Direct Photochemical C–H Carboxylation of Aromatic Diamines with CO2 under Electron-Donor- and Base-free Conditions

We report the photochemical carboxylation of o-phenylenedimamine in the absence of a base and an electron donor under an atmosphere of CO2, which afforded 2,3-diaminobenzoic acid (DBA) in 28% synthetic yield and 0.22% quantum yield (Φ(%)). The synthetic yield of DBA in this reaction increased to 58% (Φ(%) = 0.47) in the presence of Fe(II). The photochemical reaction described in this work provides an effective strategy to use light as the driving force for the direct carboxylation of organic molecules by CO2.

show characteristic signals at 6.42, 6.50, and 3.80 ppm, assignable to aromatic C-H and N-H protons. On the other hand, the spectra of 1 under N 2 or CO 2 ( Supplementary Fig. 3) did not show any clear signals, reflecting its paramagnetic nature 51 . Aromatic amines afford carbamic acids or benzimidazol-2-one from the reaction with CO 2 under basic conditions 52,53 or in the presence of catalysts [54][55][56] . However, such products could not be detected under these dark conditions.
Direct photochemical carboxylation of aromatic diamines with CO 2 by opda and 1. The UV-Vis spectra of opda and 1 after photo-irradiation (8 h) under CO 2 showed new absorption band at 347 nm (Fig. 3a). It is noteworthy that the new band was observed only when the photoreaction took place under CO 2 ( Supplementary Fig. 2). Interestingly, the absorbance of the new bands was significantly increased for 1 relative to opda, which confirms the promoting effect of the Fe(II) ion in 1. The 1 H NMR (CD 3 CN) spectrum after the photoreaction of opda under CO 2 ( Supplementary Fig. 4) exhibits two sets of doublets at 6.82 and 7.30 ppm, as (a)UV-Vis spectra of opda (6.0 × 10 −3 M) after irradiation (λ ex = 300 ± 10 nm; 63.9-66.9 mW) under CO 2 ( ) or N 2 (···), and those of 1 (2.0 × 10 −3 M) under CO 2 ( ) or N 2 (-) in THF (8 h; room temperature), together with spectrum of commercial DBA ( ). (b) Crystal structure of DBA (unit A); atomic displacement parameters set to 50% probability; color-code: blue = N, gray = C, magenta = O, and light blue = H; hydrogen atoms are depicted in ball-and-stick mode for clarity.
A reaction mechanism for the photochemical carboxylation. To get insight into the underlying reaction mechanisms, we subsequently carried out the photoreaction with aniline and Fe(II) under CO 2 . However, the UV-Vis spectrum showed no significant changes (Supplementary Fig. 8 and run 5 in Table 1). The  inertness of aniline prompted us to use m-(mpda) and p-phenylenediamine (ppda) 59,60 . The photo-irradiations (λ ex = 300 ± 10 nm) of mpda or ppda resulted in the emergence of new absorbances at 360 nm and 400 and 450 nm, respectively (Supplementary Fig. 9, runs 6 and 8 in Table 1). Curiously, the absorbances of mpda and ppda were observed even after irradiation, suggesting their poor reactivity ( Supplementary Fig. 9). ESI-MS spectra showed signals (m/z 151.05) for the carboxylated products in the crude reaction mixture ( Supplementary  Figs 10a and 11a). The newly emerged 1 H NMR signals of the carboxylated products were assigned to 2,4-and 2,5-diaminobenzoic acids ( Supplementary Figs 10b and 11b). Conversely, the treatment of mpda or ppda with Fe(II) afforded white precipitates, probably due to the formation of coordination polymers (runs 7 and 9 in Table 1) 61,62 .
Given the atmosphere-dependent photoreactions of opda and 1, we focused our attention on their excited states. The emission spectra (λ ex = 300 nm) of opda and 1 in THF under N 2 or CO 2 showed the emission bands at 350 nm, assignable to emissions from ππ* of opda or ππ* included excited state of 1 ( Supplementary Fig. 12). In the excitation spectra of opda and 1 under N 2 or CO 2 (λ obs = 350 nm), the bands were observed at 298 nm, suggesting radiative deactivation pathways for the photoreactions under N 2 and CO 2 ( Supplementary Fig. 13).
Subsequently, we attempted to identify the active species by trapping experiments. It was previously reported that 2-methylpropane-2-thiol (t-BuSH) can act as a hydrogen (H) radical scavenger forming di-tert-butyl disulfide (t-Bu 2 S 2 ) 63,64 . The detection of t-Bu 2 S 2 among the photochemical reaction products of opda and 1 revealed the H radical generation during the reaction (vide infra). The 1 H NMR spectra of t-BuSH and t-Bu 2 S 2 under CO 2 (Fig. 4a,b, and Supplementary Fig. 14) showed singlets at 1.38 and 1.29 ppm, respectively. On the other hand, we found that the new signals emerged at 0.88, 0.89, and 1.19 ppm in the 1 H NMR spectrum of a THF-d 8 solution of t-Bu 2 S 2 after photo-irradiation (λ ex = 300 ± 10 nm), which demonstrates the photoreactivity of t-Bu 2 S 2 (Fig. 4c) 63 . These resonances are thus indicative of the in-situ formation of t-Bu 2 S 2 . A mixture of opda/t-BuSH displayed a 1 H NMR spectrum similar to those of pure t-BuSH and opda ( Fig. 4d and Supplementary Fig. 14), suggesting negligible interactions in the ground state. After photo-irradiation, new singlets emerged at 0.88, 0.89, and 1.19 ppm (Fig. 4e), and these peaks are identical to those of the photochemical products derived from t-Bu 2 S 2 (Fig. 4c), suggesting the formation of t-Bu 2 S 2 during the photochemical reaction. The 1 H NMR spectrum of a mixture of 1/t-BuSH showed no significant interaction in the ground state (Fig. 4f), whereas new singlets emerged at 0.88 and 4.61 ppm after photo-irradiation ( Fig. 4g and Supplementary Fig. 14). These peaks are comparable to those of the photochemical products of opda/t-BuSH mixture (Fig. 4e), suggesting the formation of t-Bu 2 S 2 from 1/t-BuSH. Based on these results, it should be feasible to consider a reaction pathway involving the H radical generation for the photoreaction of opda and 1 under CO 2 . The lower amount of photochemically generated H 2 from them under CO 2 than N 2 thus most likely reflects the incorporation of the generated H radicals in the DBA skeleton.
Finally, to shed more light on the reaction mechanism, we compared the 13 C NMR (CD 3 CN) spectra of the reaction product of 1 under CO 2 or 13 CO 2 . In the 13 C NMR spectrum of the photochemically-produced DBA from 1 under CO 2 , the resonance derived from the carboxyl carbon was observed at 170.5 ppm (Fig. 5a). In the case of the photoreaction under 13 CO 2 , the peak intensity of the carboxyl carbon clearly increased, suggesting that the carboxyl moiety in DBA originates from CO 2 (Fig. 5b) 14,65 . Figure 6 depicts plausible mechanisms for the photochemical carboxylation of opda and 1. Given the aforementioned results, the photo-irradiation induces the generations of H and aminyl radical intermediates. The later then form a C-C bond with CO 2 via the delocalization of the unpaired electron, thus forming the carboxyl radical intermediate 66 . Subsequently, the methine proton transferrs to the imino nitrogen, whereby the aromatic stabilization could act as driving force forming a 2,3-diaminobenzoic radical species. The reaction of the intermediate  with a H radical might finally yield DBA. The role of the Fe(II) ion in this reaction should be worth investigating in detail, as it is highly plausible that the Fe(II) center perturbs the N-H moiety in opda favorably 64,67-71 .

Discussion
In this paper, we demonstrated a direct photochemical C-H carboxylation of aromatic diamines with CO 2 . Although this reaction is not catalytic, it represents the first example of atom-and step-economic direct carboxylation of a C-H bond in benzene rings in the absence of any potentially reactive electron donor and base. The promotion of this reaction by Fe(II) could be achieved using opda ligand, indicating the potential of nonprecious metal ions to accelerate or catalyze the reaction. Further efforts to gain an in-depth understanding of the mechanism and to expand the scope of the reaction by using a wider range of aromatic polyamines, nonprecious metal ions, excitation wavelengths, and catalytic protocols are currently in progress.

Methods
General procedures. All synthetic operations were performed under N 2 or CO 2 using standard Schlenk-line techniques. The ligand opda was purchased from Wako Pure Chemical Industries (Japan), while p-phenylenediamine (ppda) was obtained from Sigma-Aldrich, and m-phenylenediamine (mpda), was procured from Tokyo Chemical Industry Co., Ltd. (Japan). 2,3-Diaminobenzoic acid (DBA) was purchased from Combi-blocks (USA) and used after recrystallization from H 2 O. Dehydrated THF, THF-d 8 , CD 3 CN, and silica gel (60 N) were purchased from Kanto Chemical Co. Inc. (Japan). MeOH, CH 3 CN, and emission analysis grade THF were obtained from Nacalai Tesque, Inc. (Japan). N 2 , CO 2 , and 13 CO 2 were purchased from Kotobuki Sangyo Co. Ltd. (Japan). Prior to use, THF was degassed by at least five freeze-pump-thaw cycles, followed by N 2 or CO 2 sparging for 20 min, and subsequent dehydration over molecular sieves (4 Å, MS4A), which were purchased from Wako Pure Chemical Industries (Japan) and activated by heating under high vacuum. Complex [Fe II (opda) 3 ][ClO 4 ] 2 (1) was prepared according to a previously reported procedure 51 . Caution! Although we did not experience any difficulties manipulating perchlorate salts, these should be regarded as potentially explosive and therefore require handled with the utmost care.
UV-Vis-NIR spectra were recorded on a HITACHI U-4100 spectrophotometer at room temperature (25 °C). IR spectra were recorded on a Thermo Nicolet 6700 FT-IR spectrometer by attenuated total reflection (ATR) method. 1 H and 13 C NMR (500 and 126 MHz) spectra were recorded on a JEOL EX-500 (and A-500) spectrometer using CD 3 CN or THF-d 8 . Elemental analyses were carried out on a Perkin-Elmer 2400 II CHN analyzer. Electrospray ionization mass spectra (ESI-MS) were performed at the Global Facility Center at Hokkaido University. Emission and excitation spectra were recorded on a Horiba FluoroMax-4 spectrophotometer at room temperature (25 °C). To investigate the reactivity under photo-irradiation, 0.4 mL of the respective sample solutions were transferred into a N 2 -or CO 2 -filled 1 mm quartz cell and the UV-Vis spectrum of the initial state was measured. The remaining 4 mL of the sample solution were then transferred into a custom-made Schlenk-flask-equipped quartz tube (volume: 164 mL). After exposing this apparatus for 8 h to photo-irradiation, 0.4 mL of the sample solution were withdrawn and transferred into a N 2 -or CO 2 -filled 1 mm quartz cell in order to measure the UV-Vis spectrum. In order to examine the reactivity in the dark, 0.4 mL of the solution were transferred into a N 2 -or CO 2 -filled 1 mm quartz cell and the UV-Vis spectrum of the initial state was measured. After allowing the sample solutions to stand for 8 h, in the dark, the spectral measurements were recorded again.
Photochemical hydrogen evolution. For the photochemical hydrogen-evolution reaction (HER), the aforementioned Schlenk-flask-equipped quartz tube (volume: 164 mL) and THF solutions (4 mL) were used. The light source for the photochemical reactions was a 200 W Hg-Xe lamp (LC-8, Hamamatsu Photonics K.K.), and the intensity of the light was measured by using a power meter (Nova, Ophir Optronics Ltd.) and a thermopile sensor (3 A, Ophir Optronics Ltd.) prior to photo-irradiation experiments. Gas chromatographic analyses were conducted using a Shimadzu gas chromatograph (GC-2014) equipped with a thermal conductivity detector (TCD), a column filled with 5 Å molecular sieves, and Ar as the carrier gas (15.0 mL/min). The oven temperature was maintained at 100 °C, while the column and detector temperatures were set to 70 °C and 200 °C, respectively. Before the photo-irradiation experiments, a gas sample (0.3 mL) was collected from the headspace using a gas-tight syringe (Tokyo Garasu Kikai Co. Ltd) and analyzed by GC to confirm the successful N 2 or CO 2 purge. The samples were then exposed to irradiation in a water bath at room temperature. During the reaction, gas samples (0.3 mL) were collected from the headspace in order to determine the amount of H 2 evolved as a function of the irradiation time. Purification of DBA after the photoreactions. After the reactions in the dark or upon photo-irradiation, as well as measurements of UV-Vis spectra of the samples after the reaction, all THF solutions were transferred into a Schlenk flask and THF was removed under reduced pressure. After measuring of the 1 H NMR and ESI-MS spectra, the reaction mixtures were purified by flash column chromatography (Isolera One ACI TM Spektra, Biotage Co. Ltd.) on silica gel (60 N; Kanto Chemical Co. Inc.; eluent: CH 3 CN:MeOH = 9:1 then 0:10). The photochemical products of [Fe II (opda) 3 ][ClO 4 ] 2 or Fe II -free opda were collected and dried in vacuo. The formation of DBA was confirmed by recording the 1 H NMR spectra in CD 3 CN. Colorless single crystals of DBA suitable an X-ray crystallographic analysis were obtained from a recrystallization from THF/n-hexane.
Calculation of the quantum yields (Φ%). The THF solutions of the samples, except for those of aniline and a mixture of aniline and [Fe II (H 2 O) 6 ][ClO 4 ] 2 , were exposed to photo-irradiation (λ ex = 300 ± 10 nm) from a Hg-Xe lamp equipped with the LX0300 band pass filter (Asahi Spectra Inc.; λ = 300 ± 10 nm; half bandwidth = 10.40 nm). The THF solutions of aniline and a mixture of aniline and [Fe II (H 2 O) 6 ][ClO 4 ] 2 were exposed to photo-irradiated (λ ex = 289 ± 10 nm) from a Hg-Xe lamp equipped with a CWL289 nm filter (OptoSigma Corporation, λ = 289 ± 10 nm, half bandwidth = 10 nm). The amount of DBA formed in runs 1, 3, and 4 (Table 1) in the subsequent 8 h were used to calculate the apparent quantum yield (Φ) using Eq. 1.

Data Availability
The X-ray crystallographic coordinates for the structure of DBA reported in this Article has been deposited at the Cambridge Crystallographic Data Centre (CCDC), under deposition number CCDC-1826028. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/ data_request/cif.