Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• substituted styrene under copper(I) catalysis to give the target compounds via a Povarov reaction. A further aromatization process yields product I (Scheme 8, path I). In a closely related approach, the same group reported on the synthesis of quinolines from anilines and alkynes [37]. In this case, the alkyne

• , methyl aryl ketones, and DMSO under iron(III) catalysis and using K2S2O8 for its activation [39]. The proposed mechanism is very close to those described above, with the methyl aryl ketone taking part of the reaction in place of the styrene component in the Povarov cyclization. In this case, the imine

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• emerged as potent catalysts for red-light-mediated photoreactions. Furuyama et al. demonstrated that a ruthenium phthalocyanin complex could catalyze trifluoromethylation reactions of styrene derivatives 18 with either CF3SO2Cl or Umemoto’s reagent 19 under red-light irradiation without the need for

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• which the thiosulfonate was cleaved and then dimerized to form the disulfide. The reaction of sodium p-toluenesulfinate and styrene resulted in the generation of the corresponding vinyl sulfone (Scheme 5, reaction 2), suggesting the formation of p-toluenesulfonyl iodide during the reaction [50][51

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• , styrene derivatives bearing both electron-rich and electron-poor groups underwent the desired transformation with high yields and enantioselectivities (23g and 23h). However, the styrene scaffold bearing a trifluoromethyl group showed reduced enantioselectivity (23i). Styrenes containing heterocyclic

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• asymmetric electrocatalytic cyanophosphinoylation of vinylarenes (Figure 14) [69]. In the presence of a copper catalyst and the chiral ligand sBOX(iPr) (L8) in an electrochemical cell, these three component reactions using styrene derivatives 27, TMSCN (21), and diarylphosphine oxide 80 as starting materials

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• components consisting of styrene, α,α′-azobisisobutyronitrile (AIBN), and p-xylene were infused using a computer-controlled segmented-flow platform. These approaches allow the compartmentalization of reaction mixtures without cross-contamination and enhance experimental throughput significantly. The concept

• overlapping peaks. Its versatility was showcased through the successful completion of four comprehensive case studies, demonstrating its broad applicability across diverse analytical scenarios. Recently, we implemented in-line Raman spectroscopy to monitor the real-time conversion of styrene to polystyrene

• , utilizing a custom Python package developed in-house [53]. This approach enabled us to track the conversion process at different residence times. Specifically, we quantified the conversion by analyzing the area under the curve (AUC) of the Raman-active vibrational modes associated with the styrene–vinyl C=C

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• cycloadducts 29e and 31e in good yields (Scheme 12). Further derivatizations were also carried out: The treatment of 29e with SOCl2 led to interesting unsaturated derivative 32 in a 54% yield. The acetylation of 31e provided 33 in 76% yield. Next, an alkene metathesis of 33 with styrene led to product 34 in 72

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• -catalyzed aziridination of styrene (22) by chloramine-T (23, NaCl=NTs) as a source of nitrene in acetonitrile (Figure 5) [40]. No aziridine product was formed either without any source of copper or in the presence of a different copper salt, such as CuCl, CuCl2·2H2O, or CuOTf. Calix[4]pyrrole itself is

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• bond, revealing the amino acyl radical, which is then added to the double bond. Tetra-n-butylammonium bromide (TBAB)-catalyzed carbonylation–peroxidation of styrene derivatives 149 with TBHP and aldehydes 150, which allows for the synthesis of β-peroxy ketones 151, was described (Scheme 47) [111]. tert

• the double bond of styrene 158 to form the C-centered radical D. Recombination of the tert-butylperoxy radical F and the C-centered radical D leads to the desired product 159. The iron-catalyzed alkoxycarbonylation–peroxidation of alkenes 161 with carbazates 160 and TBHP to yield β-peroxy esters 162

• reaction mechanism was proposed as an anchored ionic type pathway, rather than the free radical one. First, the Togni reagent forms complex A with the dinuclear paddle-wheel copper nodes of Cu3(BTC)2. Complex A then adds to styrene 175 to form iodonium cation B, which is converted to intermediate D by

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• functionalization. Difunctionalizations of double and triple bonds are of high interest as they allow the introduction of two functional groups in a single step. An interesting electrochemical difunctionalization of styrene and cyclic olefin derivatives has been reported by the Hu group [23]. They combined

Phenylseleno trifluoromethoxylation of alkenes

• Clément Delobel,
• Armen Panossian,
• Gilles Hanquet,
• Frédéric R. Leroux,
• Fabien Toulgoat and
• Thierry Billard

Beilstein J. Org. Chem. 2024, 20, 2434–2441, doi:10.3762/bjoc.20.207

• (Scheme 1). It should be noted that the reaction with styrene gave low yields and the resulting products appeared very unstable. Finally, the tri-substituted alkene 1-methylcyclohexene did not give the expected products. Finally, some more elaborated molecules such as the macrolactone 2j, the clofibrate

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• mandel acetates [14], respectively. Electrolysis of styrene oxide and related 2-phenylcyclic ethers in the presence of carbon dioxide also induced carboxylation at the benzylic position by reductive cleavage of a C(sp3)–O bond to give the corresponding ω-hydroxy-2-phenylalkanoic acids [15][16]. In

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• :1.0 trans/cis mixture in 72% and 64% yield, respectively. While many styrene derivatives polymerize in HFIP [44], 1,2-disubstituted styrene derivatives were sufficiently stable to engage in the developed aziridination reaction, with cis- or trans-β-methylstyrene 1n furnishing aziridine 3n as

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• postulated for the synthesis of benzofuran derivatives from styrene derivatives by iodane reagents [29][30]. Subsequently, intermediate D is attacked by H2O at the benzylic carbon atom to afford intermediate E. Intramolecular proton shift occurs, generating the intermediate F, which undergoes phenyl

Hypervalent iodine-catalyzed amide and alkene coupling enabled by lithium salt activation

• Akanksha Chhikara,
• Fan Wu,
• Navdeep Kaur,
• Prabagar Baskaran,
• Alex M. Nguyen,
• Zhichang Yin,
• Anthony H. Pham and
• Wei Li

Beilstein J. Org. Chem. 2024, 20, 1405–1411, doi:10.3762/bjoc.20.122

• bifunctional amide nucleophiles (Scheme 1e). Results and Discussion Our studies here focused on the development of hypervalent iodine-catalyzed amide and alkene coupling reaction [53][54][55]. In this case, we started with styrene (1) and benzamide (2) as the standard substrates. Using iodotoluene A as the

• , ester, and phthalimide proceeded smoothly with good yields and excellent regioselectivities to access the oxazoline products as single regioisomers (Figure 3, products 18–22). The o-bromo-substituted styrene also afforded the corresponding product 23. Furthermore, 1,1-di-substituted α-methylstyrene and

• reaction designs. Time studies of the amide and alkene coupling. a) Iodoarene time studies: styrene (1), para-substituted iodoarenes, LiBF4, and benzamide (2). b) Li salt time studies: styrene (1), iodoanisole, Li salts, and benzamide (2). c) Alkene time studies: para-substituted styrenes, iodotoluene A

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• [28] introduced the photoredox-catalyzed hydroacylation of styrene derivatives via deoxygenation of challenging aliphatic carboxylic acids (Scheme 1). The deoxygenation was promoted by phosphine reagents to form acyl radicals. The acyl radicals reacted with the C=C bond and formed the expected product

• in decent yield (i.e., 80h–k, 49–66%). An α,β,γ-trisubstituted aldehyde (i.e., 80l, 65%) was synthesized using an α,β-disubstituted styrene, which could not be produced using the conventional method. The excited photocatalyst *Mes–Acr+ oxidized the styrene to produce the extremely electrophilic

Transition-metal-catalyst-free electroreductive alkene hydroarylation with aryl halides under visible-light irradiation

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2024, 20, 1327–1333, doi:10.3762/bjoc.20.116

• high regioselectivity. Herein, we report the electroreductive hydroarylation of electron-deficient alkenes and styrene derivatives using (hetero)aryl halides under mild reaction conditions. Notably, the present hydroarylation proceeded with high efficiency under transition-metal-catalyst-free

• 3pa and 3qa, respectively. In addition to the successful transformations of heteroaryl iodides with indole or pyridine cores (3ra, 3sa), the electroreductive synthesis of methaqualone derivatives was also achieved (3ta). Pleasingly, a series of electron-deficient alkene and styrene derivatives were

• (3ac, 3ad). In addition to styrene derivatives bearing α-substituents and electronically diverse functionalities, indene and 2-vinylpyridine were all compatible with the present electroreductive hydroarylation (3ae–ak). The reaction of iodobenzene with acrylonitrile and 4-chlorostyrene proceeded

Oxidative hydrolysis of aliphatic bromoalkenes: scope study and reactivity insights

• Amol P. Jadhav and
• Claude Y. Legault

Beilstein J. Org. Chem. 2024, 20, 1286–1291, doi:10.3762/bjoc.20.111

• hydrogens on the allylic position (see Scheme 3 for explanations). Our mechanistic understanding of the oxidative hydrolysis of styrene haloalkene analogs [19] lets us hypothesize an external bromide attack as the main reaction pathway for this catalytic oxidative transposition of dialkyl bromoalkenes

• future for the α-acetamidation of dialkyl bromoalkenes. The present work provides an operationally simple catalytic method to access a diverse range of α-bromoketones, which are versatile building blocks for synthesizing various important hetero aromatics. (a) Oxidative hydrolysis of styrene or stilbene

Mechanistic investigations of polyaza[7]helicene in photoredox and energy transfer catalysis

• Johannes Rocker,
• Till J. B. Zähringer,
• Matthias Schmitz,
• Till Opatz and
• Christoph Kerzig

Beilstein J. Org. Chem. 2024, 20, 1236–1245, doi:10.3762/bjoc.20.106

• concentrations in the catalytic cycle and, therefore, the proposed radical recombination to yield the final product (with intervening addition of the sulfonyl radical to excess styrene, see Scheme 1) can be regarded as most-likely reaction pathway. Furthermore, we carried out pK value determinations for the

• studies on inherent photostability presented below). Our observations also revealed that while the styrene does not significantly quench the singlet state of Aza-H, it quenches the triplet state, suggesting that the formation of triplet-excited styrene via energy transfer is feasible (see Figure S7

• , Supporting Information File 1) [76]. A reaction course plot in the absence of 4CP and TsNa revealed rapid decomposition of the photocatalyst, presumably in a [2 + 2]-photocycloaddition with the styrene component as observed in mass spectrometry (see Figure S17 and Figure S18 in Supporting Information File 1

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• in moderate to good yields, employing 2,7-dimethoxythioxanthone (2,2’-OMeTX) as a triplet sensitizer for BCB excitation (Scheme 3A) [38]. Starting from BCB 24, alkenes including styrene derivatives, enol ethers, and vinyl boronates could be incorporated to give 1,2-BCHs (±)-25a–d. Brown and co

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• through a solution of the alkene in diethyl ether at 0 °C or rt (Scheme 3B and 3C) [36]. Despite its effective reaction with styrene (3), the reaction displayed sluggish reactivity with 1-propenylbenzene (5). It is noteworthy, that the following HCl solutions are commercially available: 4.0 M in dioxane

• alkenes remains a commonly employed approach, yielding high yields for styrene derivatives (Scheme 4) [41][42][43]. The example by Theato is remarkable (Scheme 4A), who used HCl (gas) bubbled into neat alkene 13 for 5 hours, and obtained a relatively high yield of the monohydrochlorinated product 14 after

• broad generality and tolerates various sensitive functional groups, including aldehyde 45 and nitrile 46. However, electron-poor styrene, resulting in chloride 40, or terminal and 1,2-disubstituted alkenes forming chlorides 41–46 and cyclooctyl chloride (26) necessitated harsher reaction conditions. As

SOMOphilic alkyne vs radical-polar crossover approaches: The full story of the azido-alkynylation of alkenes

• Julien Borrel and
• Jerome Waser

Beilstein J. Org. Chem. 2024, 20, 701–713, doi:10.3762/bjoc.20.64

• as raw data in our previous work [45]. Results and Discussion SOMOphilic alkynes We started to investigate the azido-alkynylation of styrene (1a) using EBX reagent 2 as SOMOphilic alkyne (Table 1). Tosyl-azidobenziodazolone (Ts-ABZ, 3), previously developed by our group [17], was selected as an azide

• source. Upon light irradiation, it can release an azide radical by homolysis of the I−N3 bond [46]. We were pleased to see that irradiation of a mixture of styrene (1a), Ph-EBX (2) and Ts-ABZ (3) afforded 17% isolated yield of the desired homopropargylic azide 4a (Table 1, entry 1). Heating the reaction

• no impact on the reaction (Table 1, entry 12), the presence of 1.5 equivalents of HFIP slightly improved the yield (Table 1, entry 13). Increasing the amount of styrene in the reaction had no impact (Table 1, entry 14), highlighting that the issue might come from an inefficient trapping of the C

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• (TEMPO) and the corresponding radical-trapping product A could be confirmed by HRMS of both reaction mixtures, unambiguously supporting radical mechanisms (Scheme 4a). The reaction with styrene was conducted under standard conditions, but no product X could be detected, indicating the cationic

Enhanced reactivity of Li⁺@C₆₀ toward thermal [2 + 2] cycloaddition by encapsulated Li⁺ Lewis acid

• Hiroshi Ueno,
• Yu Yamazaki,
• Hiroshi Okada,
• Fuminori Misaizu,
• Ken Kokubo and
• Hidehiro Sakurai

Beilstein J. Org. Chem. 2024, 20, 653–660, doi:10.3762/bjoc.20.58

• derivatization of this novel material. In this study, we report the synthesis of Li+@C60 derivatives via the thermal [2 + 2] cycloaddition reaction of styrene derivatives, achieving significantly higher yields of monofunctionalized Li+@C60 compared to previously reported reactions. Furthermore, by combining

• range of unsaturated substrates having a relatively lower HOMO level. With the previously uncovered reactivity of Li+@C60 in hand, we synthesized Li+@C60 derivatives in this study through the thermal [2 + 2] cycloaddition of styrene derivatives, which do not react with empty C60 through the same

• of N,N,N',N'-tetraethylethynediamine and 1-morpholino-1-cyclopentene with empty C60 has been reported [17][23], while electron-rich styrene derivatives 1 and 2 can react with empty C60 only through a photoinduced SET pathway [19][22]. From these results, the energy gap between the HOMO of the alkene