MOFs catalyst discovery
The logic flow should be synthesis first and then characterization. Crystals of IMU-108 were grown under solvothermal reaction conditions from a mixture of Cu(NO3)2·3H2O and 5-mercaptoisophthalic acid (H25-mbdc) at 70°C. The dimeric 5,5'-disulfanediyldiisophthalic acid ligand (H45,5'-dsdibdc) was generated via in situ oxidation of H25-mbdc under atmospheric conditions and the final products were obtained as blue polyhedron-shaped crystals. Single crystal X-ray diffraction results reveal IMU-108 crystalizes in the I4/m space group and its asymmetric unit consists of three Cu (II) ions, one and a half of 5,5'-dsdibdc ligands, two water molecules, and one N,N − dimethylacetamide (DMA) molecule (Supplementary Fig. 2). In IMU-108, twelve Cu-Cu paddlewheel building blocks were combined with twenty-four ligands, resulting in a Cu-based cuboctahedral cage with eight triangular and six square windows (Fig. 2a). Two adjacent cuboctahedral clusters are connected by two S-S bonds (Fig. 2b), and one cuboctahedral cluster is tightly connected to a total of twelve cuboctahedral clusters through a total of twenty-four S-S bonds on the ligands with the point symbol of fcu (Fig. 2c). The IMU-108 has almost the same density of metal active sites as the classic MOP-1 synthesized by Yaghi’s group70. Moreover, in contrast with discrete MOP-1, the cuboctahedral clusters of IMU-108 are cage-based, firmly linked by in-situ S-S bonds. The S-S additional bond provides further rigid structure and stability71–74. To confirm our envision, a stability test of IMU-108 was performed. To our delight, IMU-108 shows very good stability in air, organic solvents and temperatures (Supplementary Fig. 3, Fig. 16 and Fig. 17), which demonstrates its advantages to tolerate various operational and storing conditions. Moreover, gram-scale of IMU-108 could be easily obtained, while it is typically challenging to scale up MOFs productions using the conventional autoclave method. The good crystallinity of the corresponding sample was indicated by powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM) studies (Supplementary Fig. 4). Additionally, cyclic voltammetry (CV) measurement indicated the IMU-108 has a competent reductive capability (E1/2(CuII/CuI) = 0.67 V vs. Ag/AgCl in MeCN, Supplementary Fig. 8). The photocurrent responses of IMU-108 suggested its well reproducible photocurrents upon on/off cycles of the 427 nm light irradiation (Supplementary Fig. 9). These results supported the hypothesis that IMU-108 has outstanding stability and promising photoredox activities, which endows its great potential in photoredox catalysis.
Method optimization
We began our investigation by examining conditions for the three-component union of styrenes (1a) with boronic acids (2a) and α-bromo esters (3a) to evaluate the catalytic performance of IMU-108. The model reaction was conducted in dry dichloromethane (DCM) using IMU-108 (3 mol%) as the catalyst, 4,4'-di-tert-butyl-2,2'-bipyridine (dtbpy, 20 mol%) as the ligand, with Cs2CO3 (2.0 equiv.) and diethylamine (0.5 equiv.) as the bases. The mixture was irradiated with a 427 nm LED lamp at room temperature for 20 h under a N2 atmosphere. The desired compound 4a was afforded in 90% yield under standard conditions (Table 1, entry 1). No products were produced in the absence of the catalyst IMU-108 or the base cesium carbonate (entries 2–3). Besides, a significant decrease in the yield of 4a was observed without the ligand dtbpy (entry 4). The results suggested that catalyst, bases, and ligand are necessary components in the model reaction system. We also attempted to remove diethylamine and observed a slight decrease in yield, indicating that diethylamine could enhance the reactivity (entry 5). HKUST-1 is a classical organometallic framework material with a paddlewheel structure75, we compared its reactivity with IMU-108 and found that IMU-108 performs considerably better, which is likely due to its higher photocurrent response (entry 6 and Supplementary Fig. 9). Normally, Cu (I) salt in a homogeneous system has the ability to activate the substrate by electron transfer followed by the absorption of light23. Nevertheless, when replacing IMU-108 with Cu(CH3CN)4PF6, the reaction failed to proceed and no desired product was detected (entry 7). Although IMU-108 was synthesized from Cu(NO3)2·3H2O as the Cu source, the yield of 4a was only 35% when Cu(NO3)2·3H2O was used as the catalyst (entry 8). Moreover, we investigated other homogeneous Cu (II) salts as the catalysts for the model reaction, such as Cu(OAc)2·H2O and Cu(TFA)2·xH2O. However, less than 10% of 4a was afforded (entries 9–10). The above results indicated that the reaction of ordinary copper salts is inefficient and IMU-108 exhibited enhanced reactivity as well as less catalyst loading over their homogeneous counterparts. It was the overall framework structure of IMU-108 that played a key role in the reaction process. Last but not least, increasing or decreasing the amount of Et2NH is less effective at catalyzing this reaction (entries 11–12).
Table 1 Optimization of reaction conditionsa
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)
a Reaction conditions: IMU-108 (3 mol%), dtbpy (20 mol%), styrene 1a (0.1 mmol), p-fluorophenylboronic acid 2a (2.5 equiv.), methyl 2-bromoisobutyrate 3a (2.0 equiv.), Et2NH (0.5 equiv.), Cs2CO3 (2.0 equiv.), DCM (0.03 M), room temperature, 427 nm LED irradiation, and 20 hours. bYields determined by 19F NMR spectroscopy using trifluoromethoxy benzenes as the internal standard. N. D. = not detected. dtbpy = 4,4'-di-tert-butyl-2,2'-bipyridine.
Substrate scope
We next explored the substrate scope of the three-component transformation. We first evaluated the styrene scope (Fig. 3a). The position and electronic properties of the substituents on the aromatic ring scarcely affected the yield of the desired products (Fig. 3a, 4a–4d). A broad range of functional groups were tolerated such as para-tert-butyl (4a), meso-trifluoromethyl (4b), para-acetyloxy (4c), and ortho-bromo (4d), affording desired products in 87–96% yields. It is worth pointing out that a wide range of functionalities such as 1,2-methylenedioxybenzene (4e), trimethylsilyl (4f), and BPin (4g) were well accommodated, affording the desired products in yields of 65–79%. Those results indicate the versatility of our methods in synthesizing key intermediates for further functionalization. Heterocycles are commonly found in pharmaceuticals and bioactive natural products. Therefore, we attempted to expand the styrene substrate scope with vinyl-bearing heterocycles (Fig. 3b). To our delight, the protocol showed good tolerance toward a variety of coordinating heterocycles including dibenzothiophene (4h), pyrazole (4i), pyridine (4j), and thiophene (4k), with products isolated in 72–78% yields. The compatibility of our synthetic method with various heterocycles paves the way for its potential application in the construction of complex molecules in drug discovery. Moreover, various α-carbonyl alkyl bromides were investigated to yield products in good to excellent yields (Fig. 3c). Representative examples include the esters bearing phenyl (4l) and adamantane (4m) groups, and an amide (4n). Furthermore, the variations in arylboronic acids were evaluated (Fig. 3d). We found that the reactions using arylboronic acids with either electron-withdrawing (4o) or electron-donating (4p-4q) groups can proceed efficiently under our standard conditions and 68–84% yields of products were isolated.
To demonstrate the synthetic potential of our methodology to these biaryl compounds, we evaluated the substrate scope of natural products and pharmaceutically relevant derivatives (Fig. 4). We successfully converted olefin bearing substrates into desired products (4r–4x) in 65–87% yields. A variety of complex structures in natural products and pharmaceuticals were well maintained and smoothly converted to the corresponding derivatives, such as ibuprofen (one of the most widely used painkiller, 4r), (+)-δ-tocopherol (vitamin E, 4s), gemfibrozil (treatment of hyperlipidemia, 4t), (+)-menthol (4u), naproxen (pain relief, 4v), phenylalanine (4w), and 6-hydroxy-3,4-dihydro-2(1H)-quinolone (4x). Encouragingly, the bromoacid esters of borneol, cedrol, estrone, testosterone, formononetin and dihydrocholesterol turned out to be suitable partners for the successful coupling reaction to obtain the corresponding products (4y–4ad) with up to 95% yield. Notably, more complex substrates containing intracyclic double bonds are also compatible with mild conditions and exhibit favorable reactivity such as compound 4ab in 89% yield. Of more interest, the reaction is efficiently compatible with structures having macrocyclic molecules, as compounds containing six-membered ring (4u and 4y) and seven-membered ring (4z) structures. The tremendous potential value of this protocol in the synthesis and late stage modification of active drug molecules can thus be seen. Moreover, the IMU-108-catalyzed protocol was readily scalable (Supplementary, Fig. 19) A gram-scale synthesis was achieved by mixing p-tert-butylstyrene (1a), p-fluorophenylboronic acid (2a), and methyl 2-bromoisobutyrate (3a) at a 5.0 mmol scale relative to 1a, resulting in 1.63 g (92% yield) of the corresponding 1,1-diarylalkane product 4a.
Mechanistic investigations
To test our hypothesis that IMU-108 serves as a heterogeneous catalyst in the system, analyses were performed using a filtration test during the course of reactions. IMU-108 solid can easily be separated from the reaction suspension through a simple filtration. After 10 hours of irradiation, the reaction was stopped directly by filtering out IMU-108, and the conversion rate of the filtrate remained almost unchanged in the next 10 hours of irradiation (Fig. 5a). Moreover, to confirm the consistency of the structures after the reaction with crystalline samples of IMU-108, PXRD and Single-crystal X-ray diffraction were compared. As evidenced by the data, the crystallinity and framework structure after the reaction were identical (Supplementary Table 6 and Fig. 18). The recovered IMU-108 was then recycled and reused up to six consecutive reaction cycles (Fig. 5b). At the end of each reaction cycle, the IMU-108 was collected by centrifugation, washed with methanol, dried under vacuum, and directly used in the next cycle. The recyclability and stability of IMU-108 underscored the potential in sustainability and reusability of the photoredox catalyst.
To better understand the mechanism of this reaction, we carried out several mechanistic studies. Kinetic constants of photooxidation of 1a, tetrabutylammonium bromide (TBAB) and diethylamine were calculated based on the Stern-Völmer plots from luminescence quenching experiments (Fig. 5c). The photoexcited IMU-108 with ligand dtbpy as photosensitizers (PSs) had a mild oxidizing triplet state that could be quenched by the Et2NH or TBAB, respectively. Nevertheless, IMU-108 may exhibit a preference for oxidizing the amines (KSV = 60.39 M− 1, for details see Supplementary Section 7.2) within this reaction system. The optimized Et2NH likely also improved the selectivity by accelerating transformation between CuII and CuI species, which can explain why addition of the Et2NH increased the product yield (Table 1, entries 1 and 5). Consistent with the formation of alkyl radical from α-carbonyl alkyl bromides, upon addition of butylated hydroxytoluene (BHT), 1, 1-diphenylethylene and allylic sulfones, respectively, to the reaction mixture under optimal conditions, adduct 5, 6 and 7 were detected via HR-MS or GC-MS analysis (Fig. 5d). Based on the results of our preliminary investigations and previous literature reports5, a plausible catalytic mechanism can be proposed (Fig. 5e). Initially, IMU-108 reacts with dtbpy to generate the catalytically active species LCuIIMOFs (Cu-1), which then irradiated under the LED light to yield the long-lived triplet excited state LCuIIMOFs* (Cu-1*). This active species Cu-1* undergoes single-electron transfer with the reducing species, either diethylamine or bromide anion, to form a cationic radical of diethylamine or bromine radicals and a monovalent copper reactive species LCuIMOFs (Cu-2). Subsequently, the monovalent copper species Cu-2 is excited to the triplet state LCuIMOFs* (Cu-2*) under illumination, which one-electronically reduced methyl 2-bromoisobutyrate (3a) to produce a tertiary carbon-radical intermediate (I) followed by radical addition of styrene (1) to form a stabilized benzyl radical intermediate (II). Meanwhile, monovalent copper species Cu-2 could be converted to divalent copper species LCuIIMOFs by single-electron oxidation of diethylamine cation radical, followed by transmetallation with arylboronic acid under the action of cesium carbonate to obtain the product of aryl-copper coupling product (Cu-3), then combined with benzyl radical (III), and eventually, after the reductive elimination, the product of the three-component coupling (4) will be obtained and the monovalent copper species Cu-2 would be regenerated.