Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• catalyst to produce radicals at the 2- and 5-positions of thiophene and synthesized four types of poly(3-alkylthiophene)s (PATs) with different linking ways (Scheme 10). 2.2 Polymerization by thiol–ene chemistry The thiol–ene reaction (also called alkene hydrothiolation) is the anti-Markovnikov addition of

• a thiol to a C–C double bond and was first reported in 1905 [80]. It is considered as a click chemistry reaction due to its high yield, stereoselectivity, rate, and thermodynamic driving force. Generally, the thiol–ene reaction is conducted under radical conditions, often photochemically induced [81

• ]. In a typical thiol–ene system, the polymerization undergoes a free-radical chain mechanism, involving an initiation step from a thiol group via radical transfer or homolysis (Scheme 11, initiation), radical addition of the thiyl radical to the ene functionality (propagation 1), transfer from the

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• . Synthesis of Stoddart´s BINOL-containing [2]catenanes 18/20/22/24 by π–π recognition. Synthesis of Takata´s rotaxanes featuring chiral centers on the axle: a) rotaxane (R,R,R/S)-27 obtained by thiol–ene addition and b) rotaxanes (R,R/S)-30a–f obtained by amine oxidation. Takata´s chiral polyacetylenes 32/33

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• the removal of metathesis catalysts is the formation of Ru-DMSO complexes, which do not eluate from a silica column [56]. This allowed us to remove at least the Ru contamination, but we were unable to subject 12 to further modifications such as cross metathesis or thiol-ene click reactions due to poor

• modifications, mainly for solubility reasons. Therefore, we decided to have a closer look into modifications of the longer side chain present in 11 and subjected it to thiol-ene click reactions. Since masked thiols are often found as zinc-coordinating functionalities in HDAC inhibitors, e.g., in the largazoles

• , we treated 11 with thioacetic acid and BEt3/air in THF to give 82% of the thiol-ene click product (Scheme 4). Careful analysis of the NMR spectra revealed that the intermediately formed radical cyclized in an intramolecular 5-exo-trig fashion with the internal double bond to form a tetrahydrofuran

Exfoliated black phosphorous-mediated CuAAC chemistry for organic and macromolecular synthesis under white LED and near-IR irradiation

• Azra Kocaarslan,
• Zafer Eroglu,
• Önder Metin and
• Yusuf Yagci

Beilstein J. Org. Chem. 2021, 17, 2477–2487, doi:10.3762/bjoc.17.164

• photocatalysts have been successfully applied in both small- and large-scale synthesis such as organic reactions [16][17], free radical polymerization (FRP) [18][19][20], controlled radical polymerization (CRP) [21][22], CuAAC chemistry [23][24][25], and thiol–ene chemistry [26][27]. However, most of the

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

• effect highly selective aldol reactions of simple ketones and aromatic aldehydes in flow [106]. Photoinduced thiol–ene coupling was used to tether the catalyst onto silica particles, yielding an easily handled powder which was packed into a short stainless steel column (Scheme 8). The resultant packed

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• (Scheme 3 and Scheme 9) [41][60]. In stoichiometric amounts, they generally add efficiently to π-systems and can be applied in thiol-ene reactions. Recently, Dilman and co-workers published a hydrosulfenylation of the β-difluorostyrenes 41.2 for the synthesis of the thioethers 41.3 using 9-PhAcr (OD1) as

Towards the preparation of synthetic outer membrane vesicle models with micromolar affinity to wheat germ agglutinin using a dialkyl thioglycoside

• Dimitri Fayolle,
• Nathalie Berthet,
• Bastien Doumeche,
• Olivier Renaudet,
• Peter Strazewski and
• Michele Fiore

Beilstein J. Org. Chem. 2019, 15, 937–946, doi:10.3762/bjoc.15.90

• , DCM UMR 5250, F-38000 Grenoble, France 10.3762/bjoc.15.90 Abstract A series of alkyl thioglycosides and alkyl thiodiglycosides bearing glucose and N-acetylglucosamine residues were prepared by thiol–ene coupling in moderate to good yields (40–85%). Their binding ability towards wheat germ agglutinin

• addition of thiols to alkenes – known as thiol–ene coupling, TEC – a very efficient metal-free click reaction [18][19]. We prepared n-alkyl 1-thio-β--glycosides from unprotected sugar anomeric thiols, commercial n-alkenes and one synthetic lipophilic scaffold presenting two reactive alkenyl ends. Although

• thiyl-radical-mediated reactions have been extensively investigated for the preparation of carbohydrate derivatives [20] and some dithioether phospholipid and glycolipid analogues [21][22], no examples were reported for the synthesis of n-alkyl thioglycosides by using thiol–ene coupling [18][19]. In

Artificial bioconjugates with naturally occurring linkages: the use of phosphodiester

• Takao Shoji,
• Hiroki Fukutomi,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 1946–1955, doi:10.3762/bjoc.14.169

• synthesis, otherwise subsequent steps are complicated. Synthetic chemists, armed with various elegant artificial orthogonal bond formations, including alkyne–azide cycloaddition [27][28][29][30][31][32][33][34], thiol–ene ligation [35][36][37][38], Staudinger ligation [39][40], inverse-electron-demand Diels

β-Hydroxy sulfides and their syntheses

• Mokgethwa B. Marakalala,
• Edwin M. Mmutlane and
• Henok H. Kinfe

Beilstein J. Org. Chem. 2018, 14, 1668–1692, doi:10.3762/bjoc.14.143

• 105–109 (Scheme 40) [73]. 3.5 Other synthetic routes to β-hydroxy sulfides Incorporation of amine, silyl and sulfide functional groups into C–C multiple bonds offers an attractive route to appropriately functionalized substrates. Inter- and intramolecular thiol-ene reaction is a highly efficient, free

• -radical mediated “click” process with diverse applications in small molecule and polymer synthesis and has been reviewed [74][75][76]. The importance of the thiol-ene reaction in the synthesis of β-hydroxy sulfides is exemplified by the work of Scanlan and co-workers as shown in Scheme 41 [77][78

• ]. Treatment of the thiol-ene 113 with the radical initiator 2,2-dimethoxy-2-phenylacetophenone (DPAP) and the photosensitizer 4-methoxyacetophenone (MAP) in DMF ensued to the formation of the thiyl radical 114 that underwent intramolecular cyclization to provide a mixture of biologically important thiosugars

Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• preparation of sulfides. Non-photocatalytic procedures apply the so-called radical thiol–ene or radical thiol–yne reactions for efficient cross-coupling of thiols with olefins [24][29][30]. In 2013, Yoon and co-workers developed a photoredox-catalyzed version of the radical thiol–ene reaction (Scheme 2) [31

• , which was applied to their photocatalytic radical thiol-ene reaction (Scheme 3) [32]. While the photooxidation of aliphatic thiols by excited [Ru(bpz)3](PF6)2 is thermodynamically feasible, this process is kinetically hindered. Therefore, relatively low yields are observed or the amount of thiol has to

• photoredox-catalyzed radical thiol–ene reaction for polymer postfunctionalization and step-growth addition polymerization (Scheme 4a) [33]. In contrast to Yoon’s conditions, they used [Ru(bpy)3]Cl2 as photocatalyst and N-methyl-2-pyrrolidone as solvent and were able to efficiently couple polybutadiene and

Fast and efficient synthesis of microporous polymer nanomembranes via light-induced click reaction

• Qi An,
• Youssef Hassan,
• Xiaotong Yan,
• Peter Krolla-Sidenstein,
• Tawheed Mohammed,
• Mathias Lang,
• Stefan Bräse and
• Manuel Tsotsalas

Beilstein J. Org. Chem. 2017, 13, 558–563, doi:10.3762/bjoc.13.54

• radicals. Additional thiol moieties can undergo hydrogen transfer to the vinyl radical leading to thiyl radicals and vinyl sulfides. The vinyl sulfides can then undergo a thiol–ene coupling (TEC) reaction, leading to bis-sulfide species. TYC has been used for surface modification [21][22

Synthesis and evaluation of anti-oxidant and cytotoxic activities of novel 10-undecenoic acid methyl ester based lipoconjugates of phenolic acids

• Naganna Narra,
• Shiva Shanker Kaki,
• Rachapudi Badari Narayana Prasad,
• Sunil Misra,
• Koude Dhevendar,
• Venkateshwarlu Kontham and
• Padmaja V. Korlipara

Beilstein J. Org. Chem. 2017, 13, 26–32, doi:10.3762/bjoc.13.4

• methyl 10-undecenoate which was subjected to a thiol–ene reaction with cysteamine hydrochloride. Further amidation of the amine was carried out with different phenolic acids such as caffeic, ferulic, sinapic, coumaric and cinnamic acid. All synthesized compounds were fully characterized and their

• lipoconjugates of phenolic acids is reported. The synthetic route was simple with product yields in the range of 84–86% over three steps. The lipid part, methyl 10-undecenoate was subjected to a thiol–ene reaction with cysteamine hydrochloride and the resulting intermediate was conjugated with the phenolic acid

Selective synthesis of thioethers in the presence of a transition-metal-free solid Lewis acid

• Federica Santoro,
• Matteo Mariani,
• Federica Zaccheria,
• Rinaldo Psaro and
• Nicoletta Ravasio

Beilstein J. Org. Chem. 2016, 12, 2627–2635, doi:10.3762/bjoc.12.259

• reaction of optically active (R)-1-phenylethanol gave a completely racemic compound (Scheme 1). Unfortunately allylic alcohols gave unreproducible results. However, in the case of cinnamyl alcohol (1i) we could obtain a fairly good selectivity to the product of the thiol–ene reaction 3p (Scheme 2). The

From N-vinylpyrrolidone anions to modified paraffin-like oligomers via double alkylation with 1,8-dibromooctane: access to covalent networks and oligomeric amines for dye attachment

• Daniela Obels,
• Melanie Lievenbrück and
• Helmut Ritter

Beilstein J. Org. Chem. 2016, 12, 1395–1400, doi:10.3762/bjoc.12.133

• paraffin-like oligomeric chains bearing polymerizable vinyl moieties. These oligomers were radically crosslinked in bulk with N-VP as co-monomer yielding swellable polymer disks. The vinylic side groups of the N-VP oligomers allow thiol–ene click reactions with 2-aminoethanethiol hydrochloride to obtain

• poly(ethylene glycol) side chains. Keywords: double alkylation; modified N-vinylpyrrolidone; oligomeric anthraquinone dye; paraffin-like oligomer; radical thiol-ene click reaction; Introduction Poly(N-vinylpyrrolidone) (PVP) is established in daily life due to its high water solubility and

• present the synthesis of paraffin-like oligomers via double alkylation of N-VP with 1,8-dibromooctane. Additionally, this work focuses on the use of the free double bonds for radical crosslinking as well as thiol-ene modification for subsequent dye attachment. Results and Discussion N-Vinylpyrrolidone (1

An improved procedure for the preparation of Ru(bpz)₃(PF₆)₂ via a high-yielding synthesis of 2,2’-bipyrazine

• Danielle M. Schultz,
• James W. Sawicki and
• Tehshik P. Yoon

Beilstein J. Org. Chem. 2015, 11, 61–65, doi:10.3762/bjoc.11.9

• is an effective photocatalyst in oxidatively induced photoredox transformations where less strongly oxidizing complexes (e.g., 1) are not successful. For instance, we have reported that 2 is uniquely capable of promoting radical cation mediated Diels–Alder cycloadditions [12], radical thiol–ene

Organic chemistry on surfaces: Direct cyclopropanation by dihalocarbene addition to vinyl terminated self-assembled monolayers (SAMs)

• Malgorzata Adamkiewicz,
• David O’Hagan and
• Georg Hähner

Beilstein J. Org. Chem. 2014, 10, 2897–2902, doi:10.3762/bjoc.10.307

• including azide–alkyne cycloadditions [9][10], Diels–Alder reactions [11][12], maleimide–thiol reactions [13], thiol–ene additions [14], and imine/oxime conjugations [15]. In this article we demonstrate that dihalocarbenes can be used to generate dihalocyclopropanes on olefin terminated SAMs. We recently

Investigations of thiol-modified phenol derivatives for the use in thiol–ene photopolymerizations

• Sebastian Reinelt,
• Monir Tabatabai,
• Urs Karl Fischer,
• Norbert Moszner,
• Andreas Utterodt and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 1733–1740, doi:10.3762/bjoc.10.180

• Vivadent AG, Bendererstrasse 2, 9494 Schaan, Principality of Liechtenstein Heraeus Kulzer GmbH, Philipp-Reis-Straße 8, 61273 Wehrheim, Germany 10.3762/bjoc.10.180 Abstract Thiol–ene photopolymerizations gain a growing interest in academic research. Coatings and dental restoratives are interesting

• applications for thiol–ene photopolymerizations due to their unique features. In most studies the relative flexible and hydrophilic ester derivative, namely pentaerythritoltetra(3-mercaptopropionate) (PETMP), is investigated as the thiol component. Thus, in the present study we are encouraged to investigate

• the performance of more hydrophobic ester-free thiol-modified bis- and trisphenol derivatives in thiol–ene photopolymerizations. For this, six different thiol-modified bis- and trisphenol derivatives exhibiting four to six thiol groups are synthesized via the radical addition of thioacetic acid to

Bifunctional dendrons for multiple carbohydrate presentation via carbonyl chemistry

• Davide Bini,
• Francesco Nicotra and
• Laura Cipolla

Beilstein J. Org. Chem. 2014, 10, 1686–1691, doi:10.3762/bjoc.10.177

• heterobifunctional dendrons were designed in order to have bio-orthogonal functional groups at the focal point and at their termini. More specifically, a double bond was placed at the desired matrix as the focal point for further conjugation by thiol–ene chemistry, and carbonyl groups were added at the termini. The

• dendrons in quantitative yields. The glycosylated dendrons can be exploited for further chemoselctive thiol–ene reactions with matrices suitably functionalized with thiol groups, i.e., cysteine residues in proteins. Experimental General methods All chemicals were purchased from Sigma-Aldrich and used

Orthogonal dual thiol–chloroacetyl and thiol–ene couplings for the sequential one-pot assembly of heteroglycoclusters

• Michele Fiore,
• Gour Chand Daskhan,
• Baptiste Thomas and
• Olivier Renaudet

Beilstein J. Org. Chem. 2014, 10, 1557–1563, doi:10.3762/bjoc.10.160

• Abstract We describe the first one-pot orthogonal strategy to prepare well-defined cyclopeptide-based heteroglycoclusters (hGCs) from glycosyl thiols. Both thiol–chloroactetyl coupling (TCC) and thiol–ene coupling (TEC) have been used to decorate cyclopeptides regioselectively with diverse combination of

• successive attachment of sugar residues on a core scaffold such as sugar [6][7], peptide [8][9][10], dendrimer [11][12], cyclodextrin [13][14][15] and polymer [16]. The most common synthetic strategy to build such hGCs relies on a fragment-coupling approach using thiol–ene coupling [17], copper(I)-catalyzed

• ]. Herein we report a new strategy based on both thiol–chloroactetyl coupling (TCC) and thiol–ene coupling (TEC) to prepare hGCs from glycosyl thiols and cyclopeptide scaffolds displaying chloroacetyl (ClAc) and allyloxycarbonyl (Alloc) groups and vice versa. We demonstrate that cyclopeptides

Postsynthetic functionalization of glycodendrons at the focal point

• Thisbe K. Lindhorst and
• Katharina Elsner

Beilstein J. Org. Chem. 2014, 10, 1482–1487, doi:10.3762/bjoc.10.152

• etherification, thiol-ene reaction and in particular olefin cross metathesis. Keywords: amphiphilic glycomimetics; cross metathesis; glycodendrons; multivalent glycoconjugates; multivalent glycosystems; Introduction In addition to nucleic acids and proteins, molecular life is based on a third important class

• expected in case of the glycodendrons 3–9. However, the so-called “thiol-ene” reaction [10] gave reliable results with both bivalent and tetravalent glycodendrons. The radical addition of mercaptododecane to either 3 or 7, employing AIBN as radical starter, led to the amphiphilic thioethers 12 and 13

• ). Conclusion In conclusion, it was shown that readily available polyether glycodendrons can be refined employing suitable postsynthetic modification of the focal point. We have illustrated, that alkylation, thiol-ene reaction and in particular olefin cross metathesis leads to di- and tetravalent glycolipid

Molecular recognition of surface-immobilized carbohydrates by a synthetic lectin

• Melanie Rauschenberg,
• Eva-Corrina Fritz,
• Christian Schulz,
• Tobias Kaufmann and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2014, 10, 1354–1364, doi:10.3762/bjoc.10.138

• -terminated SAMs [33], by Diels–Alder reaction of cyclopentadienes and furans on maleimide-terminated SAMs [34], by thiol–ene click reaction of functionalized thiols on alkene-terminated SAMs [35] as well as by strain promoted cycloadditions on azide- and nitriloxide-terminated SAMs [36] using μCP. Homogenous

End-group-functionalized poly(N,N-diethylacrylamide) via free-radical chain transfer polymerization: Influence of sulfur oxidation and cyclodextrin on self-organization and cloud points in water

• Sebastian Reinelt,
• Daniel Steinke and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 680–691, doi:10.3762/bjoc.10.61

• agents [23][24][25] or (b) indirect by polymer analogous modification of existing end-groups. For the post-modification highly efficient reactions are needed to ensure a high degree of functionalization. For this reason, often “click reactions” [26] such as esterifications [27], azide–alkyne [22], thiol

• –ene [28], thiol–isocyanate [29] and others are used. Thereby most studies have in common that synthesis of the polymer with thermo-responsive properties is preferably accomplished by either living anionic polymerization, or controlled radical polymerization [18][21][22][24][29][30][31][32][33][34

Synthesis of homo- and heteromultivalent carbohydrate-functionalized oligo(amidoamines) using novel glyco-building blocks

• Felix Wojcik,
• Sinaida Lel,
• Alexander G. O’Brien,
• Peter H. Seeberger and
• Laura Hartmann

Beilstein J. Org. Chem. 2013, 9, 2395–2403, doi:10.3762/bjoc.9.276

• heteromultivalent glycosylation patterns by combining building blocks presenting different mono- and disaccharides. Keywords: continuous flow; flow chemistry: flow synthesis; glycoligands; multivalency; photochemistry; solid-phase synthesis; thiol–ene; thioglycosides; Introduction Multivalent carbohydrate ligand

• [20]. Carbohydrate conjugation was achieved by copper-catalyzed azide alkyne cycloaddtion (CuAAC) of carbohydrate ligands on alkyne presenting oligomers [21]. As an alternative conjugation approach to CuAAc, a very efficient thiol–ene coupling (TEC) [22][23][24][25] protocol in a continuous flow

• removal of the desired product minimizes unwanted secondary reaction pathways [27][28][29][30][31][32][33][34][35][36][37][38][39]. We also introduced the so-called building block approach in the context of thiol–ene coupling via the continuous-flow technique. A first example involved conjugating a

Combined bead polymerization and Cinchona organocatalyst immobilization by thiol–ene addition

• Kim A. Fredriksen,
• Tor E. Kristensen and
• Tore Hansen

Beilstein J. Org. Chem. 2012, 8, 1126–1133, doi:10.3762/bjoc.8.125

• immobilization of Cinchona organocatalysts using thiol–ene chemistry, in which catalyst immobilization and bead polymerization is combined in a single step. A solution of azo initiator, polyfunctional thiol, polyfunctional alkene and an unmodified Cinchona-derived organocatalyst in a solvent is suspended in

• water and copolymerized on heating by thiol–ene additions. The resultant spherical and gel-type polymer beads have been evaluated as organocatalysts in catalytic asymmetric transformations. Keywords: asymmetric catalysis; Cinchona derivatives; organocatalysis; polymerization; thiol–ene reaction

• transformations based on radical intermediates [1]. As a result, polymeric immobilization of Cinchona derivatives by using thiol–ene addition has a substantial history, founded on procedures developed already in the early 1970s [1]. Cinchona derivatives are either copolymerized with certain comonomers, such as

Intramolecular bridges formed by photoswitchable click amino acids

• Christian Hoppmann,
• Ronald Kühne and
• Michael Beyermann

Beilstein J. Org. Chem. 2012, 8, 884–889, doi:10.3762/bjoc.8.100

• a model peptide without a preferred conformation, it was seen that the thiol–ene click reaction takes place efficiently in both cases. Upon induction of an α-helical structure by the addition of trifluoroethanol, the thiol click reaction occurs preferentially with the i,i+4 spacing. Even in the

• ; isomerization; molecular switches; photoswitchable click amino acid; thiol–ene click; Introduction Photoswitchable bridges that are site-specifically incorporated into proteins allow the conformation and activity of proteins to be modulated by light. In contrast to common bivalent thiol reactive azobenzene

• switches [1][2][3][4][5], the PSCaa described here (Scheme 1) is an α-amino acid containing, besides an azobenzene unit, a vinyl function that can react specifically with a cysteine within a putative conformational domain of a peptide or a protein by light-induced thiol–ene click reaction [6][7][8][9]. The