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

• compounds using dihalomethanes (Scheme 27) [79]. They developed a three-component reaction between amines (mainly tertiary amines), a dihalomethane, and a P(OH) species (like phosphonate, phosphinate, or secondary phosphine oxide) under catalyst-free conditions to afford α-amino phosphorus compounds 35. The

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• with CF2HCOOH or PhCF2COOH, and PIDA under additive-, base-, and metal catalyst-free conditions (Scheme 1b). Results and Discussion Initially, 1-(pent-4-en-1-yl)-1H-benzo[d]imidazole (1a), CF2HCOOH, and PIDA were chosen as the template substrates for this radical difluoromethylation and cyclization

• tricyclic and bicyclic imidazoles under additive-, base-, and metal catalyst-free conditions utilizing difluoroacetic acid and α,α-difluorobenzeneacetic acid as the readily available fluorine sources. The significant advantages of this approach, including its environmental friendliness and cost

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

Synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives via isocyanide-based multicomponent reactions

• Marzieh Norouzi,
• Mohammad Taghi Nazeri,
• Ahmad Shaabani and
• Behrouz Notash

Beilstein J. Org. Chem. 2024, 20, 2870–2882, doi:10.3762/bjoc.20.241

• , and triazolobenzodiazepine under solvent- and catalyst-free conditions. Purposefully, this approach produced various bioactive scaffolds using environmentally friendly, mild, and simple conditions. Due to their bioactive moieties, these compounds with exclusive fluorescence properties may attract

• solvent- and catalyst-free conditions (Scheme 1d). Results and Discussion Synthesis Dibenzoxazepine as imine component, cyclohexyl isocyanide, and the gem-diactivated olefin (2-benzylidenemalononitrile) were selected as the starting materials to screen the reaction conditions (Scheme 2, Table 1). First

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• -acetoacetylcoumarin 41, 3-bromoacylpyran 42, and semicarbazide 40 (Scheme 12) [65]. Alternatively, the corresponding chromenes can replace the 3-bromoacylpyrans. A notable advantage of this process is its catalyst-free nature and the achievement of good regioselectivity. Due to the high heterocycle density, this

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

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

• by preventing overreduction [39]. While the metal-catalyst-free radical cyclization of alkene-tethered aryl halides has been well documented in the literature [40][41][42][43], the efficient intermolecular hydroarylation of alkenes still relies on the use of transition-metal catalysts, including Pd

• [44], Ni [45], and Co [46] (Scheme 1a). The pioneering work by Savéant et al. demonstrated that electron-deficient (hetero)aromatics acted as efficient mediators for the metal-catalyst-free electroreductive hydroarylation of alkenes with some activated chloro-, bromo-, and iodoarenes, but the use of a

Phenotellurazine redox catalysts: elements of design for radical cross-dehydrogenative coupling reactions

• Alina Paffen,
• Christopher Cremer and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2024, 20, 1292–1297, doi:10.3762/bjoc.20.112

• significantly superior result compared to catalyst-free conditions (3aa, 22% after 3 h). Electron π-donating substituents considerably improved catalytic activity, with an optimum among tested structures for Te10 (3aa, 74% after 3 h), which is intriguingly similar to the previously reported best catalyst for

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• . Synthesis of N-methylindole-3-carboxylates from N-methylindoles and phenols through metal-catalyst-free reaction (top) and its hypothesized mechanism (bottom). Synthesis of indol-3-α-ketoamides (top) and indol-3-amides (bottom) via direct double- and monoaminocarbonylation of indole derivatives with

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• his research group for the synthesis of BIMs applying the same catalyst-free conditions as P4VPy–CuO, while employing 30 mg of the nano-BiVO4 compound with the added benefit of slightly improved product yields, ranging from 70 to 98% after 10–80 minutes [115][116]. The need for conventional heating

• the C=O bond. Thus, an innovative approach on nanocatalysis was introduced, incorporating solid grinding in catalyst-free conditions with the challenge of a high catalyst loading and lack of aliphatic aldehydes or ketones being utilized as substrates for the formation of their respective BIMs [118

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

Synthesis of 5-arylidenerhodanines in L-proline-based deep eutectic solvent

• Stéphanie Hesse

Beilstein J. Org. Chem. 2023, 19, 1537–1544, doi:10.3762/bjoc.19.110

• scaffolds is the introduction of a benzylidene moiety on C5 via a Knoevenagel reaction. Here, a facile synthesis of 5-arylidenerhodanines via a Knoevenagel reaction in an ʟ-proline-based deep eutectic solvent (DES) is reported. This method is fast (1 h at 60 °C), easy, catalyst-free and sustainable as no

• benzaldehydes with electron-donating or electron-withdrawing groups could be used as substrates. The method is fast, easy, catalyst-free, and sustainable as no classical organic solvents were used. The synthesized derivatives were studied for their antioxidant activities and as expected, all compounds with a

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• -coupling, and direct sulfenylation reactions, which are classified into three categories: sulfenylation catalyzed by i) transition metal catalysts, ii) organocompound catalysts, and iii) catalyst-free sulfenylation. Review Sulfenylation of organic compounds by N-(sulfenyl)succinimides/phthalimides Metal

• presence of TMSOTf. Catalyst-free sulfenylation by N-(sulfenyl)succinimides/phthalimides In 2015, oxysulfenylation of styrene derivatives 9 utilizing 1-(arylthio)pyrrolidine-2,5-diones 1 and alkyl/benzyl alcohols 86 toward β-alkoxy sulfides was developed by Fu et al. (Scheme 65) [95]. In this metal-free

• under catalyst-free conditions (Scheme 67) [97]. The reaction proceeded through the formation of a three-membered cyclic intermediate II by the cleavage of 1 under thermal conditions. Between the nitrogen or sulfur atom in TMSNCS, electrophilic attack of nitrogen on II led to thermodynamically favored

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• methodologies involving ether α-C(sp3)–H and aromatic C(sp2)–H bonds were investigated and these are shown in Scheme 43. Shah et al. reported a catalyst-free CDC method using only 2 equivalents of K2S2O8 in H2O under irradiation with a 27 W CFL (Scheme 43a) [123]. In this reaction, both water and the light

Metal catalyst-free N-allylation/alkylation of imidazole and benzimidazole with Morita–Baylis–Hillman (MBH) alcohols and acetates

• Olfa Mhasni,
• Jalloul Bouajila and
• Farhat Rezgui

Beilstein J. Org. Chem. 2023, 19, 1251–1258, doi:10.3762/bjoc.19.93

Selective and scalable oxygenation of heteroatoms using the elements of nature: air, water, and light

• Damiano Diprima,
• Hannes Gemoets,
• Stefano Bonciolini and
• Koen Van Aken

Beilstein J. Org. Chem. 2023, 19, 1146–1154, doi:10.3762/bjoc.19.82

• byproducts, and increased efficiency in industrial processes. As such, this field of research is of great importance and interest to both academia and industry. This work showcases a sustainable and catalyst-free oxidation method for heteroatoms (e.g., S, P, and Se) using only air, water and light. An

• flow using the HANU flow reactor, indicating scalability and improving safety. Keywords: catalyst-free; flow chemistry; oxygen; photochemistry; sustainable oxidation; Introduction Oxidation reactions are widely used in the chemical industry, but are often problematic due to challenges with

• [23][24] and methods for oxidation such as photochemistry, or electrochemistry have been developed [2][25]. However, low selectivity and the need for appropriate catalysts that are stable, cost-effective, and easy to remove remain problematic. Recently, catalyst-free procedures using O2 or air have

Copper-catalyzed N-arylation of amines with aryliodonium ylides in water

• Kasturi U. Nabar,
• Bhalchandra M. Bhanage and
• Sudam G. Dawande

Beilstein J. Org. Chem. 2023, 19, 1008–1014, doi:10.3762/bjoc.19.76

• types of hypervalent iodine reagents, diaryliodonium salts are commonly used reagents for the N-arylation of nitrogen-containing compounds, particularly for N-arylation of amines under catalyst-free conditions either in the presence of additives or at higher temperatures [26][27][28][29][30][31][32

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• -SO3H-catalyzed synthesis and proposed mechanism of pyrroles 37. Solvent-free and catalyst-free synthesis and plausible mechanism of N-substituted pyrroles 39. Nano-sulfated TiO2-catalyzed synthesis of N-substituted pyrroles 41. Copper nitrate-catalyzed Clauson–Kaas synthesis and mechanism of N

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• % yield (Table 1, entry 6). In addition, in a catalyst-free reaction under UV irradiation, no reaction occurred and the starting diazo compound 5 was recovered (Table 1, entry 7). Having identified the optimal catalyst and conditions, we then examined the scope of the cyclopropanation reaction by reacting

An efficient metal-free and catalyst-free C–S/C–O bond-formation strategy: synthesis of pyrazole-conjugated thioamides and amides

• Shubham Sharma,
• Dharmender Singh,
• Sunit Kumar,
• Vaishali,
• Rahul Jamra,
• Naveen Banyal,
• Deepika,
• Chandi C. Malakar and
• Virender Singh

Beilstein J. Org. Chem. 2023, 19, 231–244, doi:10.3762/bjoc.19.22

• established the optimal reaction conditions, we explored the generality and the scope of this metal- and catalyst-free approach by employing pyrazole C-3 carbaldehydes 1–4, secondary amines A–E and elemental sulfur as substrates. It was observed that the reaction conditions were compatible with different

• 10A in high yields (67–71%) within 1 hour of reaction time as depicted in Scheme 3. Thereafter, the substrates 4-iodopyrazole-3-carbaldehydes were further investigated for this metal- and catalyst-free sulfur insertion reaction as shown in Scheme 4. It was found that 4-iodopyrazole C-3 carbaldehydes

• elemental sulfur under metal and catalyst-free conditions. The salient features of the current protocol may be attributed to the broad substrate scope, commercially available secondary amines, operational simplicity, multicomponent character of the reaction, easy isolation of products, short reaction time

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• that hydrogen bonding is considered as one of the key factors determining the selectivity of catalyst-free sulfoxidations [68]. In such reactions, the selectivity of sulfide oxidation by oxone (sulfoxide/sulfone ratio) was controlled by the solvent nature (deeper oxidation was observed in water than in

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• heterocyclic systems are heteroanalogues of antimicrobial and antibiofilm fungal metabolites. The developed reaction represents the first example of involving 1H-pyrrole-2,3-diones fused at the [e]-side in a [4 + 1] annulation reaction. Keywords: [4 + 1] annulation; catalyst-free; diazooxindole; 1H-pyrrole

• compounds to molecules containing an enone fragment. Cycloaddition reactions involving diazo and enone moieties are usually carried out using transition-metal catalysis [18][19][20], with catalyst-free reactions being carried out only with the participation of reactive unsubstituted diazomethane [21][22][23

• ] (Scheme 1). Thus, in the present work, we report a simple, catalyst-free diastereoselective method for the synthesis of dihydrofurans spiro-annulated with an oxindole moiety for the first time. The essence of the method is the use of [e]-fused 1H-pyrrole-2,3-diones (FPDs) as the enone component in a

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• catalyst-free halogenation of phenols and anilines via liquid-assisted grinding using PEG-400 as the grinding auxiliary. A series of mono-, di-, and tri-halogenated phenols and anilines was synthesized in good to excellent yields within 10–15 min in a chemoselective manner by controlling the stoichiometry

• catalyst-free methods, the use of costly and low boiling hexafluoroisopropanol (HFIP) as solvent offered the para-selective halogenation of activated aromatic systems (Scheme 1c) [44]. It is noteworthy to mention that over-halogenation of activated systems like phenols and anilines, due to the high

• , the optimal reaction conditions for the electrophilic monobromination was set as to grind the substrates (1 mmol) in an automated grinder with 1.1 mmol of NBS at 100 rpm in PEG-400 (0.2 mL per mmol of the substrate) as a grinding auxiliary. We next explored the substrate scope of the catalyst-free

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

Efficient synthesis of ethyl 2-(oxazolin-2-yl)alkanoates via ethoxycarbonylketene-induced electrophilic ring expansion of aziridines

• Yelong Lei and
• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 70–76, doi:10.3762/bjoc.18.6

• -diazo-3-oxoalkanoates first generate alkoxycarbonylketenes, which undergo an electrophilic ring expansion with aziridines to afford alkyl 2-(oxazolin-2-yl)alkanoates in good to excellent yields under microwave heating. The current method is an activator- and catalyst-free, and clean synthetic strategy