Citation

Gao Lang, Zhou Cen, Wang Rui, Lan Feng, An Bohang, Huang Xiaozhou, Zhang Xiao. Unveiling inverse vulcanized polymers as metal-free, visible-light-driven photocatalysts for cross-coupling reactions[J]. Chin. Chem. Lett., 2024, 35(4): 108832  

Lang Gao^a, Cen Zhou^b,*, Rui Wang^a, Feng Lan^a, Bohang An^a, Xiaozhou Huang^a, Xiao Zhang^a,*     

In modern society, synthetic polymers play crucial roles in our daily life [1]. However, the vast majority of synthetic polymers are derived from non-renewable petrochemicals, which imposes a significant threat on the sustainability of environment [2,3]. It is therefore urgent to investigate high-performance polymers that are generated from renewable biomass or industrial waste [4,5]. As an unwanted by-product of petroleum refining and gas reserves, elemental sulfur (S₈) is produced in about 70 million tons annually with very little consumption [6]. Megaton quantities of S₈ have been stockpiled on the ground for decades and continuingly accumulated each year. In this regard, the emergence of organic polymers synthesized from S₈ and alkenes via inverse vulcanization has gained extensive interest (Scheme 1, top) [7–13]. Since the pioneering work of Pyun and co-workers in 2013 [14], inverse vulcanized polymers (IVPs) have found wide applications such as cathode materials for Li-S batteries [14–16], dynamic and repairable materials [17], optics applications [18], and metal sorption [19,20]. A wide range of structurally and electronically diverse unsaturated compounds have been used as the organic comonomers, which include those derived from conventional petrochemicals, renewable resources, and abundant industrial by-products. Despite the notable advances, the utilization of IVPs in organic synthesis remains previously elusive.

Scheme 1

	Download: JPG larger image
Scheme 1. The first application of inverse vulcanized polymers in catalysis for organic synthesis.

Structurally, inverse vulcanized polymers (IVPs) have high percentage of S-S bonds. The ability of each sulfur atom to accept two electrons makes IVPs exhibit excellent redox reactivity. Meanwhile, the diverse co-polymerized alkenes offer flexible handles for tuning properties [7–13]. Inspired by these intriguing redox properties of IVPs for Li-S batteries, we were curious about the behavior of IVPs upon visible-light irradiation and wondered whether IVPs could be unveiled as a new class of photocatalysts to convert abundant solar energy into chemical energy [21–36].

Here we investigate the photophysical properties of IVPs and disclose the first implementation of IVPs for synthetic chemistry (Scheme 1, bottom). Under visible-light irradiation, an eugenol allyl ether-derived inverse vulcanized polymer (IVP-EAE) is found to be capable of catalyzing cross-coupling reactions of readily available (hetero)aryl halides with pyrroles and N-arylacrylamides, respectively. Two sets of structurally important scaffolds including pyrrole-containing biaryls and 3,3′-disubstituted oxindoles are furnished in a transition-metal-free fashion. We report our results from this study.

At the beginning, several representative IVPs including the firstly disclosed IVP-DIB [14,15], industrial by-product-derived IVP-DCPD [37], and renewable resource-derived [38] IVP-EG as well as IVP-EAE, which can be accessed via inverse vulcanization (IV) reactions between elemental sulfur and the corresponding alkenes namely 1,3-diisopropenylbenzene (DIB), dicyclopentadiene (DCPD), eugenol (EG) [39], and eugenol allyl ether (EAE) [39] were chosen (Scheme 2a).

Scheme 2

	Download: JPG larger image
Scheme 2. (a) Inverse vulcanized polymers (IVPs) used in this study. (b) Solid-state UV–vis diffuse reflectance spectra (DRS) of selected IVPs. (c) Photocurrent tests of selected IVPs. (d) EIS Nyquist plots of selected IVPs. (e) Time-resolved PL spectra of selected IVPs.

To gain insights into the optical properties of these inverse vulcanized polymers, standard characterizations were performed (Schemes 2b-e). As illustrated in Scheme 2b, the solid-state UV–vis diffuse reflectance spectra (DRS) showed that all the above IVPs display visible-light absorption, although vary dramatically. Gratifyingly, the transient photocurrent experiments indicated that IVPs uniformly possess rapid photocurrent response upon visible light irradiation (Scheme 2c). Among which, IVP-EAE is more apparent than the other three. Consistently, the Nyquist curve of IVP-EAE exhibited a relatively smaller radius in the electrochemical impedance spectroscopy (EIS), suggesting a lower interfacial charge transfer resistance in IVP-EAE (Scheme 2d). Collectively, these two experiments pointed out the feasibility of photogenerated charge separation and transfer in IVPs. Moreover, the time-resolved PL decay spectroscopy showed that the average PL lifetimes of IVP-DIB, IVP-DCPD, IVP-EG, and IVP-EAE is 2.18, 2.54, 2.58, and 3.13 ns, respectively (Scheme 2e).

Encouraged by the above-mentioned photophysical properties of IVPs, we next explored their potential application in visible-light photocatalysis. Cross-coupling reactions are broadly used in both academia and industry for the synthesis of high-value molecules that range from biologically active targets to organic materials [40–42]. Although powerful, traditional cross-couplings typically require the use of palladium complexes as catalysts, two prefunctionalized partners, and elevated temperature [43]. Comparatively, photoredox catalysis offers a more sustainable and environmentally friendly approach [44] because it allows the direct cross-couplings of aryl halides with unprefunctionalized partners operated under mild reaction conditions [45–50]. Mechanistically, photoredox-catalyzed single-electron reduction of aryl halides affords aryl radicals, which add to another (hetero)arenes to generate biaryls followed by aromatization. As such, cross-coupling of aryl halides with N-methyl pyrrole was selected as the model reaction.

We initiated our studies by testing the cross-coupling between 1-(4-bromophenyl)ethan-1-one (1a) and N-methyl pyrrole (2) under blue LEDs irradiation. Encouragingly, the desired reaction took place in the presence of all the selected IVPs and elemental sulfur using DMSO as the solvent, K₂CO₃ as the base, and H₂O as the additive (Table 1, entries 1–5). Among which, IVP-EAE gave the optimal yield (81%), which is consistent with its superior photophysical properties as shown in Scheme 2 (Table 1, entry 1). The solvents exerted important impact on the reaction outcomes. While CH₃CN and acetone proved viable, the use of MeOH, DCM, THF, or H₂O instead of DMSO as the solvent failed to give any conversion (Table 1, entries 6–8). Changing the base to Cs₂CO₃, Et₃N, or DBU led to inferior results (Table 1, entries 9–11). Decreasing the loading of N-methyl pyrrole (2) to 2 equiv. amounts resulted in a drop in the yield (Table 1, entry 12). Notably, the reaction did not proceed in the absence of a base, further demonstrating the crucial role of K₂CO₃ (Table 1, entry 13). Removing H₂O from the system resulted in a slightly decreased yield for this heterobiaryl coupling (72%, entry 14, Table 1). Finally, control experiments confirmed that IVP-EAE, inert atmosphere, and visible light are all crucial for the process, as their absence shut down the reaction severely (Table 1, entries 15–17).

Table 1

Table 1 Optimization of the reaction conditions for (hetero)biaryl cross-coupling.a

Table 1 Optimization of the reaction conditions for (hetero)biaryl cross-coupling.a

With the optimized conditions in hand, the scope of (hetero)biaryl cross-coupling was evaluated. As shown in Scheme 3, a range of aryl halides bearing substituents at para-, meta-, and ortho- positions were engaged in the arylation with N-methyl pyrrole (2) to afford the corresponding heterobiaryls 3a-3g in moderate to good yields (53%−82%). This protocol is highly selective, as diverse electron-deficient functionalities such as ketones (1a-1d), aldehydes (1e-1f), and nitro group (1g) susceptible to undergoing SET reduction could be kept intact during the process. Besides, five-membered ring heteroaryl bromides based on thiophene and furan were well accommodated, leading to the formation of 3h and 3i in 77% yield and 71% yield, respectively. Furthermore, this chemistry is effective with pharmaceutically relevant six-membered ring heteroaryl bromides such as 3-bromoquinoline (1j) and 6-bromoquinoline (1k). The C3 and C6-pyrrole functionalized quinolines 3j-3k can be accessed with high efficiency (68%−75% yields). On the other hand, N-methyl pyrroles bearing substituents including aldehyde, ketone, and carboxylic acid at C2 position were tested. While the reaction of 1-methyl-1H-pyrrole-2-carboxylic acid did not work, the other two delivered the corresponding 2,5-disubstituted pyrroles in moderate to good yields (3l-3m, 57%−81%).

Scheme 3

Download: JPG larger image

Scheme 3. Substrate scope for (hetero)biaryl cross-coupling. Reaction conditions: a solution of IVP-EAE (10.0 mg), 1 (0.2 mmol, 1.0 equiv.), 2 (4.0 mmol, 20.0 equiv.), H2O (0.4 mmol, 2.0 equiv.), and K2CO3 (0.3 mmol, 1.5 equiv.) in DMSO (1.0 mL, 0.2 mol/L) was irradiated by blue LEDs (30 W) at room temperature under nitrogen atmosphere. Unless otherwise noted, (hetero)aryl bromides were used. Isolated yield. a 1-iodo-4-nitrobenzene was used.

Next, the potential of inverse vulcanized polymers to catalyze dual cross-couplings was explored. We chose to investigate the coupling of (hetero)aryl halides with N-arylacrylamides, which allows easy access to benzyl-substituted oxindoles frequently encountered in biologically active molecules [51–53]. However, this reaction is challenging due to the multiple competitive processes, such as reduction of aryl bromides, biaryl cross-coupling, and Heck-type cross-coupling. To our delight, with 1-(4-bromophenyl)ethan-1-one (1a) and N-methyl-N-phenylmethacrylamide (4a) as the model substrates, the expected transformation involving cascade arylation/cyclization occurred in the presence of IVP-EAE, delivering the corresponding benzyl-substituted oxindole 5a in 51% yield (Table 2, entry 1). While inferior performance was observed for IVP-DIB and IVP-DCPD, the cascade arylation/cyclization did not take place using either IVP-EG or elemental sulfur as the photocatalyst instead, which is largely attributed to the strong side reactions (Table 2, entries 2–5). Similarly, no reaction occurred in the absence of K₂CO₃ and the lack of H₂O gave a slightly decreased yield (Table 2, entries 6 and 7). Lastly, control experiments verified the indispensability of IVP-EAE, inert atmosphere, and visible light (Table 2, entries 8–10).

Table 2

Table 2 Investigation on dual cross-couplings and control experiments.a

Table 2 Investigation on dual cross-couplings and control experiments.a

Under the standard reaction conditions, IVP-EAE catalyst enabled the cross-coupling of a variety of (hetero)aryl halides and N-methyl-N-phenylmethacrylamide (4a) in good yields (Scheme 4, Top). Aryl halides that contain diverse functionalities including ketones, aldehydes, and nitro groups at various positions were coupled effectively (5a-5f, 45%–59% yields). Besides, the dual cross-couplings involving six-membered quinolines halogenated at various positions proceeded smoothly, enabling the incorporation of pharmaceutically important quinolines on the 3,3′-disubstituted oxindole scaffolds successfully (5g-5h, 52%–59% yields).

Scheme 4

Download: JPG larger image

Scheme 4. Substrate scope for dual cross-couplings. Reaction conditions: a solution of IVP-EAE (10.0 mg), 1 (0.2 mmol, 1.0 equiv.), 4 (0.6 mmol, 3.0 equiv.), H2O (0.4 mmol, 2.0 equiv.), and K2CO3 (0.3 mmol, 1.5 equiv.) in DMSO (1.0 mL, 0.2 mol/L) was irradiated by blue LEDs (30 W) at room temperature under nitrogen atmosphere. Unless otherwise noted, (hetero)aryl bromides were used. Isolated yield. a 1-iodo-4-nitrobenzene was used. b Ratio of 4- and 6-substituted oxindoles determined by 1H NMR analysis is 1:1.5. The major product 6l was isolated. c Ratio of 4- and 6-substituted oxindoles determined by 1H NMR analysis is 1.84:1. The major product 6m was isolated. d Ratio of 4- and 6-substituted oxindoles determined by 1H NMR analysis is 1.82:1. The major product 6n was isolated.

Then, the scope with respect to N-arylacrylamides was examined (Scheme 4, bottom). An array of substrates with varied substitution patterns including both electron-donating and electron-withdrawing groups (MeO-, ^tBu-, Me-, F-, Cl-, Br-, I-, Ac-, CO₂Me-, CN-, CF₃-) at the para-position of the aromatic skeletons was tolerated (6a-6k, 45%−60% yields). For instance, the pharmaceutically important fluorine-containing substituents as well as the halides, acetyl, and cyano groups which offer additional handles for flexible derivatization could be well retained. Besides para-position, the meta-substituted (ⁱPr-, Cl-, Br-) N-arylacrylamides were investigated under the optimal conditions. In all the cases, two isomers namely 4- and 6-substituted oxindoles were observed. While the isopropyl-substituted substrate favored the formation of 6-substituted oxindole 6l, chloro‑ and bromo‑substituted N-arylacrylamides afforded 4-substituted oxindoles 6m and 6n predominantly. This phenomenon might be attributed to the combined electronic and steric effects of meta-substituents. The structures of 6m and 6n were unambiguously confirmed by X-ray crystallographic analyses.

Furthermore, the coupling of ortho-substituted (MeO-, Me-) N-arylacrylamides with 1-(4-bromophenyl)ethan-1-one (1a) occurred smoothly, thereby furnishing the corresponding 7-substituted oxindoles (6o-6p) in 48%−56% yields. Substrates bearing multiple methyl substituents and a naphthalene derivative provided the expected oxindoles 6q-6r with complete selectivity. A tetrahydroquinoline substrate could also be engaged in this transformation, producing the tricyclic benzylated oxindole 6s in 49% yield. Intriguingly, the pyridine-derived acrylamide underwent the arylation/cyclization cascade with good yield (6t, 50% yield), which allowed an unusual C-3 functionalization of pyridine moiety. The quenching experiments with the addition of various scavengers and the proposed pathways for both reactions were depicted in Fig. S5 (Supporting information).

In conclusion, inverse vulcanized polymers (IVPs) have been exploited in catalysis for organic synthesis for the first time. In the presence of a catalytically amount of IVP-EAE derived from cost-effective waste-product elemental sulfur and renewable resource eugenol allylether (EAE), two types of important cross-coupling reactions have been achieved in a transition-metal-free fashion under visible-light irradiation. This protocol allows the rapid assembly of structurally important pyrrole-containing biaryls and 3,3′-disubstituted oxindoles with high selectivity. Further exploration of IVPs in synthetic chemistry are currently underway in our laboratory.

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

We thank the National Natural Science Foundation of China (NSFC, Nos. 22071024, 22271047), the Natural Science Foundation of Fujian Province (Nos. 2021J06020, 2022J011121), the Top-Notch Young Talents Program of China, and the Science and Technology Project of Minjiang University (No. MJY21027) for generous financial support. We thank Dr. Xue Zhou from the Core Research Facilities of CCMS (WHU) for her assistance with Solid-State NMR analysis.

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.cclet.2023.108832.