Mechanistic Insights into the Alternating Copolymerization of Epoxides

Article pubs.acs.org/JACS

Cite This: J. Am. Chem. Soc. 2017, 139, 15222-15231

Mechanistic Insights into the Alternating Copolymerization of Epoxides and Cyclic Anhydrides Using a (Salph)AlCl and Iminium Salt Catalytic System Megan E. Fieser,†,‡ Maria J. Sanford,§,‡ Lauren A. Mitchell,† Christine R. Dunbar,† Mukunda Mandal,† Nathan J. Van Zee,§ Devon M. Urness,† Christopher J. Cramer,*,† Geoffrey W. Coates,*,§ and William B. Tolman*,† †

Department of Chemistry, Center for Sustainable Polymers, Chemical Theory Center, and Minnesota Supercomputing Institute, University of Minnesota, 207 Pleasant Street SE, Minneapolis, Minnesota 55455, United States § Department of Chemistry and Chemical Biology, Baker Laboratory, Cornell University, Ithaca, New York 14853, United States S Supporting Information *

ABSTRACT: Mechanistic studies involving synergistic experiment and theory were performed on the perfectly alternating copolymerization of 1-butene oxide and carbic anhydride using a (salph)AlCl/[PPN]Cl catalytic pair. These studies showed a first-order dependence of the polymerization rate on the epoxide, a zero-order dependence on the cyclic anhydride, and a first-order dependence on the catalyst only if the two members of the catalytic pair are treated as a single unit. Studies of model complexes showed that a mixed alkoxide/carboxylate aluminum intermediate preferentially opens cyclic anhydride over epoxide. In addition, ring-opening of epoxide by an intermediate comprising multiple carboxylates was found to be ratedetermining. On the basis of the experimental results and analysis by DFT calculations, a mechanism involving two catalytic cycles is proposed wherein the alternating copolymerization proceeds via intermediates that have carboxylate ligation in common, and a secondary cycle involving a bis-alkoxide species is avoided, thus explaining the lack of side reactions until the polymerization is complete.

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INTRODUCTION The alternating copolymerization of epoxides and cyclic anhydrides is a burgeoning route to new polyesters (Scheme 1).1,2 The wide range of available monomers, including ones

complexes require addition of a nucleophilic cocatalyst to achieve high activity, with bis(triphenylphosphine)iminium salts ([PPN]X) being the most widely used and effective.8 Undesirable side reactions include epimerization, transesterification, and homopolymerization of epoxides; for most catalysts, these occur only when the limiting monomer is consumed and the polymerization is complete.15,23 While a generalized mechanistic picture has been developed for the copolymerization reaction, questions remain that are critical to answer in order to understand the molecular details and, ultimately, use that knowledge to design more effective catalysts. Prior studies focused mostly on the Cr-catalyzed copolymerization of phthalic anhydride and cyclohexene oxide and revealed that maximal rate was achieved with one equivalent of [PPN]Cl as the cocatalyst and that the rate is first-order in [epoxide], consistent with ring-opening of epoxide being rate-determining.6,24 On the basis of these findings and in analogy to what is known for CO2/epoxide copolymerizations,25 a simplified reaction pathway has been proposed (Scheme 2). According to this postulate, an epoxide binds to an

Scheme 1. Alternating Copolymerization of Epoxides and Cyclic Anhydrides

that are renewably sourced, and the opportunities for functionalization of these polyesters via postpolymerization modification enable access to myriad new materials with unique properties that are not available through condensation reactions or ring-opening of lactones. (Salen)MX complexes (M = Cr, Co, Al, Mn, and Fe) are a particularly widely used class of catalysts for the copolymerization.3−23 In general, (salen)MX © 2017 American Chemical Society

Received: August 25, 2017 Published: October 6, 2017 15222

DOI: 10.1021/jacs.7b09079 J. Am. Chem. Soc. 2017, 139, 15222−15231

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Journal of the American Chemical Society

boiling point (63 °C) to safely perform NMR experiments at the temperature required to observe reactions at reasonable rates (50 °C). Carbic anhydride (CPMA) was selected due to its higher polymerization rate compared to bulkier substrates23 and its symmetry, which facilitates NMR analysis. We performed bulk polymerization and NMR studies to establish the rate law and order in each component, and mass spectrometric (MS) and NMR studies to investigate the individual epoxide and anhydride ring-opening and initiation steps using relevant model complexes. In addition, we undertook computational studies to characterize the most energetically favorable pathway(s) and to help characterize various proposed intermediates at the atomic level of detail. Through this synergistic experimental and theoretical work, we have developed a detailed understanding of the epoxide/ anhydride mechanism that will assist future catalyst design efforts.

Scheme 2. Simplified Mechanism of Epoxide/Cyclic Anhydride Copolymerization with a (Salen)AlX Complex, Where X Is an Alkoxide, Carboxylate, or Halide, and P Is a Growing Polymer Chain

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RESULTS AND DISCUSSION Initiation. Previous studies showed that the majority of polymers have end groups consistent with the polymer chains being initiated via ring-opening of an epoxide by a chloride ion.23 We extended this work in order to better define the nature of the species responsible for initiation of the copolymerization reaction. Treatment of (salph)AlCl (0.02 M in CDCl3) with BO (1 equiv) at ∼22 °C quantitatively yielded (salph)AlOR within minutes, with preferential attack on the sterically unhindered carbon of the epoxide indicated by NMR spectroscopy (Scheme 4, Figure S26). This regioselectivity is in agreement with that previously reported.15,25f

open coordination site on the metal center and is activated for subsequent attack by a [PPN] carboxylate in the ratedetermining step. The resulting alkoxide then ring-opens an anhydride. While intuitively appealing, evidence supporting this mechanism is sparse, and many questions about the details remain unanswered. For example: Is this mechanism applicable to catalysts with metal centers other than chromium and for other epoxide/anhydride combinations? What is the identity of X in the various intermediates, and does it change during the catalytic cycle? What is the role of the cocatalyst? How are polymer chains initiated? What underlies the high degree of polymerization control? Why do side reactions primarily occur when the polymerization is complete? And what are the transition state structures and energetics of the key ringopening steps? Herein we report the results of a detailed study aimed at answering the aforementioned questions, with the ultimate goal of developing insights useful for the design of improved catalysts. We selected the catalytic pair (salph)AlCl and [PPN] Cl (Scheme 3) for mechanistic study because (a) it has been

Scheme 4. Reaction of (Salph)AlCl with 1-Butene Oxide

Scheme 3. Copolymerization System Chosen for Mechanistic Study

Further experiments were performed to test initiation by [PPN]Cl. No reaction was observed upon heating solutions of BO and [PPN]Cl at 50 °C for 6 h, although it has been reported that the copolymerization is catalyzed by [PPN]Cl at high temperatures (>100 °C).26 To test the idea that [PPN]Cl might initiate epoxide ring-opening in the presence of an aluminum species, and surmising that that species might be the rapidly formed (salph)AlOR complex, we evaluated whether that complex reacted with BO and/or CPMA in the presence of [PPN]Cl. To this end, we mixed (salph)AlCl (0.02 M in CDCl3) with BO (2 equiv) and CPMA (1 equiv), which yielded (salph)AlOR within minutes plus 1 equiv each of unreacted BO and CPMA. To this solution was injected a solution of [PPN]Cl (1 equiv, 0.02 M in CDCl3), and the resulting mixture was heated to 50 °C and monitored by NMR spectroscopy for 14 h. During this time, BO was slowly consumed (initial rate 1 × 10−8 M/s, ∼10% consumed after 14 h), but CPMA remained unreacted (Figure S28). To explain these results, two routes for consumption of additional BO may be envisioned. Epoxide could be activated by binding to (salph)AlOR and then ring-opened by [PPN]Cl

shown to exhibit reactivity toward a variety of epoxides and tricyclic anhydrides, producing new polyesters with good molecular weight control and desirable high glass transition temperature (Tg) values with negligible side reactions until the polymerization is complete,15,22,23 and (b) (salph)AlCl derivatives are diamagnetic, in contrast to other common copolymerization catalysts such as (salen)Cr and Co species, thus rendering 1H NMR experiments convenient. We chose 1butene oxide (BO) as the epoxide since it has a high enough 15223


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reacted in the experiment involving reaction of (salph)AlOR with equimolar BO and CPMA. To rationalize this observation, we postulate that the rate of reaction with CPMA is low in this case because the reactive species is present at low concentrations, as only 10% of the BO has reacted after 14 h, and neither BO or CPMA is present in a large excess as is the case under polymerization conditions. Consistent with this rationale, under conditions similar to the polymerization, albeit with the epoxide concentration lower than typical (1:1:100:100 (salph)AlCl:[PPN]Cl:CPMA:BO, where 1 equiv = 13 μmol, 19 mM), polymerization is not observed for the first ∼2 h (Figure S29). NMR spectra show that (salph)AlOR forms immediately and then slowly converts to a new species (likely the steady state catalyst for polymerization) (Figure S30). Polymerization did not occur at a discernible rate until (salph)AlOR was completely converted, consistent with the hypothesis that the catalytic polymerization cycle begins only after AA has fully formed and then reacted with CPMA. In complementary work, the pathway to species AA was evaluated by theory. In order to simplify the computations, propylene oxide and succinic anhydride were used as model monomers. In the absence of [PPN]Cl, initiation would likely require either a bimetallic process or the chloride ligand on the neutral aluminum complex to dissociate in order to act as a nucleophile. With respect to autoionization, starting from the 5coordinate aluminum chloride precatalyst, there is little change in free energy associated with binding of epoxide to the precatalyst. Subsequent chloride dissociation was found to be highly endergonic with an overall activation barrier of 26.5 kcal/mol for the first epoxide-opening step. This is inconsistent with the experimentally observed rate (within minutes at room temperature) (Figure 1, orange line; see Supporting Information (SI) for calculated mechanism). Based on prior work with salen-based chromium complexes,25a,29 it is possible that a more complicated bimetallic pathway is available in the absence of [PPN]Cl, but we have not investigated this further. Turning next to initiation in the presence of [PPN]Cl, we viewed the role of [PPN]+ to be to act as a large, and thus noncoordinating, counterion for the anionic species present during copolymerization (see SI for computed relative energies of different separated or associated anion−cation pairs). Ring-

(Scheme 5a). Alternatively, (salph)AlOR and [PPN]Cl could undergo a salt metathesis reaction, regenerating (salph)AlCl Scheme 5. Proposed Initiation Routes for [PPN]Cl

which would open BO rapidly, likely through a bimetallic pathway as found for other (salen)MX complexes (Scheme 5b).25a,27 Either route generates the same species, formally an aluminum alkoxide and [PPN][OR] which may or may not interact with each other (i.e., [PPN][(salph)Al(OR)2] or (salph)AlOR/[PPN][OR], which we term “AA” to signify the presence of two alkoxide units). A similar initiation process has been suggested for the polymerization of lactide, in which a combination of (salcy)AlCl and [PPN]Cl was reacted with propylene oxide to form a proposed bis(alkoxide) species, [(salcy)Al(OR)2]−, as the reactive catalyst.28 In our attempts to isolate the AA species, a 1:1 ratio of (salph)AlCl and [PPN]Cl was combined with BO at various concentrations. The solutions were deep red, consistent with formation of a 6coordinate [(salph)Al(OR)2]− moiety, as theory predicts anionic 6-coordinate Al compounds to absorb further into the visible region of the spectrum than related uncharged aluminum complexes (see below). However, 1H NMR spectra of these mixtures contained peaks associated with multiple ringopened products and no one species could be isolated and fully characterized (Figure S31). The failure to isolate a single AA species notwithstanding, we postulate that reaction of the bis(alkoxide) complex with CPMA would give the first repeat unit. However, no CPMA

Figure 1. Initiation mechanism with 333 K relative Gibbs free energies (kcal/mol) computed at the SMD(THF)/M06-2X/6-311+G(d,p)// SMD(THF)/M06-L/6-31+G(d,p) level of theory. All stoichiometries are balanced through appropriate inclusion of [PPN]+, Cl−, and/or propylene oxide. The orange line corresponds to reaction in the absence of [PPN]Cl, i.e., through autoionization. The blue line corresponds to reaction with exogenous Cl− from ionization of [PPN]Cl. 15224


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Journal of the American Chemical Society opening by attack of free Cl− from dissociated [PPN]Cl can occur with a predicted free energy of activation of 23.0 kcal/ mol. The resulting 6-coordinate aluminate species spontaneously dissociates the chloride ligand, leaving a site that is available for coordination of another propylene oxide (predicted now to be somewhat endergonic). Following truncation of the 1-chloroisopropoxide ligand to isopropoxide, both for computational simplicity and to be consistent with the calculated propagation mechanism discussed below, a second ring-opening reaction involving chloride is predicted to be possible with a free energy of activation of 30.7 kcal/mol. The resulting bis(alkoxide) species (AA) is that found at the start of the proposed propagation mechanism, as discussed later. It should be noted that the relatively high free energy predicted for AA is a standard-state free energy, i.e., it is the free energy when all components are at 1 M concentration. However, the enormous excess of propylene oxide compared to chloride renders the free energy of reaction for the second epoxide opening considerably more favorable under actual reaction conditions. Polymerization Kinetics. The dependence of the rate of copolymerization on the monomer, catalyst, and cocatalyst concentrations was determined using multiple methods and conditions in order to obtain the most accurate results. Two approaches were taken: (a) large scale “bulk” polymerizations monitored by quenching aliquots and (b) polymerizations monitored by 1H NMR spectroscopy using both initial rate measurements and COPASI30 fitting of full kinetic runs. We obtained high quality 1H NMR spectra in neat epoxide by placing sealed capillaries filled with a deuterated solvent and 1,4-bis(trimethylsilyl)benzene as an internal standard inside the NMR tubes, which allowed for locking, shimming and accurate determination of the reactant concentrations. Triplicate measurements indicated good agreement between runs (Table S5). The results from analysis of quenched bulk polymerizations using a (salph)AlCl:[PPN]Cl:BO:CPMA ratio of 1:0.9:500:100 are shown in Figure 2 (orange triangles). The 1:0.9 ratio of (salph)AlCl:[PPN]Cl was chosen based on previous work which showed that a slight excess of metal complex relative to cocatalyst resulted in the optimal balance of rate and control of side reactions.23 The same reaction was performed in an NMR tube and monitored by 1H NMR spectroscopy (condition 1, Table 1) and the data were also plotted in Figure 2 (blue circles). The conversions of CPMA over time for both methods are in good agreement, suggesting the conclusions made from NMR kinetics studies can be related to larger scale reactions. Notably, under these conditions of excess BO, CPMA decays linearly over time, indicating a zero order dependence of the rate on [CPMA]. A key observation was that the initially yellow polymerization solution darkens to deep red as the reaction nears completion, a result with implications for the nature of the complexes present in the reaction solution (see below). Next, a series of polymerizations was performed in which the epoxide concentration was varied from ∼5 to 8 M (200−475 equiv) and initial rates were measured (20% completion, Table 1, conditions 2−5). A linear relationship was observed between the initial rates of the polymerization and the concentration of BO (Figure 3a), indicating a first-order dependence on [BO]. Similarly, the amount of CPMA was varied (Table 1, conditions 2, 6, 7) and initial rates were measured that did not significantly change (Figure 3b), indicating a zero-order dependence on CPMA that agrees with the results of the bulk polymerization

Figure 2. (a) Conversion of CPMA over time for copolymerization with (salph)AlCl:[PPN]Cl:BO:CPMA ratio of 1:0.9:500:100 (1 equiv = 13 μmol). Results from polymerizations monitored in bulk are shown as orange triangles, and those from a single kinetic experiment monitored by 1H NMR are shown as blue circles. (b) Photographs of reaction solutions at the indicated time points.

Table 1. Effects of Varying BO and CPMA Concentrations on Copolymerization Rates and Rate Constantsa cond. #

BO/CPMA exptlb

BO:CPMA theor

initial rate (×10−4 M s−1)c

kobs (×10−5s−1)d

1 2 3 4 5 6 7

5.0(5) 4.4(4) 3.4(5) 2.8(1) 1.8(1) 6.1(4) 10(1)

500:100 475:100 400:100 300:100 200:100 475:75 475:50

2.3(3) 2.3(1) 2.0(5) 1.5(2) 1.1(1) 2.0(4) 2.1(6)

2.5(6) 2.9(2) 3.2(5) 3.0(3) 3.4(7) 2.4(6) 3.3(4)

a

The target concentration for 1 equiv of (salph)AlCl was 19 mM (13 μmol in ∼700 μL measured total volume). A constant 1:0.9 ratio of (salph)AlCl:[PPN]Cl was used. Each condition was measured in triplicate, with average values listed. bDetermined by 1H NMR using an internal standard. cCalculated initial rate at 20% conversion of anhydride. dCalculated using the equation d[Pol]/dt = kobs[BO] in the COPASI fitting software.

experiments. The data thus are consistent with an overall rate law d[Pol]/dt = kobs[BO] with an observed pseudo-first-order rate constant (kobs) of 3 × 10−5 s−1. We verified the results of the initial rate measurements by fitting the entire collected kinetic data using COPASI.30 Data for all 10 different conditions were plotted with the suggested rate law d[Pol]/ dt = kobs[BO], and good agreement was found between the predicted reaction profiles and the experimental data as illustrated by the representative case shown in Figure 4 (see Figures S6−S15 for remaining data). Additionally, the rate constant was calculated for each condition as shown in Table 1, with an average kobs = 3.1(5) × 10−5 s−1, in excellent agreement with the kobs calculated using initial rates. Taken together, the data conclusively support the pseudo-first-order rate law. 15225


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constant and the other increased (situations (a) and (b)), the rate increased, but only to a point (roughly 1−2 equiv) after which the rate remained constant (Figure 5a). These results

Figure 3. Initial rates of reaction (20% completion) versus (a) initial BO concentrations (red) and (b) initial CPMA concentrations (blue).

Figure 5. Plots of polymerization conversion with [BO]:[CPMA] = 500:100 (1 equiv = 13 μmol) in which (a) (salph)AlCl is kept constant at 1 equiv and [PPN]Cl is varied (teal circles) and [PPN]Cl is kept constant at 1 equiv and (salph)AlCl is varied (orange squares), and (b) (salph)AlCl and [PPN]Cl are varied concurrently, with linear fit shown. All reactions were quenched after heating at 50 °C for 1 h.

prompted us to view the metal complex and cocatalyst as a cooperative catalytic pair, leading to a series of experiments where both were varied together keeping their relative concentrations the same. Ideally, if the catalyst and cocatalyst worked together as a cohesive unit (i.e., generated a single active species), a first-order dependence of the rate on the pair would be observed. If the catalyst and cocatalyst worked independently, the rate would exhibit a separate first-order dependence on each and an overall second-order dependence on the pair. Indeed, when varied as a pair, CPMA conversion increased linearly as the catalyst/cocatalyst concentration was increased, suggesting a first-order dependence on the catalytic pair (Figure 5b).31 Such ion pairing in the moderately polar medium of BO as effective solvent is not unexpected. This conclusion was further verified through NMR kinetics analysis using initial rates, COPASI analysis of full data sets, and the normalized time scale method32,33 for reactions with 650:100 BO:CPMA and 1−3 equiv of the pair (details provided in the SI). Together, the data support a complete rate law of d[Pol]/dt = kp[Cat][BO], where [Cat] is the concentration of (salph)AlCl or [PPN]Cl (i.e., the catalytic pair) and kp = 1.5(2) × 10−3 M−1 s−1.

Figure 4. Representative kinetic plot for the copolymerization reaction under condition 1 (Table 1). Concentration data for BO (red), CPMA (blue), and polymer repeat unit (Pol, gray) are displayed as calculated from integrations of 1H NMR data, calibrated with an internal standard, and with COPASI fits displayed as black lines.

Because both [PPN]Cl and an Al complex must be present to observe activity, we sought to determine the kinetic order in each individually and as a cooperative pair. Experiments involving both quenching of bulk polymerizations and NMR analysis were performed. In the bulk polymerization experiments, reactions were run at 50 °C and quenched after 1 h, starting from a constant [BO]:[CPMA] ratio of 500:100 with (a) (salph)AlCl kept constant at 1 equiv (1 equiv = 13 μmol) and [PPN]Cl varied from 0.25 to 4 equiv, (b) [PPN]Cl kept constant at 1 equiv and (salph)AlCl varied from 0.25 to 3 equiv, and (c) (salph)AlCl and [PPN]Cl both varied concurrently from 0.25 to 1.5 equiv. When one concentration was kept 15226


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[PPN]+, or perhaps a weakly coordinated ion pair as suggested by the kinetic order in combined catalyst/[PPN] salt.

Synthesis and Reactivity of Intermediates. In order to gain insight into the individual reaction steps involved in the catalytic copolymerization, we targeted model complexes of possible intermediates comprising alkoxide and/or carboxylate moieties for synthesis and studies of their reactivity. The complexes (salph)AlO i Pr and (salph)AlO 2 CAd (Ad = adamantyl) were prepared from reaction of salphH2 with Al(OiPr)3 or (salph)AlCl with NaO2CAd, respectively, and were characterized by 1H and 13C NMR spectroscopy and highresolution mass spectrometry (Figure 6). While [PPN][O2CAd] could be synthesized,12 [PPN][OR] species could not be made due to their known instability.34

Figure 8. Targeted 6-coordinate Al complexes.

Since the (salph)AlOiPr and [PPN][O2CAd] mixture (AC) is capable of ring-opening both BO and CPMA, a key question concerns the rates of these two reactions, which would have to be different if AC can be considered the active species in the copolymerization. We addressed this question through two types of experiments. A competition study was conducted at 50 °C in which a mixture of (salph)AlOiPr and [PPN][O2CAd] was treated with an equimolar mixture of BO and CPMA (1 equiv each), and monitored by 1H NMR spectroscopy. This AC mixture reacted rapidly with CPMA while leaving the BO untouched, but after ∼50% of CPMA was consumed, BO began to react. In a second set of experiments, the combination of (salph)AlOiPr and [PPN][O2CAd] was reacted with each monomer separately and the reaction rates were measured. Both reactions showed an approximate first-order decay of monomer, with initial rates for the reactions with BO and CPMA equal to 1.03(2) × 10−7 and 5.4 × 10−6 M/s, respectively. Thus, anhydride ring-opening is an order of magnitude (∼50×) faster than epoxide ring-opening. At the typical bulk polymerization ratio of 500:100 epoxide to anhydride, the reaction would need to reach ∼92% completion for the rates of ring-opening of epoxide and anhydride to be comparable. We also evaluated the rate of BO ring-opening by the mixture of [PPN][O2CAd] and (salph)AlO2CAd (carboxylatecarboxylate, CC, again as a preferred 6-coordinate anionic Al complex with a weakly associated [PPN]+ counterion). The initial rate was found to be 4.4(4) × 10−7 M/s, only slightly (∼4×) faster than the ring-opening of BO by AC. We hypothesize that this rate difference is due to a trans influence. In the case of CC, BO would bind trans to a weakly donating carboxylate anion, while with AC, the trans ligand is a more strongly donating alkoxide anion, attenuating the Lewis acidity of the Al3+ center and raising the barrier for ring-opening. To obtain further insight into the nature of the active species responsible for ring-opening of BO or CPMA, we examined the mixture of (salph)AlOiPr and [PPN][O2CAd] (AC) and the mixture of (salph)AlO2CAd and [PPN][O2CAd] (CC) by NMR spectroscopy and DFT calculations, noting diagnostic solution color changes under specific sets of conditions. When a 1:1 ratio of [PPN][O2CAd] and (salph)AlO2CAd was mixed overnight at room temperature, the solution remained yellow/ orange (Figure 9F). 1H NMR spectroscopy indicated one set of broad ligand peaks, which we interpret as indicating a rapid equilibrium between (salph)AlO2CAd and “free” [PPN][O2CAd] (for full discussion, see SI). When a 1:1 ratio of (salph)AlOiPr and [PPN][O2CAd] was mixed, the initially yellow color of (salph)AlOiPr (Figure 9B) immediately became dark orange and gradually turned dark red (Figure 9E), the same color as observed at the end of the copolymerization (Figure 2, bottom). Monitoring of the reaction at 50 °C by 1H NMR spectroscopy showed the salph ligand peaks of

Figure 6. Model complexes studied as possible copolymerization intermediates.

A series of experiments was performed to probe the reactivity of individual aluminum complexes, [PPN][O2CAd], and combinations of the two. In order to maintain concentrations analogous to those of a bulk polymerization, BO (500 equiv) or CPMA (25 equiv) and one equiv (13 μmol) of each complex and/or [PPN][O2CAd] were used. These mixtures were heated at 50 °C for 1 h, quenched with methanol, and then analyzed by Direct Analysis in Real Time (DART)-HRMS for ringopened product (Figure 7). For the reactions with BO, the

Figure 7. Ring-opening reactions analyzed by DART-MS.

expected adamantoate opened epoxide was only observed when [PPN][O2CAd] was combined with either (salph)AlOiPr or (salph)AlO2CAd. This suggests that epoxide ring-opening requires an interaction between both the Al complex and [PPN][O2CAd]. Presumably the epoxide is activated through binding to the Lewis acidic metal center prior to attack from the carboxylate. For the reactions with CPMA, ring-opening only occurred when (salph)AlOiPr and [PPN][O2CAd] were combined. It is notable that an Al alkoxide alone is insufficient and that both an Al alkoxide species and a [PPN]+ carboxylate are required for anhydride ring-opening. We note that computations indicate that the thermodynamic sink for the combination of Al alkoxide and a [PPN]+ carboxylate is a 6coordinate Al anion (denoted as “AC”, Figure 8) together with 15227


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postulating that the copolymerization reaction is initiated by reaction of (salph)AlCl and [PPN]Cl with excess BO to yield [PPN][(salph)Al(OR)2] or (salph)AlOR/[PPN][OR] (AAinit; Figure 10). This species is drawn with a dashed line between

Figure 9. Solutions of Al complexes with/without added [PPN]salts: (A) (salph)AlCl, (B) (salph)AlOiPr, (C) (salph)AlO2CAd, (D) 1:1 (salph)AlCl and [PPN]Cl with excess BO, (E) 1:1 (salph)AlOiPr and [PPN][O2CAd], (F) 1:1 (salph)AlO2CAd and [PPN][O2CAd].

(salph)AlOiPr converted to new ones associated with a different (salph)Al species that reaches an equilibrium with the starting (salph)AlOiPr at an approximate 1:1 ratio (Figures S33 and S34). This new species could arise from salt metathesis between (salph)AlOiPr and [PPN][O2CAd] to form (salph)AlO2CAd and [PPN][OiPr] or a 6-coordinate anionic aluminum species, [PPN][(salph)Al(OiPr)(O2CAd)] (AC). While neither option can be definitively ruled out, the latter product is expected to be more probable since the alkoxide is likely to bind more strongly to Al than is a carboxylate and thus exchange is unlikely. 31P NMR showed no degradation of the [PPN]+ cation, which would be expected upon the formation of an unstable [PPN][OiPr] salt.34 Regardless of which product is formed, both [PPN][OiPr] and [PPN][(salph)Al(OiPr)(O2CAd)] would be expected to have a highly reactive alkoxide that could rapidly ring-open a cyclic anhydride. While all attempts to make an AA species led to dark red solutions (for example, Figure 9D), no single species could be isolated. As previously noted, when excess epoxide is used the color changes from pale yellow to deep red when all anhydride is consumed (Figure 2). To explore further the potential chromophores present in solution, linear response timedependent density functional theory (TD-DFT) calculations of proposed 5- and 6-coordinate intermediates were performed at the PBE0/6-31+G(d,p) level of theory.26,27 Intense absorptions were predicted for the HOMO to LUMO transitions of AA, AC, and CC with λmax values in the visible range of the spectrum at 466, 453, and 435 nm, respectively. By contrast, HOMO−LUMO transitions for the 5-coordinate complexes (salph)AlOiPr and (salph)AlOAc (truncated representations of the species present during the polymerization used for simplicity’s sake) were predicted to be higher in energy at 415 and 412 nm, respectively. Tests with other density functionals provided uniform agreement on the hypsochromic shift of the 5-coordinate species relative to the 6-coordinate, although individual λmax values varied. This suggests that the bright red color observed during polymerization may be attributed to the presence of AA and/or AC intermediates. However, UV−vis spectra of the solutions shown in Figure 9, which clearly showed a difference in color by visual inspection at typical polymerization concentrations, when diluted ∼600× in order to bring the absorbance values into measurable range, all displayed the same absorption spectrum (Figure S40). We attribute this finding for the AC mimic (Figure 9E) to the effect of dilution on the equilibrium between (salph)AlOiPr and [PPN][O2CAd] which would reduce the absorbance of the red product by a factor of 360 000well below the detection limit given similar expected extinction coefficients for 5- and 6coordinate complexes as discussed below. Mechanistic Hypotheses and Evaluation by Theory. The combined experimental results may be interpreted by

Figure 10. Proposed copolymerization initiation to yield bis(alkoxide) species, AAinit and AA (P = polymer chain; R1 and R2 used to simplify drawing of ring-opened CPMA).

one alkoxide and the Al3+ ion to acknowledge the uncertainty in our understanding of this interaction. In addition, we propose that a similar bis(alkoxide) species may be a catalytic intermediate, and indicate this by drawing an equivalent structure with polymeric alkoxides instead of the initially formed chlorinated species (AA). The only reasonable fate for AA is to react with anhydride to yield AC (Figure 11), again drawn with one of its ligands bound to Al via a dashed line to signify possible weak association (arbitrarily, the alkoxide). This central intermediate, AC, can revert back to AA via binding, activation, and ringopening of epoxide (cycle 1), or can react with anhydride to yield CC (cycle 2), which we choose to draw with one carboxylate bound and the other free as a [PPN]+ salt, thus poised to bind and ring-open epoxide (consistent with our finding that the CC model reacts with BO ∼4× faster than AC). Our finding that the AC model complex ring-opens CPMA ∼50× faster than BO indicates that cycle 2 is preferred when anhydride concentrations are sufficiently high, with cycle 1 only becoming important as polymerization nears completion. Accordingly, the rate-determining step involves the ring-opening of an epoxide by the CC mixture, which is also the likely steady state species formed upon initiation. This hypothesis leads to another: that as polymerization completes and anhydride is depleted the concentration of AA increases, and that this species is responsible for the red color and the tendency for side-reactions to occur at the end of the reaction. This indicates that alkoxide end groups are capable of engaging in side reactions, while carboxylate end groups are not. The productive copolymerization proceeding through cycle 2 with ring-opening of anhydride being faster than epoxide and the intimate involvement of [PPN]+ at every stage yields a rate law consistent with that observed by experiment (first-order in [BO] and in the combination of [Al] and [PPN]Cl, zero-order in [CPMA]). To evaluate these mechanistic hypotheses and gain further insights, extensive DFT calculations were performed on simplified systems (lacking para tBu groups on salph ligand, isopropoxide as alkoxide, propylene oxide as epoxide, and whenever possible, acetate instead of more complicated carboxylates; Figure 12). The analogous cycle to that drawn in Figure 11 is predicted, with 333 K relative free energies provided for all stationary points and several key observations we now highlight. Ring-opening of anhydride by AA and AC involves direct attack by the alkoxide bound to Al in 6-coordinate anionic species, with coordination of acetate to the 5-coordinate Al− 15228


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Figure 11. Proposed mechanism for copolymerization of BO and CPMA (depicted by a simplified succinic anhydride).

Figure 12. Calculated mechanism for copolymerization of propylene oxide and succinic anhydride with 333 K relative Gibbs free energies (kcal/ mol) computed at the SMD(THF)//M06-2X/6-311+G(d,p)//M06-L/6-31+G(d,p) level of theory. AA and AC represent the starting species for each cycle (1 and 2, respectively), while AA′ and AC′ represent the ending species after an epoxide is opened.

OiPr species being favored by 4.6 kcal/mol. Note that, while the anhydride opening would likely be faster with an uncoordinated alkoxide, as was noted in a similar polymerization reaction study,28 dissociation of an alkoxide from the aluminum center is predicted to be an extremely endergonic process (see SI for details). Considering the predicted energetics for the coupled reaction cycles, partitioning from reactive intermediate AC involves either a free energy of activation of 32.4 kcal/mol to

return to AA (left cycle) or a free energy of activation of 27.0 kcal/mol to proceed to CC (right cycle). This is consistent with the observed experimental preference noted above for an isolated AC to preferentially open anhydride compared to epoxide, albeit by a somewhat higher free-energy margin than would be associated with a 50-fold preference at 323 K (∼2.7 kcal/mol). The free energy of activation to return to AC by ring-opening of propylene oxide is predicted to be 33.3 kcal/ 15229


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aluminum center which could be in three combinations: two alkoxides (AA), a mixed alkoxide/carboxylate (AC), or two carboxylates (CC). The propagating mechanism could alternate between AA and AC or AC and CC. Studies of initiation indicated ring-opening of epoxides by all sources of chloride, to form an AA mixture. One ring-opening of anhydride leads to an AC mixture, which could either open epoxide to reform AA or could open anhydride to form CC. Experiment and theory both indicated a strong preference for the latter, followed by turnover-limiting opening of epoxide by CC (cycle 2). Once anhydride is fully consumed, the AC mixture opens one more equivalent of epoxide, apparently generating a deep red AA species. We propose that the preference for cycle 2 during most of the polymerization suppresses side reactions such as epimerization and transesterification which are associated with the more reactive alkoxide end groups, until such time as polymerization is complete and the concentration of AA increases.15,23 These mechanistic conclusions have potential implications for future catalyst design. For example, it is evident that enhancing the rate of epoxide opening by CC will increase the overall catalytic copolymerization rate. Moreover, we hypothesize that changes to the catalyst system that keep it operating in cycle 2 and prevent it from entering cycle 1 will circumvent deleterious side reactions. Efforts to test these hypotheses and develop superior catalysts for epoxide/anhydride copolymerizations are underway.

mol. Interestingly, this is a higher free energy of activation for epoxide opening than that associated with going from AC to AA, which is to be expected given the weaker activating power of a trans carboxylate ligand compared to a trans alkoxide ligand, but, as it is the only pathway forward from intermediate CC as reverse reaction is uphill by more than 46 kcal/mol, it becomes the turnover-limiting step for propagation. Indeed, these energetics are consistent with the experimental observation that the reaction is zero-order in anhydride and first-order in propylene oxide, as regeneration of CC by proceeding around the right reaction cycle occurs with low activation free energy compared to the turnover-limiting step involving epoxide. The overall driving force for one revolution around cycle 2 is predicted to be 14.7 kcal/mol (cf. relative free energy values associated with AC and AC′ in Figure 12). Finally, once the anhydride is fully consumed, AA can reform and ultimately be quenched upon workup. As noted above, however, experimental attempts to isolate 6-coordinate aluminum intermediates were not successful. While these species have not been ruled out as reactive intermediates during polymerization, the predicted prevalence and stability of these species, relative to 5-coordinate aluminum species, could not be experimentally confirmed.

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CONCLUSIONS Important mechanistic insights into the copolymerization of 1butene oxide and carbic anhydride by a (salph)AlCl/[PPN]Cl catalytic pair have been obtained through synergistic kinetics studies, model reaction experiments, and DFT calculations. As reported in previous work on a related system,6 we identified a first-order dependence on epoxide concentration, indicating that the turnover-limiting step is either epoxide binding or opening. We propose a bind and insert pathway, in which a free carboxylate can attack an epoxide that is activated by the metal. Theory predicts this pathway to be significantly more favorable than a concerted pathway previously proposed for epoxide/ CO2 copolymerizations.25 While 6-coordinate anionic Cr species have been successfully isolated and proposed as active intermediates in the copolymerization of epoxides with both CO2 and anhydrides,6 the analogous intermediates with aluminum were not isolable; instead, combinations of (salph)AlX and [PPN]X (X = alkoxide or carboxylate) appear to exist as dynamic mixtures that include anionic 6-coordinate aluminum species in equilibrium at high concentrations, as judged by NMR and UV−vis experiments, with the latter interpreted with the assistance of time-dependent density functional theory calculations. When the ratio of [PPN]Cl to (salph)AlCl was varied, a maximum rate was observed with a slight excess of iminium cocatalyst (∼1.5:1). A similar result was reported for (salph)CrCl/[PPN]Cl and (salph)AlCl/DMAP pairs.8 We observed a first-order dependence when both catalyst and cocatalyst were varied together in a 1:1 ratio, indicating that they need to be considered as a single catalytic unit instead of separate components, as found for an epoxide/CO2 copolymerization.6 This result, when taken with the first-order dependence on [epoxide] and zero-order dependence on [anhydride], leads us to conclude that the rate-determining step is the ring-opening of epoxide activated by coordination to the Al complex by a [PPN] carboxylate species. An important factor discovered in this study is the importance of the anions present during propagation. With a 1:1 ratio of catalyst to cocatalyst, there are two anions per

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/jacs.7b09079. Experimental and computational details, including Figures S1−S54, Tables S1−S21, and Scheme S1 (PDF)

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AUTHOR INFORMATION

Corresponding Authors

*[email protected] *[email protected] *[email protected] ORCID

Megan E. Fieser: 0000-0003-0623-3406 Maria J. Sanford: 0000-0001-5265-6886 Lauren A. Mitchell: 0000-0002-1311-0108 Christine R. Dunbar: 0000-0001-9948-4583 Mukunda Mandal: 0000-0002-5984-465X Nathan J. Van Zee: 0000-0002-7899-9163 Christopher J. Cramer: 0000-0001-5048-1859 Geoffrey W. Coates: 0000-0002-3400-2552 William B. Tolman: 0000-0002-2243-6409 Author Contributions ‡

M.E.F. and M.J.S. contributed equally.

Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Funding for this project was provided by the Center for Sustainable Polymers, an NSF Center for Chemical Innovation (CHE-1413862). This work made use of the NMR facility at Cornell University which is supported, in part, by the NSF 15230


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(27) Nakano, K.; Hashimoto, S.; Nozaki, K. Chem. Sci. 2010, 1, 369− 373. (28) Robert, C.; Schmid, T. E.; Richard, V.; Haquette, P.; Raman, S. K.; Rager, M.-N.; Gauvin, R. M.; Morin, Y.; Trivelli, X.; Guérineau, V.; Del Rosal, I.; Maron, L.; Thomas, C. M. J. Am. Chem. Soc. 2017, 139, 6217−6225. (29) Martínez, L. E.; Leighton, J. L.; Carsten, D. H.; Jacobsen, E. N. J. Am. Chem. Soc. 1995, 117, 5897−5898. (30) Hoops, S.; Sahle, S.; Gauges, R.; Lee, C.; Pahle, J.; Simus, N.; Singhal, M.; Xu, L.; Mendes, P.; Kummer, U. Bioinformatics 2006, 22, 3067−3074. (31) We hypothesize that the nonzero intercept of the indicated linear fit results from slow initiation at low concentrations of cocatalysts. (32) Burés, J. Angew. Chem., Int. Ed. 2016, 55, 2028−2031. (33) According to this method, the decay of CPMA was plotted against the normalized time scale, t[Cat]N, where t is time, [Cat] is the initial concentrations of both the catalyst and cocatalyst, (salph)AlCl and [PPN]Cl, and N is the order. The three conditions were plotted against possible reaction orders of zero, first, and second, on the normalized time scale, with the best overlay found for the first-order case (Figure S20). (34) Martinsen, A.; Songstad, J.; et al. Acta Chem. Scand. 1977, 31, 645−650.

under award number CHE-1531632. The authors acknowledge the Minnesota Supercomputing Institute (MSI) at the University of Minnesota for providing resources that contributed to the research results reported within this paper. We also thank the Minnesota NMR Center and the UMN Chemistry NMR Center for their assistance with kinetics experiments and Kiley Schmidt for assistance with the TOC graphic.

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Mechanistic Insights into the Alternating Copolymerization of Epoxides

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