Modular synthesis of block copolymers via cycloaddition of terminal azide and alkyne functionalized polymers { Joost A. Opsteen and Jan C. M. van Hest* Received (in Cambridge, UK) 23rd August 2004, Accepted 21st October 2004 First published as an Advance Article on the web 25th November 2004 DOI: 10.1039/b412930j Polymeric building blocks containing terminal azide and alkyne functionalities are prepared via atom transfer radical polymer- ization (ATRP) and used to modularly synthesize block copolymers via 1,3-dipolar cycloaddition reactions, which are quantitative according to SEC measurements. Recently, Sharpless et al. have optimized Huisgen’s 1,3-dipolar cycloaddition of azides and terminal alkynes via copper(I) catalysis. 1 This type of ‘‘click’’ reaction can be characterized as highly efficient and specific, with the starting materials being very stable to other functional groups. 2 This ‘‘click’’ chemistry has nowadays also been introduced in dendrimer and polymer synthesis 3 and utilized to cross-link block copolymer vesicles. 4 The great potential of this coupling procedure for the construction of well defined (functional) polymer architectures has been quickly recognized, and is the subject of intensive research. One of the until now still unexplored possibilities is to use this method to modularly synthesize block copolymers. Nowadays, a wide range of ‘‘living’’ or controlled polymeriza- tion techniques is available to prepare block copolymers of various architectures, solubility and functionality, via consecutive polymerization of different monomers. These polymerization techniques comprise ‘‘living’’ ionic 5 and ‘‘living’’ radical polymer- izations. 6–8 Various techniques can also be combined to synthesize a myriad of block copolymer structures. 9 The disadvantages of this so-called macroinitiation approach are that complete formation of block copolymers is hard to assess and characterization of the individual blocks is very difficult. These problems can be circumvented by applying a modular approach for the synthesis of block copolymers. Polymeric blocks bearing functional end groups are prepared separately and are linked covalently via their end groups. This approach enables full analysis (e.g. molecular weight distribution) of the separate blocks prior to coupling. A major disadvantage however of this method is that in order to have a high yield coupling reaction, reactive end groups have to be used that therefore are prone to undergo side reactions, which limits the scope of the modular approach. Here we report a novel modular strategy for the preparation of block copolymers by applying stable alkyne and azide end groups that are activated during the coupling process, circumventing the problem of loss of functionality. Additionally, in ATRP, end group functionality can be introduced either by utilizing functionalized initiators 10 or a post-polymerization end group modification. 11 The first procedure ensures complete functionali- zation of all polymer chains. In the latter case there is a chance of incomplete functionalization due to the presence of dead chain ends, which can however be suppressed in controlled polymeriza- tions, such as atom transfer radical polymerization (ATRP). Alkyne functionality was introduced in a series of poly(methyl methacrylate) (PMMA) 2a–c with different molecular weights and polystyrene (PS) 3 via ATRP, utilizing functionalized initiator 1, as depicted in Scheme 1. The alkyne functionality of this initiator was protected with a trimethylsilyl group in order to circumvent complexation with the copper catalyst during polymerization. This protective group was removed quantitatively according to 1 H NMR using tetrabutylammonium fluoride (TBAF) (Scheme 1). All polymerizations proceeded via first order kinetics, indicating good control over the polymerization process, and, as a consequence, polydispersity indices (PDI’s) were low (Table 1). As aforementioned, functionality can also be introduced by post-polymerization end group modification. This method was used for the preparation of azide mono- and bifunctionalized PS (Scheme 2). The bromide end groups which were present after performing ATRP were replaced by azides using azidotrimethyl- silane and tetrabutylammonium fluoride (TBAF). 12 Completion of these substitution reactions was confirmed by a shift of the methine protons adjacent to the end groups in 1 H NMR spectra (d 4.48–3.91 ppm) and the appearance of azide signals in FTIR-ATR spectra (2090 cm 21 ). As a third polymer, commercially available poly(ethylene glycol) methyl ether (PEG) was used. The hydroxyl group was { Electronic supplementary information (ESI) available: Experimental procedures and details. Semilogarithmic plots of all performed polymer- izations. SEC traces of all performed cycloaddition reactions. See http:// www.rsc.org/suppdata/cc/b4/b412930j/ *j.vanhest@science.ru.nl Scheme 1 Introduction of terminal alkyne functionality in polymers utilizing functionalized ATRP initiator 1. COMMUNICATION www.rsc.org/chemcomm | ChemComm This journal is ß The Royal Society of Chemistry 2005 Chem. Commun., 2005, 57–59 | 57