Selective and Orthogonal Post-Polymerization Modification using

Jun 10, 2016 - Citation data is made available by participants in Crossref's Cited-by Linking service. For a more comprehensive list of ... Multidimen...
5 downloads 10 Views 2MB Size
Download PDF
Article pubs.acs.org/Macromolecules

Selective and Orthogonal Post-Polymerization Modification using Sulfur(VI) Fluoride Exchange (SuFEx) and Copper-Catalyzed Azide− Alkyne Cycloaddition (CuAAC) Reactions James S. Oakdale,†,‡ Luke Kwisnek,†,§ and Valery V. Fokin* The Bridge at USC and Loker Hydrocarbon Research Institute, Department of Chemistry, University of Southern California, 837 Bloom Walk, Los Angeles, California 90089, United States S Supporting Information *

ABSTRACT: Functional polystyrenes and polyacrylamides, containing combinations of fluorosulfate, aromatic silyl ether, and azide side chains, were used as scaffolds to demonstrate the postpolymerization modification capabilities of sulfur(VI) fluoride exchange (SuFEx) and CuAAC chemistries. Fluorescent dyes bearing appropriate functional groups were sequentially attached to the backbone of the copolymers, quantitatively and selectively addressing their reactive partners. This combined SuFEx and CuAAC approach proved to be robust and versatile, allowing for a rare accomplishment: triple orthogonal functionalization of a copolymer under essentially ambient conditions without protecting groups.

■

INTRODUCTION Selective postsynthetic chemical modification of macromolecules can be used to alter or enhance desired properties and function, and has enabled the preparation of unique materials for use in polymer science, medicine, and materials research.1 The repertoire of chemical transformations traditionally used in this context, such as epoxide opening,2 Diels−Alder cycloadditions3 or active ester couplings,4 has been greatly expanded during the past decade through the development of click reactions.5 The copper-catalyzed azide−alkyne cycloaddition (CuAAC),6−8 thiol−ene,9 thiol−yne,10 nitrile oxide−olefin cycloadditions,11,12 and pentafluorophenyl substitutions13,14 are common examples. New and demanding applications including drug delivery,15 lithography,16 and biomimetic adhesion17,18 have all directly benefited from the versatility of these reactions. To be useful on both the laboratory and industrial scales, monomers containing functional groups for further derivatization must be compatible with polymerization conditions, the functional handles should be chemically orthogonal to each other, and their reactivity should only be revealed when and where needed by a reliable reaction with an appropriate partner. In this work, we exploited the exquisite reactivity of the sulfur(VI) fluoride moiety toward aryl silyl ethers, a facet of sulfur fluoride exchange (SuFEx) chemistry that was first reported by Gembus19 and further developed by Sharpless and our laboratories eq 1 and 2.20,21 SuFEx was also recently exploited for the postmodification of polymer brushes on surfaces,22 work highly related and complementary to our own herein. The SuFEx reactions, in combination with CuAAC eq 3, © XXXX American Chemical Society

provide a robust and modular platform for selective modification of polymers and/or other materials. Easy to prepare and manipulate, functionalized polystyrene served as our model scaffold to demonstrate the utility of SuFEx chemistries for postpolymerization modifications. The requisite monomers were readily obtained from commercial starting materials and proved inert to polymer synthesis and isolation conditions, enabling preparation of polymers containing desired amounts of each functionality. Both series of reactions, SuFEx and CuAAC, are orthogonal and initiated only in the presence of a catalyst. The strategy described here should be equally applicable for functionalization of other synthetic as well as biogenic macromolecules decorated with functional groups used in the present study. Received: January 14, 2016 Revised: April 29, 2016

A

DOI: 10.1021/acs.macromol.6b00101 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

■

RESULTS AND DISCUSSION While there are by now a host of “click” reactions that are used for polymer modification, the field still needs more synthetic methodologies with increasingly more advantages such as a “switch on” catalytic process, low temperature ambient conditions, and permanent connections. A prototypical example: the SuFEx chemistry outlined herein. When used in combination with CuAAC, up to three rounds of sequential, orthogonal postpolymer functionalization were achieved at essentially ambient conditions and without requiring functional group protection/deprotection. The SuFEx reaction entails the coupling of aromatic silyl ethers with aromatic fluorosulfates (ArOSO2F; eq 1) or aromatic sulfonyl fluorides (ArSO2F; eq 2) to provide arylsulfates and aryl-sulfonates, respectively. Enabling SuFEx requires the presence of an organic super base or fluoride source, usually employed in catalytic amounts and the use of an aprotic polar reaction solvent,23 such as dimethylformamide (DMF), dimethyl sulfoxide (DMSO) or acetonitrile (MeCN). Nonpolar solvents tend to inhibit SuFEx coupling reactions, although dichloromethane (DCM) can also be used, albeit with retarded reaction rates.19 In this work, we generally favored the readily available amidine base, DBU (1,8-diazabicycloundec-7ene), as the catalyst of choice20 and combinations of DMF/ DCM as our solvents. The byproduct of this coupling reaction is an innocuous, easily removed fluorosilane (F-SiR3). To examine the compatibility of SuFEx for postpolymerization modifications, we began by preparing substituted styrenes 3-5 (Scheme 1). tert-Butyldimethyl(4-vinylphenoxy)silane 3

obtained from the corresponding commercially available vinyl benzyl chloride.32 Compatibility of the functionalized styrene monomers with polymerization conditions was next investigated. Initially, two copolymers were synthesized: PS-37% and PS-47% (Table 1) Table 1. Synthesis of Functionalized Styrene Copolymers

polystyrene (PS) copolymer monomer compositiona polymer

v (styrene), mol %

w (OAc), mol %

x (Si), mol %

y (F), mol %

z (N3), mol %

PS-1 PS-1,3 PS-1,4 PS-3 PS-4 PS-3,5 PS-4,5 PS-3,4,5

90 91 91 93−90 93 85 98−85 92

10 3 3 − − − − −

− 6 − 7−10 − 7.5 − 6

− − 6 − 7 − 1−7.5 1

− − − − − 7.5 1−7.5 1

a

Styrene copolymers were prepared through solution polymerization at 50 °C with AIBN initiator. Mol% represent the percentage of each monomer in solution prior to polymerization.

Scheme 1. Synthesis of Functionalized Styrene Monomers

using solution polymerization at 50 °C with AIBN initiator.33 Under these conditions, each monomer successfully copolymerized with styrene. Incorporation of 3 in PS-37% was verified to be close to 7 mol % by 1H NMR, corresponding to monomer content in the feed.10,17 Quantitative determination for the incorporation of 4 in PS-47% was also obtained using 1H NMR, following postpolymerization derivatization. The fluorosulfate-derivatized styrene copolymer PS-4 was prepared in two other additional ways, Scheme 2. Phenol-

was obtained from the silyl chloride and 4-vinylphenol 2, which in turn was easily derived from 4-acetoxystyrene 1. In this work, we exclusively employed TBS (tert-butyldimethylsilyl) ethers for SuFEx reactions due to their stability under a variety of conditions. However, other silyl ethers, such as trimethyl (TMS) or triisopropyl (TIPS), also perform well in this chemistry. Treatment of 2 with sulfuryl fluoride (SO2F2) gas in the presence of triethylamine furnished fluorosulfate 4 in excellent yield. The facile preparation of aryl fluorosulfates from phenols and SO2F2 was first identified in the 1970s by Firth24,25 and others.26,27 Improved protocols described by Sharpless et al. in a recent review21 and Ishii et al. in a patent application,28 were used in this work. Other methods for the preparation of aryl fluorosulfates include the pyrolysis of diazonium fluorosulfate salts29 and the treatment of phenols with fluorosulfuryl chloride30 or fluorosulfonic acid anhydride31 in the presence of a tertiary amine base. However, these alternatives suffer from side reactions caused by the aggressive nature of sulfur(VI) reagents. In contrast, sulfuryl fluoride is an easily handled gas that can be introduced in reactions using a balloon (CAUTION: sulfuryl fluoride is a toxic, colorless and odorless gas. It should be handled with precautions to avoid exposure and inhalation). Finally, azide derivative 5 was

Scheme 2. Synthesis of Fluorosulfates Using Sulfuryl Fluoride

containing copolystyrene PS-2, obtained through deprotection of the copolymer derived from styrene and 1 (PS-1),34 was converted to PS-410% by treating with SO2F2 in the presence of triethylamine. These transformations are detailed in the Supporting Information. Similarly, the silyl ether groups of PS-310% can also be directly converted to fluorosulfates by treating the polymer with SO2F2 gas and DBU (PS-310% → PS410%). This sequence effectively represents a “gender change” B

DOI: 10.1021/acs.macromol.6b00101 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

Figure 1. UV−vis spectra of dyes 6−8 (CHCl3, 2.0 × 10−5 M), Colored circles represent dye structures in subsequent figures. The representative spectrum for 7 is shown for n = 1.

Figure 2. GPC UV−vis detector plots for initial, single functional group-containing copolymers before and after dye attachment. (A) PS-37% → PS3∧6. (B) PS-47% → PS-4∧7. Base axes are wavelength and elution time (min) while the z-axis is absorbance intensity. Dye molecules are represented by colored circles, cf. Figure 1.

from silyl ethers to their reactive counterpart, fluorosulfates, directly on the backbone. To demonstrate that silyl ether, fluorosulfate, and azide groups in the copolymers can be independently and selectively addressed, dyes containing complementary reactive groups were synthesized (6−8, Figure 1).35 These dyes have distinct λmax absoption values and include dansyl fluoride (6, λmax = 360 nm), coumarin 343 analogues (7, λmax = ∼425 nm) and a Nile red derivative (8, λmax = ∼550 nm). The covalent attachment of a specific dye could then be verified by GPC analysis using diode-array UV−vis detection: the covalently modified polymer exhibits a distinct UV signature of the corresponding dye, whereas unreacted, unattached dye elutes at a later time distinct from polymeric material as a low molecular weight species (see Supporting Information for examples of GPC traces contaminated with unattached dyes). PS-37% was derivatized with dansyl fluoride (6, 2 equiv) in DMF using DBU (0.5 equiv). As expected, the molecular weight of the resultant polymer, PS-3∧6 (where the symbol ∧ indicates covalent dye attachment) increased due to the introduction of the dansyl group (Figure 2A). A new absorbance peak at ∼360 nm was also observed coeluting with the polymer: direct evidence for the covalent attachment of 6 to the polymer. Styrene absorbance at 260 nm is shown in each spectrum and remains as a reference. Similarly, fluorosulfate-containing PS-47% was also successfully derivatized with coumarin 343, (7, 3 equiv) in DMF using

DBU (1 equiv). GPC analysis confirmed an increase in Mn and identified a new absorbance peak at ∼440 nm associated with the coumarin dye covalently attached to the polymer, PS-4∧7 (Figure 2B). In general, SuFEx polymer derivatizations were performed in DMF with DBU as the catalyst. These reactions result in nearly quantitative conversion in a reasonable amount of time,21 and reactions were allowed to proceed for at least 16 h to ensure completion. Still, we briefly studied the kinetics of polymer functionalization using a model system. TBS-ether (PS-1,3) and fluorosulfate (PS-1,4) containing polymers were treated with 2 equiv of 4-methoxyphenyl sulfurofluoridate (9) and tertbutyl(4-methoxyphenoxy)dimethylsilane (10), respectively, and catalytic DBU (25 mol %), as outlined in Figure 3. Conversion was tracked with 1H NMR by measuring the appearance of − OMe (3.79 ppm) relative to −OAc (2.28 ppm), which served as an unchanging internal standard. The reaction conditions were as follows; 0.027 M DBU (25 mol %), 0.2 mg/mL PS-1,3/4 (0.11 M PS-OTBS/OSO2F functional groups), 0.22 M 9/10, DMF, ambient temperature. From these initial kinetic experiments, both reactions appear to proceed at relatively the same rate and required ca. 20 h to reach completion. While SuFEx reactions are normally catalytic, we favored the use of 0.5−1 equiv of DBU with respect to the reactive functional groups in order to ensure high conversions. Dyes were also used in excess (2−3 equiv) and remaining, C

DOI: 10.1021/acs.macromol.6b00101 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

methoxy shift, could be detected by 1H NMR. See Supporting Information for further details. We next demonstrated the orthogonality of SuFEX and CuAAC chemistries. Each functionality in the di- and trifunctional copolymers PS-3,5, PS-4,5, and PS-3,4,5 were selectively addressed by using the appropriate reactants and conditions. PS-3,5, containing 7.5 mol % 3 and 5, was derivatized first with fluorosulfonate dye 6 using a SuFEx reaction and subsequently with the alkyne-bearing Nile red dye 8 using CuAAC, providing PS-3∧6,6∧8 (Figure 4A). The CuAAC conditions used here employed [Cu(MeCN)4]PF6 (1−5 mol %) and tris((1-tert-butyl-1H-1,2,3-triazolyl)methyl)amine (TTTA) ligand (1−5 mol %). TTTA is completely SuFEx benign and thus serves a reliable SuFEx-compatible CuAAC ligand. A copolystyrene containing 7.5 mol % each of fluorosulfate 4 and azide 5 was also prepared. However, in this instance, sequential attachment of dyes 7 and 8 resulted in considerable gelation, which occurred regardless of the order of SuFEx and CuAAC chemistries.35 This problem was circumvented by preparing a copolymer containing reduced amounts of functionality, PS-41%,51%. Its sequential derivatization proceeded smoothly to deliver PS-3∧61%,4∧71% (Figure 4B). The formation of intractable gels at higher functional group loading was concerning and could potentially limit the utility and reliability of SuFEx for polymer modifications. In an attempt to understand the cause of gelation, PS-45%,55% was treated and successfully derivatized with different small molecules, specifically 4-methoxylphenylacetylene (11) and tert-butyl(4-(tertbutyl)phenoxy)dimethylsilane (12), Scheme 3. We tentatively

Figure 3. Rate of SuFEx-mediated derivatizations with 25 mol % DBU. Conversions (%) were determined by integrating the area of −OMe relative to −OAc, which served as an internal standard.

unattached dye, as well as the catalyst, were removed by repeated MeOH precipitations. The experiments shown in Figures 2 and 3 established reliable conditions for each reaction and demonstrated that different molecules could be covalently attached to the polymer containing silyl ether and fluorosulfate reactive groups. 1H and 19 F NMR analysis confirmed quantitative conversions, while GPC analysis verified the covalent attachment of the dye to the polymer. Additionally, the SuFEx-formed sulfonate and sulfate linkers were found to be hydrolytically stable. Two methoxy group containing polystyrenes, one with sulfonate and one with sulfate connections, were synthesized from PS-37%. These polystyrenes were dissolved in 1,4-dioxane and subjected to treatment with either 10% aqueous NaOH or 1 M HCl solution at 50 °C for 16 h. No degradation, judged via integration of the

Scheme 3. Derivatization of PS-4,5 Using CuAAC Followed by SuFEx

Figure 4. GPC UV−vis detector plots for difunctional, copolymers and orthogonal attachment of dyes. A) SuFEx then CuAAC; PS-3,5 → PS3∧6,6∧8. B) CuAAC then SuFEx; PS-4,5 → PS-4∧7,6∧8. Base axes are wavelength and elution time (min) while z-axis is absorbance intensity. Dye molecules are represented by colored circles, cf. Figure 1. TTTA = tris((1-(tert-butyl-1,2,3-triazol-4-yl)methyl)amine. D

DOI: 10.1021/acs.macromol.6b00101 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

Figure 5. GPC UV−vis detector plots of a triply functional copolystyrene, PS-3,4,5, modified by orthogonal attachment of dyes 6, 7, and 8. Base axes are wavelength and elution time (min) while z-axis is absorbance intensity. Dye molecules are represented by colored circles, cf. Figure 1.

substrates. As an example, an acrylamide backbone copolymer comprising N-isopropylacrylamide (NIPAm) and a fluorosulfate functionalized acrylamide monomer was prepared. The fluorosulfate bearing monomer was obtained in 77% yield following a four step procedure starting from 4-(2-aminoethyl)phenol hydrochloride. A trifluoromethane containing monomer was also prepared in a similar manner and was incorporated in order to track fluorosulfate consumption over time via 19F NMR. SuFEx mediated attachment of coumarin 343 (7) proceeded smoothly to deliver PNIPA-F∧7, Figure 6.

conclude that gelation was caused by an unforeseen and as of yet unknown interaction between dyes 7 and 8, and not from the combination of SuFEx with CuAAC. Nevertheless, Figure 4 and Scheme 3 established the orthogonality of CuAAC and SuFEx reactions and their equally efficient performance regardless of the reaction order. Inclusion of three different functional groups and performing three selective, sequential reactions on the same macromolecule demands exquisitely narrow reactivity of the side chains and, therefore, has seldom been accomplished, especially using ambient conditions and without protecting groups.37−39 The reactions described here can be used to achieve this goal: the trifunctional polystyrene PS-3,4,5 containing 6 mol % of 3, and 1 mol % each of 4 and 5 was first derivatized with the fluorosulfonylated dye 6 under slightly modified SuFEx conditions (Figure 5). The resulting polymer, PS-3∧6,4,5, remained completely soluble, no gelation was observed and the GPC elution curve was only minimally broadened, pointing to minor, if any, cross-reactivity between silyl ether and fluorosulfate groups. 1H NMR indicated complete consumption of the TBS groups, while 19F NMR verified that OSO2F functionality remained intact. The selectivity of this dye-polymer coupling vs. polymerpolymer cross-linking hinges on the significantly higher reactivity of aromatic sulfonyl fluorides with aryl silyl ethers compared to their fluorosulfate analogues (in other words, the reaction shown in eq 2 is faster than that in eq 1).36 For this particular experiment, 15x molar equivalents of small molecule sulfonyl fluoride (6) was used relative to polymer-bound fluorosulfate. Additionally, sulfate formation (eq 1) was found to be more sensitive to the polarity of the reaction medium than its sulfonate analogue (eq 2).36 With these observations in mind, we used less polar dichloromethane instead of dimethylformamide, thus promoting sulfonate dye attachment and suppressing any potential sulfate cross-linking reactions. Following the attachment of 6, PS-3∧6,4,5 was then sequentially treated with 7 and 8 under SuFEx and CuAAC conditions, correspondingly, to produce a triply functionalized polymer, PS-3∧6,4∧7,6∧8 shown in Figure 5. All three procedures gave high conversions under experimentally simple conditions, and allowed selective covalent modification of a macromolecule with three distinctly different functional groups without any cross-reactivity and without requiring protection/ deprotection steps. Finally, although polystyrene served as a workhorse scaffold, we anticipate that this approach could be easily applied to other

Figure 6. GPC UV−vis detector plots of poly(N-isopropylacrylamide) derivatization using SuFEx. Base axes are wavelength and elution time (min) while z-axis is absorbance intensity.

■

CONCLUSIONS The sulfonate and sulfate forming reactions presented here enabled postfunctionalization of polystyrenes at room temperature without deprotection steps and also without taking special precautions to exclude air and moisture. The silyl ether and fluorosulfate-substituted styrene monomers were readily copolymerized without the need for reversible-deactivation radical “living” techniques. A series of dyes with corresponding functionalities were synthesized and attached to the copolymers. Co-elution of dye peaks with the polymer, as judged by GPC UV−vis detection and NMR analysis, confirmed covalent attachment of dyes to the polymers. Orthogonal postmodification was achieved by attaching different functional monomers in sequential fashion. A rare example of a triply E

DOI: 10.1021/acs.macromol.6b00101 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules

(7) Binder, W. H.; Sachsenhofer, R. ‘Click’ Chemistry in Polymer and Materials Science. Macromol. Rapid Commun. 2007, 28, 15−54. (8) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B. A Stepwise Huisgen Cycloaddition Process: Copper(I)-Catalyzed Regioselective “Ligation” of Azides and Terminal Alkynes. Angew. Chem., Int. Ed. 2002, 41, 2596−2599. (9) Campos, L. M.; Killops, K. L.; Sakai, R.; Paulusse, J. M. J.; Damiron, D.; Drockenmuller, E.; Messmore, B. W.; Hawker, C. J. Development fo Thermal and Photochemical Strategies for Thiol-Ene Click Polymer Functionalization. Macromolecules 2008, 41, 7063− 7070. (10) Yu, B.; Chan, J. W.; Hoyle, C. E.; Lowe, A. B. Sequential thiolene/thiol-ene and thiol-ene/thiol-yne reactions as a route to well defined mono and bis end-functionalized poly(N-isopropylacrylamide). J. Polym. Sci., Part A: Polym. Chem. 2009, 47, 3544−3557. (11) Gutsmiedl, K.; Wirges, C. T.; Ehmke, V.; Carell, T. Cooper-Free “Click” Modification of DNA via Nitrile Oxide-Norbornene 1,3Dipolar Cycloaddition. Org. Lett. 2009, 11, 2405−2408. (12) Singh, I.; Zarafshani, Z.; Heaney, F.; Lutz, J.-F. Orthogonal modification of poymer chains-ends via sequential nitrile oxide-alkyne and azide-alkyne Huisgen cycloadditions. Polym. Chem. 2011, 2, 372− 375. (13) Becer, C. R.; Babiuch, K.; Pilz, D.; Hornig, S.; Heinze, T.; Gottschaldt, M.; Schubert, U. S. Clicking Pentafluorostyrene Copolymers: Synthesis, Nanoprecipitation and Glycosylation. Macromolecules 2009, 42, 2387−2394. (14) ten Brummelhuis, N.; Weck, M. Orthogonal Mulitfunctionalization of Random and Alternating Copolymers. ACS Macro Lett. 2012, 1, 1216−1218. (15) Nyström, A. M.; Wooley, K. L. The Importance of Chemistry in Creating Well-Defined Nanoscopic Embedded Therapeutics: Devices Capable of the Dual Functions of Imaging and Therapy. Acc. Chem. Res. 2011, 44, 969−978. (16) Bang, J.; Bae, J.; Löwenhielm, P.; Spiessberger, C.; Given-Beck, S. A.; Russell, T. P.; Hawker, C. J. Facile Routes to Patterened Surface Neutralization Layers for Block Copolymer Lithography. Adv. Mater. 2007, 19, 4552−4557. (17) White, J. D.; Wilker, J. J. Underwater Bonding with Charged Polymer Mimics of Marine of Marin Mussel Adhesive Protiens. Macromolecules 2011, 44, 5085−5088. (18) Heo, J.; Kang, T.; Jang, S. G.; Hwang, D. S.; Spruell, J. M.; Killops, K. L.; Waite, J. H.; Hawker, C. J. Improved Preformance of Protected Catecholic Poysilanes for Bioinspired Wet Adhesion to Surface Oxides. J. Am. Chem. Soc. 2012, 134, 20139−20145. (19) Gembus, V.; Marsais, V.; Levacher, V. An Efficient Organocatalyzed Interconversion of Silyl Ehters to Tosylates Using DBU and p-Toluenesulfonyl Fluoride. Synlett 2008, 2008, 1463−1466. (20) Dong, J.; Sharpless, K. B.; Kwisnek, L.; Oakdale, J. S.; Fokin, V. V. SuFEx-Based Synthesis of Polysulfates. Angew. Chem., Int. Ed. 2014, 53, 9466−9470. (21) Dong, J.; Krasnova, L.; Finn, M. G.; Sharpless, K. B. Sulfur(VI) Fluoride Exchange (SuFEx): Another Good Reaction for Click Chemistry. Angew. Chem., Int. Ed. 2014, 53, 9430−9448. (22) Yatvin, J.; Brooks, K.; Locklin, J. SuFEx on the Surface: A Flexible Platform for Postpolymerization Modification of Polymer Brushes. Angew. Chem., Int. Ed. 2015, 54, 13370−13373. (23) The SuFEx reaction solvent (i.e., DMF) does not need to be scrupulously dried prior to use. However, excess water may cause hydrolysis of aryl silyl ethers by DBU. (24) Firth, W. C., Jr. Preparation of Aromatic Polysulfates and Copoly(sulfate carbonates). J. Polym. Sci., Part B: Polym. Lett. 1972, 10, 637−641. (25) Firth, Jr., W. C. Aryl Sulfate Polymers. US Patent 3,733,304, 1973. (26) Hedayatullah, M.; Guy, A.; Denivelle, L. Synthése de Fluorosulfates D’Aryle Encombres. Phosphorus Sulfur Relat. Elem. 1980, 8, 125−126.

functionalized copolystyrene was obtained via two orthogonal SuFEx reactions followed by CuAAC. This modification chemistry was further demonstrated on an acrylamide copolymer. While this work focused only on linear copolymers, we expect this methodology to find application anywhere freeradically silent yet powerful, orthogonal reactivity is required.

■

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.macromol.6b00101. Experimental procedures and compound characterization data (PDF)

■

AUTHOR INFORMATION

Corresponding Author

*(V.V.F.) E-mail: [email protected]. Present Addresses ‡

Lawrence Livermore National Laboratory, Materials Science Division 7000 East Ave., Livermore, CA 94550−5507 § DSM Functional Materials, 1122 St. Charles St., Elgin, IL 60120 Author Contributions

† These authors contributed equally. The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

Funding

This work was supported by the National Science Foundation (CHE-1302043). J.S.O. acknowledges a graduate fellowship from the National Science Foundation. Notes

The authors declare no competing financial interest.

■

REFERENCES

(1) (a) Günay, K. A.; Theato, P.; Klok, H.-A. History of Postpolymerization Modification. In Functional Polymers by Post-Polymerization Modification; Wiley-VCH Verlag GmbH & Co. KGaA: 2012; pp 1−44. (b) Günay, K. A.; Theato, P.; Klok, H.-A. Standing on the shoulders of Hermann Staudinger: Post-polymerization Modification from Past to Present. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 1− 28. (2) Iwakura, Y.; Kurosaki, T.; Ariga, N.; Ito, T. Copolymerization of methyl methacryate with glycidyl methacrylate and the reaction of the copolymer with amines. Makromol. Chem. 1966, 97, 128−138. (3) Goussé, C.; Gandini, A.; Hodge, P. Application of the Diels-Alder Reaction to Polymers Bearing Furan Moieties. 2. Diels-Alder and Retro-Diels-Alder Reactions involving Furan Rings in Some Styrene Copolymers. Macromolecules 1998, 31, 314. (4) Kakuchi, R.; Theato, P. Post-Polymerization Modifications via Active Esters. In Functional Polymers by Post-Polymerization Modification; Wiley-VCH Verlag GmbH & Co. KGaA: 2012; pp 45−64. (5) (a) Xi, W.; Scott, T. F.; Kloxin, C. J.; Bowman, C. N. Click Chemistry in Matrials Science. Adv. Funct. Mater. 2014, 24, 2572− 2590. (b) Arnold, R. M.; Patton, D. L.; Popik, V. V.; Locklin, J. A Dynamic Duo: Pairing Click Chemistry and Postpolymerization Modification To Design Complex Surfaces. Acc. Chem. Res. 2014, 47, 2999−3008. (c) Gauthier, M. A.; Gibson, M. I.; Klok, H.-A. Synthesis of Functional Polymers by Post-Polymerization Modification. Angew. Chem., Int. Ed. 2009, 48, 48. (6) Helms, B.; Mynar, J. L.; Hawker, C. J.; Fréchet, J. M. J. Dendronized Linear Polymers via “Click Chemistry. J. Am. Chem. Soc. 2004, 126, 15020−15021. F

DOI: 10.1021/acs.macromol.6b00101 Macromolecules XXXX, XXX, XXX−XXX

Article

Macromolecules (27) Falardeau, E. R.; DesMarteau, D. D. Synthesis of Pentafluorophenoxy Derivatives of Sulfur(IV) and − (VI) Fluorides. J. Chem. Eng. Data 1976, 21, 386−387. (28) Ishii, A.; Ishimaru, T.; Yamazaki, T.; Yasumoto, M. Preparation of Fluorosulfuric Acid Aryl Esters by Reacting Phenols with Sulfuryl Fluoride. PCT Publication WO2013002040 A1; PCT/JP2012/ 065311, 2013. (29) Lange, W.; Mueller, E. Aromatic Fluorosulfates. Ber. Dtsch. Chem. Ges. B 1930, 63, 2653−2657. (30) Cramer, R.; Coffman, D. New Synthesis of Aryl Fluorides and Aryl Fluorosulfonates from Oxyfluorides of Sulfur. J. Org. Chem. 1961, 26, 4164−4165. (31) Roth, G. P.; Fuller, C. E. Palladium Cross-Coupling Reactions of Aryl Fluorosulfonates: An Alternative to Triflate Chemistry. J. Org. Chem. 1991, 56, 3493−3496. (32) Lammens, M.; Skey, J.; Wallyn, S.; O’Reilly, R.; Du Prez, F. Polymeric Ligands as Homogeneous, Reusable Catalyst Systems for Copper Assisted Click Chemistry. Chem. Commun. 2009, 46, 8719− 8721. (33) Monomers 3 and 4 also tolerated bulk copolymerization with styrene at 110 °C with no observable chain transfer. (34) Chen, X.; Jankova, K.; Kops, J.; Batsberg, W. Hydrolysis of 4Acetoxystyrene Polymers Prepared by Atom Transfer Radical Polymerization. J. Polym. Sci., Part A: Polym. Chem. 1999, 37, 627−633. (35) For further details see the Supporting Information. (36) Competition experiments between sulfonyl flourides and fluorosulfates in both DCM and DMF can be found in the Supporting Information, page S57. (37) Schaefer, M.; Hanik, N.; Kilbinger, A. F. M. ROMP Coplymers for Orthoganol Click Functionalizations. Macromolecules 2012, 45, 6807−6818. (38) Kempe, K.; Hoogenboom, R.; Jaeger, M.; Schubert, U. S. ThreeFold Metal-Free Efficient (“Click”) Reactions onto a Multifunctional Poly(2-oxazoline) Designer Scaffold. Macromolecules 2011, 44, 6424− 6432. (39) Gunay, U. S.; Durmaz, H.; Gungor, E.; Dag, A.; Hizal, G.; Tunca, U. 3-Miktoarm Star Terpolymers using Triple Click Reactions: Diels-Alder, Copper-Catalyzed Azide-Alkyne Cycloaddition, and Nitroxide Radical Coupling Reactions. J. Polym. Sci., Part A: Polym. Chem. 2012, 50, 729−735.

G

DOI: 10.1021/acs.macromol.6b00101 Macromolecules XXXX, XXX, XXX−XXX