Takaya Terashima

Transition Metal-Catalyzed Living Radical Polymerization: Toward Perfection in Catalysis and Precision Polymer Synthesis

2.1.6. Tacticity and Sequence: Advanced Control 4967 2.2. Transition Metal Catalysts 4967 2.2.1. Overviews of Catalysts 4967 2.2.2. Ruthenium 4967 2.2.3. Copper 4971 2.2.4. Iron 4971 2.2.5. Nickel 4975 2.2.6. Molybdenum 4975 2.2.7. Manganese 4976 2.2.8. Osmium 4976 2.2.9. Cobalt 4976 2.2.10. Other Metals 4976 2.3. Cocatalysts (Additives) 4977 2.3.1. Overview of Cocatalysts 4977 2.3.2. Reducing Agents 4977 2.3.3. Free Radical Initiators 4977 2.3.4. Metal Alkoxides 4977 2.3.5. Amines 4978 2.3.6. Halogen Source 4978 2.4. Initiators 4978 2.4.1. Overview of Initiators: Scope and Design 4978 2.4.2. Alkyl Halides 4978 2.4.3. Arenesulfonyl Halides 4979 2.4.4. N-Chloro Compounds 4979 2.4.5. Halogen-Free Initiators 4979 2.5. Solvents 4980 2.5.1. Overview of Solvents 4980 2.5.2. Catalyst Solubility and Coordination of Solvent 4981 2.5.3. Environmentally Friendly Solvents 4981 2.5.4. Water 4981 2.5.5. Catalytic Solvents: Catalyst Disproportionation 4981

Single-chain folding of polymers for catalytic systems in water

Enzymes are a source of inspiration for chemists attempting to create versatile synthetic catalysts. In order to arrive at a polymeric chain carrying catalytic units separated spatially, it is a prerequisite to fold these polymers in water into well-defined compartmentalized architectures thus creating a catalytic core. Herein, we report the synthesis, physical properties, and catalytic activity of a water-soluble segmented terpolymer in which a helical structure in the apolar core is created around a ruthenium-based catalyst. The supramolecular chirality of this catalytic system is the result of the self-assembly of benzene-1,3,5-tricarboxamide side chains, while the catalyst arises from the sequential ruthenium-catalyzed living radical polymerization of the different monomers followed by ligand exchange. The polymers exhibit a two-state folding process and show transfer hydrogenation in water.

Sequence-Regulated Copolymers via Tandem Catalysis of Living Radical Polymerization and In Situ Transesterification

Sequence regulation of monomers is undoubtedly a challenging issue as an ultimate goal in polymer science. To efficiently produce sequence-controlled copolymers, we herein developed the versatile tandem catalysis, which concurrently and/or sequentially involved ruthenium-catalyzed living radical polymerization and in situ transesterification of methacrylates (monomers: RMA) with metal alkoxides (catalysts) and alcohols (ROH). Typically, gradient copolymers were directly obtained from the synchronization of the two reactions: the instantaneous monomer composition in feed gradually changed via the transesterification of R(1)MA into R(2)MA in the presence of R(2)OH during living polymerization to give R(1)MA/R(2)MA gradient copolymers. The gradient sequence of monomers along a chain was catalytically controlled by the reaction conditions such as temperature, concentration and/or species of catalysts, alcohols, and monomers. The sequence regulation of multimonomer units was also successfully achieved in one-pot by monomer-selective transesterification in concurrent tandem catalysis and iterative tandem catalysis, providing random-gradient copolymers and gradient-block counterparts, respectively. In contrast, sequential tandem catalysis via the variable initiation of either polymerization or in situ transesterification led to random or block copolymers. Due to the versatile adaptability of common and commercially available reagents (monomers, alcohols, catalysts), this tandem catalysis is one of the most efficient, convenient, and powerful tools to design tailor-made sequence-regulated copolymers.

Design of AB divinyl “template monomers” toward alternating sequence control in metal-catalyzed living radical polymerization

For alternating repeat-unit sequence via living radical polymerization, “template monomers” were designed and polymerized, where two polymerizable alkene (vinyl) functions [e.g., methacrylate (M) and acrylate (A)] were placed side by side at the 1,8-positions on a rigid naphthalene scaffold. Even for such a divinyl monomer, highly selective intramolecular radical propagation was achieved with metal-catalyzed living radical polymerization systems, to give linear controlled polymers without cross-linking. The naphthalene template was cleaved viahydrolysis from the resultant polymer, and subsequently methylated for sequence characterization. 1H NMR analysis demonstrated that the polymers consisted of highly alternating sequences (A-M-A: >80%), practically free from homo triad sequences (M-M-M).

Concurrent Tandem Living Radical Polymerization: Gradient Copolymers via In Situ Monomer Transformation with Alcohols

We developed concurrent tandem living radical polymerization as a novel methodology to efficiently, conveniently, and in one-pot produce gradient copolymers via in situ monomer transformation. The key is to employ a metal alkoxide [Al(Oi-Pr)(3), Ti(Oi-Pr)(4)] and an alcohol solvent (ROH) in ruthenium-catalyzed polymerization of conventional ester-based methyl (meth)acrylate [M(M)A], where the monomer was directly transformed into R(M)A via in situ transesterification to gradually vary the monomer composition during the copolymerization. Typically, methyl methacrylate (MMA) was polymerized with a ruthenium catalyst in the presence of excess ethanol (EtOH) and Al(Oi-Pr)(3) cocatalyst to give well-controlled gradient copolymers from MMA to EMA along the polymer chain, in which the original MMA was gradually converted into ethyl methacrylate (EMA) by the cocatalyst. This concurrent tandem polymerization, in conjunction with a wide variety of alcohols, efficiently and conveniently produced various gradient copolymers including long alkyl chain and PEG pendent groups. The obtained copolymers further exhibited unique physical properties different from the corresponding random and block counterparts.

Polymeric pseudo-crown ether for cation recognition via cation template-assisted cyclopolymerization

Cyclopolymerization is a chain polymerization of bifunctional monomers via alternating processes of intramolecular cyclization and intermolecular addition, to give soluble linear polymers consisting of in-chain cyclic structures. Though cyclopolymers comprising in-chain multiple large rings potentially show unique functionality, they generally require the elaborate design of bifunctional monomers. Here we report cation template-assisted cyclopolymerization of poly(ethylene glycol) dimethacrylates as an efficient strategy directly yielding polymeric pseudo-crown ethers with large in-chain cavities (up to 30-membered rings) for selective molecular recognition. The key is to select a size-fit metal cation for the spacer unit of the divinyl monomers to form a pseudo-cyclic conformation, where the two vinyl groups are suitably positioned for intramolecular cyclization. The marriage of supramolecular chemistry and polymer chemistry affords efficient, one-pot chemical transformation from common chemical reagents with simple templates to functional cyclopolymers.

Arm-Cleavable Microgel Star Polymers: A Versatile Strategy for Direct Core Analysis and Functionalization

Arm-cleavable microgel star polymers were developed, where the arm chains can readily be cleaved by acidolysis after the synthesis, allowing isolation of the core, direct analysis of its structure, and also the creation of functional nanometer-sized microgels. The key is to employ a macroinitiator (PEG-acetal-Cl) that carries an acetal linkage between a poly(ethylene glycol) arm chain and a chloride initiating site. From this, star polymers were synthesized via the linking reaction with a divinyl monomer and a ruthenium catalyst in living radical polymerization. The arms were subsequently cleaved by acidolysis of the acetal linker to give soluble microgels (cores free from arms). Full characterization revealed that the microgel cores are spherical, nano-sized (<20 nm), and of relatively low density. Amphiphilic, water-soluble, and thermosensitive arm-free microgels can be obtained by additionally employing functional methacrylate upon arm linking.

Amphiphilic/fluorous random copolymers as a new class of non-cytotoxic polymeric materials for protein conjugation

Herein, amphiphilic/fluorous random copolymers bearing poly(ethylene glycol) (PEG) chains and perfluorinated alkane pendants were developed as novel non-cytotoxic polymers for protein conjugation. Three kinds of random copolymers with different initiating terminals (carboxylic acid, pyridyl disulfide, and N-hydroxysuccinimide ester) were prepared by reversible addition–fragmentation chain transfer (RAFT) copolymerization of a PEG methyl ether methacrylate and a perfluorinated alkane methacrylate with the corresponding functional chain transfer agents. All of the polymers were soluble in water to form nanostructures with perfluorinated compartments via fluorous interaction: large aggregates from the intermolecular multi-chain association and compact unimer micelles from the intramolecular single-chain folding. Such a PEGylated and perfluorinated random copolymer was non-cytotoxic to NIH 3T3 mouse embryonic fibroblast cells and human umbilical vein endothelial cells (HUVECs). Additionally, a random copolymer with a pyridyl disulfide terminal was also successfully conjugated with a thiolated lysozyme.

Efficient and Robust Star Polymer Catalysts for Living Radical Polymerization: Cooperative Activation in Microgel-Core Reactors

Multifunctional microgel-core star polymers with ruthenium catalysts are designed as catalyst-bearing nanoreactors to improve activity, controllability, and functionality tolerance in living radical polymerization. Multifunctional ligands are efficiently incorporated into the core of star polymers by sequential tandem procedures: 1) ruthenium-catalyzed living radical polymerization, 2) in situ core hydrogenation, and 3) core-ruthenium removal. Typically, the star polymer ligands comprising multiple phosphines and amines within the core cooperatively enclose a ruthenium complex (>100 per core). As a result, the in-core pseudo hetero P,N-chelation of the ruthenium complexes not only showed high activity for methyl methacrylate but also high tolerance to unprotected methacrylic acid.

Synthesis of fluorinated gradient copolymers via in situ transesterification with fluoroalcohols in tandem living radical polymerization

Fluorinated gradient copolymers were synthesized by the tandem catalysis of ruthenium-catalyzed living radical polymerization (LRP) and titanium alkoxide-mediated transesterification of methyl methacrylate (MMA) with fluoroalcohols. Although transesterification using less nucleophilic fluoroalcohols is generally regarded as difficult, we found that MMA was efficiently transesterified with fluoroalcohols (RFOH) into fluorinated methacrylates (RFMA) by Ti(Oi-Pr)4 catalysts (2–8 mol%) in the presence of molecular sieves 4A (MS 4A). The yield of RFMA increased with increasing the alkyl spacer (carbon number) between a hydroxyl group and a fluorinated alkyl segment in fluoroalcohols: propyl (4,4,5,5,5-pentafluoro-1-pentanol: 5FPOH) > ethyl (1H,1H,2H,2H-nonafluoro-1-hexanol: 9FHOH) > methyl (1H,1H-heptafluoro-1-butanol). Tandem polymerization of MMA was conducted with a ruthenium catalyst, a chloride initiator, and Ti(Oi-Pr)4 in toluene/fluoroalcohol mixtures (1/1, v/v) at 80 °C. Typically, in the presence of 4 mol% Ti and MS 4A, transesterification of MMA with 5FPOH or 9FHOH was efficiently synchronized with LRP to produce well-controlled MMA/5FPMA or MMA/9FHMA gradient copolymers in high yield (Conv. >95%, Mw/Mn = 1.2).