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Advertisement Advertisement Nature Communications * View all journals * Search * Log in * Explore content * About the journal * Publish with us * Sign up for alerts * RSS feed 1. nature 2. nature communications 3. articles 4. article Artificial photosynthesis directed toward organic synthesis Download PDF Download PDF * Article * Open access * Published: 27 February 2025 Artificial photosynthesis directed toward organic synthesis * Shogo Mori ORCID: orcid.org/0000-0002-2535-9293^1, * Riku Hashimoto^2, * Takashi Hisatomi ORCID: orcid.org/0000-0002-5009-2383^3, * Kazunari Domen ORCID: orcid.org/0000-0001-7995-4832^3,4 & * ... * Susumu Saito ORCID: orcid.org/0000-0003-0749-2020^1,2 Show authors Nature Communications volume 16, Article number: 1797 (2025) Cite this article * 10k Accesses * 86 Altmetric * Metrics details Subjects * Artificial photosynthesis * Energy * Heterogeneous catalysis * Synthetic chemistry methodology * Photocatalysis Abstract In nature, plants convert solar energy into chemical energy via water oxidation. Inspired by natural photosynthesis, artificial photosynthesis has been gaining increasing interest in the field of sustainability/green science and technology as a non-natural and thermodynamically endergonic (DGdeg > 0, uphill) solar-energy-driven reaction that uses water as an electron donor and a source material. Among the artificial-photosynthesis processes, inorganic-synthesis reactions via water oxidation, including water splitting and CO[2] -to-fuel conversion, have been attracting much attention. In contrast, the synthesis of high-value functionalized organic compounds via artificial photosynthesis, which we have termed artificial photosynthesis directed toward organic synthesis (APOS), remains a great challenge. Herein, we report a synthetically pioneering and meaningful strategy of APOS, where the carbohydroxylation of C = C double bonds is accomplished via a three-component coupling with H[2] evolution using dual functions of semiconductor photocatalysts, i.e., silver-loaded titanium dioxide (Ag/TiO[2]) and rhodium-chromium-cobalt-loaded aluminum-doped strontium titanate (RhCrCo/SrTiO[3]:Al). 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Based on the characteristic features of naturally occurring photosynthesis, artificial photosynthesis has been defined by Inoue as a non-natural and thermodynamically uphill reaction (DGdeg > 0) driven by solar energy using water as an electron donor and a source material^3,4. Water splitting and CO[2]-to-fuel conversion represent promising artificial photosynthesis approaches in which the starting materials are inorganic compounds such as water and CO[2]^5,6. For a carbon-neutral and sustainable society, the development of chemical transformations of relatively large and functionalized organic compounds to produce value-added chemicals using environmentally friendly methods is essential^7. We use the term, artificial photosynthesis directed toward organic synthesis (APOS), to describe a synthetically useful organic-to-organic transformation meeting all the criteria of artificial photosynthesis (Fig. 1a, right)^8. There are seminal works of endergonic organic synthesis partially meeting the criteria of artificial photosynthesis, where water has rarely been used as an electron donor; and/or synthetic utility has scarcely been discussed in terms of scalability and applicability to structurally complex/pharmaceutically relevant organic substrates^9, 10,11,12,13,14,15,16,17,18. Fig. 1: Overview of this study. figure 1 a Natural photosynthesis (left) and artificial photosynthesis directed toward organic synthesis (APOS) (right, this work). b Radical-to-cation crossover-cascade mechanism of the carbohydroxylation of styrene derivatives in a wasteful manner (previous work) and through clean C-H bond activation with H[2] evolution (this work). LG = leaving group, e.g., AcO^-, N[2] + BF[4]^ -, ArI + BF[4]^-; X^* = heteroatom-centered radical, e.g., ^tBuO^*, ^ iPrO^*; e^- = electron. Full size image The carbohydroxylation of C = C double bonds in styrene derivatives is one of the most powerful and straightforward tools for the one-step construction of highly functionalized alcohols (Fig. 1b)^19, 20,21,22,23. In a representative radical-to-cation crossover-cascade (conversion of a carbon-centered radical to a carbocation) mechanism, the addition of a carbon-centered radical (^*R) to a C = C double bond in a styrene derivative gives a relatively stable benzylic radical intermediate, which is converted to a carbocation. The cationic center intercepts water, affording an alcohol as the three-component coupling product. Although several transition-metal-catalyzed, electrochemical, and photocatalytic methods are available for the carbohydroxylation of styrene derivatives using activated initial radical precursors^24,25,26,27,28 ,29,30,31, the use of the radical precursors with leaving groups (LG [?] H) inevitably leads to the formation of stoichiometric quantities of thermodynamically stable waste (DGdeg < 0, downhill), and some LGs undergo undesirable substitution with nucleophilic water (Fig. 1b, top left)^24. A greener alternative and more attractive strategy for achieving the carbohydroxylation involves C-H bond activation to generate the carbon-centered radicals, in which two electrons and two protons are in total released from organic substrates and water (Fig. 1b, bottom)^32. From the viewpoint of atom economy, the ideal byproduct is H[2], whose molecular weight is no more than 2 g/mol. Furthermore, H[2] is in practice not wasteful and an attractive energy source/carrier because it is nonpolluting and releases a drastic amount of heat or electric energy along with clean water upon its combustion with O[2] (e.g., in a fuel cell)^33. However, in previously reported carbohydroxylation reactions via C-H bond activation, excess amounts of oxidants giving X^* (X^* = heteroatom-centered radical) were used, leading to stoichiometric quantities of energy-poor waste (XH) instead of energy-rich H[2] (Fig. 1b, center left)^34,35,36. These conventional processes become thermodynamically exergonic (DGdeg < 0) because energy is released/ consumed when waste is formed; in other words, not energy-productive. Even though well-designed photocatalytic systems have recently enabled unique dehydrogenative transformations^8,37,38, sunlight has not yet been used, and the role of water as the electron donor as well as the potential scalability of such reactions for organic synthesis remain to be established. We have previously reported that C-H bonds of organic solvents can be activated to cleanly generate carbon-centered radicals through hydrogen-atom transfer (HAT) to an aqueous hydroxyl radical (^*OH), which is oxidatively generated from water on a silver-loaded titanium dioxide (Ag/TiO[2]) photocatalyst under near-UV-light irradiation (Fig. 2a left)^39. Hisatomi and Domen have developed a highly efficient rhodium-chromium-cobalt-loaded aluminum-doped strontium titanate (RhCrCo/SrTiO[3]:Al) photocatalyst for overall water splitting evolving H[2] through water oxidation to O[2] under near-UV- or solar-light irradiation (Fig. 2a right)^40,41,42. Fig. 2: Development of a photocatalytic system based on dual semiconductors. figure 2 a Our previous achievements in organic synthesis (left) and in water splitting (right). b Optimization study. Reaction conditions: 1a (0.1 mmol), 2a (1 mL, 19.0 mmol), H[2]O (100 mL), PC-1 (10.0 mg), PC-2 (10.0 mg), and LiOH (2 mmol) under LED irradiation (l = 365 nm) and an N[2] atmosphere at room temperature for 24 h. The yields of 3aa, 4, and 5 were determined by ^1H NMR analysis (theoretical yield of 5: 50 mmol); H[2] was quantified by mGC-TCD. ^aConversion of 1a: 100%, selectivity to 3aa: 72%, yield of CO[2]: 7 mmol, yield of O[2]: <1 mmol. ^bYield of CO[2]: 22 mmol, yield of O[2]: 24 mmol. Full size image Here, we show a synthetically meaningful and thus potentially scalable example of APOS. Aiming at the three-component, carbohydroxylation reactions via APOS, we propose a redox-efficient dual photocatalytic system of Ag/TiO[2] and RhCrCo/SrTiO[3]:Al involving a stoichiometric oxidant-free multi-redox cascade, starting with the homolytic cleavage of one O-H bond of water to give a ^*OH (oxidation), followed by a homolytic C-H bond scission by the ^*OH (oxidation), a radical-to-cation crossover (oxidation), and H[2] evolution (reduction) (Fig. 1b bottom and 2a). Remarkably, water plays multifunctional roles in this coupling reaction: as a ^*OH source to promote the C-H bond activation, as an electron donor for H [2] evolution, and as a source of the oxygen atom incorporated into the alcohol product (-OH). The reaction proceeds under light irradiated from near-UV LEDs and also from a solar simulator. Density-functional-theory (DFT) calculations suggest that this transformation is thermodynamically uphill (DGdeg > 0: endergonic). The synthetic potential of the present transformation is highlighted by a short synthesis of terfenadine, a pharmaceutically important anti-histamine compound. Results Reaction optimization Our investigations started by exploring various combinations of semiconductor photocatalysts (Fig. 2b, PC-1 and PC-2) for the three-component coupling of a-methyl styrene (1a), acetonitrile (2a), and water to furnish alcohol 3aa and H[2]. Using Ag/TiO[2] in the absence of other photocatalysts afforded 4 as the two-component adduct of 1a and 2a (14%; Entry 1), which is consistent with our previous work^39. Pristine SrTiO[3]:Al in combination with Ag/TiO[2] also gave 4 (4: 15%; Entry 2), whereas RhCr/SrTiO[3]:Al selectively gave three-component-coupling product 3aa with H[2] evolution (3aa: 22%, 4: <1%, H[2]: 90 mmol; Entry 3). Meanwhile, RhCrCo/SrTiO[3]:Al drastically improved the yield of 3aa and H[2], which were obtained along with a small amount of 5, most likely resulting from the dimerization of the benzylic radical intermediate (3aa: 72%, 5: 9%, H [2]: 160 mmol; Entry 4). Although using Pt/TiO[2] instead of RhCrCo/ SrTiO[3]:Al prevented the formation of 4 and promoted the H[2] evolution, 5 was obtained as the major product instead of 3aa (3aa: <10%, 5: 42%, H[2]: 80 mmol; Entry 5). This result suggests that RhCrCo/SrTiO[3]:Al plays a critical role not only in the H[2] evolution but also in the oxidative radical-to-cation crossover from the benzylic radical to the corresponding benzylic cation. Using RhCrCo/SrTiO[3]:Al in the absence of the Ag/TiO[2] photocatalyst, oxidative side reactions of 1a proceeded, affording CO[2] (22 mmol) with H[2] (220 mmol) (Entry 6; Supplementary Figs. 4b and 6). Thus, RhCrCo/SrTiO[3]:Al independently extracts electrons from the organic compounds, causing their oxidative degradation accompanied by the evolution of H[2]. This could partially account for the fact that an excess of H[2] (160 mmol) was detected along with CO[2] (7 mmol) (Fig. 2b, Entry 4; Supplementary Figs. 4a and 5; a more detailed elucidation of the mass balance is shown in Supplementary Fig. 10). Although the products generated via the C-H bond activation of 2a were hardly detected in the absence of Ag/TiO[2] (3aa, 4, and 5: <1%; Entry 6), pristine TiO[2] catalyzed this transformation in combination with RhCrCo/SrTiO[3]:Al, albeit with a relatively low efficiency (3aa: 31%; Entry 7). Accordingly, Ag/TiO[2] is indispensable for the efficient activation of the C-H bond. All these results are consistent with the mechanistic blueprint of the dual photocatalytic semiconductors system (Fig. 2a). Further optimization showed that loading an appropriate amount of Ag on TiO[2] was critical (0.5 wt% Ag; Supplementary Table 1). Moreover, the optimal ratio between Ag/TiO[2] and RhCrCo/SrTiO[3]:Al was determined to be 1:1 (w/w; Supplementary Table 2). Although the three-component coupling also proceeded to some extent under more neutral conditions without base additives, LiOH more effectively promoted the reaction (Supplementary Table 3). The concentration and volume of the aqueous solution of LiOH were optimized (H[2]O: 100 mL, LiOH: 2 mmol; Supplementary Table 4). The positive role of a tiny amount of LiOH is speculated as follows: LiOH provides Li^+ and ^-OH. Referring to a survey of LiOH-promoted (photo)electrochemical water oxidation using cocatalyst-loaded TiO[2] electrodes^43, the adsorption of ^-OH on the TiO[2] photocatalytic surface is enhanced by Li^+ through noncovalent interactions formed as in TiO[2]-OH-Li^+(OH[2])[x] (x = hydration number), and ^-OH would be more easily oxidized to ^*OH^8. In contrast, a larger amount of LiOH would form inorganic salt layers on the TiO[2] surface, which causes the inhibition of adsorption/ activation of organic molecules including 2a on the TiO[2] surface^43 ,44^. A series of control experiments revealed that each photocatalyst, water, N[2] substitution, and near-UV-light irradiation were indispensable (Supplementary Table 5). After the optimization study, the standard conditions shown in Fig. 3 (footnote) were established. Fig. 3: Substrate scope. figure 3 Standard conditions: 1 (0.1 mmol), 2 (1 mL), H[2]O (100 mL), Ag (0.5 wt%)/TiO[2] (10.0 mg), RhCrCo/SrTiO[3]:Al (10.0 mg), LiOH (2 mmol) under LED irradiation (l = 365 nm) and an N[2] atmosphere at room temperature for 24 h. Isolated yield of 3. H[2] was quantified by mGC-TCD. Reaction time: ^a36 h, ^b48 h, ^c72 h, ^d96 h. ^e2a (2 mL), H[2]O (200 mL), LiOH (4 mmol). ^fAg/TiO[2] (20.0 mg), ^ gRhCrCo/SrTiO[3]:Al (20.0 mg). ^h1 mmol scale reaction using two Kessil lamps (l = 370 nm). ^iDetermined by ^1H NMR analysis of the crude mixture. Full size image Substrate scope With the standard conditions in hand, we explored the substrate scope of styrene derivatives (Fig. 3, top and center). In all cases, more than stoichiometric amounts of H[2] were detected (>0.1 mmol) after the reactions. A wide variety of functionalized styrene derivatives is compatible with the present conditions. A relatively electron-rich methyl styrene 1b underwent this transformation more smoothly than electron-deficient derivatives 1c-1f (3ba: 51%; 3ca-3fa: 20-38%). These results suggest that the electron-donating group on the aromatic ring in the benzylic radical intermediate would be thermodynamically advantageous in the radical-to-cation crossover step^45. F, Cl, and Br halogens were well tolerated (3da-3fa: 34-38%). An a,b-nonsubstituted styrene derivative gave the corresponding product in a relatively low yield (3ga: 35%), whereas 1,1-diarylethenes were more suitable substrates (3ha-3na: 44-71%). A reaction on the 1 mmol scale using 1,1-diphenylethylene was also successful (3 ha: 75%; Supplementary Fig. 1). Vinylpyridine and vinylthiophene derivatives as well as a b-methylated styrene derivative gave the products in moderate yield (3oa: 54%; 3pa: 19%; 3qa: 41%). A styrene derivative with a relatively complex structure synthesized from a drug molecule (fenofibrate) using the Wittig reaction was converted into a more functionalized product (3ra: 52%). A fully aliphatic 1,1-dialkylalkene (methylenecyclohexane) also gave the corresponding product, albeit in a low yield (12%, Supplementary Information pages 25). We next investigated the applicability of carbon-centered radical precursors with different C-H bonds (Fig. 3, bottom). Water-miscible organic solvents were well suited to this transformation. The C-H bond functionalization of acetone smoothly furnished an equilibrium mixture of alcohol and cyclic hemiacetal in good yield (3hb + 6: 75%). The C(sp^2)-H bond of acetaldehyde was functionalized smoothly (3hc: 52%). It was also possible to introduce a wide variety of functionalities into the organic frameworks, including cyclic ether ( 3hd, 3he: >70%), amide (3hf: 49%, 3hg: 42%), and carbamide (3hh: 36%) moieties. A relatively hydridic C-H bond of 1,4-dioxane (2 d) was selectively cleaved when 2a was used as a solvent (10 equivalent of 2 d and 190 equivalent of 2a, relative to 1 h) due to the electrophilic nature of ^*OH (3hd: 57%, 3 ha: 17%, Supplementary Table 6)^45. In the case of acetic acid, C-H bond functionalization followed by cyclization gave g-butyrolactone as a minor product (7: 9%), while 8 (16%) and 9 (43%) were obtained as major products via the addition of the O-centered carboxyl radical and the decarboxylatively formed methyl radical to the C = C double bond, respectively. These results suggest significant potential for carboxylic acids to serve as O-centered/C-centered carboxyl and alkyl radical sources in three-component coupling reactions with H[2] evolution^25,26,46,47,48,49,50. In contrast, less polar solvents did not give the two- and three-component coupling products, even though these are structurally similar to the successful ones (Supplementary Table 7). Such a solvent-specific behavior is consistent with our previous C-H bond functionalization reactions using aqueous ^*OH generated from water via Ag/TiO[2] photocatalysis^39. Demonstration of APOS To further illustrate the synthetic potential of this method, the synthesis of terfenadine (10; a histamine H1 receptor antagonist)^51 was performed via the key carbohydroxylation (Fig. 4a and Supplementary Information pages 23-24). The reaction of commercially available 4-tert-butylstyrene (1g, 1 mmol) with 2a and water afforded a mixture of alcohol and ketone as the three-component coupling products (3ga: 32%; 11: 15%). The mixture of 3ga and 11 was subjected to reducing conditions using DIBAL-H to produce the identical cyclic hemiacetal (g-hydroxy aldehyde) intermediate at low temperature. Subsequent reductive amination with amine 12 afforded terfenadine (10 ; 38% over three steps from 1 g). 1,1-Diarylethene 1s with a tethered nucleophilic hydroxy group gave 1,3-dihydroisobenzofuran derivative 13 (39%; Fig. 4b). This intramolecular cyclization, which proceeded via the smooth addition of the tethered alcohol to the benzylic cation, could be useful for the synthesis of bioactive molecules^52. Fig. 4: Demonstration of APOS. figure 4 Demonstration of the synthetic potential of this transformation: a synthesis of terfenadine and b application for cyclization. Meeting the requirements for artificial photosynthesis: c a solar-induced endergonic reaction with H[2] evolution and d H[2]O serving as the oxygen source. e Plausible reaction mechanism; e^- = electron, h^+ = hole. Full size image Finally, to confirm whether the main pathway involving the three-component coupling meets the criteria of artificial photosynthesis^3, several control experiments and theoretical calculations were carried out. The endergonic nature of the reactions was confirmed by means of DFT calculations at the B3LYP/6-31 G(d, p) level (synthesis of 3aa: DGdeg = +60 kJ mol^-1; 3 ha: DGdeg = +77 kJ mol^ -1; Fig. 4c, Supplementary Table 8). The synthesis of 3 ha with H[2] evolution was also realized under irradiation with a xenon-lamp-based solar simulator (Fig. 4c and Supplementary Fig. 2). A labeling experiment using ^18OH[2] almost exclusively furnished ^18O-labeled 3 ha, suggesting that water is the main source of the oxygen atoms incorporated into the alcohol products (Fig. 4d and Supplementary Fig. 3). Overall, the obtained experimental and theoretical results demonstrate that the present transformation can be regarded as an APOS. Plausible mechanism On the basis of the present results and those obtained in our previous studies on the C-H bond functionalization by Ag/TiO[2]^39 and water splitting by RhCrCo/SrTiO[3]:Al^40, a plausible redox-efficient mechanism can be proposed (Fig. 4e). Upon photoexcitation, TiO[2] and SrTiO[3]:Al generate excited electron-hole pairs. The excited electrons and holes of SrTiO[3]:Al are accommodated in RhCr particles and in Co particles on the SrTiO [3]:Al surface, respectively^40. Meanwhile, the excited electrons of TiO[2] are deployed in the Ag particles on TiO[2], and the holes are trapped by water molecules adsorbed on the TiO[2] surface^53. The interfacial water is oxidized to aqueous ^*OH by the holes of TiO[2] (Since this reaction also proceeds in the absence of LiOH, H[2]O is depicted in Fig. 4e). The HAT to ^*OH from a C-H bond of a water-miscible organic molecule (2, R-H) restores water and produces a carbon-centered radical (R^*)^39. After the addition of R^* to the C = C double bond of styrene derivative 1, the resulting benzylic radical is oxidized to the benzylic cation intermediate by the holes in the Co particles on the SrTiO[3]:Al surface, since Ag/TiO[2] can barely oxidize benzylic radicals^39. The nucleophilic attack of water on the carbocation affords three-component coupling product 3. Concurrently, water is oxidized to O[2] by the holes in the Co particle on the SrTiO[3]:Al surface^40. In practice, using RhCrCo/ SrTiO[3]:Al with organic substrates (1a and 2a) and water in the absence of Ag/TiO[2], 24 mmol of O[2] (Supplementary Figs. 4b and 6) was produced, whereas O[2] was hardly detected after the three-component coupling under the standard conditions using the dual system of Ag/TiO[2] and RhCrCo/SrTiO[3]:Al (O[2]: <1 mmol, Supplementary Figs. 4a and 5). This result suggests that O[2] generated via the RhCrCo/SrTiO[3]:Al-promoted water oxidation is consumed by quenching the excited electrons at the Ag particles on the TiO[2] surface, to restore water^54. In this plausible scenario, O[2] functions as a redox mediator (electron shuttle) between two semiconductors^55,56,57, and O[2] does not appear in the APOS scheme shown in Fig. 1a. Another possible product of water oxidation would be hydrogen peroxide; however, it was detected only in negligible quantities in a titration experiment using a titanium-porphyrin complex (Supplementary Fig. 9)^58,59,60,61. Finally, a couple of excited electrons of SrTiO[3]:Al and a couple of protons accumulate and combine on the RhCr particles to produce H[2]. In summary, we developed a photocatalytic system using water by merging the dual functions of Ag/TiO[2] and RhCrCo/SrTiO[3]:Al semiconductors into a one-batch operation for APOS. This system differs from our previously reported organic synthesis based on alcohol (an organic variant of water) splitting to produce aldehydes and H[2] (DGdeg > 0) using an acidic aqueous media, since water was not necessarily an electron and hydrogen source in the latter case^11. The carbohydroxylation of styrene derivatives with H[2] evolution via C-H bond activation is an endergonic reaction induced by simulated solar light, where water plays three roles: as the ^*OH source, as the electron donor, and as the oxygen atom source. It should also be underlined that the round-trip step, from H[2]O to ^*OH (oxidation) and from ^*OH to H[2]O (reduction), is so fast and robust that this redox/HAT catalysis is essentially non-destructive and occurs inexhaustibly by using sufficient water. The chemoselective three-component coupling involves multiple redox/HAT processes to access a useful synthetic intermediate and enabled the rapid and greener synthesis of valuable and rather complex organic frameworks, including a pharmaceutical compound. The high-performance water splitting RhCrCo/SrTiO[3]:Al catalyst was found to be a competent catalyst for the simultaneous H[2] evolution and radical-to-cation crossover in organic synthesis when combined with another semiconductor. The artificial photosynthesis presented here would pave the way for useful green and sustainable organic synthesis methods promoted by semiconductor photocatalysts. Methods An oven-dried Pyrex glass test tube was charged with a magnetic stirrer bar, Ag/TiO[2] (10.0 mg) and RhCrCo/SrTiO[3]:Al (10.0 mg). The vessel was sealed with a rubber septum and placed under nitrogen, and then 1 (0.10 mmol), 2 (1 mL) and an aqueous solution of LiOH (0.02 M, 100 mL) were added (1 that was not volatile was added with photocatalysts). The mixture was sonicated and then stirred under LED irradiation (l = 365 nm). After 24 h, the gas phase was analyzed by mGC-TCD. The reaction mixture was diluted with EtOAc and dried over Na[2]SO[4]. After filtration through a 0.45 mm membrane filter and concentration under reduced pressure (80 mmHg, 40 degC), the crude product was purified by flash column chromatography on silica gel. Data availability The data generated in this study, including experimental procedures and characterization of products, are provided in the Supplementary Information. Data supporting the findings of this manuscript are also available from the corresponding author upon request. References 1. Johnson, M. P. Photosynthesis. Essays in Biochemistry 60, 255-273 (2016). Article PubMed PubMed Central MATH Google Scholar 2. Ulmer, U. et al. Fundamentals and applications of photocatalytic CO[2] methanation. Nat. Commun. 10, 3169 (2019). Article ADS PubMed PubMed Central MATH Google Scholar 3. Kuttassery, F. et al. 1. Artificial photosynthesis sensitized by metal complexes: utilization of a ubiquitous element. Electrochemistry 82, 475-485 (2014). Article CAS Google Scholar 4. Lewis, N. S. & Nocera, D. G. Powering the planet: Chemical challenges in solar energy utilization. Proc. Natl. Acad. Sci. USA. 103, 15729-15735 (2006). Article ADS CAS PubMed PubMed Central MATH Google Scholar 5. Wang, Q. & Domen, K. Particulate photocatalysts for light-driven water splitting: mechanisms, challenges, and design strategies. Chem. Rev. 120, 919-985 (2020). Article CAS PubMed MATH Google Scholar 6. Yoshino, S., Takayama, T., Yamaguchi, Y., Iwase, A. & Kudo, A. CO [2] Reduction using water as an electron donor over heterogeneous photocatalysts aiming at artificial photosynthesis. Acc. Chem. Res. 55, 966-977 (2022). Article CAS PubMed PubMed Central Google Scholar 7. Anastas, P. & Eghbali, N. Green chemistry: principles and practice. Chem. Soc. Rev. 39, 301-312 (2010). Article CAS PubMed MATH Google Scholar 8. Yamauchi, M., Saito, H., Sugimoto, T., Mori, S. & Saito, S. Sustainable organic synthesis promoted on titanium dioxide using coordinated water and renewable energies/resources. Coord. Chem. Rev. 472, 214773 (2022). Article CAS MATH Google Scholar 9. Wang, H., Tian, Y.-M. & Konig, B. Energy- and atom-efficient chemical synthesis with endergonic photocatalysis. Nat. Rev. Chem. 6, 745-755 (2022). Article CAS PubMed MATH Google Scholar 10. Sumin, A. L. & Knowles, R. R. Organic synthesis away from equilibrium: contrathermodynamic transformations enabled by excited-state electron transfer. Acc. Chem. Res. 57, 1827-1838 (2024). Article CAS PubMed MATH Google Scholar 11. Liu, Z., Caner, J., Kudo, A., Naka, H. & Saito, S. Redox-selective generation of aldehydes and H[2] from alcohols under visible light. Chem. Eur. J. 19, 9452-9456 (2013). Article CAS PubMed MATH Google Scholar 12. Masuda, Y., Ishida, N. & Murakami, M. Light-driven carboxylation of o-alkylphenyl ketones with CO[2]. J. Am. Chem. Soc. 137, 14063-14066 (2015). Article CAS PubMed MATH Google Scholar 13. Mifsud, M. et al. Photobiocatalytic chemistry of oxidoreductases using water as the electron donor. Nat. Commun. 5, 3145 (2014). Article ADS PubMed MATH Google Scholar 14. Guo, Y., An, W., Tian, X., Xie, L. & Ren, Y.-L. Coupling photocatalytic overall water splitting with hydrogenation of organic molecules: a strategy for using water as a hydrogen source and an electron donor to enable hydrogenation. Green Chem. 24, 9211-9219 (2022). Article CAS Google Scholar 15. Yuzawa, H. et al. Reaction mechanism of aromatic ring hydroxylation by water over platinum-loaded titanium oxide photocatalyst. J. Phys. Chem. C 116, 25376-25387 (2012). Article CAS MATH Google Scholar 16. Yuzawa, H., Kumagai, J. & Yoshida, H. Reaction mechanism of aromatic ring amination of benzene and substituted benzenes by aqueous ammonia over platinum-loaded titanium oxide photocatalyst. J. Phys. Chem. C 117, 11047-11058 (2013). Article CAS Google Scholar 17. Yuzawa, H. et al. Anti-Markovnikov hydration of alkenes over platinum-loaded titanium oxide photocatalyst. Catal. Sci. Technol. 3, 1739-1749 (2013). Article CAS MATH Google Scholar 18. Park, S., Jeong, J., Fujita, K., Yamamoto, A. & Yoshida, H. Anti-Markovnikov hydroamination of alkenes with aqueous ammonia by metal-loaded titanium oxide photocatalyst. J. Am. Chem. Soc. 142, 12708-12714 (2020). Article CAS PubMed Google Scholar 19. Courant, T. & Masson, G. Recent progress in visible-light photoredox-catalyzed intermolecular 1,2-difunctionalization of double bonds via an ATRA-type mechanism. J. Org. Chem. 81, 6945-6952 (2016). Article CAS PubMed MATH Google Scholar 20. Lan, X.-W., Wang, N.-X. & Xing, Y. Recent advances in radical difunctionalization of simple alkenes. Eur. J. Org. Chem. 39, 5821-5851 (2017). Article MATH Google Scholar 21. Bao, X., Li, J., Jiang, W. & Huo, C. Radical-mediated difunctionalization of styrenes. Synthesis 51, 4507-4530 (2019). Article CAS MATH Google Scholar 22. Sharma, S., Singh, J. & Sharma, A. Visible light assisted radical-polar/polar-radical crossover reactions in organic synthesis. Adv. Synth. Catal. 363, 3146-3169 (2021). Article CAS MATH Google Scholar 23. Cramer, J., Sager, C. P. & Ernst, B. Hydroxyl groups in synthetic and natural-product-derived therapeutics: a perspective on a common functional group. J. Med. Chem. 62, 8915-8930 (2019). Article CAS PubMed MATH Google Scholar 24. Speckmeier, E., Fuchs, P. J. W. & Zeitler, K. A synergistic LUMO lowering strategy using Lewis acid catalysis in water to enable photoredox catalytic, functionalizing C-C cross-coupling of styrenes. Chem. Sci. 9, 7096-7103 (2018). Article CAS PubMed PubMed Central Google Scholar 25. Shibutani, S., Nagao, K. & Ohmiya, H. Organophotoredox-catalyzed three-component coupling of heteroatom nucleophiles, alkenes, and aliphatic redox active esters. Org. Lett. 23, 1798-1803 (2021). Article CAS PubMed Google Scholar 26. Tlahuext-Aca, A., Garza-Sanchez, R. A. & Glorius, F. Multicomponent oxyalkylation of styrenes enabled by hydrogen-bond-assisted photoinduced electron transfer. Angew. Chem. Int. Ed. 56, 3708-3711 (2017). Article Google Scholar 27. Fumagalli, G., Boyd, S. & Greaney, M. F. Oxyarylation and aminoarylation of styrenes using photoredox catalysis. Org. Lett. 15, 4398-4401 (2013). Article CAS PubMed Google Scholar 28. Altmann, L.-M., Zantop, V., Wenisch, P., Diesendorf, N. & Heinrich, M. R. Visible light promoted, catalyst-free radical carbohydroxylation and carboetherification under mild biomimetic conditions. Chem. Eur. J. 27, 2452-2462 (2021). Article CAS PubMed Google Scholar 29. de Souza, E. L. S., Wiethan, C. & Correia, C. R. D. Iron-catalyzed meerwein carbooxygenation of electron-rich olefins: studies with styrenes, vinyl pyrrolidinone, and vinyl oxazolidinone. ACS Omega 4, 18918-18929 (2019). Article PubMed PubMed Central Google Scholar 30. Kindt, S., Wicht, K. & Heinrich, M. R. Thermally induced carbohydroxylation of styrenes with aryldiazonium salts. Angew. Chem. Int. Ed. 55, 8744-8747 (2016). Article CAS MATH Google Scholar 31. Xiong, P. et al. Electrochemically enabled carbohydroxylation of alkenes with H[2]O and organotrifluoroborates. J. Am. Chem. Soc. 140, 16387-16391 (2018). Article CAS PubMed Google Scholar 32. Dalton, T., Faber, T. & Glorius, F. C-H activation: toward sustainability and applications. ACS Cent. Sci. 7, 245-261 (2021). Article CAS PubMed PubMed Central MATH Google Scholar 33. Yue, M. et al. Hydrogen energy systems: a critical review of technologies, applications, trends and challenges. Renew. Sustain. Energy Rev. 146, 111180 (2021). Article MATH Google Scholar 34. Yang, W.-C. et al. Vanadyl species-catalyzed complementary b-oxidative carbonylation of styrene derivatives with aldehydes. Org. Biomol. Chem. 13, 2385-2392 (2015). Article CAS PubMed MATH Google Scholar 35. Zheng, M. et al. Visible-light-driven, metal-free divergent difunctionalization of alkenes using alkyl formates. ACS Catal. 11, 542-553 (2021). Article MATH Google Scholar 36. Ha, T. M., Chatalova-Sazepin, C., Wang, Q. & Zhu, J. Copper-catalyzed formal [2+2+1] heteroannulation of alkenes, alkylnitriles, and water: method development and application to the total synthesis of (+-)-sacidum lignan D. Angew. Chem. Int. Ed. 55, 9249-9252 (2016). Article CAS Google Scholar 37. Wang, H., Gao, X., Lv, Z., Abdelilah, T. & Lei, A. Recent advances in oxidative R^1-H/R^2-H cross-coupling with hydrogen evolution via photo-/electrochemistry. Chem. Rev. 119, 6769-6787 (2019). Article CAS PubMed MATH Google Scholar 38. Qi, M.-Y., Conte, M., Anpo, M., Tang, Z.-R. & Xu, Y.-J. Cooperative coupling of oxidative organic synthesis and hydrogen production over semiconductor-based photocatalysts. Chem. Rev. 121, 13051-13085 (2021). Article CAS PubMed Google Scholar 39. Mori, S. & Saito, S. C(sp^3)-H bond functionalization with styrenes via hydrogen-atom transfer to an aqueous hydroxyl radical under photocatalysis. Green Chem. 23, 3575-3580 (2021). Article CAS MATH Google Scholar 40. Lyu, H. et al. An Al-doped SrTiO[3] photocatalyst maintaining sunlight-driven overall water splitting activity for over 1000 h of constant illumination. Chem. Sci. 10, 3196-3201 (2019). Article CAS PubMed PubMed Central MATH Google Scholar 41. Takata, T. et al. Photocatalytic water splitting with a quantum efficiency of almost unity. Nature 581, 411-414 (2020). Article ADS CAS PubMed MATH Google Scholar 42. Nishiyama, H. et al. Photocatalytic solar hydrogen production from water on a 100 m^2-scale. Nature 598, 304-307 (2021). Article ADS CAS PubMed MATH Google Scholar 43. Ding, C. et al. Abnormal effects of cations (Li^+, Na^+, and K^+) on photoelectrochemical and electrocatalytic water splitting. J. Phys. Chem. B 119, 3560-3566 (2015). Article CAS PubMed MATH Google Scholar 44. Chen, H. Y., Zahraa, O. & Bouchy, M. Inhibition of the adsorption and photocatalytic degradation of an organic contaminant in an aqueous suspension of TiO[2] by inorganic ions. J. Photochem. Photobiol., A 108, 37-44 (1997). Article CAS Google Scholar 45. Garwood, J. J. A., Chen, A. D. & Nagib, D. A. Radical polarity. J. Am. Chem. Soc. 146, 28034-28059 (2024). CAS Google Scholar 46. Xue, Q. et al. Metal-free, n-Bu[4]NI-catalyzed regioselective difunctionalization of unactivated alkenes. ACS Catal. 3, 1365-1368 (2013). Article CAS MATH Google Scholar 47. Prathima, P. S., Maheswari, C. U., Srinivas, K. & Rao, M. M. CuI/ l-proline-catalyzed selective one-step mono-acylation of styrenes and stilbenes. Tetrahedron Lett. 51, 5771-5774 (2010). Article CAS Google Scholar 48. Li, Y., Song, D. & Dong, V. M. Palladium-catalyzed olefin dioxygenation. J. Am. Chem. Soc. 130, 2962-2964 (2008). Article CAS PubMed Google Scholar 49. Zhu, Q. & Nocera, D. G. Photocatalytic hydromethylation and hydroalkylation of olefins enabled by titanium dioxide mediated decarboxylation. J. Am. Chem. Soc. 142, 17913-17918 (2020). Article CAS PubMed MATH Google Scholar 50. Schwarz, J. & Konig, B. Decarboxylative reactions with and without light - a comparison. Green Chem. 20, 323-361 (2018). Article CAS MATH Google Scholar 51. Perlmutter, J. I. et al. Repurposing the antihistamine terfenadine for antimicrobial activity against staphylococcus aureus. J. Med. Chem. 57, 8540-8562 (2014). Article CAS PubMed PubMed Central MATH Google Scholar 52. Ha, T. M., Wang, Q. & Zhu, J. Copper-catalysed cyanoalkylative cycloetherification of alkenes to 1,3-dihydroisobenzofurans: development and application to the synthesis of citalopram. Chem. Commun. 52, 11100-11103 (2016). Article CAS Google Scholar 53. Shirai, K. et al. Effect of water adsorption on carrier trapping dynamics at the surface of anatase TiO[2] nanoparticles. Nano Lett. 16, 1323-1327 (2016). Article ADS CAS PubMed MATH Google Scholar 54. Kanakaraju, D., anak Kutiang, F. D., Lim, Y. C. & Goh, P. S. Recent progress of Ag/TiO[2] photocatalyst for wastewater treatment: doping, co-doping, and green materials functionalization. Appl. Mater. Today 27, 101500 (2022). Article Google Scholar 55. Cheng, Y. et al. Spatiotemporally synchronous oxygen self-supply and reactive oxygen species production on Z-scheme heterostructures for hypoxic tumor therapy. Adv. Mater. 32, 1908109 (2020). Article CAS Google Scholar 56. Nosaka, Y. & Nosaka, A. Y. Generation and detection of reactive oxygen species in photocatalysis. Chem. Rev. 117, 11302-11336 (2017). Article CAS PubMed MATH Google Scholar 57. Maeda, K. Z-Scheme water splitting using two different semiconductor photocatalysts. ACS Catal. 3, 1486-1503 (2013). Article CAS MATH Google Scholar 58. Lachheb, H. et al. Photochemical oxidation of styrene in acetonitrile solution in presence of H[2]O[2], TiO[2]/H[2]O[2] and ZnO/H[2]O[2]. J. Photochem. Photobiol. A 346, 462-469 (2017). Article CAS Google Scholar 59. Li, X., Wang, Q., Lyu, J. & Li, X. Recent investigation on epoxidation of styrene with hydrogen peroxide by heterogeneous catalysis. ChemistrySelect 6, 9735-9768 (2021). Article CAS MATH Google Scholar 60. Yu, W. & Zhao, Z. Catalyst-free selective oxidation of diverse olefins to carbonyls in high yield enabled by light under mild conditions. Org. Lett. 21, 7726-7730 (2019). Article CAS PubMed MATH Google Scholar 61. Matsubara, C., Kawamoto, N. & Takamura, K. Oxo[5,10,15,20-tetra (4-pyridyl)porphyrinato]titanium(IV): an ultra-high sensitivity spectrophotometric reagent for hydrogen peroxide. Analyst 117, 1781-1784 (1992). Download references Acknowledgements This work was partially supported by MEXT/JSPS Grant-in-aid for Early-Career Scientists, Specially Promoted Research, Transformative Research Areas (A): Green Catalysis, and International Leading Research, KAKENHI (Grant # 24K17676 to S.M., 23H05404, 23H04904, and 22K21346 to S.S.). This work was also partially supported by JST CREST (Grant # JPMJCR22L2 to S.S.), Yashima Environment Technology Foundation (to S.M.), Iketani Science and Technology Foundation (to S.M.), The Naito Research Grant (to S.M.), and Foundation of Public Interest of Tatematsu (to S.M.). Author information Authors and Affiliations 1. Integrated Research Consortium on Chemical Sciences, Nagoya University, Chikusa, Nagoya, 464-8602, Japan Shogo Mori & Susumu Saito 2. Graduate School of Science, Nagoya University, Chikusa, Nagoya, 464-8602, Japan Riku Hashimoto & Susumu Saito 3. Research Initiative for Supra-Materials, Interdisciplinary Cluster for Cutting Edge Research, Shinshu University, 4-17-1 Wakasato, Nagano, Nagano, 380-8553, Japan Takashi Hisatomi & Kazunari Domen 4. Office of University Professors, The University of Tokyo, 2-11-16 Yayoi, Bunkyo, Tokyo, 113-8656, Japan Kazunari Domen Authors 1. Shogo Mori View author publications You can also search for this author in PubMed Google Scholar 2. Riku Hashimoto View author publications You can also search for this author in PubMed Google Scholar 3. Takashi Hisatomi View author publications You can also search for this author in PubMed Google Scholar 4. Kazunari Domen View author publications You can also search for this author in PubMed Google Scholar 5. Susumu Saito View author publications You can also search for this author in PubMed Google Scholar Contributions S.M. and S.S. conceived the project. S.M. and R.H. carried out the experiments. S.S., T.H., and K.D. supervise the research. S.M. and S.S. wrote the manuscript with contributions from all other authors. Corresponding author Correspondence to Susumu Saito. Ethics declarations Competing interests The authors declare no competing interests. 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The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/ licenses/by-nc-nd/4.0/. Reprints and permissions About this article Check for updates. Verify currency and authenticity via CrossMark Cite this article Mori, S., Hashimoto, R., Hisatomi, T. et al. Artificial photosynthesis directed toward organic synthesis. Nat Commun 16, 1797 (2025). https://doi.org/10.1038/s41467-025-56374-z Download citation * Received: 21 September 2024 * Accepted: 15 January 2025 * Published: 27 February 2025 * DOI: https://doi.org/10.1038/s41467-025-56374-z Share this article Anyone you share the following link with will be able to read this content: Get shareable link Sorry, a shareable link is not currently available for this article. 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