolerated in classical carboxylation chemistry. Over 50 examples of C─H functionalizations using CO2 or ketones illustrate a broad applicability. The method opens new opportunities for the valorization of common arenes and may find application in late-stage C─H carboxylation. Carbon dioxide (CO2) is an attractive one-carbon (C1) building block in terms of sustainability and abundance. However, its low reactivity limits applications in organic synthesis as typically high-energy reagents are required to drive transformations. Here, we present a redox-neutral C─H carboxylation of arenes and styrenes using a photocatalytic approach. Upon blue-light excitation, the anthrolate anion photocatalyst is able to reduce many aromatic compounds to their corresponding radical anions, which react with CO2 to afford carboxylic acids. High-throughput screening and computational analysis suggest that a correct balance between electron affinity and nucleophilicity of substrates is essential. This novel methodology enables the carboxylation of numerous aromatic compounds, including many that are not tolerated in classical carboxylation chemistry. Over 50 examples of C─H functionalizations using CO2 or ketones illustrate a broad applicability. The method opens new opportunities for the valorization of common arenes and may find application in late-stage C─H carboxylation. Photosynthesis, the most important photobiological process on our planet, allows photoautotrophs to store energy in the form of chemical bonds by absorbing sunlight. Driven by that energy, carbon dioxide (CO2) is captured from the atmosphere and serves as a carbon feedstock for the organisms to build up sugars and biomass in the Calvin cycle.1Hou H.J.M. Najafpour M.M. Moore G.F. Allakhverdiev S.I. Photosynthesis: Structures, Mechanisms, and Applications. Springer International Publishing, 2017Crossref Scopus (1) Google Scholar The electrochemical and catalytic dihydrogen reductions of CO2 have been developed in the field of renewable energy storage.2Nitopi S. Bertheussen E. Scott S.B. Liu X. Engstfeld A.K. Horch S. Seger B. Stephens I.E.L. Chan K. Hahn C. et al.Progress and perspectives of electrochemical CO2 reduction on copper in aqueous electrolyte.Chem. Rev. 2019; 119: 7610-7672Crossref PubMed Scopus (1551) Google Scholar, 3Küngas R. Review— electrochemical CO2 reduction for CO production: comparison of low- and high-temperature electrolysis technologies.J. Electrochem. Soc. 2020; 167044508Crossref Scopus (146) Google Scholar, 4Nielsen D.U. Hu X.M. Daasbjerg K. Skrydstrup T. Chemically and electrochemically catalysed conversion of CO2 to CO with follow-up utilization to value-added chemicals.Nat. Catal. 2018; 1: 244-254Crossref Scopus (267) Google Scholar However, the use of CO2 as a C1 building block in organic synthesis has received far less attention, despite resembling the principle of biological carbon fixing process the most.5Liu Q. Wu L. Jackstell R. Beller M. Using carbon dioxide as a building block in organic synthesis.Nat. Commun. 2015; 6: 5933Crossref PubMed Scopus (1397) Google Scholar The high thermodynamic stability and kinetic inertness of CO2 require the use of stoichiometric amounts of reactive reaction partners, such as Grignard reagents or organolithium compounds for chemical conversion.6Correa A. Martín R. Metal-catalyzed carboxylation of organometallic reagents with carbon dioxide.Angew. Chem. Int. Ed. Engl. 2009; 48: 6201-6204Crossref PubMed Scopus (317) Google Scholar Aiming for a better efficiency and an increased atom economy, a variety of catalytic carboxylation methods have been developed. These processes make use of the readily available aryl bromides, which undergo carboxylation with CO2 in the presence of catalytic Pd(OAc)2, as reported by Martín and Correa.7Correa A. Martín R. Palladium-catalyzed direct carboxylation of aryl bromides with carbon dioxide.J. Am. Chem. Soc. 2009; 131: 15974-15975Crossref PubMed Scopus (282) Google Scholar Daugulis showed that Cu(I) catalyzes the carboxylation of aryl iodides.8Tran-Vu H. Daugulis O. Copper-catalyzed carboxylation of aryl iodides with carbon dioxide.ACS Catal. 2013; 3: 2417-2420Crossref Scopus (100) Google Scholar Tsuji and co-workers applied NiCl2(PPh3)2 to carboxylate more inert aryl and vinyl chlorides under 1 atm CO2 at room temperature.9Fujihara T. Nogi K. Xu T. Terao J. Tsuji Y. Nickel-catalyzed carboxylation of aryl and vinyl chlorides employing carbon dioxide.J. Am. Chem. Soc. 2012; 134: 9106-9109Crossref PubMed Scopus (261) Google Scholar The reaction scope was extended to sulfonates,10Liu Y. Cornella J. Martin R. Ni-catalyzed carboxylation of unactivated primary alkyl bromides and sulfonates with CO2.J. Am. Chem. Soc. 2014; 136: 11212-11215Crossref PubMed Scopus (158) Google Scholar ester derivatives,11Correa A. León T. Martin R. Ni-catalyzed carboxylation of C(sp2)- and C(sp3)-O bonds with CO2.J. Am. Chem. Soc. 2014; 136: 1062-1069Crossref PubMed Scopus (238) Google Scholar,12Moragas T. Cornella J. Martin R. Ligand-controlled regiodivergent Ni-catalyzed reductive carboxylation of allyl esters with CO2.J. Am. Chem. Soc. 2014; 136: 17702-17705Crossref PubMed Scopus (143) Google Scholar allylic alcohols,13Mita T. Higuchi Y. Sato Y. Highly regioselective palladium-catalyzed carboxylation of allylic alcohols with CO2.Chemistry. 2015; 21: 16391-16394Crossref PubMed Scopus (72) Google Scholar benzylic ammonium salts,14Moragas T. Gaydou M. Martin R. Nickel-catalyzed carboxylation of benzylic C−N bonds with CO2.Angew. Chem. Int. Ed. Engl. 2016; 55: 5053-5057Crossref PubMed Scopus (163) Google Scholar arylsulfonium salts,15Yanagi T. Somerville R.J. Nogi K. Martin R. Yorimitsu H. Ni-catalyzed carboxylation of C(sp2)–S bonds with CO2: evidence for the multifaceted role of Zn.ACS Catal. 2020; 10: 2117-2123Crossref Scopus (32) Google Scholar and unsaturated hydrocarbons.16Gaydou M. Moragas T. Juliá-Hernández F. Martin R. Site-selective catalytic carboxylation of unsaturated hydrocarbons with CO2 and water.J. Am. Chem. Soc. 2017; 139: 12161-12164Crossref PubMed Scopus (190) Google Scholar, 17Michigami K. Mita T. Sato Y. Cobalt-catalyzed allylic C(sp3)-H carboxylation with CO2.J. Am. Chem. Soc. 2017; 139: 6094-6097Crossref PubMed Scopus (101) Google Scholar, 18Williams C.M. Johnson J.B. Rovis T. Nickel-catalyzed reductive carboxylation of styrenes using CO2.J. Am. Chem. Soc. 2008; 130: 14936-14937Crossref PubMed Scopus (319) Google Scholar, 19Tortajada A. Ninokata R. Martin R. Ni-catalyzed site-selective dicarboxylation of 1,3-dienes with CO2.J. Am. Chem. Soc. 2018; 140: 2050-2053Crossref PubMed Scopus (87) Google Scholar, 20Huguet N. Jevtovikj I. Gordillo A. Lejkowski M.L. Lindner R. Bru M. Khalimon A.Y. Rominger F. Schunk S.A. Hofmann P. Limbach M. Nickel-catalyzed direct carboxylation of olefins with CO2: one-pot synthesis of α,β-unsaturated carboxylic acid salts.Chemistry. 2014; 20: 16858-16862Crossref PubMed Scopus (88) Google Scholar However, all these systems require stoichiometric reducing reagents based on Et2Zn, AlMe3, Mn, and Zn powders or prefunctionalized starting materials.21Yang Y. Lee J.W. Toward ideal carbon dioxide functionalization.Chem. Sci. 2019; 10: 3905-3926Crossref PubMed Scopus (99) Google Scholar Electrical current may also be used to drive reductive carboxylation chemistry. Buckley and co-workers reported the regioselective hydrocarboxylation of styrenes using a non-sacrificial electrode system.22Alkayal A. Tabas V. Montanaro S. Wright I.A. Malkov A.V. Buckley B.R. Harnessing applied potential: selective β-hydrocarboxylation of substituted olefins.J. Am. Chem. Soc. 2020; 142: 1780-1785Crossref PubMed Scopus (55) Google Scholar Ackermann et al. showed that allyl chlorides derived from cinnamyl chloride are carboxylated in the presence of a cobalt catalyst.23Ang N.W.J. de Oliveira J.C.A. Ackermann L. Electroreductive cobalt-catalyzed carboxylation: cross-electrophile electro-coupling with atmospheric CO2.Angew. Chem. Int. Ed. Engl. 2020; 59: 12842-12847Crossref PubMed Scopus (53) Google Scholar Concomitantly, difunctionalizations of alkenes via radical addition and subsequent reduction were reported affording thio-,24Ye J.H. Miao M. Huang H. Yan S.S. Yin Z.B. Zhou W.J. Yu D.G. Visible-light-driven iron-promoted thiocarboxylation of styrenes and acrylates with CO2.Angew. Chem. Int. Ed. Engl. 2017; 56: 15416-15420Crossref PubMed Scopus (158) Google Scholar carbo-,25Wang H. Gao Y. Zhou C. Li G. Visible-light-driven reductive carboarylation of styrenes with CO2 and aryl halides.J. Am. Chem. Soc. 2020; 142: 8122-8129Crossref PubMed Scopus (98) Google Scholar, 26Yatham V.R. Shen Y. Martin R. Catalytic intermolecular dicarbofunctionalization of styrenes with CO2 and radical precursors.Angew. Chem. Int. Ed. Engl. 2017; 56: 10915-10919Crossref PubMed Scopus (173) Google Scholar, 27Hou J. Ee A. Cao H. Ong H.W. Xu J.H. Wu J. Visible-light-mediated metal-free difunctionalization of alkenes with CO2 and silanes or C(sp3)-H alkanes.Angew. Chem. Int. Ed. Engl. 2018; 57: 17220-17224Crossref PubMed Scopus (157) Google Scholar phosphono-,28Fu Q. Bo Z.Y. Ye J.H. Ju T. Huang H. Liao L.L. Yu D.G. Transition metal-free phosphonocarboxylation of alkenes with carbon dioxide via visible-light photoredox catalysis.Nat. Commun. 2019; 10: 3592Crossref PubMed Scopus (110) Google Scholar or silylcarboxylation27Hou J. Ee A. Cao H. Ong H.W. Xu J.H. Wu J. Visible-light-mediated metal-free difunctionalization of alkenes with CO2 and silanes or C(sp3)-H alkanes.Angew. Chem. Int. Ed. Engl. 2018; 57: 17220-17224Crossref PubMed Scopus (157) Google Scholar products. Non-catalytic C(sp2)-H carboxylations typically require stoichiometric amounts of either strong bases, such as NaH29Luo J. Preciado S. Xie P. Larrosa I. Carboxylation of phenols with CO2 at atmospheric pressure.Chemistry. 2016; 22: 6798-6802Crossref PubMed Scopus (50) Google Scholar or LiOtBu,30Yoo W.J. Capdevila M.G. Du X. Kobayashi S. Base-mediated carboxylation of unprotected indole derivatives with carbon dioxide.Org. Lett. 2012; 14: 5326-5329Crossref PubMed Scopus (88) Google Scholar,31Shigeno M. Hanasaka K. Sasaki K. Nozawa-Kumada K. Kondo Y. Direct carboxylation of electron-rich heteroarenes promoted by LiO-tBu with CsF and (18)crown-6.Chemistry. 2019; 25: 3235-3239PubMed Google Scholar or Lewis acids, like AlX3 (X = Br, Cl),32Suzuki Y. Hattori T. Okuzawa T. Miyano S. Lewis acid-mediated carboxylation of fused aromatic compounds with carbon dioxide.Chem. Lett. 2002; 31: 102-103Crossref Scopus (30) Google Scholar, 33Nemoto K. Yoshida H. Suzuki Y. Morohashi N. Hattori T. Beneficial effect of TMSCl in the lewis acid-mediated carboxylation of aromatic compounds with carbon dioxide.Chem. Lett. 2006; 35: 820-821Crossref Scopus (22) Google Scholar, 34Nemoto K. Yoshida H. Egusa N. Morohashi N. Hattori T. Direct carboxylation of arenes and halobenzenes with CO2 by the combined use of AlBr3 and R3SiCl.J. Org. Chem. 2010; 75: 7855-7862Crossref PubMed Scopus (60) Google Scholar, 35Olah G.A. Török B. Joschek J.P. Bucsi I. Esteves P.M. Rasul G. Surya Prakash G.K. Efficient chemoselective carboxylation of aromatics to arylcarboxylic acids with a superelectrophilically activated carbon dioxide-Al2Cl6/Al system.J. Am. Chem. Soc. 2002; 124: 11379-11391Crossref PubMed Scopus (172) Google Scholar Me2AlCl,36Nemoto K. Onozawa S. Egusa N. Morohashi N. Hattori T. Carboxylation of indoles and pyrroles with CO2 in the presence of dialkylaluminum halides.Tetrahedron Lett. 2009; 50: 4512-4514Crossref Scopus (38) Google Scholar and EtAlCl237Nemoto K. Onozawa S. Konno M. Morohashi N. Hattori T. Direct carboxylation of thiophenes and benzothiophenes with the aid of EtAlCl2.Bull. Chem. Soc. Jpn. 2012; 85: 369-371Crossref Scopus (23) Google Scholar,38Tanaka S. Watanabe K. Tanaka Y. Hattori T. EtAlCl2/2,6-disubstituted pyridine-mediated carboxylation of alkenes with carbon dioxide.Org. Lett. 2016; 18: 2576-2579Crossref PubMed Scopus (39) Google Scholar to activate CO2. Transition metal-catalyzed directed C(sp2)–H carboxylation reactions have been reported with Au,39Boogaerts I.I.F. Fortman G.C. Furst M.R.L. Cazin C.S.J. Nolan S.P. Carboxylation of N-H/C-H bonds using N-heterocyclic carbene copper(I) complexes.Angew. Chem. Int. Ed. Engl. 2010; 49: 8674-8677Crossref PubMed Scopus (269) Google Scholar Cu,39Boogaerts I.I.F. Fortman G.C. Furst M.R.L. Cazin C.S.J. Nolan S.P. Carboxylation of N-H/C-H bonds using N-heterocyclic carbene copper(I) complexes.Angew. Chem. Int. Ed. Engl. 2010; 49: 8674-8677Crossref PubMed Scopus (269) Google Scholar,40Zhang L. Cheng J. Ohishi T. Hou Z. Copper-catalyzed direct carboxylation of C-H bonds with carbon dioxide.Angew. Chem. Int. Ed. Engl. 2010; 49: 8670-8673Crossref PubMed Scopus (305) Google Scholar and Rh41Suga T. Mizuno H. Takaya J. Iwasawa N. Direct carboxylation of simple arenes with CO2 through a rhodium-catalyzed C-H bond activation.Chem. Commun. (Camb.). 2014; 50: 14360-14363Crossref PubMed Google Scholar complexes.42Hong J. Li M. Zhang J. Sun B. Mo F. C-H Bond carboxylation with carbon dioxide.ChemSusChem. 2019; 12: 6-39Crossref PubMed Scopus (96) Google Scholar Moreover, direct carboxylation of non-activated C(sp2)-H was reported in molten alkali carbonate salts under elevated temperatures (>200°C) and high CO2 pressure.43Banerjee A. Dick G.R. Yoshino T. Kanan M.W. Carbon dioxide utilization via carbonate-promoted C-H carboxylation.Nature. 2016; 531: 215-219Crossref PubMed Scopus (256) Google Scholar,44Kudo K. Shima M. Kume Y. Ikoma F. Mori S. Sugita N. Carboxylation of cesium 2-naphthoate in the alkali metal molten salts of carbonate and formate with CO2 under high pressure.J. Jpn. Petrol. Inst. 1995; 38: 40-47Crossref Scopus (13) Google Scholar More recently, photoredox catalysis has been applied in the field of carboxylation chemistry. Photocatalytic carboxylation of aryl-45Shimomaki K. Murata K. Martin R. Iwasawa N. Visible-light-driven carboxylation of aryl halides by the combined use of palladium and photoredox catalysts.J. Am. Chem. Soc. 2017; 139: 9467-9470Crossref PubMed Scopus (177) Google Scholar,46Meng Q.Y. Wang S. König B. Carboxylation of aromatic and aliphatic bromides and triflates with CO2 by dual visible-light-nickel catalysis.Angew. Chem. Int. Ed. Engl. 2017; 56: 13426-13430Crossref PubMed Scopus (141) Google Scholar and alkyl-halides46Meng Q.Y. Wang S. König B. Carboxylation of aromatic and aliphatic bromides and triflates with CO2 by dual visible-light-nickel catalysis.Angew. Chem. Int. Ed. Engl. 2017; 56: 13426-13430Crossref PubMed Scopus (141) Google Scholar were the first transformations to be reported, followed by direct C─H carboxylation of alkynes47Hou J. Ee A. Feng W. Xu J.H. Zhao Y. Wu J. Visible-light-driven alkyne hydro-/carbocarboxylation using CO2 via iridium/cobalt dual catalysis for divergent heterocycle synthesis.J. Am. Chem. Soc. 2018; 140: 5257-5263Crossref PubMed Scopus (148) Google Scholar and styrenes.48Meng Q.Y. Wang S. Huff G.S. König B. Ligand-controlled regioselective hydrocarboxylation of styrenes with CO2 by combining visible light and nickel catalysis.J. Am. Chem. Soc. 2018; 140: 3198-3201Crossref PubMed Scopus (129) Google Scholar,49Murata K. Numasawa N. Shimomaki K. Takaya J. Iwasawa N. Construction of a visible light-driven hydrocarboxylation cycle of alkenes by the combined use of Rh(I) and photoredox catalysts.Chem. Commun. (Camb.). 2017; 53: 3098-3101Crossref PubMed Google Scholar These methods utilize a dual catalytic approach consisting of a photocatalyst and an in-situ generated low-valent transition metal complex enabled by an excess amount of a sacrificial electron donor. Visible-light mediated benzylic C─H carboxylation was recently reported by the use of 4CzIPN and an organo-silanethiol hydrogen-atom-transfer (HAT) reagent, which allowed to generate carbanions.50Meng Q.Y. Schirmer T.E. Berger A.L. Donabauer K. König B. Photocarboxylation of benzylic C–H Bonds.J. Am. Chem. Soc. 2019; 141: 11393-11397Crossref PubMed Scopus (134) Google Scholar Direct UV-light excitation of polyaromatic hydrocarbons in the presence of sacrificial amines and CO2 was reported to yield the corresponding carboxylic acids.51Tagaya H. Onuki M. Tomioka Y. Wada Y. Karasu M. Chiba K. Photocarboxylation of naphthalene in the presence of carbon dioxide and an electron donor.Bull. Chem. Soc. Jpn. 1990; 63: 3233-3237Crossref Scopus (13) Google Scholar,52Minabe M. Isozumi K. Kawai K. Yoshida M. An observation on carboxylation of 4H-Cyclopenta[def]phenanthrene.Bull. Chem. Soc. Jpn. 1988; 61: 2063-2066Crossref Google Scholar Jamison employed p-terphenyl, which forms a radical anion upon UV-light excitation in the presence of amines.53Seo H. Liu A. Jamison T.F. Direct β-selective hydrocarboxylation of styrenes with CO2 enabled by continuous flow photoredox catalysis.J. Am. Chem. Soc. 2017; 139: 13969-13972Crossref PubMed Scopus (137) Google Scholar The p-terphenyl radical anion is capable of the kinetically slow one-electron reduction of CO2 to its radical anion, which is used in the hydrocarboxylation of styrenes. Murakami and co-workers employed UV-excited xanthone as HAT reagent in combination with a Cu complex or a Ni catalyst to carboxylate allylic54Ishida N. Masuda Y. Uemoto S. Murakami M. A light/ketone/copper system for carboxylation of allylic C−H bonds of alkenes with CO2.Chemistry. 2016; 22: 6524-6527Crossref PubMed Scopus (103) Google Scholar and benzylic55Ishida N. Masuda Y. Imamura Y. Yamazaki K. Murakami M. Carboxylation of benzylic and aliphatic C-H bonds with CO2 induced by light/ketone/nickel.J. Am. Chem. Soc. 2019; 141: 19611-19615Crossref PubMed Scopus (74) Google Scholar C(sp3)–H, respectively. However, despite the great progress achieved in thermal and photochemical carboxylation methods (Schemes 1 and S20), the efficient redox-neutral carboxylation of C(sp2)–H in arenes, heteroarenes and alkenes remains challenging. Here, we report a mechanistically different catalytic approach in which aromatic compounds are converted into their radical anions by a photoinduced single-electron transfer (SET) from a visible-light excited anthrolate anion. The generated nucleophilic arene radical anions react with CO2 to provide (hetero)aromatic carboxylic- and cinnamic acids. Recently, we showed that upon photoexcitation, the anionic form of commercially available 9-anthrone and derivatives (Scheme S2) readily generate strong reductants capable of activating aryl chlorides.56Schmalzbauer M. Ghosh I. König B. Utilising excited state organic anions for photoredox catalysis: activation of (hetero)aryl chlorides by visible light-absorbing 9-anthrolate anions.Faraday Discuss. 2019; 215: 364-378Crossref PubMed Google Scholar While comparing the reported reduction potentials of various aromatic compounds, we noticed that many arenes lay within the range of the approximated excited state oxidation potential of the strongest photo-reductant 2,3,6,7-tetramethoxyanthracen-9(10H)-one (TMAH) [Eox (TMA⋅/TMA−∗) = −2.92 V versus SCE] shown in that series. We thus envisioned a direct activation of arenes via radical anion formation, which may subsequently react with CO2 to form aromatic carboxylic acids. Strong carbon nucleophiles (e.g., organolithium and -magnesium reagents)57Mutule I. Suna E. Arylzinc species by microwave assisted Grignard formation-transmetallation sequence: application in the Negishi coupling.Tetrahedron. 2005; 61: 11168-11176Crossref Scopus (30) Google Scholar, 58Hussey A.S. The carbonation of Grignard reagent solutions.J. Am. Chem. Soc. 1951; 73: 1364-1365Crossref Scopus (11) Google Scholar, 59Nagaki A. Takahashi Y. Yoshida J. Extremely fast gas/liquid reactions in flow microreactors: carboxylation of short-lived organolithiums.Chemistry. 2014; 20: 7931-7934Crossref PubMed Scopus (69) Google Scholar, 60Polyzos A. O’Brien M. Petersen T.P. Baxendale I.R. Ley S.V. The continuous-flow synthesis of carboxylic acids using CO2 in a tube-in-tube gas permeable membrane reactor.Angew. Chem. Int. Ed. Engl. 2011; 50: 1190-1193Crossref PubMed Scopus (196) Google Scholar or carbanions are well known to react with CO2. By contrast, aromatic radical anions formed in the presence of alkali metal have always been considered poor nucleophiles,61Holy N.L. Reactions of the radical anions and dianions of aromatic hydrocarbons.Chem. Rev. 1974; 74: 243-277Crossref Scopus (297) Google Scholar yet, still showed reactivity toward CO2.62Schlenk W. Bergmann E. Forschungen auf dem gebiete der alkaliorganischen Verbindungen. I. Über produkte der addition von alkalimetal an mehrfache kohlenstoff-kohlenstoff-bindungen.Justus Liebigs Ann. Chem. 1928; 463: 1-97Crossref Scopus (108) Google Scholar,63Walker J.F. Scott N.D. Sodium naphthalene. II. Preparation and properties of dihydronaphthalene dicarboxylic acids.J. Am. Chem. Soc. 1938; 60: 951-955Crossref Scopus (22) Google Scholar With a strongly reducing photoredox catalyst in hand and inspired by early literature reports, we questioned if a similar reactivity of aromatic radical anions toward CO2 can be obtained under much milder photocatalytic conditions. We chose acenaphthene (1a, Scheme 2) as a model substrate and applied the established combination of TMAH as the photocatalyst and cesium carbonate as the base. To our delight, after 18 h of irradiation with a blue LED light and an acidic work-up, the desired carboxylic acid 2a could be isolated in a 37% yield as a single regioisomer. Encouraged by this first result, we run an intensive screening of the reaction conditions (Table 1). During the optimization studies, we observed that the reaction outcome was dependent on the amount of Cs2CO3. The use of less than 3 equivalents of the base led to a significantly lower product yield (entry 2), while more equivalents of Cs2CO3 reduced the yield (entry 3). A lower catalyst loading reduced the overall amount of base required, while the carboxylated product 2a was still obtained in a good yield (entry 4–5). Note that the base is not only necessary for the in-situ activation of the photocatalyst but also to trap the released proton upon re-aromatization and hence to maintain alkaline reaction conditions. K2CO3, although being scarcely soluble in DMSO, was also able to promote the carboxylation reaction and useful product yields were obtained in combination with crown-ether (entry 6). Monitoring the reaction progress over time (Figure S8) showed that the reaction was not complete after 6 h (entry 7). An overpressure of CO2 was found to be beneficial for the reaction outcome (entries 8 and 9). The solubility of CO2 was reported to be higher in DMF compared with DMSO, yet, a better yield was obtained in the latter (entry 10).64Gennaro A. Isse A.A. Vianello E. Solubility and electrochemical determination of CO2 in some dipolar aprotic solvents.Journal of Electroanalytical Chemistry and Interfacial Electrochemistry. 1990; 289: 203-215Crossref Scopus (171) Google Scholar When using green light (535 nm), a reduced product yield was obtained (entry 11), which can be explained by both weaker catalyst absorption and LED radiant flux. Control experiments revealed that all reagents and light are crucial, as no product was detected in the absence of either photocatalyst, cesium carbonate, carbon dioxide, or light (entry 12–15).Table 1Optimized Reaction Conditions and Effects upon DeviationEntryDeviations from Optimized ConditionsYield 2a (%)aProduct yield was determined after acidic work-up by crude 1H-NMR with an internal standard.1None68bCombined isolated yield of four reactions.2Cs2CO3 (2 equiv)37bCombined isolated yield of four reactions.3Cs2CO3 (4 equiv)594TMAH (5 mol %), Cs2CO3 (2 equiv)545TMAH (10 mol %), Cs2CO3 (2 equiv)606cCrown ether 18-crown-6 (1 equiv) was added to the reaction.TMAH (10 mol %), K2CO3 instead of Cs2CO3, 18-crown-64776 h instead of 18 h448no CO2 pressure (1 atm)37911 cm3 CO2 instead of 22 cm34810DMF instead of DMSO3511dRadiant flux is lowered by a factor of eight compared with 455 nm LED (see Supplemental Information).535 nm instead of 455 nm2912no TMAHn.d.13no Cs2CO3n.d.14N2 (1 atm) instead of CO2n.d.15eReaction mixture was stirred in the dark.no lightn.d.Optimized reaction conditions: 1a (0.1 mmol), TMAH (20 mol %) and Cs2CO3 (0.3 mmol) were added to a 5 mL crimp top vial equipped with a stirring bar. The vial was sealed, evacuated and backfilled with CO2 (5×). Degassed, anhydrous DMSO (1 mL) was added via syringe. The septum was further sealed with Parafilm® and gaseous CO2 (22 cm3) was added to the headspace via syringe. While stirring, the reaction was irradiated from the bottom side (blue LED, 455 ± 15 nm) and constant temperature was maintained by an aluminum cooling block and a water-cooling circuit. For the complete optimization table, please see Table S1; Information. n.d., not detected.a Product yield was determined after acidic work-up by crude 1H-NMR with an internal standard.b Combined isolated yield of four reactions.c Crown ether 18-crown-6 (1 equiv) was added to the reaction.d Radiant flux is lowered by a factor of eight compared with 455 nm LED (see Supplemental Information).e Reaction mixture was stirred in the dark. Open table in a new tab Optimized reaction conditions: 1a (0.1 mmol), TMAH (20 mol %) and Cs2CO3 (0.3 mmol) were added to a 5 mL crimp top vial equipped with a stirring bar. The vial was sealed, evacuated and backfilled with CO2 (5×). Degassed, anhydrous DMSO (1 mL) was added via syringe. The septum was further sealed with Parafilm® and gaseous CO2 (22 cm3) was added to the headspace via syringe. While stirring, the reaction was irradiated from the bottom side (blue LED, 455 ± 15 nm) and constant temperature was maintained by an aluminum cooling block and a water-cooling circuit. For the complete optimization table, please see Table S1; Information. n.d., not detected. With the optimized reaction conditions in hand (cf Table 1), we explored the scope of this novel transformation. Naphthalene derivatives were investigated, as their reported potentials are in a feasible range (−2.49 up to −2.65 V versus SCE)65Montalti M. Credi A. Prodi L. Gandolfi M.T. Handbook of Photochemisty.Third Edition. CRC Press, 2006Crossref Google Scholar for reduction by the photocatalyst (Scheme 3). We were pleased to see that unsubstituted as well as substituted naphthalene derivatives were converted to the corresponding aromatic carboxylic acids (2b–2g) and could be isolated in useful yields. The regioselectivity of the reaction was found to be affected by strong electron-donating groups (−OMe 2c, −NMe2 2d) in the C1-position, giving selectively 5-naphthoic acids as single regioisomers. In contrast, the directing effect of electronically neutral substituents (−Me, 2e) was minor and led to a mixture of 4- and 5-naphthoic acids. Remarkably, carboxylation in the C8-position was not observed. Notably, unprotected hydroxyl groups (2f and 2g) were tolerated. Utilizing 1-naphthol (1f) led to the formation of two regioisomers of the corresponding acid in 2- and 4-positions. 2,7-Dihydroxynaphthalene (1g) reacted smoothly under our reaction conditions to yield the corresponding 1-naphthoic acid 2g as a single regioisomer. Quinoline (1h), isoquinoline or quinazoline, although quenching the photoexcited state of the catalyst, failed to yield any product (see Figure S12A). Pleasingly, many other heteroaromatic compounds were suitable substrates for our carboxylation method (Scheme 4). Thiophenes, bearing electron-deficient (3a–3d, 3f, 3i–3k) and -neutral (3e, 3g–3h, 3l–3n) substituents smoothly converted into the corresponding thiophenecarboxylic acids 4a–4n in a good to excellent yield. Remarkably, a broad range of functional groups, including ketones, esters,