Living Radical Polymerization - American Chemical Society

Chapter 11

Click Functionalization of Well-Defined Copolymers Prepared by Atom Transfer Radical Polymerization 1

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Brent S. Sumerlin , Nicolay V. Tsarevsky , Haifeng Gao , Patricia Golas , Guillaume Louche , Robert Y. Lee , and Krzysztof Matyjaszewski 2

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Downloaded by COLUMBIA UNIV on August 8, 2012 | http://pubs.acs.org Publication Date: September 7, 2006 | doi: 10.1021/bk-2006-0944.ch011

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Department of Chemistry, Southern Methodist University, P.O. Box 750314, Dallas, TX 75275 Department of Chemistry, Carnegie Mellon University, 4400 Fifth Avenue, Pittsburgh, PA 15213

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Copper(I)-catalyzed 1,3-dipolar cycloaddition of azides and alkynes has proven to be a promising method to functionalize well-defined polymers prepared by atom transfer radical polymerization (ATRP). Due to high efficiency and fidelity under moderate reaction conditions, this "click chemistry" method allows the modification of polymer end groups to give functional telechelic polymers. Additionally, ATRP of azide -containingmonomers results in polymer with azido groups in each monomer unit. These polymers demonstrate enhanced reactivity for click reactions, as compared to the monomer with comparable structure. This review will describe the progress made in the combination of ATRP and click chemistry to prepare functional materials by highly efficient post-polymerization modification.

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© 2006 American Chemical Society

In Controlled/Living Radical Polymerization; Matyjaszewski, K.; ACS Symposium Series; American Chemical Society: Washington, DC, 2006.

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Introduction Controlled/living radical polymerization (CRP) techniques facilitate the preparation of a broad variety of polymeric materials with predetermined molecular weights, narrow molecular weight distributions, and high degrees of chain end functionalization (7). When compared to their ionic counterparts, CRP methods provide comparable control while having the advantage of enhanced functional group tolerance and the ability to be conducted under less stringent conditions. Atom transfer radical polymerization (ATRP) (2-5) has emerged as one of the most widely used CRP methods due to facile experimental setup and the use of readily accessible and inexpensive initiators and catalysts. Post-polymerization modification remains a viable means to incorporate functionality potentially incompatible with polymerization, characterization, or processing conditions (6,7). A potential drawback of such a method of functionalization is the possibility of relatively low yields and side reactions with other groups within the polymer. Therefore, efficient and specific reactions are desirable in order for post-polymerization modification to be successful. Two independent groups recently reported that with the use of a Cu(I) catalyst, azide (8) -terminal alkyne coupling reactions result in the highly specific and efficient preparation of 1,4-disubstituted 1,2,3-triazole products under moderate reaction conditions (9,10). These particular reactions can be conducted in aqueous or organic media and little or no side reactions are observed. The practicality and versatility of the Cu(I)-catalyzed coupling reaction led to its inclusion in the class of efficient and specific organic reactions, commonly termed "click chemistry", as coined by Sharpless et al (77). Due to its utility for the preparation of functional polymers, ATRP, combined with the efficiency of click chemistry, is an interesting and promising strategy to synthesize various end-fimctionalized polymers. Recently, several groups have reported the synthesis of (co)polymers via CRP and subsequent click reactions (12-18). Herein, we review the progress in the synthesis and characterization of well-defined (copolymers via ATRP and the subsequent functionalization of monomer unit or chain end functionality by click chemistry. Particular focus is given to our own contributions, but the work of others is highlighted as well in order to more fully describe the current state-of-the-art in the field. Due to the near-quantitative yields and high fidelity associated with the copper(I)-catalyzed Huisgen 1,3-dipolar cycloadditions, these reactions offer potential in the functionalization of polymeric materials. Two approaches of post-polymerization modification can be envisioned: (i) end group and (ii) monomer unit functionalization. In each case, efficient and specific reactivity is desirable.


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End Group Functionalization With the advent of click chemistry and, in particular, the azide-alkyne coupling reactions mentioned above, a new strategy has been realized for the functionalization of end groups for polymers prepared by ATRP. Two approaches for the end group fiinctionalization of polymers prepared by ATRP are possible (Scheme 1). First, the polymers produced by ATRP preserve the terminal halogen atom(s) and can be successfully converted into various end groups through appropriate transformation, especially nucleophilic substitutions. For instance, the transformation of a terminal halogen atom to an azide anion is very efficient (6,19-22). The second approach consists of employing a functional initiator to prepare polymers by ATRP. Including the functional moiety in the initiator structure assures that each chain contains the functional group, and postpolymerization modification may not be necessary. Regardless of the method used, the obtained organic azido group can be employed for a variety of chemical transformations to produce numerous types of end functional groups, such as amino, hydroxy, carboxy moieties.

ΛΛΛΛΛΛΛΛΛΛΛΛΠ

YN^ A

R

T

R

P

D

*

M

" ι

^Jnit-N

3

,

ATRP

_ ^ Post-polymerization Modification ",'

ΛΛΛΛΛΛΛΛΛΛΛΛΡ

γ

3

=

Imt

=

—

Scheme 1. Methods for the ATRP synthesis of azide- or alkyne-terminal polymers to be subsequently employed in click reactions.

Polymer-Small Molecule Click Reactions Reacting azide- or alkyne-terminal polymers with a complimentary small molecule containing additional functionality is a viable means to prepare telechelic chains with particularly interesting end groups. For instance, Lutz et al. reported the polymerization of styrene via ATRP and terminal substitution with the azide anion resulted in polymers that were subsequently reacted with various functional alkynes in order to obtain telechelic functional polymers (12).


143 We employed a similar approach to prepare α,ω-telechelic polystyrene (23). As outlined in Scheme 2, a difiinctional initiator was used in the polymerization of styrene to yield homopolymer contained α,ω-bromo end groups. After reacting with NaN , α,ω-diazido polystyrene (PS) was obtained, and *NMR spectroscopy indicated that nearly all of the bromo end groups were substituted by the azide (Figure 2). The resulting homotelechelic polystyrene was reacted with propargyl alcohol (PgOH) in DMF with CuBr as a catalyst. CuBr is sufficiently soluble in DMF, and no additional ligand was employed during the click process. Under these moderate conditions, the click process was essentially complete after 4 h at room temperature, as determined by H NMR spectroscopy. 3


L

Scheme 2. Synthesis of difunctional PS viaATRP and subsequent azidation and clickfunctionalization with propargyl alcohol. (Adapted with permission from reference 19. Copyright 2005 American Chemical Society.) While the average number of hydroxyls per PS chain end was determined to be greater than 0.96, the results from NMR spectra were not able to provide complete information about the success of the click reaction. Therefore, gradient polymer elution chromatography (GPEC) (24,25) was employed to evaluate the distribution of the hydroxyl groups along the PS chains. GPEC is a method of affinity chromatography that separates polymers according to their interaction with a stationary column. A mobile phase is gradually changed from a poor solvent to a good solvent, and the polymer chains with weaker column interaction elute first. In this case, a normal phase bare-silica column was used as the stationary phase. When the eluent composition changed from hexanes (poor


144 solvent) to THF (good solvent), the linear PS chains containing less hydroxyl end-groups elute earlier. The GPEC traces corroborated the results obtained from NMR by indicating that nearly all of the terminal azide groups were converted to hydroxyls within 8.5 h at room temperature (Figure 1) (25). Due to separation based on chemical functionality, the unreacted starting material (N -PS-N , I) was resolved from both the mono- (N -PS-OH, II) and difiinctional (HO-PS-OH, ΙΠ) products. Integration of the appropriate peaks allowed the concentration of each species (IIII) to be followed with time. This facilitated the determination of rate constants for the reaction of both the first and second groups with PgOH as k\ = (3.2 ± 0.2) χ 10" s" and k = (1.1 ± 0.1) χ 10" s' , respectively. Terminal functionality capable of derivatization by click chemistry can also be achieved by employing functional initiators. Mantovani et al. prepared azidoterminated polymers by ATRP (15) of methyl methacrylate with an azidecontaining initiator. Depending on the length of the aliphatic spacer between the azido group and the initiating halogen, this approach could be accompanied by side reactions that resulted in loss of the terminal azide. Nonetheless, due to the 3

3

3

4

1

4

1


2

I 13*7111L

10 12 14 16 18 20 22 24 Elution volume (mL)

Figure 1. GPECelution chromatograms of α,ω-dibromo- (I), α,ω-diazido- (II), and a, (O-dihydroxy-terminatedflll) PS at different times during the reaction of N 3 - P S - N 3 with PgOH. (Adapted with permissionfromreference 19. Copyright 2005 American Chemical Society.)


145

1.0 0.8 §

0.6

S Ο

2

0.4


IL

0.2 0.0 0 1 2 3 4 5 6 7 8 9

Time (h)

10

Figure 2. Fraction of dihydroxy-, monohydroxy-, and nonhydroxy-PS as a function of reaction time ofN -PS-N and PgOH. (Adapted with permission from reference 19. Copyright 2005 American Chemical Society.) 3

3

lower rates of substitution associated with the functionalization of the tertiary halogens of methacrylates, this approach is an attractive alternative for preparing azide-terminated polymethacrylates. The resulting poly(methyl methacrylate) (PMMA) was then UV or fluorescently labeled by reaction with alkynefunctionalized dyes.

Polymer-Polymer Click Reactions

Post-polymerization coupling reactions between two polymers with functional groups present in only a low concentration are generally associated with low yields and reduced rates of reactions. Employing a highly-efficient reaction pathway may facilitate higher coupling efficiencies (26), which makes azide-alkyne coupling reactions a particularly attractive candidate mechanism. Post-polymerization modification by nucleophilic substitution of terminal halogens allowed Opsteen and van Hest to prepare azide-terminated polymers that were subsequently reacted with other polymers containing alkyne end



146 groups (13). Due to the high efficiency and rates of reactions associated with the click coupling mechanism, this method proved a reliable means to prepare block copolymers in a modular format. This could be particularly attractive when it is desirable to obtain block copolymers from two homopolymers that cannot be easily prepared with a common polymerization mechanism. Along similar lines, we employed azide-alkyne coupling of difiinctional homo- or hetero-telechelic polymers as a step-growth polymerization mechanism to make higher molecular weight materials from polymeric "monomers" (14) (Scheme 3). Propargyl 2-bromoisobutyrate (PgBiB) was used to initiate the polymerization of styrene, and the bromine end group of the resulting polymer was reacted with sodium azide to give a-alkyne-œ-azido-terminated PS (Scheme 3, A). After isolation and purification, this polymer was self-coupled in the presence of CuBr and an increase in molecular weight from M = 2,590 to 21,500 g/mol was observed. The increased chain length was due to a stepgrowth polymerization via azide-alkyne coupling of the end groups. In addition to the high molecular weight polymer prepared, there was evidence of an intramolecular reaction to yield macrocycles. A second approach involved a click reaction being performed using a 1:1 mixture of diazido-terminated polystyrene and propargyl ether (Scheme 3, B). Thus, homo-telechelic polymer chains were coupled via reaction with a complimentary difiinctional small molecule. The M of the original diazidoterminated PS was 2,020 g/mol, and after step-growth coupling with propargyl ether in the presence of CuBr, an A/ of 16 700 g/mol was obtained. As indicated from the studies mentioned above, azide-alkyne coupling of polymers is a viable means to prepare block copolymers by a modular method or higher molecular weight materials by coupling of homopolymers. While polymer-polymer reactions specifically between end groups can often be associated with low yields due to steric hindrance, click chemistry is an attractive alternative that facilitates increased efficiency under relatively moderate conditions. n

n

n

Monomer Unit Functionalization Incorporating a desirable functionality throughout a polymer chain can be accomplished by direct polymerization of functional monomers or by postpolymerization modification on reactive monomer units (Scheme 4). Subsequent functionalization should be highly efficient due to the large number of monomer units to be derivatized, and specificity is important due to the possibility of side reactions with other moieties along the chain. These requirements make click chemistry an attractive method of modifying polymers to increase their pendant functionality.



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Scheme 3. (A) Synthesis of a-acetylene-w-azido-terminated PS and its subsequent homocoupling and (B) Synthesis of diazido-terminated PS and its coupling with propargyl ether. (Adapted with permissionfromreference 14. Copyright 2005 American Chemical Society.)


148

Π Post-polymerization ATRP Modification

ATRP

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- / = "

A Ν

3

Ν Ν Ν 3

3


R Ν

3

Ν

3

Ν Ν Ν 3

3

3

^

* ΥΝ

3

3

Scheme 4. Methods for introducing pendant azido or alkyne functionality in polymers prepared by ATRP. These two approaches have been employed to introduce azido and alkyne groups into polymers. Helms and coworkers polymerized trimethylsilylprotected vinyl acetylene, and subsequent deprotection permitted coupling with benzyl ether dendritic azides to yield dendronized linear polymers (27). However, because the polymerization was by a conventional radical mechanism, the resulting backbone was rather ill-defined. Previously, Tsarevsky et al. reported the preparation of well-defined homoand copolymers of acrylonitrile by ATRP. Another form of click chemistry was employed to derivatize the acrylonitrile structural units to yield 5-vinyl tetrazole units by reacting with NaN (28). We extended this approach by polymerizing the azide functional monomer 3-azidopropyl methacrylate (AzPMA) by ATRP (Scheme 5) (29). Good control was observed, as indicated by the semilogarithmic kinetic plot and the linear increase in M with conversion for two polymerizations with varying [M] : [I] ratios. The controlled nature of the polymerization was further denoted by the successful synthesis of block copolymers using poly(AzPMA) as a macroinitiator for a block copolymerization with W,N-dimethylaminoethyl methacrylate. High blocking efficiency with the second monomer confirmed chain end retention. Post-polymerization-modification of polyAzPMA (M = 18,400 g/mol, MJM = 1.33), with PgOH in the presence of CuBr led to near-quantitative functionalization in less than 2 h at room temperature in DMF, as evidenced by H N M R spectroscopy. Other functional propargyl species were reacted with similar high yields, including propargyl triphenylphosphonium bromide, propargyl 2-bromoisobutyrate, and 4-pentynoic acid. The success observed for the latter example establishes coupling of acid-containing alkynes to polymeric azides as an additional alternative for introducing carboxylic acid groups that are incompatible with the conditions typically employed for ATRP. 3

n

0

0

n

n

l



Scheme 5. Synthesis ofAzPMA and the subsequent ATRP and post-polymerization modification with various functional alkynes.

R



150 Because of steric constraints and inaccessibility of functional groups along polymer chains, post-polymerization modification reactions are often slower and less efficient than the analogous reaction between two low molecular weight species. However, the rate of azide-alkyne coupling of polyAzPMA was observed to be significantly higher than that for AzPMA monomer (Figure 3) (29). Vinyl monomers are known to coordinate to Cu(I) (50), which could potentially affect the activity of the catalyst, but taking into account that methacrylate coordination is relatively weak, it is unlikely that this is the reason for the discrepancy in rates between monomer and polymer. Moreover, the reaction of PgOH with 3-azidopropanol resulted in similar kinetic profiles as those observed for the monomer. The accelerated rate of reaction with the polymer was somewhat unexpected but can potentially be explained by anchimeric assistance. Previous reports have shown that polytriazoles can sufficiently solubilize Cu(I) (57). This phenomenon was particularly important for the case of poly(AzPMA) since the click reaction was conducted in DMF without an additionally added ligand. Thus, as the click reaction proceeded, triazoles formed along the backbone complexed Cu(I), leading to an effective higher local catalyst concentration in the immediate vicinity of neighboring unreacted azido groups. Similar autocatalytic results were reported by Rodionov et al. (32) during the coupling of alkynes to diazido compounds.

1.0

• PAzPMA • AzPMA

•

o.8 ^

I

Φ 0.6 \

2 c ο ο

•

•

0.2 -\

0.0

Ψ0

• 50

100

150

200

Time (min)

Figure 5. Conversion vs. time for the reaction ofPgOH with polyAzPMA. (Adapted with permission from reference 23. Copyright 2005 American Chemical Society.)


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Summary Click chemistry via Cu(I)-catalyzed 1,3-dipolar cycloaddition of azides and alkynes is a promising method to functionalize (co)polymers of various structures. Combining the high efficiency and fidelity of click chemistry with the control of molecular weight and chain end retention facilitated by ATRP allows the modification of well-defined (co)polymers to give terminal or pendant functional macromolecules. Accordingly, block copolymers and chain extended homopolymers have been prepared by coupling end-functional polymers, and enhanced functionality has been introduced along the backbone of polymers that contained azido groups in the monomer units. Due to the multiplicity of functionality and the propensity of Cu(I)-facilitated azide-alkyne coupling to be autocatalytic, reactions on polymers may often be even more efficient than the reaction of low molecular weight analogs. These findings, along with the reports of others, indicate the combination of click chemistry and precise polymer synthesis is an attractive means to prepare novel functional polymeric materials.

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152 14. Tsarevsky, Ν. V.; Sumerlin, B. S.; Matyjaszewski, K. Macromolecules 2005, 38, 3558-3561. 15. Mantovani, G.; Ladmiral, V.; Tao, L.; Haddleton, D. M . Chem. Commun. 2005, 2089-2091. 16. Joralemon, M . J.; O'Reilly, R. K.; Hawker, C. J.; Wooley, K. L. J. Am. Chem. Soc. 2005, 127, 16892-16899. 17. O'Reilly, R. K.; Joralemon, M . J.; Wooley, K. L.; Hawker, C. J. Chem. Mat. 2005, 17, 5976-5988. 18. Wu, P.; Malkoch, M.; Hunt, J. N.; Vestberg, R.; Kaltgrad, E.; Finn, M . G.; Fokin, V. V.; Sharpless, K. B.; Hawker, C. J. Chem. Commun. 2005, 57755777. 19. Coessens, V.; Matyjaszewski, K. J. Macromol. Sci., Pure Appl. Chem. 1999, A36, 667-679. 20. Coessens, V.; Nakagawa, Y.; Matyjaszewski, K. Polym. Bull. 1998, 40, 135-142. 21. Matyjaszewski, K.; Nakagawa, Y . ; Gaynor, S. G. Macromol. Rapid Commun. 1997, 18, 1057-1066. 22. Nakagawa, Y.; Matyjaszewski, K. Polym. J. 1998, 30, 138-141. 23. Gao, H.; Louche, G.; Sumerlin, B. S.; Jahed, N.; Golas, P.; Matyjaszewski, K. Macromolecules 2005, 38, 8979-8982. 24. Glockner, G. Gradient HPLC and Chromatographic Cross-Fractionation; Springer: Heidelberg, 1991. 25. Philipsen, H. J. Α.; Klumperman, Β.; German, A. L. J. Chromatogr., A 1996, 746, 211. 26. Sarbu, T.; Lin, K.-Y.; Spanswick, J.; Gil, R. R.; Siegwart, D. J.; Matyjaszewski, K. Macromolecules 2004, 37, 9694-9700. 27. Helms, B.; Mynar, J. L.; Hawker, C. J.; Frechet, J. M . J. J. Am. Chem. Soc. 2004, 126, 15020-15021. 28. Tsarevsky, Ν. V.; Bernaerts, Κ. V.; Dufour, B.; Du Prez, F. E.; Matyjaszewski, K. Macromolecules 2004, 37, 9308-9313. 29. Sumerlin, B. S.; Tsarevsky, Ν. V.; Louche, G.; Lee, R. Y.; Matyjaszewski, K. Macromolecules 2005, 38, 7540-7545. 30. Braunecker, W. Α.; Pintauer, T.; Tsarevsky, Ν. V.; Kickelbick, G.; Matyjaszewski, K. J. Organomet. Chem. 2005, 690, 916-924. 31. Chan, T. R.; Hilgraf, R.; Sharpless, Κ. B.; Fokin, V. V. Org. Lett. 2004, 6, 2853-2855. 32. Rodionov, V. O.; Fokin, V. V.; Finn, M . G. Angew. Chem. Int. Ed. 2005, 44, 2-6.


Living Radical Polymerization - American Chemical Society

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