Bidirectional metal‐free ROMP from difunctional organic initiators

Abstract

Ditopic initiators were evaluated for bidirectional organocatalyzed ROMP. Incorporation of monomer was found to be successful for both inward and outward polymer growth, stemming from divinyl ethers with different relative orientation of alkoxy moieties. Macroinitiators were also used to prepare a triblock and graft copolymers that were found to be easily cleaved with acid catalyst. Ring-opening metathesis polymerization (ROMP) has enabled access to a diverse array of polymeric materials.1, 2 The structural control that has been made possible from well-defined metal-based initiators includes a broad scope of monomer classes with diverse functional group tolerance,3-9 stereocontrol,2, 10-12 sequence specificity,13-15 and copolymer constructs.16-22 Inspired by the breadth of tunability afforded by metal-mediated ROMP, we have recently investigated opportunities from an organocatalyzed variant.23-28 The organocatalyzed approach makes use of vinyl ethers as initiators, which are activated in situ via one-electron oxidation. We envisioned the use of vinyl ether initiators to provide unique synthetic routes to multitopic initiators, such as those that could lead to bidirectional polymer chain growth, multiarm star polymers, or graft-from brush polymers. Such architectures have been achieved via metal-mediated ROMP, but to our knowledge the organocatalyzed method has not been put to this challenge. A potential caveat of the vinyl ether initiators is that high effective concentrations of initiator sites could lead to unwanted intramolecular reactions between oxidized and neutral species. To investigate the feasibility of organocatalyzed ROMP from multitopic initiators, we evaluated a series of small and macromolecular initiators bearing two or more vinyl ethers. We first investigated divinyl ether initiators with different relative orientation of alkoxy moieties (1 and 2, Fig. 1). Our intention was to preserve the spacing between reactive sites of the vinyl ethers while varying the nature of the monomer incorporation. Specifically, initiator 1 would incorporate monomers via insertion at the center of the outwardly-growing polymer, whereas initiator 2 would propagate via an active chain end mechanism. Top, small molecule divinyl ether initiators and pyrylium photoredox catalyst used in this study. Bottom, organocatalyzed ROMP of norbornene. Each initiator was found to undergo metal-free ROMP of norbornene (3) under our previously reported conditions (Fig. 2) using 2,4,6-tris(4-methoxyphenyl)pyrylium tetrafluoroborate (4) as a photoredox catalyst. Averaged data from three parallel runs are summarized in Table 1. Using an initial monomer to vinyl ether molar ratio ([3]0/[VE]0) of 50:1, initiator 1 provided polynorbornene 5 with excellent agreement between theoretical and experimental Mn values (entry 1). Notably, these initiator efficiencies, which are near unity, are considerably higher than observed for organocatalyzed ROMP using ethyl propenyl ether as initiator under similar conditions. In comparison with 1, initiator 2 also proceeded with high conversion of monomer (entry 2) although the initiator efficiency was found to be lower than for 1, and more consistent with previous polymerizations using ethyl propenyl ether. Attempts to identify products of deleterious reaction pathways from the initiators were met with limited success. Conversion versus time for organocatalyzed ROMP from initiators 1 (black) and 2 (white). Despite the differences in initiator efficiency, we found that 1 and 2 gave comparable rates of polymerization (Fig. 2). This suggested to us that since 2 suffers from some nonproductive initiator consumption (lower initiator efficiency), the rate of monomer incorporation with 2 is likely higher than for 1. We speculate that disparate steric access to the active vinyl ether site is the cause of the different propagation rates. The vinyl ether moieties in polymer 5 provide opportunities for postpolymerization modification and controlled degradation. In our studies, we were able to confirm the bidirectional chain growth from initiator 1 via hydrolysis experiments. We first prepared a higher molecular weight sample (Table 1, entry 3, Mn = 46.0 kDa, Đ = 1.2) such that the daughter fragments would be of sufficient molecular weight for analysis. After subjecting this sample of polymer 5 to vinyl ether hydrolysis using Amberlyst 15 ion-exchange resin, we found that the resulting polynorbornene product had a Mn = 24.0 kDa (Đ = 1.1), roughly half that of the initial polymer (Fig. 3). These results are consistent with about equal chain lengths having been synthesized from each initiator site. GPC traces of polymer 5 (Mn = 45 kDa) as isolated via precipitation (solid) and after hydrolysis (dashed, Mn = 24 kDa). Motivated by the success of the bidirectional chain growth, we considered broader applications in the synthesis of degradable triblock copolymers. Toward this end, we prepared a ditopic macroinitiator (7) from poly(propylene glycol) (PPG) as shown in Figure 4 (Mn = 1.0 kDa). Organocatalyzed ROMP proceeded smoothly with 67% monomer conversion to yield triblock copolymer 8 having Mn = 15.9 kDa (Đ = 1.2) based upon GPC analysis of the polymer after isolation by precipitation (Fig. 5, top). Upon hydrolysis, GPC analysis revealed a product polymer with Mn = 5.9 kDa (Đ = 1.3), slightly less than half that of the original polymer (minus the PPG block). Additionally, a low molecular peak was observed that was consistent with the retention time of the PPG initiator. These results were consistent with roughly uniform polymer growth from each initiator site. MF-ROMP from macroinitiators. GPC traces of macroinitiators (dotted), copolymers (solid), and hydrolyzed polymers (dashed). Top, GPC traces for 7, 8, and hydrolysis of 8. Middle, GPC traces for 9, 10, and hydrolysis of 10. Bottom, GPC traces for 11, 12, and hydrolysis of 12. Using a similar approach, we also prepared difunctional macroinitiator 9 based upon poly(ethylene glycol) (PEG). Again, MF-ROMP provided an ABA triblock copolymer (10) after moderate (51%) monomer conversion. GPC analysis of 10 (Fig. 5, middle) after isolation by precipitation revealed Mn = 8.6 kDa (Đ = 1.5). After hydrolysis with Amberlyst 15 resin, the resulting polymer was found to have Mn = 5.1 kDa (Đ = 1.6). We next turned our attention toward grafting from a statistical copolymer. Toward this end, macroinitiator 11 was prepared by a sequence of atom-transfer radical polymerization, dehalogenation of the chain end, and isomerization of the side chain olefins (see Experimental Section). Analysis of 11 by GPC (Fig. 5, bottom) revealed Mn = 2.2 kDa (Đ = 1.1) and 1H NMR analysis was consistent with an average of three vinyl ether moieties per chain. When subjected to MF-ROMP conditions, polymer 12 was obtained with 64% monomer conversion. The isolated polymer was found to have Mn = 28.2 kDa (Đ = 1.6) by GPC analysis. After treatment with Amberlyst 15 ion-exchange resin, the resulting polymer was found to have a reduced molecular weight of Mn = 18.3 kDa (Đ = 1.7). Assuming complete hydrolysis of all vinyl ether moieties, the molecular weight of the cleaved polynorbornene daughter fragments are consistent with about 53% of the vinyl ether moieties having initiated MF-ROMP. In conclusion, we have demonstrated bidirectional polymer growth in organocatalyzed ROMP from difunctional initiators. Evaluation of inwardly-growing polymers versus outwardly-growing polymers revealed that incorporation of monomers at chain-end and chain-centered active sites was successful. The ability to grow polymer chains from internal active sites enabled rapid access to cleavable copolymers based upon PPG, PEG, and polystyrene macroinitiators. The relative ease with which vinyl ether moieties can be installed on potential initiator structures holds promise for access to a broader diversity of organocatalyzed ROMP nanostructures. Herein, we established the feasibility and first steps toward this end. Dimethylformamide (DMF), dimethyl sulfoxide (DMSO), dichloromethane (CH2Cl2), and tetrahydrofuran (THF) were obtained from a solvent purification system. For polymerization of norbornene, CH2Cl2 was dried over 4 Å molecular sieves before use. Norbornene was sublimed prior to use. The pyrylium tetrafluoroborate was prepared according to literature procedure.29 All other reagents and solvents were obtained from commercial sources and used as received unless otherwise noted. All polymerizations were carried out in standard borosilicate glass vials with magnetic stirring. Irradiation of photochemical reactions was done using a 2 W Miracle Blue LED indoor gardening bulb purchased from Amazon. 1H and 13C NMR spectra were recorded on Bruker AVance 300 MHz or 500 MHz spectrometers. Chemical shifts are reported in delta (δ) units, expressed in parts per million (ppm) downfield from tetramethylsilane using the residual protio-solvent as an internal standard (CDCl3, 1H: 7.26 ppm and 13C: 77.0 ppm). Data are reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, dd = doublet of doublet, dt = doublet of triplets, q = quartet, m = multiplet, br = broad peak), coupling constants (Hz) and integration. Gel permeation chromatography (GPC) was performed using a GPC setup consisting of: an Agilent pump, three in-line columns, and light scattering and refractive index detectors (Wyatt Technology Corp.) with THF as the mobile phase. Weight average molecular weight (Mw) and number average molecular weight (Mn) were calculated from light scattering and refractive index data, respectively, using Astra software from Wyatt Technology Corp. To a suspension of NaH (2.8 g, 69.96 mmol) in DMF (20 mL) at 0 °C was added a DMF solution of 1,6-hexanediol dropwise (20 mL, 1.06 M, 21.2 mmol). The ice bath was then removed and the reaction mixture was stirred at room temperature for 30 min. Then, the ice bath was returned and allyl bromide (4 mL, 46.5 mmol) was added dropwise into the solution at 0 °C. The reaction was then stirred for 17 h, during which time the ice bath expired. Deionized water (5 mL) was then added dropwise into the reaction mixture at 0 °C. More deionized water (100 mL) was then poured into the resulting suspension and the final mixture was extracted with Et2O (4 × 50 mL). The combined organic layers were dried with Na2SO4 and decanted. The solvent was then removed under reduced pressure to give the crude product as a yellow oil, which was then purified by flash chromatography on silica gel (10:1 hexanes/ether). The spectral data matched those previously reported.30 The diallyl ether obtain the previous step (1.1 g, 5.5 mmol) was dissolved in DMSO (30 mL) at 0 °C and then potassium tert-butoxide (5.0 g, 40.9 mmol) was added in a single portion. The reaction was stirred for 6 h, during which time the ice bath expired. Then, deionized water (5 mL) was added dropwise into the solution at 0 °C. More deionized water (100 mL) was then poured into the mixture and the resulting suspension was extracted with Et2O (4 × 50 mL). The combined organic layers were dried with Na2SO4 and then decanted. The solvent was then removed under reduced pressure to give the crude product as a yellow oil, which was purified by passing through a silica plug using hexanes as eluent (75% yield over two steps). The spectral data matched those previously reported.30 To a suspension of 1,12-dodecanediol (2.02 g, 10 mmol) in CH2Cl2 (30 mL) was added 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) (313 mg, 2 mmol) and PhI(OAc)2 (7.09 g, 22 mmol). After 20 h, the reaction mixture was diluted with CH2Cl2 (30 mL) and the solution was washed with saturated aqueous Na2S2O3 solution (60 mL). The aqueous phase was then extracted with CH2Cl2 (3 × 20 mL). The combined organic layers were dried with Na2SO4 and then decanted. The solvent was removed under reduced pressure and the crude product was then purified by flash chromatography on silica gel (8:1 hexanes/ethyl acetate). The spectral data matched those previously reported.31 A solution of potassium tert-butoxide (2.97 g, 24.3 mmol) in 8 mL of THF was slowly added to a solution of [Ph3PCH2OCH3]Cl (8.3 g, 24.3 mmol) in 30 mL of THF. After stirring the solution for 1 h, a solution of the dialdehyde obtained from the prior step (1.6 g, 8.1 mmol) in 10 mL THF was added dropwise. The resulting mixture was then stirred at room temperature for 2 h, and then diluted with ether and washed with deionized water. The organic phase was dried with Na2SO4 and the solvent was evaporated. The crude mixture was then taken up in hexanes and then decanted. The filtrate was then concentrated under reduced pressure. Residual Ph3P was then consumed by stirring the crude mixture for 12 h with 1.5 mL of CH3I, leading to precipitation of [Ph3PCH3]I. The mixture was then filtered through a plug of silica with diethyl ether as eluent. The product was prepared according to above procedure in 50% yield over two steps (2:3 cis to trans ratio as judged by 1H NMR spectroscopy). 1H NMR (500 MHz, CDCl3) δ = 6.27 (d, J = 12 Hz, 1H, trans) 5.85 (d, J = 6 Hz, 0.7H, cis) 4.72 (dt, J = 12 Hz, 7.5 Hz, 1H, trans) 4.33 (dt, J = 6 Hz, 7.5 Hz, 0.7H, cis) 3.56 (s, 2H, cis) 3.49 (s, 3H, trans) 2.04 (q, J = 7 Hz, 1.4H, cis) 1.90 (q, J = 7 Hz, 2.6H, trans) 1.22–1.35 (m, 16H, cis/trans); 13C NMR (125 MHz, CDCl3) δ = 147.1, 146.1, 107.3, 103.4, 59.5, 56.0, 30.9, 30.0, 29.8, 29.6, 29.4, 29.2, 27.8, 24.0; GC-MS (m/z) calcd. for C16H30O2, 254.2; found, 254.3. To a suspension of NaH (3.0 g, 75.00 mmol) in DMF (20 mL) at 0 °C was added a DMF solution of PPG-diol dropwise (10 mL, 0.50 M, 5.00 mmol). The reaction mixture was then removed from the ice bath and stirred at room temperature for 30 min. Then, the mixture was returned to an ice bath and allyl bromide (4.3 mL, 50 mmol) was added dropwise. The reaction mixture then stirred for 24 h, during which time the ice bath expired. Deionized water (5 mL) was then added dropwise into the reaction mixture at 0 °C. More deionized water (100 mL) was then poured into the resulting suspension and the final mixture was extracted with Et2O (4 × 50 mL). The combined organic layers were dried with Na2SO4 and then decanted. The solvent was then removed under reduced pressure to give the crude product as a yellow oil, which was then purified by flash chromatography on silica gel (20:1 CH2Cl2/methanol) to give α,ω-diallyl PPG. 1H-NMR (500 MHz, CDCl3) δ = 5.93–5.85 (m, 2H) 5.24 (d, J = 17.5 Hz, 2H) 5.11 (d, J = 10.5 Hz, 2H) 4.05–4.02 (m, 4H) 3.75–3.25 (br, 52H) 1.14–1.06 (br, 52H). To a solution of the PPG-diallyl ether (2.7 g, 2.7 mmol) in DMF (20 mL) at 0 °C was added potassium tert-butoxide (2.0 g, 16.3 mmol) in a single portion. The reaction mixture was then stirred for 24 h, during which time the ice bath expired. Then, deionized water (5 mL) was added dropwise into the solution at 0 °C. More deionized water (100 mL) was then poured into the solution and the resulting suspension was extracted with Et2O (4 × 50 mL). The combined organic layers were dried over Na2SO4 and then decanted. The solvent was then removed under reduced pressure to give the crude product as a yellow oil. Purification by flash chromatography on silica gel (15:1 CH2Cl2/methanol) gave initiator 7 in 70% yield for the two steps. 1H-NMR (300 MHz, CDCl3) δ = 6.05–5.97 (m, 2H) 4.40–4.29 (m, 2H) 3.89–3.77 (m, 2H) 3.62–3.26 (br, 58H) 1.54 (dd, J = 6.9 Hz, 1.8Hz, 6H) 1.19 (dd, J = 6.6Hz, 2.4Hz, 6H) 1.15–1.07 (br, 54H). To a suspension of NaH (3.0 g, 75.00 mmol) in DMF (20 mL) at 0 °C was added a DMF solution of PEG-diol dropwise (10 mL, 0.50 M, 5.00 mmol). The reaction mixture was stirred at room temperature for 30 min. Then, allyl bromide (4.3 mL, 50 mmol) was added dropwise into the solution at 0 °C. The reaction flask was then removed from the ice bath. After 24 h, the reaction flask was again placed into an ice bath and then deionized water (5 mL) was added dropwise into the solution. Next, more deionized water (100 mL) was poured into the mixture and the suspension was extracted with CH2Cl2 (4 × 50 mL). The combined organic layers were dried with Na2SO4 and then decanted. The solvent was then removed under reduced pressure to give the crude product as a yellow solid which was then purified by flash chromatography (20:1 CH2Cl2:methanol). 1H-NMR (500 MHz, CDCl3) δ = 5.93–5.85 (m, 2H) 5.20 (d, J = 17.5 Hz, 2H) 5.11 (d, J = 10.5 Hz, 2H) 3.98–3.91 (m, 4H) 3.62–3.54 (br, 92H). To a solution of PEG-diallyl ether (2.7 g, 2.7 mmol) in DMF (20 mL) at 0 °C was added potassium tert-butoxide (2.0 g, 16.32 mmol) in a single portion. The reaction flask was then removed from the ice bath. After 24 h, the reaction flask was again placed into an ice bath and then deionized water (5 mL) was added dropwise into the reaction at 0 °C. Next, more deionized water (100 mL) was poured into the mixture and the suspension was extracted with CH2Cl2 (4 × 50 mL). The combined organic layers were dried with Na2SO4 and then decanted. The solvent was then removed under reduced pressure to give the crude product as a yellow solid which was purified by flash chromatography (15:1 CH2Cl2:methanol). The initiator 9 was isolated in 80% yield for the two steps. 1H-NMR (300 MHz, CDCl3) δ = 6.01–5.91 (m, 2H) 4.43–4.31 (m, 2H) 3.89–3.82 (m, 6H) 3.66–3.61 (br, 92H) 1.54 (dd, J = 6.9 Hz, 1.8 Hz, 6H). 4-Vinylbenzyl alcohol was first obtained according to literature procedure.32 To a suspension of NaH (2.7 g, 67 mmol) in DMF (75 mL) at 0 °C was added a DMF solution of 4-vinylbenzyl alcohol dropwise (20 mL, 2.23 M, 44.5 mmol). The reaction mixture was then stirred at room temperature for 30 min. Then, allyl bromide (4.25 mL, 49 mmol) was added dropwise into the reaction mixture at 0 °C. The reaction flask was then removed from the ice bath. After 17 h, deionized water (5 mL) was added dropwise into the reaction at 0 °C. Then, more deionized water (100 mL) was poured into the solution and the suspension was extracted with Et2O (4 × 50 mL). The combined organic layers were dried with Na2SO4 and then decanted. The solvent was then removed under reduced pressure to give the crude product as a colorless oil which was purified by flash chromatography (10:1 hexane:ether eluent). The product was prepared according to above procedure in 80% yield. 1H NMR (300 MHz, CDCl3) δ = 7.42 (d, J = 8.1 Hz, 2H) 7.33 (d, J = 8.1 Hz, 2H) 6.74 (dd, J = 17.4 Hz, 10.8 Hz, 1H) 6.04–5.92 (m. 1H) 5.76 (dd, J = 17.7 Hz, 1H) 5.37–5.21 (m, 3H) 4.53 (s, 2H) 4.05 (d, J = 5.7 Hz, 2H); 13C NMR (75 MHz, CDCl3) δ = 138.1, 137.1, 136.7, 134.9, 128.0, 126.3, 117.2, 113.8, 71.9, 71.2. In a nitrogen-filled drybox, initiator 1-bromoethyl benzene (51.7 mg, 0.279 mmol, 1.0 equiv.), styrene (2.6 ml, 22.7 mmol, 80 equiv.), the monomer obtained in the previous step (977 mg, 5.6 mmol, 20 equiv.), toluene (2 mL), and a magnetic stir bar were added into a 20 mL scintillation vial. A solution of CuBr (20.2 mg, 0.14 mmol, 0.5 equiv.) and PMDETA (24.2 mg, 0.14 mmol, 0.5 equiv.) in toluene (1.0 mL) was then added to the reaction mixture. The vial was sealed with a PTFE-lined screw cap and taken to a hood. There, the reaction solution was stirred at 90 °C for 3 h. Then, the reaction mixture was opened to air after the vial cooled to room temperature. The viscous solution was diluted with CH2Cl2 and the solution was filtered through a neutral alumina plug. The solution volume was reduced under vacuum to about 3 mL under reduced pressure. The solution was then added dropwise into an excess of cold MeOH causing the polymer to precipitate from solution. The precipitated polymer was collected by filtration and dried under reduced pressure. The polymer was isolated in 20% yield according to above procedure. 1H NMR (300 MHz, CDCl3) δ = 7.35–6.28 (br, 87H) 6.09–5.85 (br, 3H) 5.42–5.12 (br, 6H) 4.60–4.25 (br, 6H) 4.15–3.80 (br, 6H) 2.60–0.90 (br, 54H). In a nitrogen-filled drybox, the copolymer obtained in the previous step, dry toluene (2 mL) and a magnetic stir bar were added into a 20 mL scintillation vial. A solution of CuBr (7.2 mg, 0.05 mmol) and PMDETA (8.7 mg, 0.05 mmol) in toluene (1.0 mL) was then added to the reaction mixture. The vial was then sealed with a rubber septum. Then, tributyltin hydride (80 µL) was added into the reaction mixture by syringe. The reaction solution was stirred at 90 °C for 5 h. Then, the vial was opened to air after cooling back to room temperature. The viscous solution was diluted with CH2Cl2 and then filtered through a neutral alumina plug. The solution volume was reduced under vacuum to about 3 mL under reduced pressure. The solution was then added dropwise into an excess of cold MeOH causing the polymer to precipitate from solution. The precipitated polymer was collected by filtration and dried under reduced pressure. The polymer was isolated in 90% yield according to above prodecure. 1H NMR (300 MHz, CDCl3) δ = 7.35–6.28 (br, 87H) 6.09–5.85 (br, 3H) 5.42–5.12 (br, 6H) 4.60–4.25 (br, 6H) 4.15–3.80 (br, 6H) 2.60–0.90 (br, 54H). The copolymer obtained in the previous step was dissolved in dry DMF (20 mL) at 0 °C and then potassium tert-butoxide (240 mg, 1.96 mmol) was added in a single portion. The reaction was warmed to room temperature. The reaction flask was then removed from the ice bath. After 20 h, the reaction solution was filtered through a neutral alumina plug. The solvent was then removed under reduced pressure. Then, the crude copolymer was dissolved in 3 mL of CH2Cl2 and resulting solution was added dropwise into cold MeOH, causing precipitation of the polymer. The copolymer was collected by filtration and dried under reduced pressure. The macroinitiator 11 was isolated in 80% yield according to above prodedure. 1H NMR (300 MHz, CDCl3) δ = 7.35–6.28 (br, 87H) 6.11–5.93 (br, 3H) 4.82–4.58 (br, 6H) 4.51–4.35 (br, 3H) 2.45–1.15 (br, 63H) To a 2-dram vial containing a magnetic stir bar was added pyrylium salt 4 (1.3 mg, 0.003 mmol) followed by norbornene. CH2Cl2 was then added, followed by the corresponding initiator (0.045 mmol). The vial was then sealed with a PTFE-lined cap and irradiated with blue LEDs (λ = 450–480 nm, 2 W) at a distance of 2.0 cm. Aliquots were taken for analysis to determine the conversion of norbornene by 1H NMR spectroscopy. The contents of the vial were then diluted with CH2Cl2 and filtered over neutral alumina to remove 4. The filtrate was then partially concentrated and then added slowly into an excess of cold methanol, causing the polymer to precipitate. The solids were collected by filtration, washed with methanol, and then dried under reduced pressure to give the final polymer. To a 4-dram vial containing a magnetic stirbar was added polynorbornene followed by THF (polymer concentration = 5 mg/mL). Then, Amberlyst 15 ion-exchange resin was added. The vial was sealed with a PTFE-lined cap and transferred into an oil-bath preheated to 45 °C. The hydrolysis progress was monitored by GPC and judged to have reached maximum conversion when there was further no shift of retention time for the solution aliquot. Financial support of this research by the Army Research Office (grant no. W911NF-15–1-0139), Washington Research Foundation, and Camille and Henry Dreyfus Foundation. Additional Supporting Information may be found in the online version of this article. 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