Chemoselective Polymerization of Fully Biorenewable α-Methylene-γ-Butyrolactone Using Organophosphazene/Urea Binary Catalysts Toward Sustainable Polyesters

Abstract

Open AccessCCS ChemistryRESEARCH ARTICLE1 Jan 2021Chemoselective Polymerization of Fully Biorenewable α-Methylene-γ-Butyrolactone Using Organophosphazene/Urea Binary Catalysts Toward Sustainable Polyesters Yong Shen, Wei Xiong, Yongzheng Li, Zhichao Zhao, Hua Lu and Zhibo Li Yong Shen State Key Laboratory Base of Eco-Chemical Engineering, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042 Google Scholar More articles by this author , Wei Xiong Beijing National Laboratory for Molecular Sciences, Center for Soft Matter Science and Engineering, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871. Google Scholar More articles by this author , Yongzheng Li Key Laboratory of Biobased Polymer Materials, Shandong Provincial Education Department, College of Polymer Science and Engineering, Qingdao University of Science and Technology, Qingdao 266042 Google Scholar More articles by this author , Zhichao Zhao State Key Laboratory Base of Eco-Chemical Engineering, College of Chemical Engineering, Qingdao University of Science and Technology, Qingdao 266042 Google Scholar More articles by this author , Hua Lu *Corresponding author(s): E-mail Address: [email protected] E-mail Address: [email protected] Beijing National Laboratory for Molecular Sciences, Center for Soft Matter Science and Engineering, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871. Google Scholar More articles by this author and Zhibo Li *Corresponding author(s): E-mail Address: [email protected] E-mail Address: [email protected] Key Laboratory of Biobased Polymer Materials, Shandong Provincial Education Department, College of Polymer Science and Engineering, Qingdao University of Science and Technology, Qingdao 266042 Google Scholar More articles by this author https://doi.org/10.31635/ccschem.020.202000232 SectionsSupplemental MaterialAboutAbstractPDF ToolsAdd to favoritesDownload CitationsTrack Citations ShareFacebookTwitterLinked InEmail Despite the great potential of biorenewable α-methylene-γ-butyrolactone (MBL) to produce functional, recyclable polyester, the ring-opening polymerization (ROP) of MBL remains a challenge due to the competing polymerization of the highly reactive exocyclic double bond and low-strained five-membered ring. In this contribution, we present the first organocatalytic chemoselective ROP of MBL to exclusively produce functional unsaturated polyester by utilizing a phosphazene base/urea binary catalyst. We show that delicate chemoselectivity can be realized by controlling the temperature and using selected urea catalysts. The obtained polyester can be completely recycled back to its monomer by chemolysis under mild conditions. Experimental and theoretical calculations provide mechanistic insights and indicate that the ROP pathway is kinetically favored by using urea with stronger acidity at low temperatures. Download figure Download PowerPoint Introduction Sustainable polymers derived from renewable feedstocks have attracted increasing attention due to growing concerns over the eventual consumption of finite fossil fuels and the concomitant environmental pollution caused by the production and disposal of petroleum-based polymeric materials.1–4 Aliphatic polyesters are probably the most intensively investigated sustainable polymers, such as poly(ɛ-caprolactone) (PCL), poly(glycolic acid) (PGA), and poly(l-lactide) (PLLA).5 Although these aliphatic polyesters can be readily degraded to CO2 and water in nature, recycling remains as a challenge. For example, the thermal or chemical depolymerization of PLLA produces a mixture of lactide stereoisomers, cyclic oligomers, and other impurities, which require tedious purification before recycled L-LA can be reused.6–8 An approach to address the end-of-use issue of polymeric materials is to develop chemical recyclable polymers with closed-loop life cycles that can be completely depolymerized to their monomers under mild and energy efficient conditions.9,10 One emerging frontier in chemical recyclable polymers is the design and preparation of polyesters using lactones with five-membered rings as building blocks.11–18 For example, Hong and Chen11 realized the ring-opening polymerization (ROP) of γ-butyrolactone (γBL) under readily accessible conditions by utilizing La- or Y-based organometallic catalysts. Organophosphazene superbases, such as tert-Bu-P4 and a new cyclic trimetric phosphazene superbase (CTPB; Figure 1), were later demonstrated to be effective organocatalysts for the ROP of γBL.12,13 Significantly, the resultant polyester, PγBL, can be selectively and quantitatively depolymerized to its monomer γBL by simply heating the bulk material or chemolysis with a catalyst. A trans-cyclohexyl-ring-fused γBL (3,4-T6GBL) at the α and β positions with increased ring strain energy relative to γBL was recently developed, which can be readily polymerized into a high molecular weight polymer under room temperature and solvent-free conditions.14,15 The obtained polymer can also be recycled back to its monomer and successfully establish a circular life cycle. The same group recently presented the organocatalytic ROP of similar six–five bicyclic lactone (4,5-T6GBL) to produce high molecular weight recyclable polyesters utilizing organobase/(thio)urea binary catalysts.19 Figure 1 | (a) Two different polymerization pathways of MBL and (b) the chemical structures of CTPB and ureas used in this study. Download figure Download PowerPoint Despite the success achieved in recyclable polymers over the past several years, fully recyclable polymeric materials are still limited, especially those with functional groups. Lu et al.20 recently developed recyclable polythioesters from biomass-sourced bridged bicyclic thiolactones with side chain allyl functional groups, which can be further modified and provide opportunities to adjust the polythioesters’ properties. Another functionalizable monomer with potential chemical recyclability is MBL, the simplest derivative of γBL bearing a low-strained five-membered ring and an exocyclic double bond. MBL is naturally found in tulips and can be produced from biosourced feedstocks.21 MBL has been intensively investigated as a sustainable alternative to the petroleum-based methyl methacrylate (MMA) monomer due to a higher glass transition temperature and better solvent durability of the MBL-derived polymer compared with poly(methyl methacrylate) (PMMA).22 However, most studies have reported the vinyl-addition polymerization (VAP) of MBL through Michael-type addition across the exocyclic double bond to produce P(MBL)VAP (Figure 1a, pathway a) that is not fully degradable or recyclable.22–27 The selective ROP of MBL to produce recyclable polyesters is even more challenging compared with the ROP of γBL due to the competing polymerization between the highly reactive exocyclic double bond and the low-strained five-membered lactone ring. To the best of our knowledge, the only selective ROP of MBL was performed by Chen et al. by utilizing La[N(SiMe3)2]3 or yttrium-based catalysts. Intriguingly, the ROP product of MBL, P(MBL)ROP (Figure 1a, pathway b), has been shown to be recyclable to MBL in the presence of a simple catalyst, LaCl3.28 Considering the high functional group tolerance, metal-free nature, and facile removal of catalyst residues from polymers, organocatalysts will be highly desirable for the chemoselective ROP of MBL.29 Herein, we have reported the first organocatalytic chemoselective ROP of MBL to produce exclusively unsaturated recyclable P(MBL)ROP by utilizing an organophosphazene base in combination with ureas as cocatalysts, which makes (PMBL)ROP a metal-free sustainable polyester. Experimental Methods General polymerization procedure A typical polymerization procedure (Table 1, run 5) is described as follows. A flame-dried Schlenk tube was charged with (0.05 mmol, 5.2 μL) benzyl alcohol (BnOH), (0.05 mmol, 59.9 mg) CTPB, (0.15 mmol, 42.95 mg) U4, and 0.187 mL tetrahydrofuran (THF) in a glove box. The Schlenk tube was sealed with a septum and immersed into a cooling bath set to −50 °C. After equilibrium at −50 °C for 10 min, (5 mmol, 0.44 mL), MBL was injected into the Schlenk tube via a gastight syringe to begin the polymerization. The polymerization was conducted at −50 °C for 4 h before quenching via the addition of a few drops of acetic acid. About 3 mL dichloromethane (DCM) was used to dissolve the product. An aliquot of solution was withdrawn and used for MBL conversion determination with 1H NMR measurement. The remaining solution was poured into excess cold methanol (−20 °C). The obtained precipitate was washed with cold methanol once more and then dried under vacuum at room temperature to give PMBL as a white powder with 41.2% (202 mg) yield. Table 1 | Results of ROP of MBL with CTPB/Urea as Catalystsa Run Initiator Urea [M]/[B]/[U]/[I] Sol. Temperature (°C) Time (h) C(ROP) (%)b C(VAP) (%)b Mn (kDa)c Ðc 1 BnOH 100/1/0/1 THF −50 4 0 20 n.d. n.d. 2 BnOH U1 100/1/3/1 THF −50 4 0 100 n.d. n.d. 3 BnOH U2 100/1/3/1 THF −50 4 54 24 n.d. n.d. 4 BnOH U3 100/1/3/1 THF −50 4 51 4 5.2 1.57 5 BnOH U4 100/1/3/1 THF −50 4 50 0 5.9 1.29 6 BnOH U5 100/1/3/1 THF −50 4 18 0 2.3 1.25 7d BnOH U4 100/1/3/1 THF −50 4 12 0 n.a. n.a. 8 BnOH U4 100/1/3/1 THF −50 2 35 0 4.0 1.19 9 BnOH U4 100/1/3/1 THF −50 8 62 0 6.1 1.46 10 BnOH U4 100/1/3/1 TOL −50 4 16 0 n.a. n.a. 11 BnOH U4 100/1/3/1 DMF −50 4 9 0 n.a. n.a. 12 BnOH U4 100/1/3/1 THF −20 4 0 0 n.a. n.a. 13 BnOH U4 100/1/3/1 THF 25 4 0 37 n.d. n.d. 14 BnOH U4 100/1/2/1 THF −50 4 65 0 5.2 1.34 15e BnOH U4 100/1/1/1 THF −50 4 n.d. n.d. n.d. n.d. 16 BnOH U4 100/1/3/5 THF −50 4 47 0 3.2 1.31 17 BnOH U4 100/1/3/2 THF −50 4 52 0 4.4 1.33 18 BnOH U4 100/1/3/0.67 THF −50 4 45 0 6.7 1.34 19 BnOH U4 200/2/6/1 THF −50 4 43 0 6.4 1.56 20 iPrOH U4 100/1/3/1 THF −50 4 49 0 5.4 1.28 21 Ph2CHOH U4 100/1/3/1 THF −50 4 35 0 5.8 1.32 22f – U4 100/1/3 THF −50 4 32 0 6.0 1.35 aConditions: (5 mmol, 490 mg) MBL was used. CTPB was used as the base. The polymerization was conducted at [MBL] = 8 M in THF. n.d.= not determined (Mn and Ð not determined due to poor solubility in THF). n.a. = not available (no polymer precipitation occurred). bDetermined by 1H NMR. cDetermined by SEC in THF relative to PS standards. dThe MBL concentration was 6 M. eThe conversions were not determined due to cross-linking. fNo initiator was added. 1H NMR (DMSO-d6, 400 MHz): δ (ppm): 6.10 (s, 1H, =CH2), 5.71 (s, 1H, =CH2), 4.20(t, 2H, J = 6.2 Hz, –OCH2–), 2.58 (t, 2H, J = 6.2 Hz, –CH2–). 13C NMR (DMSO-d6, 100 MHz): δ (ppm): 165.69, 136.32, 127.41, 62.66, and 30.76. Depolymerization of P(MBL)ROP A flame-dried Schlenk tube was charged with (0.005 mmol, 6 mg) CTPB, (0.015 mmol, 7.2 mg) U6, and 1 mL THF in a glove box. About 49 mg P(MBL)ROP (produced by MBL/KOMe/U4 = 100/1/3, Mn = 6.5 kDa, Ð = 1.49) was then added into the aforementioned solution. The Schlenk tube was then immersed into an oil bath at 50 °C for 48 h. An aliquot of solution was then withdrawn and used for 1H NMR measurement. Postfunctionalization of P(MBL)ROP A mixture of 39.2 mg P(MBL)ROP (Mn = 6.1 kDa, prepared by CTPB/U4), (5 equiv., 2 mmol, 174 μL) benzyl mercaptan, and (0.05 equiv., 0.02 mmol, 2.8 μL) triethylamine was dissolved in 0.4 mL dimethyl sulfoxide (DMSO). The reaction was conducted at 40 °C for 5 h. An aliquot of reaction mixture was withdrawn and used to determine the conversion by 1H NMR measurement. The remaining mixture was poured into excess cold methanol (−20 °C). The obtained precipitate was washed with cold methanol twice and then dried under vacuum at room temperature. 1H NMR (CDCl3, 400 MHz): δ (ppm): 7.27 (br, 5H, Ph–), 4.05 (br, 2H, –OCH2–), 3.66 (br, 2H, PhCH2–), 2.65 (br, 2H, –SCH2–), 2.53 (br, 1H, –CH<), 1.90 (br, 2H, –CH2–). 13C NMR (CDCl3, 100 MHz): δ (ppm): 173.51, 137.97, 128.99, 128.67, 127.27, 62.53, 42.42, 36.68, 33.05, 30.38. Results and Discussion Chemoselective ROP of MBL To realize the selective ROP of MBL, one should activate the low-strained five-membered γBL ring while inhibiting the VAP of the highly reactive exocyclic double bond simultaneously. Waymouth and coworkers reported the rapid and highly selective ROP of cyclic lactones, lactides, and carbonates by utilizing alkoxides in combination with (thio)ureas as catalysts.30,31 Interestingly, the (thio)urea anions generated by deprotonation of (thio)ureas with alkoxides are more effective at the activation of cyclic lactones compared to linear open-chain esters.30,31 Very recently, our group and others have successfully prepared high molecular weight PγBL with a strong base/(thio)urea binary catalytic system, in which (thio)urea anions were shown to also effectively activate the γBL ring.32–34 The strong base/(thio)urea binary catalysts also showed high activity toward the ROP of other cyclic monomers.35,36 According to previous studies, we believe that urea anions can also effectively promote the ROP of MBL through activation of the γBL ring. On the other hand, the VAP pathway of MBL is proposed to proceed via the generation of a carbanion intermediate, which requires catalysts with considerably stronger basicity than those suitable for the ROP pathway. As such, we speculate that MBL may undergo chemoselective ROP by judicious selection of suitable combinations of organobases and ureas. As a proof of concept, a series of ureas bearing a cyclohexyl group and a substituted phenyl group was designed and screened for the chemoselective ROP of MBL since ureas with asymmetric structures were proven to be more effective at γBL ring activation (Figure 1b, see Supporting Information Figures S1–S5).34 It was reported that the ROP of MBL gave an enthalpy change of ΔH = −5.9 kJ mol−1 and an entropy change of ΔS = −40.1 J mol−1 K−1, which corresponded to a ceiling temperature of −14 °C at [MBL]0 = 8 M or −52 °C at [MBL]0 = 5 M.28 To achieve the ROP of MBL, the polymerization should be conducted at a low temperature to meet the thermodynamic requirements. As a consequence, the experiments were first conducted at low temperature (−50 °C) and high monomer concentration (8 M) in THF to favor the ROP of MBL in the presence of BnOH as the initiator. As a control experiment, the polymerization conducted with CTPB in the absence of urea achieved a low MBL conversion of 20%, exclusively producing VAP product P(MBL)VAP (Table 1, run 1). A urea with a 4-methoxyphenyl group (U1) was then attempted in combination with CTPB as the base for the polymerization of MBL at a feeding molar ratio of MBL/CTPB/U1/BnOH = 100/1/3/1. The polymerization achieved 100% MBL conversion within 4 h but still proceeded exclusively through the VAP pathway (Table 1, run 2). By changing the substituent at the para-position of the phenyl ring from methoxy to hydrogen and chloro, a mixture of P(MBL)VAP and P(MBL)ROP was obtained, and the accompanying MBL conversion through the VAP pathway decreased from 100% to 24% and 4% (runs 3 and 4), respectively. The exclusive ROP of MBL was achieved with U4 as a cocatalyst, which features a 4-trifluoromethylphenyl group. An MBL conversion of 50% was obtained within 4 h, producing P(MBL)ROP with a molecular weight of Mn = 5.9 kDa and a relatively narrow distribution of Ð = 1.29 (run 5). The basicity of the deprotonated urea anions was expected to sequentially decrease from U1 to U4, considering the gradual increase of the electron-withdrawing effect of the substitution group on the aromatic ring. Thus, the aforementioned results appear to agree well with our initial hypothesis on using a weaker basic catalyst to favor the ROP of MBL and inhibit the VAP pathway in the meantime. Nevertheless, although cocatalyst U5 bearing a more electron-withdrawing substituent of 3,5-bis(trifluoromethyl)phenyl group also produced P(MBL)ROP exclusively, the MBL conversion dropped to only 18% and the resulting polymer showed a decreased Mn = 2.3 kDa (run 6). This result indicated that while a less basic urea anion can generally improve ROP selectivity, it may also result in decreased catalytic activity.30,37 Next, we focused on U4 for further optimization because it appeared to give balanced selectivity and catalytic activity. The polymerization was further investigated with CTPB/U4 as the catalyst under different conditions. The polymerization conducted at a lower initial monomer concentration of 6 M resulted in much lower MBL conversions, and no polymers were obtained by precipitation (run 7). An extended polymerization time to 8 h led to a slightly higher MBL conversion to 62% and a comparable molecular weight of Mn = 6.1 kDa but with a broader polydispersity of Ð = 1.46, which is likely due to the intra- or intermolecular transesterification (run 9). Switching the solvent from THF to toluene (TOL) or N,N-dimethylformamide (DMF) still led to good chemoselectivity through the ROP pathway but resulted in lower MBL conversions (run 10 and 11). The decreased MBL conversion in TOL is probably due to the decreased solubility of CTPB/U4 in TOL. Of note, the MBL conversions for the polymerizations conducted in THF can exceed the thermodynamic equilibrium limit because the resulting polymer can precipitate out of the reaction system. In contrast, the same polymerization in DMF gave a lower monomer conversion because the polymerization remained as a homogeneous system. The polymerization was then conducted at different temperatures to investigate the effect of temperature on chemoselectivity. No polymerization was observed either via the VAP or ROP pathway at −20 °C (run 12). Further elevating the polymerization temperature to 25 °C resulted in the exclusive formation of P(MBL)VAP (run 13). These results suggested that low temperature was necessary to provide negative Gibbs free energies to thermodynamically drive the ROP of the γBL ring as discussed earlier.11 The molar ratio of CTPB/urea also plays a critical role on the conversion of MBL and polymerization chemoselectivity. For example, a slightly higher MBL conversion of 65% through the ROP pathway can be obtained at CTPB/U4 = 1/2 at −50 °C (run 14), but a further decrease in the U4 amount to CTPB/U4 = 1/1 resulted in formation of cross-linked networks probably due to the coexistence of the VAP and ROP pathways (run 15). It was reported that the urea anions can activate the propagating chain end by hydrogen bonding.30 The addition of excess neutral ureas might reduce the activity of propagating chains by forming hydrogen bonding with urea anions.30 Here, we speculate that the basicity and catalytic activity of the U4-/U4 pair were subtly adjusted by the amount of neutral U4, which served as not only an acid but also a hydrogen bonding donor participating in the polymerization.30,37 Overall, the polymerizations prefer to proceed via the ROP pathway at a lower temperature and excess U4 can effectively inhibit the VAP pathway. P(MBL)ROP with varied molecular weights can be successfully prepared by adjusting the feeding molar ratio of MBL to BnOH. The molecular weight of P(MBL)ROP increased from 3.2 to 4.4 kDa and 6.7 kDa as MBL/BnOH increased from 100/5 to 100/2 and 100/0.67 (see Supporting Information Figure S7), respectively. Two other alcohol initiators, isopropanol (iPrOH) and diphenylmethanol (Ph2CHOH), also resulted in exclusive formation of P(MBL)ROP. iPrOH as an initiator gave similar results as Ph2CHOH with gave lower MBL conversion (runs 20 and The polymerization conducted in the absence of initiator also led to chemoselective ROP of MBL but resulted in lower MBL conversion (run In addition to CTPB, the chemoselective ROP of MBL can also be achieved by utilizing in combination with U4, such as and (see Supporting Information Table It is out that the CTPB/U4 binary catalyst described showed a higher compared to the reported For example, the polymerization conducted at the same conditions utilizing La[N(SiMe3)2]3 as the catalyst achieved a lower MBL conversion of producing P(MBL)ROP with a lower Mn = kDa (see Supporting Information Table On the other hand, the reported yttrium-based catalyst the best catalytic activity as indicated by its to produce high molecular weight P(MBL)ROP to Mn = In our more is to the molecular weight of P(MBL)ROP utilizing the organophosphazene base/urea catalytic system. The of the obtained P(MBL)ROP was further with NMR and As shown in Figure the 1H NMR of the obtained P(MBL)ROP double bond at 6.10 and 5.71 the presence of P(MBL)VAP which is expected to show at and the of chain end that the obtained P(MBL)ROP were by and as The 13C NMR of P(MBL)ROP shown in Supporting Information Figure is also in good with a than a vinyl-addition The of P(MBL)ROP the linear of obtained P(MBL)ROP with expected chain which is with the aforementioned NMR (see Supporting Information Figures For example, the of a low molecular weight P(MBL)ROP by BnOH series of molecular in which the are as linear P(MBL)ROP with chain and the are as linear with chain (see Supporting Information Figure the presence of a amount of is also by the 1H NMR (see Supporting Information Figure which is to the amount of γBL in the MBL (see Supporting Information Figure Figure 2 | 1H NMR of P(MBL)VAP and P(MBL)ROP by and Ph2CHOH in solvent as Download figure Download PowerPoint and of P(MBL)ROP The thermal of the obtained P(MBL)ROP were investigated with and Supporting Information Figure the and of P(MBL)ROP with different molecular weights as well as a P(MBL)VAP (see Supporting P(MBL)ROP a which is with a previous The temperature at weight from to °C as the molecular weight of P(MBL)ROP increased from 4.4 to 5.9 On the other hand, P(MBL)ROP gave a temperature at °C. In contrast, the P(MBL)VAP a with a much higher of °C and a of °C. A series of P(MBL)ROP with varied molecular weights were to and the results are in Supporting Information Table The P(MBL)ROP were found to be polyester although were no observed at a 10 heating probably due to their (Figure gave a glass transition temperature in the of to °C at a 2 heating A cold transition temperature and a temperature in the from to °C and from to can be observed at a 2 heating As the molecular weights of the P(MBL)ROP the and slightly Figure 3 | for heating of P(MBL)ROP with molecular weights at different heating (a) 10 and (b) 2 Table 1, run Table 1, run Table 1, run Table 1, run Download figure Download PowerPoint The double bond of P(MBL)ROP can be further by or a reaction as reported Herein, we presented the of P(MBL)ROP by a addition was used as a to with P(MBL)ROP in at 40 °C in the presence of triethylamine as the catalyst. The of double bond as shown in the 1H NMR the conversion of P(MBL)ROP to produce a polyester (Figure Figure 4 | of 1H NMR in of (a) P(MBL)ROP (Mn = 6.1 kDa, prepared by and (b) the obtained polyester produced by addition reaction solvent as Download figure Download PowerPoint Chemical recycling of P(MBL)ROP to P(MBL)ROP generated by the or the P(MBL)ROP obtained by organocatalytic ROP can also be completely recycled back to its monomer Although simple such as have been used for chemolysis of our on the depolymerization of P(MBL)ROP by an organophosphazene base/urea catalyst. with CTPB/U4 or as the catalyst at 25 °C to MBL as indicated by the formation of To inhibit the VAP a urea with more electron-withdrawing U6, was used as a cocatalyst in combination with CTPB see Supporting Information Figure recycling of MBL monomer can be achieved by heating a M solution of P(MBL)ROP in THF at 50 °C within 48 h in the presence of = CTPB relative to as by the 1H NMR (Figure 5). More experiments are still in our group to further the chemolysis conditions. Figure 5 | of 1H NMR in of P(MBL)ROP (Mn = 6.5 kDa, prepared by the obtained reaction mixture heating P(MBL)ROP in the presence of = in THF at 50 °C for 48 the MBL monomer for solvent as Download figure Download PowerPoint To give more the binary ROP of MBL, NMR experiments were then conducted to investigate the of CTPB, and BnOH. Figure 6 the 1H NMR of U4, CTPB/U4 = = and = in at room temperature. The deprotonation of U4 by CTPB to urea anions was by the of of the urea (see Supporting Information Figure and the concomitant of other of U4 and to which is with previous addition of the formation of hydrogen bonding between BnOH and the U4 anion than the formation of the anion was indicated by the of the (b) from to as well as the of the (see Supporting Information Figure The addition of excess U4 led to the effect to (b) of BnOH as by the slightly of (b) from to This result suggested weaker hydrogen bonding as well as weaker activation of the of BnOH in the mixture of = compared to the of = In 1H NMR of = showed that the same (b) to (see Supporting Information Figure stronger activation of the group of BnOH by the U1 This is not we