Modular Synthesis of Polyferrocenylsilane Block Copolymers by Cu

Article pubs.acs.org/Macromolecules

Modular Synthesis of Polyferrocenylsilane Block Copolymers by Cu-Catalyzed Alkyne/Azide “Click” Reactions Meng Zhang,† Paul A. Rupar,‡ Chun Feng,† Kaixiang Lin,† David J. Lunn,‡ Alex Oliver,‡ Adam Nunns,‡ George R. Whittell,‡ Ian Manners,*,‡ and Mitchell A. Winnik*,† †

Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, M5S 3H6 Ontario, Canada School of Chemistry, University of Bristol, Bristol, BS8 1TS United Kingdom

‡

S Supporting Information *

ABSTRACT: This paper reports a new synthetic strategy for the preparation of polyferrocenylsilane (PFS) block copolymers. The block copolymers were prepared by Cu-catalyzed alkyne/azide cycloaddition of two homopolymer precursors that allows access to new functional PFS block copolymers (e.g., polyferrocenylsilane-block-poly(N-isopropylacrylamide)) (PFS-b-PNIPAM)). Trimethylsilyl-protected, alkyne-terminated PFS homopolymer was first prepared via living anionic polymerization, terminating living PFS with commercially available 4-[(trimethylsilyl)ethynyl]benzaldehyde. Subsequent deprotection of the trimethylsilyl group with NaOMe yielded the ethynyl-terminated PFS (ω-alkyne-PFS). This method should be readily applicable to other polymers prepared by living anionic polymerization. Subsequently, non-PFS homopolymers containing a complementary “clickable” azide functional group were synthesized either by anionic polymerization, modification of a commercially available polymer, or atom transfer radical polymerization via two different approaches. In an azide postpolymerization modification approach, polystyrene (PS) and poly(methyl methacrylate) (PMMA) were functionalized by azide substitution of the terminal halide after ATRP. Alternatively, the azide moiety was incorporated into the ATRP initiator prior to polymerization, e.g., to give PNIPAM-N3 and poly(2-(dimethylamino)ethyl methacrylate) (PDMAEMA-N3). Finally, the alkyne-terminated PFS segment and the azide functionalized counter block were coupled through the formation of a 1,2,3triazole ring. In this report, PFS-b-PNIPAM, PFS-b-PDMAEMA, PFS-b-PS, PFS-b-PMMA, PFS-b-polydimethylsiloxane, and PFS-block-poly(ethylene oxide) have been synthesized via this convenient modular protocol in high yield and high purity.

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INTRODUCTION

Almost all previous examples of PFS block copolymers were synthesized by sequential anionic polymerization. This method has been broadly employed to generate many different types of block copolymers, where the addition of the monomers follows an order of decreasing end-group reactivity.10 Although this polymerization technique allows access to high-molecularweight polymers of controlled length and low polydispersity, it has several significant limitations. The reactive anions typical of anionic polymerization will not tolerate monomers that contain an acidic proton (e.g., acrylamide, N-alkylacrylamides), or reactive functional groups where side reactions may occur (e.g., acrylates or methacrylates). Other monomers that can undergo anionic polymerization, such as 2-vinylpyridine (2VP) or ethylene oxide (EO), will not react and polymerize with the propagating PFS anion, and at the same time, a propagating P2VP carbanion is not nucleophilic enough to initiate polymerization of dimethylsilaferrocenophane, 1, the precursor to PFS. In this example, a strategy first reported by Rehahn (addition of dimethylsilacyclobutane followed by 1,1-diphenyl-

Polyferrocenylsilanes (PFSs) are an interesting class of mainchain transition-metal-containing polymers that are readily available via the ring-opening polymerization (ROP) of siliconbridged ferrocenophane monomers (e.g., dimethylsilaferrocenophane, 1).1,2 Block copolymers containing PFS segments are attracting growing attention as functional materials due to their intriguing self-assembly properties,3 including the preparation of rodlike micelles of nearly monodisperse length.4 A remarkable feature of these micelles is that they can be extended in length by further addition of a block copolymer as a solution in a common solvent. This “living growth” property also allows one to create block comicelles by adding a second block copolymer with a different corona-forming block or one with a core-forming block that has a crystal structure similar to PFS, such as polyferrocenylgermane that will grow epitaxially off the semicrystalline PFS micelle core.5 The well-defined architectures of PFS block copolymers that one can obtain in solution and in the solid state have been employed as precursors for magnetic ceramics,2c,6 as materials with catalytic activity,7 as lithographic etch resists,8 and as redox-active materials.9 © 2013 American Chemical Society

Received: September 28, 2012 Revised: January 6, 2013 Published: February 7, 2013 1296

dx.doi.org/10.1021/ma302054q | Macromolecules 2013, 46, 1296−1304

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Scheme 1. Synthetic Protocol for the Synthesis of Alkyne-Functionalized PFS Homopolymer (ω-Alkyne-PFS)

Scheme 2. Synthesis of PFS Block Copolymers via the CuAAC Reaction

ethylene) can be used to amplify the reactivity of the PFS anion, followed by addition of another monomer such as 2VP or MMA.11 While this methodology works well, it is not particularly convenient. PFS can also be prepared by photoactivated anionic polymerization. Exposure of dimethylsilaferrocenophane 1 to light in the presence of an anionic initiator leads to photocontrolled ring-opening polymerization (PROP). The photoirradiation selectively activates the iron−cyclopentadienyl bond in 1, so that PROP exhibits higher compatibility with functional groups than the butyllithium-initiated anionic polymerization of 1.12 While a range of PFS block copolymers are accessible via the versatile PROP method,13 this approach does not allow one to synthesize PFS-b-acrylate, PFS-bmethacrylate, or PFS-b-acrylamide block copolymers by sequential anionic polymerization, as the uncoordinated cyclopentadienyl propagating site is insufficiently reactive. For these reasons, it would be useful to have alternative strategies for synthesizing PFS block copolymers. Over the past several years there has been a strong and growing interest in the coupling of two presynthesized homopolymer precursors as a method to prepare well-defined block copolymers. This strategy relies on a class of reactions like the Cu-catalyzed alkyne/azide cycloaddition (CuAAC) reaction and some other types of reactions (e.g., thiol−ene, Diels−Alder, pyridyl disulfide) that are categorized as robust, efficient, and orthogonal.14 This approach has been used recently for the fabrication of soft materials,15 drug delivery constructs,16,17 and novel structures.18 CuAAC is the most well-known “click” reaction that meets the philosophy introduced by Sharpless et al. in 2001.19 For the synthesis of block copolymers, it allows a chemist to use near equimolar amounts of the building blocks to obtain products in high yields under mild conditions, without tedious fine-tuning of the reaction conditions or purification process.20

Recently, the combination of controlled polymerization techniques with CuAAC “click” chemistry has significantly expanded the accessibility of macromolecular materials with novel functionality (e.g., bioconjugation and fluorescence labeling), controlled architecture, and versatile chemical composition.15a,21 The fundamental idea of this approach is to generate a target polymer by covalently assembling the individually prepared “clickable” building blocks. Irrespective of the specific polymerization techniques used to construct the building blocks, the preparation approaches for assembling the target molecules generally fit into three categories based on how the “clickable” subunits are introduced: (i) one can incorporate the alkyne or azide functional group into the initiator; (ii) one can modify the polymer if it contains an appropriate terminal group (such as the chloride or bromide in a polymer synthesized by atom transfer radical polymerization, ATRP); (iii) one can introduce a monomer or comonomer with a “reactive” pendant group into a polymerization to obtain precursors for brushlike copolymers.22 The synthesis of polymers containing “reactive” end groups or pendant groups has been extensively studied for controlled radical polymerization.15a,18,23 In contrast, there are very few applications of these methods to polymers synthesized by living anionic polymerization, even though anionic polymerization provides access to high-molecular-weight polymers, has the advantage of fine control over molecular weight distribution (MWD), and can be used to polymerize many interesting classes of monomers (e.g., dienes). One of the first examples was reported recently by Touris and Hadjichristidis,24 where they described the synthesis of a protected acetylene-functionalized organolithium species, which was able to initiate styrene polymerization and, as a macroinitiator, reinitiate isoprene polymerization. Another report, by Reinicke and Schmalz,25 described an azido-functionalized poly(2-vinylpyridine)-blockpoly(ethylene oxide) (P2VP-b-PEO-N3), obtained by terminat1297


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MALDI-TOF measurements were performed using an Applied Biosystems 4700 Proteomics analyzer running in the reflector mode. Samples were prepared using a dithranol matrix (20 mg/mL, THF). The polymer sample (10 mg/mL, THF) was mixed in a 10:1 (v/v) ratio (matrix:analyte). Approximately 1 μL of the mixed solution was deposited onto the sample plate and allowed to dry in air. Preparation of ω-(TMS-Alkyne)-PFS. In an Ar-filled glovebox at room temperature, n-BuLi (19 μL, 1.6 M in hexanes) was added to a stirred THF solution (3 mL) of dimethylsilaferrocenophane (181 mg, 0.748 mmol). After 60 min, the color of the solution changed from red to amber, indicating complete conversion of monomer. 4[(Trimethylsilyl)ethynyl]benzaldehyde (TSEBA) (61 mg, 0.34 mmol) was added to quench the reaction. The mixture was allowed to stir overnight before precipitating into 50 mL of methanol. ω(TMS-alkyne)-PFS was purified by three cycles of precipitation from THF into methanol. The polymer was dried at 40 °C overnight under vacuum, with yield of 180 mg (96%). The GPC trace (Figure S1) and 1 H NMR spectrum (Figure S2) are available in the Supporting Information. Preparation of ω-Alkyne-PFS. ω-(TMS-alkyne)-PFS (150 mg, 0.023 mmol) was dissolved in a mixed solvent of THF/MeOH (10:1, v/v) in the presence of an excess of sodium methoxide (60 mg, 1.1 mmol) The mixture was allowed to stir for 24 h at room temperature before precipitating in methanol. The ω-alkyne-PFS was purified by another three cycles of dissolution in THF followed by precipitation in methanol and then dried overnight at 40 °C under mild vacuum. The alkyne-functionalized PFS homopolymer was collected as a light orange powder (yield 140 mg, 94%) and analyzed by MALDI-TOF, GPC, and 1H NMR. General Procedure for the Preparation of PFS Diblock Copolymers via the CuAAC Reaction. PFS block copolymers were prepared via Cu-catalyzed alkyne azide cycloaddition (CuAAC) between ω-alkyne-PFS and its counterparts, α-azido-PNIPAM, ωazido-PEO, α-azido-PDMAEMA, ω-azido-PMMA, and ω-azido-PS. (Experimental details of the synthesis of these azido polymers are reported in the Supporting Information.) In this report, all of the individual coupling reactions followed an identical protocol. Experimental details are provided for one such reaction. [PFS + PNIPAM]. The ω-alkyne-PFS (63 mg, 0.010 mmol), αPNIPAM100 (120 mg, 0.0120 mmol), CuBr (14 mg, 0.12 mmol), and PMDETA (21 μL, 0.10 mmol) were dissolved in THF (10 mL) in a Schlenk tube equipped with a magnetic stir bar and a molar ratio of [alkyne]:[azide]:[Cu]:[ligand] = 1:1.2:10:10. After three cycles of freeze−pump−thaw, the reaction was allowed to stir at 50 °C for 24 h and then stopped by exposing the reaction to air. Aliquots of the mixture were removed before and after the coupling reaction and examined by GPC to monitor the progress of the coupling reaction. The CuBr/PMDETA catalytic system was removed by passing the reaction mixture through a short column filled with basic aluminum oxide. Purification of the PFS Diblock Copolymers. In all instances reported here, except in the synthesis of PFS-b-PDMS, the residual excess azido-functional homopolymer could be readily removed by selective dissolution of the homopolymer and sedimentation of the block copolymer by centrifugation. Table 1 lists the choice of selective solvents that were used to remove the azido-polymers. The dried crude product was suspended in the selective solvent under stirring (ca. 1 mL of solvent for every 20 mg of crude product). The mixture was then subjected to 10 min centrifugation at 4000 rpm. The azidohomopolymer remained in the supernatant, while PFS block copolymer was collected as an orange sediment. In the cases of [PFS + PMMA] and [PFS + PNIPAM], small amounts of unreacted ω-alkyne-PFS were also found after the CuAAC coupling reaction. The residual PFS homopolymer was removed by flushing the polymer mixture through a short silica column (1 cm in diameter and 5 cm in height) by flash chromatography using neat dichloromethane as eluent. A more polar eluent was then used to elute the purified block copolymers, DCM plus 5% methanol for PFS-bPMMA and DCM plus 1% triethylamine for PFS-b-PNIPAM.

ing the anionic polymerization of ethylene oxide with 2azidoisobutyryl chloride. This paper describes the synthesis of a series of PFS block copolymers via a CuAAC coupling reaction in which the PFS block was synthesized by anionic polymerization and the second polymer contained a complementary reactive end group. The strategy we employed began with preparation of an alkyne-terminated PFS homopolymer (ω-alkyne-PFS), as illustrated in Scheme 1. The alkyne was introduced quantitatively following living anionic polymerization of 1 using 4-[(trimethylsilyl)ethynyl]benzaldehyde (TSEBA) containing a protected alkyne to terminate the polymerization. In parallel, a series of azido-terminated non-PFS homopolymers were synthesized. Some were prepared by ATRP, via two different approaches, as illustrated in Scheme 2. For postpolymerization modification, the azide functional group was introduced after polymerization and isolation of the polymer. Alternatively, the azide moiety was incorporated into the ATRP initiator prior to polymerization. Finally, a coppercatalyzed coupling reaction was carried out between the alkyneterminated PFS homopolymer and the azido-terminated nonPFS block to produce a PFS diblock copolymer, where the two building blocks were covalently linked via the formation of a 1,2,3-triazole ring. Compared to conventional sequential living anionic polymerization, this strategy offers a more convenient and modular protocol to prepare PFS block copolymers. It also allows access to new PFS block copolymers (e.g., polyferrocenylsilane-block-poly(N-isopropylacrylamide) (PFS-b-PNIPAM) and a more convenient synthesis of linear PFS-b-PEO).

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EXPERIMENTAL SECTION

Materials and Methods. Styrene (99+%), methyl methacrylate (99%), and 2-(dimethylamino)ethyl methacrylate (DMAEMA) (98%) were purified by passing through a basic aluminum oxide column. NIsopropylacrylamide (NIPAM) (99+%) was recrystallized three times from benzene/hexane (2:1 v/v) prior to use. 4-[(Trimethylsilyl)ethynyl]benzaldehyde (97%) was sublimed under reduced pressure prior to use. CuBr was purified following a standard procedure.26 Hexamethylcyclotrisiloxane (98%) was purified by dissolving in pentane, drying with CaH2, then filtering and subliming on to a 0 °C cold finger. 2-(2-Chloroethoxy)ethanol (99%), sodium azide (99.5%), tetrabutylammonium iodide (99%), dicyclohexanol-18crown-6 (99%), ethyl α-bromoisobutyrate (98%), 2-bromoisobutyryl bromide (98%), triethylamine (99%), tris(2-dimethylaminoethyl)amine (Me6TREN), n-butyllithium solution (1.6 M in hexane), 1,1,4,7,10,10-hexamethyltriethylenetetramine (HMTETA, 97%), secbutyllithium solution (1.4 M in cyclohexane), ferrocene (98%), N,N,N′,N′,N′-tetramethylethylenediamine (99%), N,N,N′,N′,N′-pentamethyldiethylenetriamine (PMDETA, 99%), and monomethyl ether mesylated poly(ethylene glycol) were used as-received. (Bromomethyl)chlorodimethylsilane (97%) and dichlorodimethylsilane (99.5%) was distilled prior to use. All chemicals were purchased from Aldrich except for tris(2-dimethylaminoethyl)amine (Alfa Aesar). PEO113-N3 was synthesized using an established synthetic procedure.27 Instrumentation. Gel Permeation Chromatography (GPC) was carried out on a Viscotek GPCmax chromatograph equipped with a triple detector array and a UV detector. Polystyrene standards (Aldrich) were used for calibration, and THF was used as the eluent. The flow rate was 1.0 mL/min. For PDMAEMA, PFS-b-PDMAEMA, PNIPAM, and PFS-b-PNIPAM, the flow rate was 0.6 mL/min and a THF solution containing 0.25 g/L tetra-n-butylammonium bromide in THF was used as the eluent. 1 H and 13C NMR (400 MHz) spectra were recorded on a Varian Hg 400 or a Varian VnmrS 400 spectrometer with a 45° pulse width and 10 s delay time at 25 °C. 1298


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initiator.29 The reaction was allowed to proceed for 60 min, over which time the color of the solution changed from red to amber, indicating complete conversion of the monomer. Excess TSEBA (300 μmol for 30 μmol of polymer) was added to terminate the polymerization through reaction of the ferrocene carbanion with the electrophilic aldehyde of TSEBA, to install a trimethylsilyl (TMS)-protected alkyne moiety at the polymer chain end. The resulting ω-(TMS-alkyne)-PFS was isolated and analyzed before deprotection of the alkyne group. Gel permeation chromatography (GPC) measurements with a triple detector system (Figure S1) showed that the polymer was characterized by Mn = 6400 g/mol and a narrow molecular weight distribution (PDI = 1.03). From the 1H NMR spectrum of the ω-(TMS-alkyne)-PFS (Figure S2), we calculated a mean degree of polymerization (DPn) of 26, by comparing the integrals of the proton signals from the ferrocenyl groups (δ = 4.27, 4.10 ppm) and the dimethylsilyl moieties (δ = 0.54 ppm), with the characteristic peaks of the TSEBA adduct (−Si(CH3)3 at δ = 0.26 ppm and the phenyl ring peaks at δ = 7.73, 7.40 ppm). The agreement between the degree of polymerization calculated from the GPC measurements and that obtained by 1 H NMR end-group analysis suggests that end-group functionalization was essentially quantitative. To remove the protecting group from the terminal alkyne, ω(TMS-alkyne)-PFS was allowed to stir for 24 h in the presence of excess sodium methoxide, in a mixed solvent of THF/ MeOH (10:1, v/v) at room temperature. The ω-alkyne-PFS was collected by precipitation from methanol and dried in a vacuum oven overnight. The 1H NMR spectrum of ω-alkynePFS provides clear evidence for the complete deprotection due to disappearance of the −Si(CH3)3 signal at 0.26 ppm, as shown in Figure 1 inset. A GPC trace of ω-alkyne-PFS is

Table 1. Solvents Employed for the Selective Dissolution of Azido-Functionalized Homopolymers in the Presence of Their PFS Diblock Copolymers

selective solvent

PS-N3

PMMAN3

PNIPAMN3

PEON3

PDMAEMAN3

acetone

acetone

H2O

H2O

CH3OH

In the case of [PFS + PDMAEMA], small amounts of unreacted ωalkyne-PFS were found after the CuAAC coupling reaction. To remove the residue PFS homopolymer, the reaction mixture was dissolved in 2 mL of THF under gentle stirring. As hexane (6 mL) was added dropwise, a precipitate appeared. After 20 min centrifugation at 3000 rpm, the purified block copolymer was collected as the sediment. In the case of [PFS + PDMS], the block copolymer was purified via size exclusion chromatography to afford the pure block copolymer. All PFS block copolymers were dried at 40 °C under vacuum and analyzed by GPC and 1H NMR. The results are compiled in Table 2.

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RESULTS AND DISCUSSION Preparation of ω-Alkyne-PFS Homopolymer. The diblock copolymers described in this paper share a common PFS block. The key step common to the preparation of all of these polymers is the synthesis of PFS, prepared by anionic polymerization, followed by essentially quantitative trapping of the propagating anion with 4-[(trimethylsilyl)ethynyl]benzaldehyde (TSEBA), a convenient and commercially available reagent. This final quenching step introduces a protected terminal alkyne that provides the alkyne functionality for subsequent coupling reactions. The strategy for synthesizing the ω-alkyne-PFS is illustrated in Scheme 1. Dimethylsilaferrocenophane (1) was polymerized in THF at room temperature in an Ar-filled glovebox using n-BuLi as an

Figure 1. 1H NMR spectrum of ω-alkyne-PFS in C6D6. Inset: magnified 1H NMR spectra (δ = 0 to 1 ppm) of ω-(TMS-alkyne)-PFS (black trace) and ω-alkyne-PFS (red trace) are compared. The proton signal of the TMS protecting group is marked by a black arrow. The mark “x” above several peaks refers to signals from the butylated hydroxytoluene inhibitor in THF, which was evaporated prior to dissolving the sample in C6D6. 1299


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tion of a commercial sample of MeO-PEO-mesylate,27 and poly(dimethylsiloxane) (PDMS) was synthesized by anionic polymerization. Polystyrene and PMMA were chosen as common polymers easily synthesized by ATRP to serve as an initial trial to assess the copper-catalyzed alkyne−azide cycloaddition with ωalkyne-PFS. However, PDMAEMA and PNIPAM are more interesting as partners for block copolymer formation with PFS. Both of these polymers are soluble in alcohols as well as water, opening the possibility for interesting studies of the selfassembly of PFS-b-PDMAEMA and PFS-b-PNIPAM block copolymers. PFS-b-PDMAEMA has been synthesized previously by sequential anionic polymerization, but the synthesis was very challenging, and the examples reported had very short PFS chain lengths.30 PFS-b-PNIPAM cannot be synthesized directly by sequential anionic polymerization because of the acidic amide proton.31 Ishizone et al. avoided this problem for the synthesis of PNIPAM homopolymer by polymerizing Nmethoxymethyl-protected NIPAM monomer with diphenylmethylpotassium in the presence of Et2Zn, followed by hydrolysis with aqueous HCl.32 This approach will not work for PFS-bPNIPAM due to PFS block degradation under the acidic workup conditions. PNIPAM is particularly interesting because of its thermally responsive properties in aqueous solutions. A longer term goal of our research is to examine the properties of PFS-bPNIPAM micelles in water. PFS-b-PEO should also have interesting self-assembly behavior in alcohols and in water. The only example of a PFS-b-PEO diblock copolymer reported in the literature was prepared by coupling of a PFS homopolymer and a PEO homopolymer, each with a terpyridine group at one end, by coordination to a Ru(II) center.33 Preparation of the Azide End-Functionalized Homopolymers. For the polymers prepared by ATRP, two approaches were employed to install the azide moiety at the polymer chain ends, as illustrated in Scheme 2. In the azide postpolymerization modification approach illustrated on the left-hand side of Scheme 2, polymerization was initiated with a traditional initiator that installed a bromine atom at the distal end of the polymer. In a second step, the bromine was converted to an azide. Here, ω-bromo-PS and ω-bromoPMMA were prepared by ATRP, using ethyl α-bromoisobutyrate (EBiB) as the initiator. The terminal bromine on these polymers was then converted to an azide group by treating the polymers with azidotrimethylsilane (TMS-N3) in THF at room temperature for 24 h in the presence of tetrabutylammonium fluoride (TBAF).34 GPC traces for ω-azido-PS (Figure S6A) and for ω-azido-PMMA (Figure S6B) are presented in the Supporting Information. The values of DP and PDI obtained by GPC analysis for these polymers are presented in Table 2. One of the problems with this postpolymerization modification approach is that it is very difficult to quantify the extent of conversion of the bromine to azide, although it is normally thought to take place in high yield.35 In addition, dead

presented in Figure 2A, showing the superposition of the refractive index (RI) trace (black) and UV−vis trace (red) at

Figure 2. Normalized GPC traces (A) and MALDI-TOF spectrum (B) of ω-alkyne-PFS homopolymer. The GPC UV−vis signal was monitored at 480 nm.

480 nm, corresponding to the characteristic optical absorbance of ferrocene. In Figure S3, we compare the GPC traces of ω(TMS-alkyne)-PFS and ω-alkyne-PFS, showing that the shift in molecular weight is small and that the narrow molecular weight distribution of the polymer is preserved after deprotection. To further confirm the degree of end-group functionalization, ωalkyne-PFS was examined by MALDI-TOF as shown in Figure 2B, where m/z peaks were found at 242.02n + 188.12 (242.02 is the molecular weight of PFS monomer, and 188.12 is the sum of n-butyl and the aryl-alkyne end groups). These experiments demonstrate a convenient and quantitative addition of a terminal alkyne to a living PFS homopolymer using a commercially available capping reagent. We envision that this approach can be applied to install a “clickable” alkyne unit at the ends of other types of polymers prepared by living anionic polymerization. Choice of the Azide End-Functionalized Homopolymers. To test the generality of using ω-alkyne-PFS for the preparation of diblock copolymers by alkyne−azide coupling, six different homopolymers with an azide end group were synthesized. Four of these polymers [polystyrene (PS), poly(methyl methacrylate) (PMMA), poly[2-(dimethylamino)ethyl methacrylate] (PDMAEMA), and poly(N-isopropylacrylamide) (PNIPAM)] were synthesized by atom transfer radical polymerization (ATRP). Azide-terminated methoxypoly(ethylene glycol) (MeO-PEO-N3) was obtained by modifica-

Table 2. Degrees of Polymerization (DP) and the Molecular Weight Distribution of ω-Alkyne-PFS and Azide-Containing Homopolymers DP PDI

PFS−CCHa

PS-N3a,c

PMMA-N3a,c

PNIPAM-N3b,d

PDMAEMA-N3b,d

PEO-N3b

PDMS-N3b

26 1.03

29 1.10

227 1.14

105 1.16

400 1.28

113 1.16

80 1.10

a

DP values obtained from GPC analysis. bDP values obtained from 1H NMR end-group analysis. cThe azide group was introduced following the azide postpolymerization modification approach. dThe azide group was introduced via the azido-initiator. 1300


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Figure 3. GPC traces (upper panels) of the CuAAC coupling reaction between ω-alkyne-PFS and ω-azido-PS. Black traces represent the homopolymers prior to the coupling reaction, and red traces represent the crude reaction mixture. The purified PFS-b-PS block copolymer (blue traces) is shown in the lower panels. (A) and (C) recorded the RI signal; (B) and (D) recorded the optical absorbance at 480 nm. In (A), a dashed circle was drawn to point out the excess of ω-N3-PS residue.

CH protons adjacent to the amide nitrogen (−CONHCH−) in the repeat unit to that of the (−CH2−O−CH2−) signals of the initiator fragment. DMAEMA was polymerized in o-dichlorobenzene at 75 °C in the presence of the azido-functionalized initiator, with CuBr/ HMTETA as the catalyst. A 1H NMR spectrum of this polymer is presented in Figure S12. A value for DPn was obtained by end-group analysis by comparing the integral of the signal of the CH2 protons (−COOCH2−, e) in the repeat unit to that of the integral of the (−CH2−O−CH2−, b, c) signals of the terminal. For both polymers, polydispersities were determined by GPC. We prepared an azido-functionalized MeO-PEO building block from a commercially available monomesylated MeO-PEO following an established procedure.27 A GPC trace of ω-azidoPEO is presented in Figure S7. A bromomethyl-terminated PDMS was synthesized by anionic ROP of hexamethylcyclotrisiloxane initiated by n-butyllithium. The anionic ROP reaction was subsequently quenched with (bromomethyl)chlorodimethylsilane. The reaction of PDMS-Br with NaN3, in the presence of TBAB (phase transfer catalyst), yielded the desired PDMS-N3. A GPC trace of PDMS-N3 is presented in Figure S10A. Preparation of PFS Block Copolymers via Cu(I)Catalyzed Alkyne/Azide Cycloaddition. In this section we examine the Cu(I)-catalyzed coupling of ω-alkyne-PFS to a series of different azide-end-capped polymers as a test of the CuAAC coupling to form PFS block copolymers, as shown in Scheme 2. These 1,3-dipolar cycloaddition coupling reactions were all carried out in THF solution under essentially identical conditions using a CuBr−pentamethyldiethylenetriamine (PMDETA) complex as the catalyst at 50 ◦C for 24 h. In each case, a slight excess (e.g., 1.2 equiv) of the azidefunctionalized block was used in order to drive the coupling

chains are an inevitable byproduct of controlled radical polymerization reactions. Thus, some (small) fraction of polymer chains will not have a reactive end group. For the ω-azido-PS and ω-azido-PMMA samples in our experiments, these are not serious issues because we considered them only as test polymers for proof-of-concept experiments on the CuAAC process, and these homopolymers are easily removed by our block copolymer purification protocol. As an alternative, we considered the introduction of the azide moiety into the ATRP initiator, as shown on the right-hand side of Scheme 2. To explore this approach, we prepared 2-(2azidoethoxy)ethyl bromoisobutyrate (AEBiB) as an ATRP initiator, following a protocol reported by Agut et al.28 The polymerization of DMAEMA and NIPAM by ATRP poses certain challenges that have been discussed in the literature. The problem is that the pendant groups compete for chelation of Cu(I) and can interfere with the polymerization reaction. For the synthesis of PDMAEMA and PNIPAM homopolymers, this problem has been overcome by careful selection of the ligand to provide strong selective chelation of the copper ions. We took advantage of this work to choose Cu(I)/Me6TREN (tris[2-(dimethylamino)ethyl]amine) as the catalyst for the polymerization of NIPAM and Cu(I)/ HMTETA (1,1,4,7,10,10-hexamethyltriethylenetetramine) for the polymerization of DMAEMA.16,28,36 We carried out the polymerization of NIPAM with the azidofunctionalized initiator in the presence of CuBr/Me6Tren in a mixed solvent of DMF/H2O (1:1 v/v) at room temperature. The α-azido-PNIPAM obtained was analyzed by GPC in THF containing 0.25 g/L tetra-n-butylammonium bromide and showed a symmetric RI signal with a narrow PDI (Figure S8). A 1H NMR spectrum of this polymer is presented in Figure S9. The degree of polymerization was obtained by endgroup analysis by comparing the integral of the signal of the 1301


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material. In the GPC trace of the reaction mixture after 24 h (Figure S13), we noted not only the residual α-azido-PNIPAM but also a small amount of unreacted ω-alkyne-PFS. The reaction was allowed to proceed for another 24 h, but there was no further change in the GPC trace. The block copolymer was purified in two steps. To remove PNIPAM homopolymer, the crude product was suspended in deionized water, a selective solvent for PNIPAM. The block copolymer mixed with residual PFS homopolymer was sedimented, collected, and dried. To remove the PFS homopolymer, we sought chromatography conditions to meet two criteria. Initially, we wanted conditions where the PFS would elute with the solvent front (i.e., Rf = 1) and the block copolymer would remain on the column (i.e., Rf = 0). Then through a change in solvent, we wanted the block copolymer to elute rapidly from the column. Using silica gel for flash chromatography and dichloromethane as the eluent, PFS was rapidly eluted. Under these conditions, PFS-b-PNIPAM remained on the column. The purified PFS-b-PNIPAM was collected using dichloromethane containing 1% (v/v) triethylamine as the eluent. The formation of the PFS-b-PNIPAM block copolymer is illustrated in Figure 4, where the RI signal of both building

reaction to completion. At the end of the reaction, the Cu/ PMDETA catalyst was readily removed by passing the reaction solution through a basic aluminum oxide column using THF as the eluent. As an initial investigation of the effectiveness of the coupling reaction, we examined the reaction between ω-alkyne-PFS and ω-azido-PS. To set a reference for following the reaction by GPC, we removed an aliquot of the reaction mixture before adding the catalyst. As shown by the black trace in Figure 3A, the RI signal in the GPC trace resolved both building blocks: the ω-alkyne-PFS at Ve = 15.5 mL and the ω-azido-PS at Ve = 16.6 mL. After the coupling reaction (red trace in Figure 3A), the GPC trace showed a clear shift to higher molecular weight (Ve = 15.0 mL). The coupling process could be further confirmed by the UV−vis signal, taking advantage of the absorbance of PFS at 480 nm. Since ω-azido-PS does not absorb at this wavelength, one only detects peaks for polymers that contain PFS. For the starting materials, one observes the peak at Ve = 15.4 mL that corresponds to ω-alkyne-PFS (black trace in Figure 3B). The red trace in Figure 3B shows that the 480 nm signal for the coupling product shifted completely to Ve = 14.9 mL as found for the RI signal. Recall that the reaction was run in the presence of ca. 20% excess of ω-azido-PS. The excess homopolymer is highlighted by the dashed circle in Figure 3A but does not appear in the GPC trace of the crude reaction product as monitored by the UV−vis signal at 480 nm. In order to remove this excess homopolymer from the crude coupling product, we sought a selective solvent as a precipitant for the block copolymer. To proceed, the dried crude product was suspended in acetone, a good solvent for low-molecular-weight PS, but a bad solvent for PFS. The suspension was then centrifuged, and the sediment was collected and dried overnight to yield the block copolymer in a yield of 82%. A GPC scan of the purified polymer is shown as the RI and UV−vis traces in Figure 3C,D. Both peaks are unimodal, symmetric, and narrow, indicating efficient formation of the PFS-b-PS diblock copolymer. The block ratio was calculated from peak integrals in the 1H NMR spectrum (presented in Figure S15D) of the block copolymer. This ratio corresponded (see Table 3) to the known values of the two polymers prior to coupling. Table 3. DP Ratio, PDI, and Yield of PFS Block Copolymers

PFS-b-PS PFS-b-PMMA PFS-bPNIPAM PFS-bPDMAEMA PFS-b-PEO PFS-b-PDMS

DP ratio of block copolymera

DP ratio of homopolymers

PDIb

yieldc (%)

26:30 26:225 26:110

26:29 26:227 26:105

1.10 1.07 1.08

82 70 50

26:400

26:420

1.19

86

26:131 26:100

26:113 26:80

1.13 1.13

42 70

Figure 4. (A) RI and (B) UV−vis GPC traces of PFS-b-PNIPAM (red) and the ω-alkyne-PFS and α-azido-PNIPAM precursors prior to coupling (black).

a c

Obtained from 1H NMR analysis. bObtained from GPC analysis. Yield after purification.

blocks (Ve,PFS = 7.50 mL, Ve,PNIPAM = 6.48 mL) disappeared and a new peak at Ve = 6.42 mL emerged. At the same time, the UV−vis signal of PFS shifted from Ve = 7.43 mL to a higher molecular weight region Ve = 6.35 mL. Note that the full width of half-maximum of the purified PFS-b-PNIPAM block copolymer is identical in both the RI and UV−vis traces, indicating complete removal of homopolymer residues.

The preparation of PFS-b-PNIPAM block copolymer followed the same protocol (feed ratio, catalyst, solvent, and reaction time) as described above for PFS-b-PS. GPC analyses of both the starting polymers and the coupled product were carried out using a THF eluent containing 0.25 g/L tetra-nbutylammonium bromide to reduce undesirable interactions between the polar polymer chains and the column packing 1302


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The GPC traces of PFS-b-PEO, PFS-b-PMMA, PFS-bPDMS, and PFS-b-PDMAEMA prepared by the same modular protocol using identical reaction recipes and standardized simple purification procedures are shown in Figure S16. The results from GPC and 1H NMR analysis (see Figure S15) confirmed the efficient coupling and complete removal of any precursor residues, as listed in Table 3.

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SUMMARY AND CONCLUSIONS We have described a convenient method to construct a wide variety of PFS block copolymers, including several that cannot be prepared by sequential anionic polymerization. The block copolymers were constructed via a Cu(I)-catalyzed alkyne/ azide cycloaddition, in which one of the key contributions of this work was the introduction of a terminal alkyne to the anionically polymerized PFS homopolymer. The reaction involved the addition of the propagating cyclopentadienyl anion of the polymer to the aldehyde group of 4[(trimethylsilyl)ethynyl]benzaldehyde (TSEBA), directly installing a TMS-protected alkyne. The ω-alkyne-PFS homopolymer obtained in this way was reacted with a series of azideend-capped polymers, in which only a small excess of azide polymer was employed. Block copolymer isolation and purification was straightforward, leading to novel polymer materials in high yield and high purity. In addition to opening the door to a broad library of novel PFS block copolymers, the use of TSEBA to quench reactive carbanions should also enable introduction of a terminal alkyne to other polymers prepared by anionic polymerization.

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ASSOCIATED CONTENT

S Supporting Information *

Experimental details for the synthesis of the azide-containing ATRP initiator and for the synthesis of ω-azido-PS, ω-azidoPMMA, α-azido-PDMAEMA, α-azido-PNIPAM, ω-azido-PEO, and ω-azido-PDMS; 1H NMR spectra for these species as well as GPC traces of the azido polymers; figures showing GPC traces and 1H NMR spectra of ω-alkyne-PFS26 and the coupled PFS block copolymers as well as the purification of PFS-bPDMAEMA and PFS-b-PNIPAM. This material is available free of charge via the Internet at http://pubs.acs.org.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected] (I.M.); mwinnik@chem. utoronto.ca (M.A.W.). Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The Toronto authors thank NSERC of Canada for financial support. P.A.R. is grateful to the NSERC of Canada for a Postdoctoral Fellowship and the EU for a Marie Curie Fellowship. The Bristol authors thank the EU in the form of an ERC Advanced Investigator Grant to I.M. for support. D.J.L. thanks the Bristol Chemical Synthesis Doctoral Training Centre, funded by EPSRC (EP/G036764/1) and the University of Bristol, for the provision of a Ph.D. studentship.

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REFERENCES

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Modular Synthesis of Polyferrocenylsilane Block Copolymers by Cu

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