Aqueous metal-catalyzed living radical polymerization: highly active water-assisted catalysis

Polymer Journal (2012) 44, 51–58 & The Society of Polymer Science, Japan (SPSJ) All rights reserved 0032-3896/12 $32.00 www.nature.com/pj ORIGINAL ARTICLE Aqueous metal-catalyzed living radical polymerization: highly active water-assisted catalysis Makoto Ouchi, Hiroaki Yoda, Takaya Terashima and Mitsuo Sawamoto Catalytic aqueous living radical polymerization was achieved through a ligand design for a ruthenium-based catalyst. A phenolic phosphine ligand [PPh2(pPhOH)] was combined with a pentamethylcyclopentadienyl (Cp*)-based tetrameric ruthenium precursor, and the resulting complex showed a high catalytic activity for aqueous living radical polymerizations of hydrophilic methacrylates (for example, poly(ethylene glycol) methacrylate and 2-hydroxyethyl methacrylate) in conjunction with a chlorine initiator [H–(MMA)2–Cl]. The catalytic system allowed very fast living polymerizations, block copolymerizations and syntheses of high-molecular-weight polymers (DPnB1000) with narrow-molecular-weight distributions. Importantly, the activity was high enough to control the polymerization using a catalytic amount of the complex, even though the polymerizations were performed at low temperature (40 1C). Such advanced catalysis was achieved by not only simple hydrophilicity of the ligand but also by a water-assisted dynamic transformation from the original coordinatively saturated form [Cp*RuCl(PR3)2; 18e; PR3¼phosphine] into an unsaturated and active form [Cp*RuCl(PR3); 16e]. Water molecule(s) may also coordinate for further stabilization as demonstrated by 31P NMR analyses. Polymer Journal (2012) 44, 51–58; doi:10.1038/pj.2011.59; published online 3 August 2011 Keywords: aqueous polymerization; block copolymerization; catalyst; living radical polymerization; phosphine; ruthenium INTRODUCTION Biological reactions occur in water with precise control and selectivity. Reactive sites recognize water-soluble substrates (or vice versa) via hydrogen bonding, hydrophobic and other weak interactions by which rigorously selective reactions proceed efficiently under mild conditions. On the other hand, chemists are generally not good at precise reaction control in aqueous systems because water is among the most ‘polar’ compounds and often promote side reactions and deactivation of substrates, intermediates and/or catalysts. This comparison indicates that one might achieve similar aqueous selectivity by mimicking biological reactions, particularly by utilizing the weak interactions found in water. In sharp contrast to ionic polymerizations and related polar organic reactions, radical polymerization is inherently ‘robust’ against highly polar media and functionalities, and is thus generally immune to the ‘poisonous’ effect of water, because radical species are electronically neutral and are thus tolerant of polar groups. It is therefore common in industrial polymer production to conduct free radical polymerization in aqueous media, typically in emulsion and dispersion processes. Though these processes are technically established, precise radical polymerization in water is generally not possible. Now that living radical polymerization has been demonstrated for a variety of monomers including functional derivatives,1–4 the precise control of radical polymerization in water is of interest not only for a wider range of functional and hydrophilic monomers but is also important from environmental viewpoints and for bioapplications. In particular, ‘polymer bioconjugation’5–7 or covalently linking synthetic polymers to biopolymers, has attracted attention in pharmaceutical and fine material applications. For these applications, fine control in ‘aqueous’ polymerization is required because most biomolecules are only soluble, properly structured and active in water. Contemporary living radical polymerizations frequently involve transition metal-catalysts.1,8–14 Herein, a metal catalyst catalyzes the reversible activation of the carbon–halogen bond (BBC–X 2BBC; X¼halogen) of an alkyl halide initiator and/or dormant polymer terminal in a one-electron redox step (Mtn2XMtn+1; Mt¼transition metal such as Ru, Fe, Ni and Cu), to generate a growth-active radical intermediate at a low concentration and thereby suppress bimolecular termination and other side reactions (Scheme 1). With high initiation efficiency and precise control, the metal-catalyzed systems are superior to other living radical polymerizations in the synthesis of well-defined architectures (for example, block copolymers) and hybridization/conjugation with other (bio)molecules. On the other hand, the metal catalysts are usually sensitive to polar functionalities that often induce unfavorable interactions and thus suffer from a limitation in applicable monomers and solvents and from the contamination of resultant polymers with residual catalyst. Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Kyoto, Japan Correspondence: Professor M Ouchi or Professor M Sawamoto, Department of Polymer Chemistry, Graduate School of Engineering, Kyoto University, Katsura, Nishikyo-ku, Kyoto 615-8510, Japan. E-mail: or Received 25 February 2011; revised 11 April 2011; accepted 18 April 2011; published online 3 August 2011 Aqueous metal-catalyzed living radical polymerization M Ouchi et al 52 Scheme 1 Metal-catalyzed living radical polymerization. Ligand 8 PR3 Ru Cl R–Cl Initiator Ru Cl Ru Cl Cl Ru Cl Ru [Cp*Ru(µ3-Cl)]4 Precursor PR3 PR3 Catalyst Monomer N OH Cocatalyst in Ethanol at 40°C Living Radical Polymerizations of Functional Methacrylates Scheme 2 Pentamethylcyclopentadienyl (Cp*)-based ruthenium catalyst for ethanol-mediated living radical polymerization. It is thus increasingly important to develop transition metal catalysts that are robust with respect to polar groups, soluble in water and active enough to allow the extreme reduction of catalyst does. The perfect system then calls for fine reaction control in water to allow for hydrophilic monomers, a ‘catalytic’ amount of the catalyst and ready removal of its residues from the products. To our knowledge, however, truly aqueous catalysis is thus far unknown for living radical polymerization,15 and most ‘aqueous’ systems require a relatively high amount of catalyst ([catalyst]0/[initiator]0B1) for fine control.16–20 This is likely due to the poor solubility of the metal complexes in water and their high sensitivity to interactions with water. We have recently found that pentamethylcyclopentadienyl (Cp*) ruthenium complexes [Cp*Ru(Cl)L2: L¼phosphine], prepared in situ from a tetrameric precursor ([Cp*Ru(m3-Cl)]4), are active, robust and universal catalysts for living radical polymerization in ethanol (EtOH) (Scheme 2).21 The ligand/co-catalyst combination of tri-m-tolylphosphine [P(mTol)3; mTol¼m-MeC6H4] and a hydrophilic amine [2-dimethylamino-1-ethanol: Me2N(CH2)2OH] supported fast-living radical polymerizations and fine molecular weight control (M (...truncated)