Reactivity of Amine/E(C6F5)3 (E = B, Al) Lewis Pairs toward Linear and Cyclic Acrylic Monomers: Hydrogenation vs. Polymerization

This work reveals the contrasting reactivity of amine/E(C6F5)3 (E = B, Al) Lewis pairs toward linear and cyclic acrylic monomers, methyl methacrylate (MMA) and biorenewable γ-methyl-α-methylene-γ-butyrolactone (γMMBL). While mixing of 2,2,6,6-tetramethylpiperidine (TMP) and B(C6F5)3 leads to a frustrated Lewis pair (FLP), Et3N reacts with B(C6F5)3 to form disproportionation products, ammonium hydridoborate ionic pair and iminium zwitterion. On the other hand, the stoichiometric reaction of either TMP or Et3N with Al(C6F5)3 leads to clean formation of a classic Lewis adduct (CLA). Neither TMP nor Et3N, when paired with E(C6F5)3, polymerizes MMA, but the Et3N/2B(C6F5)3 pair promotes transfer hydrogenation of MMA to form methyl isobutyrate. In contrast, the amine/E(C6F5)3 pairs promote rapid polymerization of γMMBL carrying the more reactive exocyclic methylene moiety, achieving full conversion in less than 3 min even at a low catalyst loading of 0.0625 mol %. TMP is more effective than Et3N for the polymerization when paired with either the borane or the alane, while the alane exhibits higher polymerization activity than the borane when paired with Et3N. Overall, the TMP/Al(C6F5)3 system exhibits the highest polymerization activity, achieving a maximum turn-over frequency of 96,000 h−1 at 0.125 mol % of catalyst loading, producing high molecular weight PγMMBL with Mn = 1.29 × 105 g∙mol−1.

We have been interested in developing new polymerization methods enabled by Lewis pairs, namely Lewis Pair Polymerization (LPP) [56], to synthesize different classes of polymers. In this type of polymerization, Lewis pairs are involved in monomer substrate activation, chain initiation, as well as chain propagation and termination/transfer steps (Scheme 1). We have demonstrated, for example, FLPs or classic Lewis adducts (CLAs) consisting of bulky phosphine or N-heterocyclic carbene (NHC) LBs and the highly acidic Al(C6F5)3 LA are capable of promoting rapid polymerization of conjugated polar alkenes such as linear acrylic monomer methyl methacrylate (MMA) and cyclic biorenewable γ-methyl-α-methylene-γ-butyrolactone (γMMBL) into high molecular weight polymers [57][58][59]. Such LPP system is also effective for the polymerization of monomers featuring the C=C-C=N functionality, including 2-vinyl pyridine and 2-isopropenyl-2-oxazoline [60,61]. Controlled Ring-opening (co)polymerization of other monomers such as lactide and lactones into cyclic polymers has been achieved by employing Zn(C6F5)2-based Lewis pairs [62], while radical polymerization of styrene is successfully mediated by a persistent FLP-NO aminoxyl radical generated by N,N-cycloaddition of a cyclohexylene-linked intramolecular P/B system to nitric oxide [63]. More recently, we found that the boron-based LA, in combination with various NHC or phosphine LBs, can be highly effective for polymerization of MMA and γMMBL: while the B/P FLP systems exhibit no or negligible polymerization reactivity, the P→B and NHC→B CLAs have been found to exhibit unexpectedly high activity for the polymerization of γMMBL [64]. This unique polymerization method has now been employed to the regio-controlled polymerization of dissymmetric divinyl polar monomers [57,65].
A search of the current array of LPP systems reveals that the combination of LAs and amines is scarce and not well-established [58]. In contrast, the B/N system has been studied extensively in the area of the FLP chemistry with respect to the LA-LB interaction, small molecule activation [25], catalysis [28,44,66,67] as well as mechanistic investigations [68]. In this context, we set out to examine the polymerization reactivity of two widely used amines, triethylamine (Et3N) and 2,2,6,6-tetramethylpiperidine (TMP), coupled with two strong organo-LAs, E(C6F5)3 (E = B, Al). We envisioned that the introduction of such sterically encumbered amines with different structural and electronic properties will present an opportunity to probe the polymerization activity of the amine/E(C6F5)3 (E = B or Al) system toward two representative acrylic monomers, linear MMA and cyclic γMMBL (Scheme 1).

Scheme 1.
Generalized chain initiation and propagation mechanism for polymerization of conjugated polar alkenes carrying a functional group (FG) by Lewis pairs through zwitterionic active species or intermediates [56], and the structure of LAs, LBs and monomers examined in this study.

Reaction of Amines and E(C6F5)3 in the Absence of Monomer
A survey of the recent literatures indicates that the coordination chemistry and structural characterizations of several amine/E(C6F5)3 pairs have been reported. Preceding the discovery of the FLP system, earlier studies focused on systems featuring direct B-N and Al-N bond formation with less sterically hindered amines. For instance, Lancaster and co-workers [69] reported that both the borane and alane E(C6F5)3 form stable adducts with a variety of primary and secondary amines. In addition, in all of the cases, the two Lewis acids show invariable reactivity towards these amines. On the other hand, we observed markedly different polymerization activity between the borane and the alane, when used as (co)catalysts and monomer activators for both transition-metal-catalyzed and LPP processes [59,[70][71][72][73]. In general, the alane is more effective than borane due to its higher Lewis acidity, oxophilicity and larger radius. Our recent work showed that the alane displays clear advantages over the borane in several different types of FLP-type catalysis [74]. In this LPP work, we chose two sterically congested amines, Et3N and TMP, as the LB to pair with E(C6F5)3 (Scheme 1).
These two amines exhibit FLP-type reactivity when coupled with the borane [25,75], but their reaction with the alane has not yet been examined. An earlier study showed that, mixing of B(C6F5)3 and Et3N results in a disproportionation reaction of the Lewis pair to form ammonium hydridoborate (C6F5)3B-H···H-N(C2H5)3, concomitant with equimolar iminium zwitterion (C6F5)3B-CH2-CH=N(C2H5)2 [75] (Scheme 2). B(C6F5)3 is known to abstract a hydride from the α-position of a bulky amine with α-hydrogens and form an FLP with the one without α-hydrogens such as TMP. The latter system was utilized for dihydrogen activation and CO2 reduction [25,44]. We speculated that switching from B(C6F5)3 to its congener Al(C6F5)3 could achieve different coordination reactivity. As expected, the alane, considered possessing higher Lewis acidity and less steric hindrance, forms a dative bond with both Et3N and TMP. In the stoichiometric reaction between Al(C6F5)3 and Et3N, the crystalline adduct Et3N·Al(C6F5)3 was isolated in a yield of 81%. Only one set of ethyl and one set of C6F5 resonances were presented in the 1 H-and 19 F-NMR spectra, respectively ( Figure 1). Apparently, the direct Al-N bonding prevents other reactions such as hydride abstraction, which stands in contrast to the borane. Similarly, the TMP·Al(C6F5)3 adduct was isolated as colorless crystals in a yield of 85%, in which the complex formation was confirmed by both 1 H-and 19 F-NMR spectroscopy ( Figure 2). In the 1 H-NMR spectrum, the N-H signal is significantly downfield shifted to 3.71 ppm (cf. 0.64 ppm for the free TMP), as a result of the enhanced acidity after coordination to the electron-deficient alane. This adduct is stable in solution up to 2 days, which precludes the possibility of catalyst decomposition (e.g., protonolytic cleavage of the Al-C bond by the N-H proton) during the course of polymerization (vide infra). In addition, an intramolecular FLP (5) [67] was also included for the LPP study.

Scheme 2. Different amine/E(C6F5)3 (E = B or Al) systems employed for this LPP study
and their corresponding reactivity in the absence of monomer.  .

Stoichiometric Hydrogenation of MMA to Methyl Isobutyrate by Et3N/B(C6F5)3
We first examined the activity of the current amine/LA pairs toward polymerization of the linear methacrylate, MMA, but found no polymerization activity under our standard polymerization conditions for all five amine/LA systems. To gain further insight into this observation, we carried out NMR scale reactions for the amine/LA pairs with equimolar MMA (Figure 3). Accordingly, upon mixing stoichiometric amounts of Et3N/B(C6F5)3/MMA, only the signals of MMA and the products of the disproportionation reaction of Et3N/B(C6F5)3 were observed, regardless of the mixing sequence. Interestingly, addition of more B(C6F5)3 into the above mixture resulted in the consumption of MMA and formation of a new species, which was identified as methyl isobutyrate, Me2CHC(=O)OMe, a product of C=C double bond hydrogenation of MMA (Scheme 3). This transfer hydrogenation was fast and clean, and all of the MMA was consumed in the presence of an additional equivalent of B(C6F5)3. Noteworthy is the inability to generate the ammonium enolborate initiation species, which was further supported by the presence of the geminal protons (=CH2) NMR signals derived from a 1:1:1 mixture of TMP/B(C6F5)3/MMA (see Supporting Information). Similarly, mixing of a preformed Et3N·Al(C6F5)3 adduct with MMA only resulted in the replacement of Et3N with MMA, as indicated by the generation of free Et3N and the remaining geminal protons (=CH2) signals. Overall, these NMR experiments showed that the combination of Et3N or TMP with E(C6F5)3 provides insufficient activation for the polymerization of MMA, either due to the reduction of MMA into the inactive methyl isobutyrate, or the steric bulkiness around the amine, which impairs the effective formation of the active species for polymerization.

Characteristic of γMMBL Polymerization by Amine/E(C6F5)3
Next, we set out to investigate activity of the amine/E(C6F5)3 systems toward cyclic γMMBL, the results of which were summarized in Table 1 , thus achieving an averaged turn-over frequency (TOF) of 12,000 or 24,000 h −1 for the borane or alane, respectively (entries 1 and 3). Increasing the ratio to 800:2:1 resulted in an increase of Mn to 5.13 or 3.30 × 10 4 g·mol −1 for the B and Al LA, respectively, although a significantly prolonged polymerization period of 60 or 30 min was needed to achieve full monomer conversion (entries 2 and 4). Overall, the alane showed two-fold higher activity over the borane when coupled with Et3N. Moreover, the reverse addition sequence, in which equimolar Et3N and LA were premixed, followed by addition to a CH2Cl2 solution of γMMBL, was also effective, albeit a slightly slower rate compared to the standard procedure, with or without an additional equivalent of LA. A stoichiometric reaction of Et3N/B(C6F5)3/γMMBL revealed that all of the monomer was rapidly consumed, with generation of PγMMBL (see Supporting Information). We reasoned that ammonium hydridoborate, formed by premixing of Et3N and B(C6F5)3, can initiate the polymerization via the nucleophilic hydride, whereas the Et3N·Al(C6F5)3 adduct formed via premixing can dissociate in the presence of γMMBL and thus promote the subsequent initiation and bimolecular, activated monomer propagation.
As mentioned above, the combination of the alane or the borane with TMP offered more well-defined coordination chemistry (i.e., either CLA or FLP addition sequences. Impressively, the polymerizations were finished within 1 min for a ratio up to of 800:2:1 (entries 5-9 and 11-15), and even under lower catalyst loading (0.0625 mol % relative to TMP) conditions (1600:2:1), the polymerizations were completed in 3 min (entries 10 and 16). Thus, the polymerization by the B/TMP and Al/TMP Lewis pairs was very rapid with TOF up to 96,000 h −1 (for Al), providing polymers with Mn ranging from medium 6.75 × 10 4 to high 2.55 × 10 5 g·mol −1 (Đ = 1.54 to 1.92) and medium 6.96 × 10 4 to high 1.38 × 10 5 g·mol −1 (Đ = 2.16 to 2.42) for the borane and alane, respectively. Interestingly, under the current standard conditions, if the LAs were premixed with TMP and added to a CH2Cl2 solution of the monomer, the polymerization proceeded rapidly as well. This result confirmed that the TMP·Al(C6F5)3 adduct formed via premixing can rapidly dissociate in the presence of γMMBL monomer and promote the subsequent initiation and bimolecular, activated monomer propagation [58,59], while the B/TMP FLP should be active regardless of the addition sequence.

Materials, Reagents, and Methods
All syntheses and manipulations of air-and moisture-sensitive materials were carried out in flamed Schlenk-type glassware on a dual-manifold Schlenk line, on a high-vacuum line, or in an inert gas-filled glovebox. NMR-scale reactions were conducted in Teflon-valve-sealed J. Young-type NMR tubes. HPLC-grade organic solvents were first sparged extensively with nitrogen during filling 20 L solvent reservoirs and then dried by passage through activated alumina (for Et2O, THF, and CH2Cl2) followed by passage through Q-5 supported copper catalyst (for toluene and hexanes) stainless steel columns. Benzene-d6 and toluene-d8 were dried over sodium/potassium alloy and vacuum-distilled or filtered, whereas CD2Cl2 and CDCl3 were dried over activated Davison 4 Å molecular sieves. HPLC-grade dimethyl formamide (DMF) was degassed and dried over CaH2 overnight, followed by vacuum distillation (CaH2 was removed before distillation). NMR spectra were recorded on Varian Inova 300 (300 MHz, 1 H; 75 MHz, 13 C; 282 MHz, 19 F) or a Varion 400 MHz spectrometer. Chemical shifts for 1 H-, 19 F-and 13 C-spectra were referenced to internal solvent resonances and are reported as parts per million relative to SiMe4.

Typical Procedure for the NMR Scale Reactions (TMP/B(C6F5)3/MMA as an Example)
A CD2Cl2 (0.7 mL) solution of MMA (5.0 L, 0.0469 mmol) in a J. Young NMR tube was added B(C6F5)3 (24 mg, 0.0469 mmol), followed by addition of TMP (7.98 L, 0.0469 mmol). The mixture was allowed to react for 10 min before 1 H-NMR measurement, which indicated the retention of the geminal protons of MMA.
In the case of the alane, a different addition sequence was adopted, in which the preformed amine/Al adduct was transferred to the corresponding monomer in specific deuterated solvents as the solvent will decompose the alane upon mixing directly.

General Polymerization Procedures
Polymerizations were performed either in 25 mL flame-dried Schlenk flasks interfaced to the dual-manifold Schlenk line for runs using external temperature bath, or in 20 mL glass reactors inside the glovebox for ambient temperature (ca. 25 °C) runs. In a typical polymerization procedure, a predetermined amount of B(C6F5)3 or Al(C6F5)3 was first dissolved in a monomer (0.5 mL of MMA or γMMBL, 200 equiv relative to the LB) and 2.0 mL of solvent (CH2Cl2) inside a glovebox. The polymerization was started by rapid addition of a solution of a LB (1 equiv of an amine) in 0.5 mL of CH2Cl2 via a gastight syringe to the above mixture containing the LA and monomer under vigorous stirring. The amount of the monomer was fixed for the varied [M]/[LB] ratio runs. In a second procedure of polymerization, the premixed LA/LB system (or the intramolecular Lewis pair) was dissolved in 0.5 mL of toluene (for the alane system since the alane is known to decompose in CH2Cl2 in the absence of a monomer) or CH2Cl2 (for the borane system), followed by addition to a CH2Cl2 (2.0 mL) solution of monomer (0.5 mL) to initiate the polymerization. After the measured time interval, a 0.2 mL aliquot was taken from the reaction mixture via syringe and quickly quenched into a 4-mL vial containing 0.6 mL of undried "wet" CDCl3 stabilized by 250 ppm of BHT-H; the quenched aliquots were later analyzed by 1 H-NMR to obtain the percent monomer conversion data. After the polymerization was stirred for the stated reaction time and then the polymer was immediately precipitated into 200 mL of methanol, stirred for 1 h, filtered, washed with methanol, and dried in a vacuum oven at 50 C overnight to a constant weight.

Polymer Characterizations
Polymer number-average molecular weights (Mn) and molecular weight distributions (Đ = Mw/Mn) were measured by gel permeation chromatography (GPC) analyses carried out at 40 °C and a flow rate of 1.0 mL·min −1 , with DMF as the eluent, on a Waters University 1500 GPC instrument equipped with one PLgel 5 μm guard and three PLgel 5 μm mixed-C columns (Polymer Laboratories; linear range of molecular weight = 200-2,000,000). The instrument was calibrated with 10 PMMA standards, and chromatograms were processed with Waters Empower software (version 2002).

Conclusions
In summary, Lewis pairs consisting of bulky amine Et3N and TMP as LBs and bulky E(C6F5)3 as strong organo-LAs were employed for investigation into their reactivity toward two acrylic monomers, including linear MMA and cyclic γMMBL. While TMP and B(C6F5)3 form an FLP, Et3N reacts with B(C6F5)3 to form disproportionation products ammonium hydridoborate ionic pair and iminium zwitterion. On the other hand, the stoichiometric reaction of Et3N and TMP with Al(C6F5)3 leads to clean formation CLAs.
In the case of linear MMA, the Et3N/2B(C6F5)3 pair promotes transfer hydrogenation of MMA to form methyl isobutyrate. The TMP/B(C6F5)3 FLP is also incapable of polymerizing MMA, attributable to the steric hindrance and low nucleophilicity at N in TMP, which resulted in no formation of the active propagating species. In contrast, the amine/LA pairs promote rapid polymerization of γMMBL carrying the more reactive exocyclic methylene moiety, achieving full conversion in less than 3 min even at a low catalyst loading of 0.0625 mol %. The Al/Et3N pair displays higher activity when compared with the B/Et3N pair. Meanwhile, TMP is more efficient than Et3N when paired with either the borane or the alane. Of the four LA/LB pairs investigated in this study, the TMP/Al(C6F5)3 pair exhibits the highest activity, achieving a maximum TOF of 96,000 h −1 at 0.125 mol % of catalyst loading or 32,000 h −1 at 0.0625 mol %, producing high molecular weight PγMMBL with Mn = 1.29 × 10 5 or 1.38 × 10 5 g·mol −1 , respectively. As compared with the previous LBs employed for LPP, such as phosphines and NHCs, the current LPP system utilizing the inexpensive, readily available and more stable and environmentally friendly amine LBs will provide a greener alternative approach toward bio-renewable polymers based on γMMBL and other monomers.