Precise synthesis of sulfur-containing polymers via cooperative dual organocatalysts with high activity

Metal-free and controlled synthesis of sulfur-containing polymer is still a big challenge in polymer chemistry. Here, we report a metal-free, living copolymerization of carbonyl sulfide (COS) with epoxides via the cooperative catalysis of organic Lewis pairs including bases (e.g.: phosphazene, amidine, and guanidine) and thioureas as hydrogen-bond donors, afford well-defined poly(monothiocarbonate)s with 100% alternating degree, >99% tail-to-head content, controlled molecular weights (up to 98.4 kg/mol), and narrow molecular weight distributions (1.13–1.23). The effect of the types of Lewis pairs on the copolymerization of COS with several epoxides is investigated. The turnover frequencies (TOFs) of these Lewis pairs are as high as 112 h−1 at 25 °C. Kinetic and mechanistic results suggest that the supramolecular specific recognition of thiourea to epoxide and base to COS promote the copolymerization cooperatively. This strategy provides commercially available Lewis pairs for metal-free synthesis of sulfur-containing polymers with precise structure.

T he finding of fresh monomers 1,2 and the development of active catalysts 3,4 are the central topics in synthetic polymer chemistry. Carbonyl sulfide (COS), a key intermediate of the atmospheric sulfur cycle and the most abundant sulfurcontaining gas in the troposphere, causes haze, acid rain, and ozonosphere damage 5 , and is also a one-carbon (C 1 ) heterocumulene and structural analog of carbon dioxide (CO 2 ). Utilizing COS to copolymerize with epoxides is a emerging atomeconomic and versatile approach to produce functional sulfurcontaining polymers [6][7][8][9][10][11] . In contrast, traditional synthesis of sulfur-containing polymers often involves the condensation of thiols with phosgene and ring-opening polymerization (ROP) of cyclic thiocarbonates that are generally derived from thiols and phosgene 6 .
The above-mentioned catalysts have the coordination bonds that are responsible to the activation of the monomers. Whereas very few of reports suggested an anionic copolymerization process involved C 1 monomers. For example, Nozaki et al., disclosed that [PPN]Cl could solely catalyze the carbon-disulfide (CS 2 )/ propylene sulfide copolymerization 16 . Feng and Gnanou et al. presented that alkoxide/benzyl alcohol (BnOH) could effectively initiate the CO 2 /epoxide copolymerization 17,18 . However, anionic copolymerization of COS with epoxides remains unexplored. In contrast with the CO 2 /epoxide copolymerization that is often expected to attain fully alternating structure and no production of side cyclic carbonate (i.e., 100% polycarbonate) [19][20][21][22][23][24] , the chemistry of COS/epoxide copolymerization is more complicated 6 .  One is the possible occurrence of oxygen/sulfur exchange reactions (O/S ERs), which cause the production of CO 2 , and thiirane intermediate, will produce randomly distributed dithiocarbonate and carbonate units in the final copolymer 8,[25][26][27] . The other is that the copolymerization of structurally asymmetric COS with a terminated epoxide, will generate four consecutive monothiocarbonate diads, i.e.,: head-to-tail (H-T), tail-to-head (T-H), tail-to-tail (T-T), and head-to-head (H−H) diads 6 . As a result, metal-free catalyst for anionic COS/ epoxide copolymerization should avoid O/S ER, attain highly regioselectivity involved two asymmetric monomers and be precisely controlled by varying the monomer to initiator ratios under mild condition. Herein, we have developed a living copolymerization of COS with various epoxides with high activity, using commonly available thioureas (TUs) and organic LBs (DBU, MTBD, P4, P2, and P1, Fig. 1c). This catalyst system was developed based on the hypothesis that the cooperative catalytic process of Lewis pairs composed of TU and base, undergoing a non-covalent mode to activate and stabilize the alcohol initiator/chain end for controlling the anionic copolymerization [28][29][30][31] . The resulting poly (monothiocarbonate)s have perfectly alternating structure with regioregularity, controlled molecular weights and narrow PDIs, and are colorless ( Supplementary Fig. 1).
Chain microstructures of COS/PO copolymers. The perfectly alternating structure and regioregularity of the PPMTCs were also revealed by MALDI-TOF MS spectroscopy (Fig. 2). Figure 2a showed one distribution of α-OH, ω-OH-terminated [H + (PO + COS) m + n + (PS + COS) + PO + OH + K + ] copolymer, i.e., a single PPTMC with two -OH end groups and one dithiocarbonate unit (M n : 6.5 kg/mol; PDI: 1.15). Furthermore, highresolution 1 H( 13 C) NMR spectra ( Supplementary Fig. 13a, b) revealed that the copolymer contained two secondary -OH end groups with minimal regio-defect (one dithiocarbonate unit) 40 . These results were indicative of inclusively regioselective attack of the sulfur anion to the CH 2 site of PO, and thus the sole production of the T-H diad via the organocatalysis 40 . In the presence of BnOH, only one distribution of α-OBn, ω-OH copolymer-terminated [BnO + (PO + COS) n + H + K + ] (Fig. 2b) with >99% T-H diad content ( Supplementary Fig. 13c, d) was obtained without dithiocarbonate unit (M n : 4.4 kg/mol; PDI: 1.14), meant that BnOH was a very efficient initiator and depressed the production of the dithiocarbonate unit.
Living COS/PO copolymerization catalyzed by Lewis pairs. Remarkably, the TU/LB pair catalysis allowed for the copolymerization exhibiting the living features. Take the TU-1/DBU pair-catalyzed COS/PO copolymerization with or without using BnOH (Fig. 3a, b) as instances: linear increase of M n with PO conversion, narrow PDIs (1.11-1.12, 1. 16-1.19) to high PO conversion (89% and 83%, respectively). Simultaneously, the decay in monomer concentration follows zero-order kinetics under various loading of the TU-1/DBU pair in the presence or absence of BnOH or using TU-1/P2 pair without adding BnOH ( Supplementary Fig. 15). In addition, the determined molecular weights by GPC and NMR (i.e.: M n GPC and M n NMR ) were in well agreement with the calculated M n Theo that increased with the increase of the [PO]/[BnOH] molar ratio in a good linear fashion (Fig. 3c, Supplementary Table 3 Table 4 and Figs. 20-22). As a result, such TU/LB pairs are robust for the copolymerization under mild conditions. We further explored the chain extension reaction via tandem synthesis ( Fig. 3d and Supplementary Fig. 23). PO and COS were copolymerized firstly using TU-1/DBU pair without using BnOH Kinetic and mechanistic study. The cooperative catalysis of TU-1/LB pair for the COS/PO copolymerization was firmly supported by the kinetic studies (Fig. 4a). The apparent rate constant (k app ) obtained from the slopes of the best-fit lines to the plots of PO conversion vs. time, is well proportional to [TU-1] + [DBU] in the absence or presence of BnOH, suggesting that the TU-1/DBU pair behaved as a discreet catalyst species [(a) in Fig. 6]. As expected, k app of the TU-1/P2 pair was 13.6 ± 0.3*10 −2 h −1 and higher than that of TU-1/DBU pair (5.7 ± 0.8*10 −2 h −1 ) for the copolymerization under the same conditions due to the stronger basicity of P2. This result is in agreement with the binding constant via 1 H NMR dilution (see Methods, Supplementary  Fig. 24) that was 10.3 ± 2.5 for TU-1/DBU pair and 21.2 ± 2.2 for TU-1/P2 pair in equilibrium in CDCl 3 at 25°C (Fig. 4b). Because the H-bond interaction could be weakened by elevating the temperature 30 , the TU-1/DBU pair catalysis for COS/PO copolymerization at high temperatures (≥55°C) produced considerable amounts of the cyclic products (Supplementary Table 2), which is consistent with the catalysis involving only the bases for the coupling reaction of COS with PO 41 .
We have further studied the combining capabilities of TU-1, DBU, COS, and PO in CDCl 3 using 1 H NMR spectra (Fig. 5 and Supplementary Fig. 25). In a high concentration of TU-1 and DBU (0.5 M), the H-bond interaction was clearly revealed by the proton signal of NH group (5.65 ppm) of TU-1 disappearing while the six protons (NCH 2 ) of DBU became chemically equivalent ( Supplementary Fig. 25). Of interest, TU-1 was shown to solely activate PO and did not interact with COS in CDCl 3 (Fig. 5a)  NCH 2 of DBU rather than activate PO (Fig. 5b). Such supramolecular specific recognition of TU-1 to PO and DBU to COS in TU-1/DBU pair promoted the copolymerization cooperatively.
The introduction of BnOH into the polymerization system led to the prior formation of the BnOC(=O)S − …DBUH + owing to the deprotonation of BnOH by DBU, generated species (b) and (c) in Fig. 6, as revealed by 1 H NMR spectra ( Supplementary  Fig. 26) 42 . Since PO was activated by TU-1 through H-bond [species (d) in Fig. 6, revealed by Fig. 5b], the chain growth could be accelerated (Table 1). On the other hand, in the absence of BnOH, trace water (i.e., R=H, Fig. 6) could also initiate the copolymerization via the similar activation route of BnOH by TU/LB pair. Such H 2 O initiation led to the formation of the end -S(O=C)-OH group, which was thermodynamically unstable and thus converted to -SH group via decarboxylation process 6,40 . Since the end -SH group has the stronger acidity than -OH group, it was rapidly deprotonated, generating bifunctional initiator for further chain growth, a copolymer with two end secondary -OH groups and one dithiocarbonate unit (f) was produced, which was clearly revealed by Fig. 2a (Supplementary  Figs. 13 and 22).
The impact of Lewis pairs on COS/epoxides copolymerizations. Different Lewis pairs including other thioureas were also investigated for the copolymerization of COS with several epoxides. Two other thioureas, TU-2 and TU-3 were synthesized 43 and successfully utilized for the COS/PO copolymerization (entries 1-4 in Table 2). H-bond interactions of both TU-2 and TU-3 with DBU are similar to that of the DBU/TU-1 pair (Supplementary Fig. 28). The TU-3/DBU pair was more active than TU-1 (TU-2)/DBU pairs for the copolymerization, but with a slightly lower copolymer selectivity of 93%. Both TU-2 and TU-3 paired with P2 showed the same TOFs (29 h −1 , entries 3-4, Table 2) for the COS/PO copolymerization. Totally, TU-3 with more electronwithdrawing group resulted in the production of slightly more amounts of cyclic products. In addition, two epoxides, glycidyl phenyl ether (PGE) and cyclohexene oxide (CHO) were copolymerized with COS by using P2/TU-1, P4/TU-1 pairs, affording fully alternating copolymers (entries 5-8, Table 2). Thereof, the COS/PGE copolymerization were fully regioselective with T-H diad content of >99% ( Supplementary Fig. 29), while COS/CHO copolymerization could proceed at 40°C, afforded well-defined copolymer with perfect alternating degree and >99% copolymer selectivity (Supplementary Fig. 30). These results illustrate the use of several low-cost thioureas for the copolymerization of COS and epoxides with different structures.

Discussion
We have described the synthesis of perfectly alternating and regioregular poly(monothiocarbonate)s from COS and epoxides by employing thioureas and organic bases under mild conditions. Of importance, the use of thioureas and BnOH led to living/ controlled COS/epoxide copolymerization, improved catalytic activity and copolymer selectivity than previous systems. One of the key features of such metal-free catalyst systems is that it can were purchased from Alfa Aesar Chemical Co. and Aldrich Chemical Co., respectively, which were purified by distillation over distillation over CaH 2 and stored in an inert gas (N 2 )-filled glove box. Sodium hydride (95%) was purchased from Sigma and used directly. Carbonyl sulfide (COS) (99.9%) was purchased from the APK (shanghai) Gas Company LTD and used as received.
Representative procedure for copolymerization reactions. All polymerizations were carried out in glove box under N 2 atmosphere unless otherwise specified. A 10-ml autoclave with magnetic stirrer was first dried in an oven at 110°C overnight, then immediately placed into the glove box chamber. After keeping under vacuum for 1-2 h, the reaction vessel was put into the glove box under nitrogen atmosphere. The copolymerization of COS with PO described below is taken from entry 17 in Table 1 as an example. TU-1 (1.4 mg, 0.007 mmol) was added to the reactor firstly. PO (1.0 ml, 14 mmol) was then carefully added into the vessel. Afterwards, DBU (1.05 μl, 0.007 mmol) and BnOH (0.75 μl, 0.007 mmol) were added into the reactor, respectively. The reactor was sealed and then taken out for charging with the set amounts of COS. The copolymerization was performed at 25°C for 24 h. Then, the reactor was cooled in ice-water bath, and the unreacted COS was slowly vented. An aliquot was taken from the resulting crude product for the determination of the PO conversion and the molar ratio of copolymer/cyclic products by 1 H NMR spectrum. Traces of acetic acid were then added for 1 H NMR spectrum, in order to prevent degradation of the crude product. Next, the crude product was quenched with HCl in ethanol (1 mol/l). The crude product was dissolved with CH 2 Cl 2 and then precipitated in cold methanol. The product was collected by centrifugation and dried in vacuum at 40°C until a constant weight.
Characterization. 1 H and 13 C NMR spectra were performed on a Bruker Advance DMX 400 MHz or 600 MHz spectrometer. And chemical shift values were referenced to TMS at 0 ppm for 1 H NMR and 13 C NMR. The number-average molecular weight (M n ) and molecular weight distribution (Ð = M w /M n ) of the resultant copolymers were determined with a PL-GPC220 chromatograph (Polymer Laboratories) equipped with an HP 1100 pump from Agilent Technologies. The GPC columns were eluted with THF with 1.0 ml/min at 40°C. The sample concentration was 0.4 wt. %, and the injection volume was 50 μl. Calibration was performed using monodisperse polystyrene standards. Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometric measurements were performed on a Waters MALDI Micro MX mass spectrometer, equipped with a nitrogen laser delivering 3 ns laser pulses at 337 nm. Dithranol (97%, Alfa), was used as the matrix. CH 3 COOK ( ≥ 98%, Aladdin) was added for ion formation.
Binding constant studies. Equations used for binding studies 44 : where: δ 0 is the chemical shift of the ortho-protons of pure TU-1; [A] 0 is concentration of TU-1 or a base; δ i is the chemical shift of the ortho-protons of TU-1 in the solution when [TU-1] = [base] = [A] 0 ; δ ∞ is the chemical shift ortho-protons of the "pure complex" TU-1 with a base, (δ 0 -δ ∞ ) is a constant; K eq is the binding constant between TU-1 and a Base. Following a similar procedure reported by Matthew K. Kiesewetter 29 , NMR dilution experiments were carried in CDCl 3 with the concentration of [TU-1] = [base] varied from 0.01 M to 0.06 M in CDCl 3 . DBU and P2 were employed as bases respectively. The 1 H NMR spectra was shown in Supplementary Fig. 24. The binding constants (K eq ) were determined from the slope of the linear forms of the binding equation (above). And the error in K eq is exactly the error in the slope of the line, which can be determined from linear regression.
Calculation of copolymer selectivity, PO conversion and TOF. Copolymer selectivity and PO conversion were calculated based on the 1 H NMR spectrum of the crude product. Taking entry 11 in Table 1 as an example, spectrum of the crude product was showed in Supplementary Fig. 35. Protons with chemical shifts at 4.80, 3.52, 3.26 and 1.51 ppm belong to the methenyl (d), methene (e), and methyl (f) groups, respectively, the peaks in 5.16, 3.08, and 1.36 ppm [also seen in Supplementary Fig. 5, a purified PPTMC] belong to the methenyl (a), methene (b), and methyl (c) groups in the copolymer. And the area ratio of these two parts was taken as the copolymer selectivity. The corresponding peaks in 3.02, 2.77, and 2.46, 1.32 ppm belong to methenyl (h), methene (g) and methyl (i) in PO which was not consumed. On the base of 1 H NMR spectra, we have: Thus, Data availability. The authors declare that the data supporting this study are available within the paper and its Supplementary Information File. All other data is available from the authors upon reasonable request.