Complex polymer architectures via RAFT polymerization: From fundamental process to extending the scope using click chemistry and nature's building blocks

Reversible addition fragmentation chain transfer (RAFT) polymerization has made a huge impact in macromolecular design. The first block copolymers were described early on, followed by star polymers and then graft polymers. In the last five years, the types of architectures available have become more and more complex. Star and graft polymers now have block structures within their branches, or a range of different branches can be found growing from one core or backbone. Even the synthesis of hyperbranched polymers can be positively influenced by RAFT polymerization, allowing end group control or control over the branching density. The creative combination of RAFT polymerization with other polymerization techniques, such as ATRP or ring-opening polymerization, has extended the array of available architectures. In addition, dendrimers were incorporated either as star core or endfunctionalities. A range of synthetic chemistry pathways have been utilized and combined with polymer chemistry, pathways such as ‘click chemistry’. These combinations have allowed the creation of novel structures. RAFT processes have been combined with natural polymers and other naturally occurring building blocks, including carbohydrates, polysaccharides, cyclodextrins, proteins and peptides. The result from the intertwining of natural and synthetic materials has resulted in the formation of hybrid biopolymers. Following these developments over the last few years, it is remarkable to see that RAFT polymerization has grown from a lab curiosity to a polymerization tool that is now been used with confidence in material design. Most of the described synthetic procedures in the literature in recent years, which incorporate RAFT polymerization, have been undertaken in order to design advanced materials.     

Synthesis and functionalization of nanoengineered materials using click chemistry

The synthesis of nanoengineered materials with precise control over material composition, architecture and functionality is integral to advances in diverse fields, including biomedicine. Over the last 10 years, click chemistry has emerged as a prominent and versatile approach to engineer materials with specific properties. Herein, we highlight the application of click chemistry for the synthesis of nanoengineered materials, ranging from ultrathin films to delivery systems such as polymersomes, dendrimers and capsules. In addition, we discuss the use of click chemistry for functionalizing such materials, focusing on modifications aimed at biomedical applications.     

“Click” reactions in polysaccharide modification

Polysaccharide chemistry is enjoying accelerating development thanks to advances in synthetic techniques, biochemistry and solvents, which enable polysaccharide materials to be useful in a variety of demanding applications. Among the synthetic advances, click chemistry has reconfigured the realm of polysaccharide modification that previously was dominated by conventional synthetic approaches such as esterification and etherification. “Click” reactions provide mild, modular, and efficient modification pathways, and equally importantly allow us to synthesize derivatives with novel functionality, architecture, and properties, that are otherwise difficult to obtain via conventional methods. Herein, we review application in polysaccharide modification of six groups of click reactions; CuAAC (copper catalyzed alkyne/azide cycloaddition), metal-free [3+2] cycloaddition, Diels–Alder reaction, oxime click, thiol-Michael reaction, and thiol-ene reaction, as well as one click-like reaction that is the subject of our own research, olefin cross-metathesis.     

“链接”化学在高分子合成中的应用

简介了"链接"化学的基本特点,综述了近几年来叠氮-炔"链接"化学在合成不同结构聚合物中的应用。     

Click dendrimers and triazole-related aspects: catalysts, mechanism, synthesis, and functions. A bridge between dendritic architectures and nanomaterials

One of the primary recent improvements in molecular chemistry is the now decade-old concept of click chemistry. Typically performed as copper-catalyzed azide-alkyne (CuAAC) Huisgen-type 1,3-cycloadditions, this reaction has many applications in biomedicine and materials science. The application of this chemistry in dendrimer synthesis beyond the zeroth generation and in nanoparticle functionalization requires stoichiometric use of the most common click catalyst, CuSO(4)·5H(2)O with sodium ascorbate. Efforts to develop milder reaction conditions for these substrates have led to the design of polydentate nitrogen ligands. Along these lines, we have described a new, efficient, practical, and easy-to-synthesize catalytic complex, [Cu(I)(hexabenzyltren)]Br, 1 [tren = tris(2-aminoethyl)amine], for the synthesis of relatively large dendrimers and functional gold nanoparticles (AuNPs). This efficient catalyst can be used alone in 0.1% mol amounts for nondendritic click reactions or with the sodium-ascorbate additive, which inhibits aerobic catalyst oxidation. Alternatively, catalytic quantities of the air-stable compounds hexabenzyltren and CuBr added to the click reaction medium can provide analogously satisfactory results. Based on this catalyst as a core, we have also designed and synthesized analogous Cu(I)-centered dendritic catalysts that are much less air-sensitive than 1 and are soluble in organic solvents or in water (depending on the nature of the terminal groups). These multivalent catalysts facilitate efficient click chemistry and exert positive dendritic effects that mimic enzyme activity. We propose a monometallic CuAAC click mechanism for this process. Although the primary use of click chemistry with dendrimers has been to decorate dendrimers with a large number of molecules for medicinal or materials purposes, we are specifically interested in the formation of intradendritic [1,2,3]-triazole heterocycles that coordinate to transition-metal ions via their nitrogen atoms. We describe applications including molecular recognition of anions and cations and the stabilization of transition metal nanoparticles according to a principle pioneered by Crooks with poly(amido amine) (PAMAM) dendrimers, and in particular, the control of structural and reactivity parameters in which the intradendritic [1,2,3]-triazoles and peripheral tripodal tri(ethylene glycol) termini play key roles in the click-dendrimer mediated synthesis and stabilization of gold nanoparticles (AuNPs). By varying these parameters, we have stabilized water-soluble, weakly liganded AuNPs between 1.8 and 50 nm in size and have shown large differences in behavior between AuNPs and PdNPs. Overall, the new catalyst design and the possibilities of click dendrimer chemistry introduce a bridge between dendritic architectures and the world of nanomaterials for multiple applications.     

Thermally curable main-chain benzoxazine prepolymers via polycondensation route

Polybenzoxazines are addition-cure thermosetting polymers exhibiting versatility in a wide range of applications due to their good mechanical properties, dimensional stability, chemical resistivity, flame resistance property phenolic or epoxy resins have myriad applications in diverse fields starting from commodity materials to high technology aerospace industries. In this paper, we present synthetic strategies to incorporate thermally curable benzoxazine functionality into polymers as main-chain fashion in order to further improve various properties. The strategies successfully employed including monomer synthesis and polycondensation routes like Mannich reaction, click chemistry, hydrosilylations, and coupling reactions. The structure–property relationships of the cured materials have also been presented and discussed.     

Thiol Michael addition reaction: a facile tool for introducing peptides into polymer‐based gene delivery systems

Polymers, as widely used non‐viral gene carriers, suffer from high cytotoxicity and relatively low transfection efficiency. Such crucial drawbacks of polymers could be solved by incorporating short and bioactive peptides. The resulting synthetic polymer–peptide conjugates can not only maintain their own special characteristics, but also gain novel characteristics far beyond those of their parent polymer and peptide components to overcome barriers to gene delivery. There are various chemoselective reactions applied in the synthesis of polymer–peptide conjugates, such as Heck, Sonogashira and Suzuki coupling, Diels–Alder cycloaddition, click chemistry, Staudinger ligation, reductive alkylation and oxime/hydrazone chemistry. Among them, thiol–ene click reactions, including thiol–ene radical and thiol Michael addition reactions, are common methods for preparing peptide–polymer conjugates. In this review, we focus on thiol Michael addition reactions, elaborate on their mechanisms and highlight their applications in the synthesis of polymer–peptide conjugates for gene delivery. © 2017 Society of Chemical Industry     

Soft vesicles in the synthesis of hard materials

Vesicles of surfactants in aqueous solution have received considerable attention because of their use as simple model systems for biological membranes and their applications in various fields including colloids, pharmaceuticals, and materials. Because of their architecture, vesicles could prove useful as "soft" templates for the synthesis of "hard materials". The vesicle phase, however, has been challenging and difficult to work with in the construction of hard materials. In the solution-phase synthesis of various inorganic or macromolecular materials, templating methods provide a powerful strategy to control the size, morphology, and composition of the resulting micro- and nanostructures. In comparison with hard templates, soft templates are generally constructed using amphiphilic molecules, especially surfactants and amphiphilic polymers. These types of compounds offer advantages including the wide variety of available templates, simple fabrication processes under mild conditions, and easy removal of the templates with less damage to the final structures. Researchers have used many ordered molecular aggregates such as vesicles, micelles, liquid crystals, emulsion droplets, and lipid nanotubes as templates or structure-directing agents to control the synthesis or assembly hard micro- and nanomaterials composed from inorganic compounds or polymers. In addition to their range of sizes and morphologies, vesicles present unique structures that can simultaneously supply different microenvironments for the growth and assembly of hard materials: the inner chamber of vesicles, the outer surface of the vesicles, and the space between bilayers. Two main approaches for applying vesicles in the field of hard materials have been explored: (i) in situ synthesis of micro- or nanomaterials within a specific microenvironment by vesicle templating and (ii) the assembly or incorporation of guest materials during the formation of vesicles. This Account provides an in-depth look at the research concerning the association of soft vesicles with hard materials by our laboratory and others. We summarize three main principles of soft vesicle usage in the synthesis of hard materials and detailed procedures for vesicle templating and the characterization of the synthetic mechanisms. By use of these guiding principles, a variety of inorganic materials have been prepared, such as quantum dots, noble metal nanoparticles, mesoporous structures, and hollow capsules. Polymerization within the vesicle bilayers enhances vesicle stability, and this strategy has been developed to synthesize hollow polymer materials. Since 2004, our group has pursued a completely different strategy in the synthesis of micro- and nanomaterials using vesicles as reactive templates. In this method, the vesicles act not only as templates but also as reactive precursors. Because of the location of metal ions on the bilayer membranes, such reactions are restricted to the interface of the vesicle membrane and solution. Finally, using the perspective of soft matter chemistry, we stress some basic criteria for vesicle templating.     

Porous manganese oxide octahedral molecular sieves and octahedral layered materials

This Account first gives a historical overview of the development of octahedral molecular sieve (OMS) and octahedral layer (OL) materials based on porous mixed-valent manganese oxides. Unique properties of such systems include excellent semiconductivity and porosity. Materials that are conducting and porous are rare and can offer novel properties not normally available with most molecular sieve materials. The good semiconductivity of OMS and OL systems not only permits potential applications of the conductivity of these materials but also allows characterization of these systems where charging effects are often a problem. Porous manganese oxide natural materials are found as manganese nodules, and these materials when dredged from the ocean floors have been used as excellent adsorbents of metals such as from electroplating wastes and have been shown to be excellent catalysts. Rational for synthesis of novel OMS and OL materials is related to the superb conductivity, microporosity, and catalytic activity of these natural materials. The natural systems are often found as mixtures, are poorly crystalline, and have incredibly diverse compositions due to exposure to various aqueous environments in nature. Such exposure allows ion exchange to occur. Preparation of pure crystalline OL and OMS systems is one of the very significant goals of this work. The status of this research area is one of moderate development. Opportunities exist for preparation of a multitude of novel materials. Some applications of these materials have recently been achieved primarily in the area of catalysis and membranes, and others such as sensors and adsorptive systems are likely. Characterization studies are becoming more sophisticated as new materials and proper preparation of materials for such characterization studies are being done. The research area involved in this work is solid state chemistry. The fields of materials synthesis, characterization, and applications of materials are all important in developments of this field. Researchers in chemistry, chemical engineering, materials science, physics, and biological sciences are actively pursuing research in this area. The most significant results found in this work are related to the novel structural and physical properties of porous manganese oxide materials. Variable pore size materials have been synthesized using structure directors and with a variety of synthetic methodologies. Transformations of tunnel materials with temperature and in specific atmosphere have recently been studied with in situ synchrotron methods. Conductivities of these materials appear to be related to the structural properties of these systems with more open structures being less conductive. Catalytic properties of these OMS and OL materials have been shown to be related to the redox cycling of various oxidations states of manganese such as Mn2+, Mn3+, and Mn4+. Chemists interested in synthesis of new materials, the chemistry of solids, enhancing the rates of catalytic reactions, and finding new applications of materials would be interested in these novel materials. Fundamental properties of electron transfer are critical to this research. Concepts of nonstoichiometry, defects, oxygen vacancies, and intermediates are fundamental to many of the syntheses, characterization, and applications such as fuel cells, catalysis, adsorption, sensors, batteries, and related applications.     

The development of versatile methods for palladium-catalyzed coupling reactions of aryl electrophiles through the use of P(t-Bu)3 and PCy3 as ligands

Metal-catalyzed coupling reactions of aryl electrophiles with organometallics and with olefins serve as unusually effective tools for forming new carbon-carbon bonds. By 1998, researchers had developed catalysts that achieved reactions of aryl iodides, bromides, and triflates. Nevertheless, many noteworthy challenges remained; among them were couplings of aryl iodides, bromides, and triflates under mild conditions (at room temperature, for example), couplings of hindered reaction partners, and couplings of inexpensive aryl chlorides. This Account highlights some of the progress that has been made in our laboratory over the past decade, largely through the appropriate choice of ligand, in achieving these synthetic objectives. In particular, we have established that palladium in combination with a bulky trialkylphosphine accomplishes a broad spectrum of coupling processes, including Suzuki, Stille, Negishi, and Heck reactions. These methods have been applied in a wide array of settings, such as natural-product synthesis, materials science, and bioorganic chemistry.     

Flow Chemistry – A Key Enabling Technology for (Multistep) Organic Synthesis

Laboratory scaled flow‐through processes have seen an explosive development over the past decade and have become an enabling technology for improving synthetic efficiency through automation and process optimization. Practically, flow devices are a crucial link between bench chemists and process engineers. The present review focuses on two unique aspects of modern flow chemistry where substantial advantages over the corresponding batch processes have become evident. Flow chemistry being one out of several enabling technologies can ideally be combined with other enabling technologies such as energy input. This may be achieved in form of heat to create supercritical conditions. Here, indirect methods such as microwave irradiation and inductive heating have seen widespread applications. Also radiation can efficiently be used to carry out photochemical reactions in a highly practical and scalable manner. A second unique aspect of flow chemistry compared to batch chemistry is associated with the option to carry out multistep synthesis by designing a flow set‐up composed of several flow reactors. Besides their role as chemical reactors these can act as elements for purification or solvent switch.     

Gold-Catalyzed Alkynylation: Acetylene-Transfer instead of Functionalization

Over the last fifteen years, gold has been raised from the status of an inert noble metal to one of the most-often-used catalysts in synthetic chemistry. The functionalization of the triple bond of alkynes has been especially successful in this respect. In contrast, gold-catalyzed alkynylation reactions only began to emerge in 2007. Since then, three different approaches have been successfully used for this transformation. 1) Gold nanoparticles have been shown to promote catalytic cycles based on the oxidative arylation of aryl halides to give a “palladium-free Sonogashira reaction”. 2) The use of benziodoxol(on)e hypervalent iodine compounds as oxidative alkynylation reagents has allowed the C H functionalization of electron-rich heterocycles under mild conditions with a very broad functional-group tolerance. 3) The use of iodobenzene acetate or Selectfluor as an external oxidant has led to the first alkynylation methods based on direct C H/C H coupling reactions. In only six years, gold-catalyzed alkynylation methods have grown from non-existent to useful synthetic procedures for the synthesis of structurally diverse alkynes. Considering that acetylenes are among the most-important building blocks for applications in synthetic chemistry, chemical biology, and materials science, there is tremendous potential for the further development of gold-catalyzed alkynylation reactions in the future.     

Pd催化芳基重氮盐的Suzuki偶联反应研究进展

综述了不同Pd催化剂催化的芳基重氮盐的Suzuki偶联反应,并对其优缺点进行了比较,同时对Suzuki偶联反应的应用进行了阐述。     

Supramolecular Chemistry in Solid State Materials such as Metal-Organic Frameworks

Supramolecular chemistry has enriched the scientific research for more than fifty years reaching one of its summits in 2016, when the Chemistry Nobel Prize was awarded for the design and synthesis of molecular machines, in which host-guest chemistry plays a fundamental role. Recently, the groups of Omar Yaghi and Fraser Stoddart, among others, have demonstrated that this chemistry can be extended to the pores of metal-organic frameworks (MOFs). This heterogenization of supramolecular chemistry can be achieved through the incorporation of macrocycles to the organic struts of these highly porous and crystalline materials. Throughout this short review we summarize interesting examples of selective recognition by naturally occurring and synthetic macrocycles in solution and solid state; and later we survey important milestones to achieve specific recognition sites and develop host-guest chemistry at the pores of MOFs. This summary contains examples of different synthetic strategies to incorporate macrocycles to solid state materials, and in particular, to prepare supramolecular MOFs with particular properties and related applications. Specifically, the revised research includes the incorporation of both naturally occurring and synthetic macrocycles to solid state materials such as polymers, metal nanoparticles, etc., as prelude of the solid phase recognition studied in MOFs. An important number of the contributions presented here feature porous solids with smooth access to the host's cavity incorporated in the pores, allowing specific recognition of guest molecules. This smooth access to those active recognition sites in materials with extremely high surface area such as MOFs, open the possibility to develop the next generation of frontier materials with application in fields such as selective capture of water toxins and heterogeneous catalysis, among others.     

Neues aus der Chemie der Iminiumsalze

Recent Developments in Iminium Salt Chemistry Iminium salts are of continuing interest as versatile building blocks in organic synthesis. This progress report from different laboratories highlights some current research activities in iminium salt chemistry. Several contributions focus on novel synthetic applications of isolable, functionalized iminium systems such as α,β-unsaturated iminium salts (e.g. vinamidinium, 3-trifloxy, 3-chloro-, 3-isocyanato- and 3-thiopropene iminium, as well as propyne iminium salts), furthermore on phosgene iminium chloride and trifluoromethyl-substituted iminium salts. Iminium intermediates occur in various synthetic transformations; for example, cyclopropane iminium ions are intermediates in nucleophilic substitution reactions at bicyclic aminocyclopropanes. Also reported is the synthesis of a variety of novel orthoamides and their use as synthetic building blocks. Research directed to the application of vinamidinium salts in materials science is also presented.     

William von Eggers Doering's many research achievements during the first 65 years of his career in chemistry

This Account highlights William von Eggers Doering's important discoveries in many fields of chemistry. His synthetic and mechanistic studies have contributed to areas including non-benzenoid aromatics, carbenes, pericyclic reactions, and diradical intermediates. Doering's synthesis with L. H. Knox of the highly stable tropylium ion and their investigation of its reactivity were the starting point for the development of the field of non-benzenoid aromatics. Working with A. K. Hoffmann, Doering demonstrated the synthesis of dichloro- and dibromocarbene by base-induced alpha elimination of HCl or HBr from CHCl3 or CHBr3 under anhydrous conditions. These results allowed for the synthesis of a variety of cyclopropanes and derivatives including allenes. Using 14C labeling experiments, Doering and Prinzbach showed that the mechanism of insertion of singlet methylene into a C-H bond was a concerted process.In their work on the Cope rearrangement, Doering and Roth's outstanding stereochemical analysis showed that the rearrangement of acyclic 1,5-hexadienes proceeds concertedly, passing over a chairlike transition state. This work has had an enormous impact on the understanding of stereochemical control in synthetic organic chemistry, and many fruitful applications in synthesis have stemmed directly from this finding. Transition-state resonance structures analogous to those for ground-state aromatics can qualitatively explain the relatively large substituent effects on the rate of the Cope rearrangement. However, quantum chemical calculations have quantitatively described these effects. The rapid degenerate Cope rearrangements in the cis-divinylcyclopropane units of 3,4-homotropilidene, barbaralone, and bullvalene establish these molecules as having fluxional structures. The unique molecule bullvalene has more than 1.2 million possible structures interconnected by degenerate Cope rearrangements, which average all H and all C atoms. Doering has also examined stepwise thermal reorganizations that pass through intermediary 1,3- or 1,4-diradicals and do not show conformational equilibration as would be expected for classical intermediates. Doering calls these processes "not-obviously concerted". He discusses "continuous diradicals" as transition states and rationalizes the course of these reactions through the concept of a "caldera" (a flat surface with small energy wells as found on the top of volcanoes).The understanding of fundamental chemical reactions remains the focus of Doering's research. In his terms, "understanding" means not only gaining deep insight but also the intellectual control that allows researchers to predict a reaction's course. Because the interplay between theory and experiment has led to great progress in this predictive ability, Doering's experimental work has provided an important input for computational chemistry and to the essential understanding of chemical reactions.     

Towards macromolecular architectures of corannulene

In an attempt to introduce corannulene chemistry to macromolecular science, my research program is dedicated to synthetic strategies leading to corannulene-based polymers with interesting architectures and properties. In this brief account, I will discuss the synthesis of a variety of corannulene-based building blocks (monomers) and their utility in the preparation of a wide range of corannulene-rich macromolecular structures.     

Use of microwave irradiation in the grafting modification of the polysaccharides - A review

Polysaccharides are a natural and renewable feed stock for synthesizing high performance macromolecular materials. A popular, versatile and convenient route to develop polysaccharide based materials is the grafting of synthetic polymers onto natural polysaccharides. In spite of the attractive chemical and physical properties of polysaccharide based copolymeric materials, undesired homopolymer formation in the concurrent competing reaction lowers the copolymer yield, posing problems in the commercialization of the grafting procedures. Moreover, the requirement for an inert atmosphere is an added disadvantage for many conventional grafting procedures. The use of microwave irradiation has been exploited in the past two decades to alleviate these limitations in the synthesis of a range of graft modified polysaccharide materials. Indeed, increasing interest in clean and green environment friendly chemistry has motivated the use of microwaves in the polysaccharide grafting modification for various applications. Microwave irradiation significantly reduces the use of toxic solvents, as well as the reaction time for almost all the grafting reactions of interest here, ensuring high yields, product selectivity and clean product formations. Moreover, in many instances, microwave synthesized polysaccharide copolymers exhibit better properties for commercial exploitation than their conventionally synthesized counterparts. This review highlights recent applications of microwave heating in the grafting modifications of polysaccharides and discusses the underlying mechanisms and issues.     

Isodesmic Reactions in Catalysis – Only the Beginning?

In this perspective article, we discuss catalytic isodesmic reactions, a group of chemical reactions that proceed through the redistribution of chemical bonds – i. e. all bonds present in the starting materials are reformed in the products. These reactions are usually reversible and provide a complementary approach to the kinetically controlled strategies traditionally employed in chemical synthesis. To emphasize the power of these reactions across the molecular sciences, we present selected applications of these reactions in organic synthesis, chemical biology, biomass valorization, waste treatment, and materials science. We finally speculate that the development of novel catalytic isodesmic reactions beyond the “classics” (alkene/alkyne metathesis and transfer hydrogenation) holds great promise to solve crucial challenges in synthetic chemistry in the years to come.     

环氧化合物亲核开环反应过程强化研究进展

环氧化合物因其特殊环应变而具有显著的反应性，在酸或碱的催化下与许多亲核试剂进行开环反应，可用于制备各种合成中间体。环氧化合物开环反应的区域选择性和立体选择性是合成化学的核心课题。本文综述了环氧化合物亲核开环反应过程强化的国内外进展，从新材料（介质）强化、外场强化、过程装备强化等方面介绍了不同强化策略对环氧化合物亲核开环反应的影响，重点分析了新型多孔材料、金属氧化物、离子液体等几类材料对环氧化合物亲核开环反应的催化性能的影响，并指出了实际工业生产中环氧化合物亲核开环反应强化技术中依然存在转化率和选择性不高、反应能耗大的问题。提出建立基于环氧化合物开环反应特性的多种强化技术耦合的过程强化方法是今后的发展方向。