Radical Thiol-ene Reaction Research Articles

A Versatile Platform to Generate Shell-Cross-Linked Uniform Π-Conjugated Nanofibers with Controllable Length, High Morphological Stability, and Facile Surface Tailorability.

Living crystallization-driven self-assembly (CDSA) has emerged as an efficient route to generate π-conjugated-polymer-based nanofibers (CPNFs) with promising applications from photocatalysis to biomedicine. However, the lack of efficient tools to endow CPNFs with morphological stability and surface tailorability becomes a frustrating hindrance for expanding application spectrum of CPNFs. Herein, a facile strategy to fabricate length-controllable OPV-based (OPV = oligo(p-phenylenevinylene)) CPNFs containing a cross-linked shell with high morphological stability and facile surface tailorability through the combination of living CDSA and thiol-ene chemistry by using OPV5 -b-PNAAM32 (PNAAM = poly(N-allyl acrylamide)) as a model is reported. Uniform fiber-like micelles with tunable length can be generated by self-seeding of living CDSA. By taking advantage of radical thiol-ene reaction between vinyls of PNAAM corona and four-arm thiols, the shell of micelles can be cross-linked with negligible destruction of structure of vinylene-containing OPV core. The resulting micelles show high morphological stability in NaCl solution and PBS buffer, even upon heating at 80°C. The introduced extra thiol groups in the cross-linked shell can be further employed to install extra functional moieties via convenient thiol-Michael-type reaction. Given the negligible cytotoxicity of resulting CPNFs, this strategy opens an avenue to fabricate various CPNFs of diverse functionalities for biomedicine.

Difunctionalization of 1,3-Butadiene via Sequential Radical Thiol-ene Reaction and Allylation by Dual Photoredox and Titanium Catalysis.

Recently, radical difunctionalization of the feedstock 1,3-butadiene has become an attractive strategy for increasing molecular complexity. Herein, we present a novel approach that effectively combines radical thiol-ene chemistry with TiIII catalysis to enable a three-component aldehyde allylation using 1,3-butadiene as an allyl group source under visible light conditions. This sustainable and straightforward method has facilitated the rapid production of diverse allylic 1,3-thioalcohols with exceptional regio- and diastereoselectivity.

"Clickable" Polymer Brush Interfaces: Tailoring Monovalent to Multivalent Ligand Display for Protein Immobilization and Sensing.

Facile and effective functionalization of the interface of polymer-coated surfaces allows one to dictate the interaction of the underlying material with the chemical and biological analytes in its environment. Herein, we outline a modular approach that would enable installing a variety of “clickable” handles onto the surface of polymer brushes, enabling facile conjugation of various ligands to obtain functional interfaces. To this end, hydrophilic anti-biofouling poly(ethylene glycol)-based polymer brushes are fabricated on glass-like silicon oxide surfaces using reversible addition–fragmentation chain transfer (RAFT) polymerization. The dithioester group at the chain-end of the polymer brushes enabled the installation of azide, maleimide, and terminal alkene functional groups, using a post-polymerization radical exchange reaction with appropriately functionalized azo-containing molecules. Thus, modified polymer brushes underwent facile conjugation of alkyne or thiol-containing dyes and ligands using alkyne–azide cycloaddition, Michael addition, and radical thiol–ene conjugation, respectively. Moreover, we demonstrate that the radical exchange approach also enables the installation of multivalent motifs using dendritic azo-containing molecules. Terminal alkene groups containing dendrons amenable to functionalization with thiol-containing molecules using the radical thiol–ene reaction were installed at the interface and subsequently functionalized with mannose ligands to enable sensing of the Concanavalin A lectin.

Cellulose allylcarbamate with high content of reactive double bonds for thiol-ene reaction

Polysaccharide phenylcarbonates react with amines to form carbamates with high efficiency and can be used to introduce reactive CC bonds into a biopolymer, which may be converted by thiol-ene click reactions. Thus, cellulose phenylcarbonates are allowed react with allylamine by nucleophilic reaction to yield cellulose allylcarbamate of very high degree of substitution (DS). The DS of allylcarbamate moieties could be controlled by the molar ratio of allylamine to phenylcarbonate groups. Pure products without remaining phenylcarbonate substituents were accessible. The allylcarbamate moieties are reactive regarding the radical thiol-ene reaction that was exemplified by the reaction of cellulose allylcarbamate with 2-(diethylamino)ethane-1-thiol hydrochloride (DEAET) in dimethyl sulfoxide using a photoinitiator under mild conditions. The phenylcarbonates- and allylcarbamates of cellulose as well as the DAEAET adduct were characterized by elemental analysis, NMR- and FTIR spectroscopy.

Directing-Group-Assisted Markovnikov-Selective Hydrothiolation of Styrenes with Thiols by Photoredox/Cobalt Catalysis.

In contrast with the well-developed radical thiol-ene reaction to access anti-Markovnikov-type products, the research on the catalytic Markovnikov-selective hydrothiolation of alkenes is very restricted. Because of the catalyst poisoning of metal catalysts by organosulfur compounds, limited examples of transition-metal-catalyzed thiol-ene reactions have been reported. However, in this work, a directing-group-assisted hydrothiolation of styrenes with thiols by photoredox/cobalt catalysis is found to proceed smoothly to afford Markovnikov-type sulfides with excellent regioselectivity.

Ultrafast microwave assisted recycling of PET to a family of functional precursors and materials

A series of terephthalamides were successfully produced by rapid catalyst-free microwave-assisted aminolysis of polyethylene terephthalate (PET). The produced terephthalamides from chemical recycling of PET were further utilized as reactants for fabrication of plastic films by a radical thiol-ene reaction or they were evaluated as plasticizers for polylactide (PLA). The chemical recycling by aminolysis was performed with four different amines: allylamine, ethanolamine, furfurylamine or hexylamine. The microwave-assisted process led selectively to good yields of well-defined terephthalamides with different terminal functional groups depending on the used amine. The reaction time varied from 10 to 60 min. The end-product obtained after aminolysis with allylamine was further reacted with a thiol through a radical thiol-ene reaction, producing good quality films with glass transition temperature (Tg) above room temperature. The three other terephthalamides were mixed with PLA at 10 wt% and evaluated as plasticizers. The terephthalamide produced by aminolysis with furfurylamine, increased the strain at break 20 times compared to the strain at break of neat PLA. The results illustrate that chemical recycling of PET by aminolysis is a viable and versatile option, producing a library of valuable chemical compounds ready for further use in material applications.

Multifunctional and Transformable 'Clickable' Hydrogel Coatings on Titanium Surfaces: From Protein Immobilization to Cellular Attachment.

Multifunctionalizable hydrogel coatings on titanium interfaces are useful in a wide range of biomedical applications utilizing titanium-based materials. In this study, furan-protected maleimide groups containing multi-clickable biocompatible hydrogel layers are fabricated on a titanium surface. Upon thermal treatment, the masked maleimide groups within the hydrogel are converted to thiol-reactive maleimide groups. The thiol-reactive maleimide group allows facile functionalization of these hydrogels through the thiol-maleimide nucleophilic addition and Diels–Alder cycloaddition reactions, under mild conditions. Additionally, the strained alkene unit in the furan-protected maleimide moiety undergoes radical thiol-ene reaction, as well as the inverse-electron-demand Diels–Alder reaction with tetrazine containing molecules. Taking advantage of photo-initiated thiol-ene ‘click’ reactions, we demonstrate spatially controlled immobilization of the fluorescent dye thiol-containing boron dipyrromethene (BODIPY-SH). Lastly, we establish that the extent of functionalization on hydrogels can be controlled by attachment of biotin-benzyl-tetrazine, followed by immobilization of TRITC-labelled ExtrAvidin. Being versatile and practical, we believe that the described multifunctional and transformable ‘clickable’ hydrogels on titanium-based substrates described here can find applications in areas involving modification of the interface with bioactive entities.

Thiol-Ene Cationic and Radical Reactions: Cyclization, Step-Growth, and Concurrent Polymerizations for Thioacetal and Thioether Units.

Thiol-ene cationic and radical reactions were conducted for 1:1 addition between a thiol and vinyl ether, and also for cyclization and step-growth polymerization between a dithiol and divinyl ether. p-Toluenesulfonic acid (PTSA) induced a cationic thiol-ene reaction to generate a thioacetal in high yield, whereas 2,2'-azobisisobutyronitrile resulted in a radical thiol-ene reaction to give a thioether, also in high yield. The cationic and radical addition reactions between a dithiol and divinyl ether with oxyethylene units yielded amorphous poly(thioacetal)s and crystalline poly(thioether)s, respectively. Under high-dilution conditions, the cationic and radical reactions resulted in 16- and 18-membered cyclic thioacetal and thioether products, respectively. Furthermore, concurrent cationic and radical step-growth polymerizations were realized using PTSA under UV irradiation to produce polymers having both thioacetal and thioether linkages in the main chain.

Nanogel-Based Filler-Matrix Interphase for Polymerization Stress Reduction

A novel filler-resin matrix interphase structure was developed and evaluated for dental composite restoratives. Nanogel additives were chemically attached to the filler surface to use this created interphase as a potential source of compliance to minimize stress development during polymerization. In addition, we evaluated the effects of free nanogel dispersion into the resin matrix, combined or not with nanogel-modified fillers. Nanogels with varied characteristics were synthesized (i.e., size, 5 and 11 nm; glass transition temperature, 28 °C to 65 °C). Glass fillers were treated with trimethoxyvinylsilane and further reacted with thiol-functionalized nanogels via a free radical thiol-ene reaction. γ-Methacryloxypropyltrimethoxysilane-surface treated fillers were used as a control. Composites were formulated with BisGMA/TEGDMA resin blend with 60 wt% fillers with nanogel-modified fillers and/or free nanogel additives at 15 wt% in the resin phase. Polymerization kinetics, polymerization stress, volumetric shrinkage, and rheological and mechanical properties were evaluated to provide comprehensive characterization. Nanogel-modified fillers significantly reduced the polymerization stress from 2.2 MPa to 1.7 to 1.4 MPa, resulting in 20% stress reduction. A significantly greater nanogel content was required to generate the same magnitude stress reduction when the nanogels were dispersed only in the resin phase. When the nanogel-modified filler surface treatment and resin-dispersed nanogel strategies were combined, there was a stress reduction of 50% (values of 1.2 to 1.1 MPa). Polymerization rate and volumetric shrinkage were significantly reduced for systems with nanogel additives into the resin. Notably, the flexural modulus of the materials was not compromised, although a slight reduction in flexural strength associated with the nanogel-modified interphase was observed. Overall, modest amounts of free nanogel additives in the resin phase can be effectively combined with a limited nanogel content filler-resin interphase to lower volumetric shrinkage and dramatically reduce overall polymerization stress of composites.

Phosphate-Based Cross-Linked Polymers from Iodo-ene Photopolymerization: Tuning Surface Wettability through Thiol-ene Chemistry.

Motivated by the various reported potential applications of poly(phosphine oxide) materials, a visible light photoinitiated iodo-ene reaction was successfully employed in network polymerization between the phosphorus-containing multifunctional monomer, tris(allyloxymethyl)phosphine oxide (TAOPO), and diiodoperfluorobutane. The cross-linked poly(phosphine oxide) network exhibited a higher glass transition temperature than a similarly cross-linked polymer formulated with trimethylolpropane triallyl ether (TMPTAE). Interestingly, the TMPTAE/DIPFB cross-linked polymer, changed color from clear to yellow within 10 min of exposure to air, whereas the cross-linked poly(phosphine oxide) underwent a similar change only upon heating. Upon investigation, it was determined that alkenes were generated within the polymer network, presumably via elimination, accounting for the observed color. These double bonds, formed in the polymer matrix, permitted surface modification via radical thiol-ene reaction. The successful surface functionalization with PEG-SH resulted in increasing the surface wettability. Additionally, the phosphorus-containing network polymer with double bonds in the polymer matrix showed shape memory capability, this representing an exciting and versatile materials platform.

Studies about reactive ene-functionalized dextran derivatives for Thiol-ene click reactions

Dextran was applied for the design of biopolymers bearing reactive CC double bond for subsequent “click” reaction with thiols. The polysaccharide was functionalized with maleimido- and norbornene moieties as “ene” compound for thiol-Michael and radical thiol-ene reaction, respectively. The hydroxyl groups of dextran were esterified with 6-maleimidohexanoic acid or 5-norbornene-2-carboxylic acid in an efficient, homogeneous one-step synthesis applying different in-situ activation methods of the carboxylic acids. The water- or organo-soluble dextran derivatives obtained were allowed to react with N-acetyl-L-cysteine to study the reactivity of the ene-functionalized derivatives in thiol-ene “click” reactions dependent on solvent, reaction time, and activation/initiation reagent. The dextran esters and the corresponding N-acetyl-L-cysteine adducts were characterized by means of elemental analysis, NMR-, and FT-IR spectroscopy.

New allyl-functional catalytic comonomers for sequential thiol-Michael and radical thiol-ene reactions

Soft poly(thioether) thermosets have been synthesized by employing a two-step curing procedure based on click chemistry. The first stage of curing is a thiol-Michael addition between acrylates (or methacrylates) and thiols in excess, catalyzed by a set of novel tertiary amine catalyst comonomers with allyl functionality. Subsequently, the pendant allyl groups of the comonomer get incorporated into the polymer network by undergoing thiol-ene UV photopolymerization with the remaining thiols. The strong catalysis by the high concentration of tertiary amine groups facilitates quantitative conversions at the end of the first stage. All remaining functional groups are depleted after a short period of UV irradiation. Final materials are clear, transparent, and exhibit homogeneous network structures with alpha relaxation temperatures in the range 3–25 °C. This sub-ambient relaxation temperature range suggests these materials may be suitable for coating applications where delicate substrates are involved such as plastic, wood and paper.

Sequence Controlled Polymers from a Novel β-Cyclodextrin Core.

In this work the synthesis and use of a novel β-cyclodextrin-based single electron transfer-living radical polymerization (SET-LRP) initiator are reported. Three different approaches toward the synthesis of this initiator, based on several "click"-like reactions (copper(I)-catalyzed azide-alkyne cycloaddition, nucleophilic thiol-ene reaction, and radical thiol-ene reaction), are explored and discussed. Synthesis via radical thiol-ene proves to be most successful in achieving this. The β-cyclodextrin-based initiator is subsequently used for the polymerization of several acrylates in a controlled fashion, yielding 7-arm multiblock copolymers. The achieved sequence-controlled polymers exhibit low dispersities (≤1.12) and are completed under 6.5 h at high monomer conversion (≥95%) for each block.

New bio-based materials obtained by thiol-ene/thiol-epoxy dual curing click procedures from eugenol derivates

Novel bio-based and dual-curable thermosets were prepared from eugenol derivatives. The curing sequence combined two click reactions, a photoinduced radical thiol-ene reaction followed by a thermally activated thiol-epoxy reaction.Eugenol was transformed into a triallyl (3A-EU) and a diallyl glycidyl derivative (2AG-EU) with high yields, and they were used as starting monomers in order to study the thiol-ene reaction and the dual-curing process, respectively. Three different thiol crosslinkers were tested, one commercially available tetrathiol derived from pentaerythritol (PETMP) and two other that were also synthesized: a trithiol derived from eugenol (3SH-EU) and a hexathiol derived from squalene (6SH-SQ).FTIR and DSC were used to monitor both curing stages and analyze the obtained materials. The results evidenced the occurrence of side reactions that led to incomplete thiol-ene reaction. The dual-curable materials showed higher Tgs than the materials obtained by a simple thiol-ene process and presented higher mechanical and thermomechanical performance.

Visible-Light-Mediated Thiol-Ene Reactions through Organic Photoredox Catalysis.

Synthetically useful radical thiol-ene reactions can be initiated by visible-light irradiation in the presence of an organic photocatalyst, 9-mesityl-10-methylacridinum tetrafluoroborate. The key thiyl radical intermediates are generated upon quenching of the photoexcited catalyst with a variety of thiols. The success of this method requires only the use of near-stoichiometric levels of alkene coupling partners. Using these highly efficient metal-free conditions, thiol-ene reactions between carbohydrates and peptides can be accomplished in excellent yields.

Dynamic furan/maleimide bond-incorporated cyclic polymer for topology transformation

The transformation of polymer topological structures by using an external stimulus has gained increasing attention because it is a versatile method to modify the properties of polymeric materials. Herein, cyclic poly(methyl methacrylate) linked by a dynamic covalent furan/maleimide bond was rationally designed and prepared. SEC, FTIR, NMR, and MALDI-TOF characterizations all confirmed the successful preparation of the polymer. By using the (retro)Diels-Alder reaction at a high temperature (110°C), the cyclic polymer was transformed to a linear monopolymer or linear multiblock polymer. In addition, the cyclic topology can also be fixed by eliminating the vinyl double group of furan/maleimide adduct by the photoinduced radical thiol-ene reaction. This work provides a novel and facile approach for cyclic-to-linear topological transformation, and many potentials based on this thermal-responsive polymer are envisioned.

Visible light photocatalysis with benzophenone for radical thiol-ene reactions

Abstract We report herein a simple, metal- and oxidant-free visible light promoted strategy for an anti-Markovnikov hydrothiolation of unactivated olefins using benzophenone as an inexpensive photocatalyst at room temperature. Anti-Markovnikov adducts of a wide variety of olefins and thiols are formed in highly regioselective manner and good to excellent yields. The present radical thiol-ene reaction is operationally simple and well tolerates a variety of functional groups.

Orthogonal thiol-ene 'click' reactions: a powerful combination for fabrication and functionalization of patterned hydrogels.

A combination of 'orthogonal' thiol-ene 'click' reactions is utilized for fabrication and functionalization of micro-patterned hydrogels. A furan-protected maleimide-containing parent copolymer is partially activated via the retro Diels-Alder reaction to obtain an 'orthogonally' functionalizable copolymer, where the different functional groups can be exploited for multi-functionalization or fabrication of functional hydrogels using combination of the nucleophilic and radical thiol-ene reactions.

Multireactive Poly(2-oxazoline) Nanofibers through Electrospinning with Crosslinking on the Fly.

Crosslinked hydrophilic poly(2-oxazoline)-based nanofibers amenable to facile multifunctionalization are fabricated using alkene-containing poly(2-alkyl-2-oxazoline)s (PAOx) via in situ photoinitiated radical thiol-ene crosslinking during electrospinning. The resulting crosslinked nanofibers are demonstrated to be multifunctionalizable using different chemistries as they contain two functional handles, being the alkene moieties from the parent copolymer and the residual thiol groups from the tetra-thiol-based crosslinker. While the thiol groups in these nanofibers could be passivated or conjugated to install functional molecules through thiol-maleimide conjugation, the alkene groups could sequentially be modified with thiol-containing molecules using photoinitiated radical thiol-ene reactions. Utilization of the photochemically induced conjugation of thiol-bearing molecules to the alkene groups on the nanofibers is used to obtain functionalization in a spatially controlled manner.

Anionic flow polymerizations toward functional polyphosphoesters in microreactors: Polymerization and UV-modification

The polymerization of cyclic phosphates to poly(phosphoester)s, PPEs, is optimized for chip-based microreactors under continuous flow conditions. The anionic ring-opening polymerization of 2-isobutyoxy-2-oxo-1,3,2-dioxaphospholane (iBP) via the use of two organocatalytic systems allowed to polymerize to nearly quantitative monomer conversion within 10 or 3min, respectively at a reaction temperature of 40°C. Further, the optimized polymerization protocol was applied to 2-butenoxy-2-oxo-1,3,2-dioxaphospholane (BP) which yields a polymer that carries an alkene functionality per monomer repeating unit. This material can be postmodified in an UV-induced radical thiol–ene reaction, which was also shown to proceed with very high efficiency under UV-flow conditions. Eventually, both reactions were coupled in a two-stage reactor setup, showing that the thermally-activated polymerization can be coupled with high efficiency to the UV-activated post-polymerization modification reaction. The introduced reactor setup can in the future be used to produce and screen a broad variety of functional PPE materials with various functionalities and physical properties.