Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• ring was then constructed via an intramolecular reductive Heck reaction from vinyl bromide 10 with exclusive regioselectivity. Considering the strain of forming the 7-membered ring, this highly efficient 7-endo-trig (vs 6-exo-trig) transannular Heck cyclization reaction was remarkable to be realized in

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• insertion to achieve C3 selectivity, whereas nickel catalysis involved alkene isomerization to generate a (2,3-dihydropyrrolyl) intermediate Int-35, followed by C2-selective coupling. In 2024, the Zheng group reported a catalyst-controlled cyclization reaction of bicyclo[1.1.0]butanes (BCBs) 32 with α

• the critical role of reaction medium polarity in modulating reactive intermediates, offering a strategic lever to toggle between C–H functionalization and reductive manifolds in photochemical transformations. In 2024, the Cheng group developed a palladium/chiral norbornene (NBE)-catalyzed cyclization

• reaction between aryl iodides 45 and phosphoramides 46 under varying solvent conditions of toluene (PhMe) and acetonitrile (MeCN), based on their studies of the Catellani reaction (Scheme 12) [41]. This method exhibited a broad substrate scope for both aryl iodides and phosphoramides, and enabled

Chitosan-supported CuI-catalyzed cascade reaction of 2-halobenzoic acids and amidines for the synthesis of quinazolinones

• Xuhong Zhao,
• Weishuang Li,
• Mengli Yang,
• Bojie Li,
• Yaoyao Zhang,
• Lizhen Huang and
• Lei Zhu

Beilstein J. Org. Chem. 2025, 21, 839–844, doi:10.3762/bjoc.21.67

• catalytic efficiency (up to 99% yield). Keywords: chitosan-supported CuI catalyst; cyclization reaction; mild conditions; quinazolinone; Introduction Quinazolinones are not only a key core of nitrogen-containing benzo heterocyclic compounds found in many natural products and bioactive molecules [1][2][3

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• et al. [59] reported an electrochemical method for the synthesis of phosphorylation of oxindoles and indolo[2,1-a]isoquinoline-6(5H)-ones using Cp2Fe through a radical addition/cyclization reaction at room temperature under argon gas. This research shows that this method is effective with various

Copper-catalyzed domino cyclization of anilines and cyclobutanone oxime: a scalable and versatile route to spirotetrahydroquinoline derivatives

• Qingqing Jiang,
• Xinyi Lei,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2025, 21, 749–754, doi:10.3762/bjoc.21.58

• the desired product. Keywords: copper catalysis; cyclobutane-fused tetrahydroquinolines; domino cyclization reaction; green synthesis; Introduction Tetrahydroquinolines (THQs) represent a privileged scaffold in medicinal chemistry, exhibiting a broad spectrum of biological activities and serving as

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• , NaOAc) did not improve the efficiency of the anodic decarboxylation/cyclization reaction (Table 1, entries 2–4). Even though the amount of hemiaminal 10a was slightly reduced, the formation of amino acid ester 11a as side product was observed in the crude reaction mixture (Table 1, entries 2–4). The

• latter could be suppressed completely by using non-basic anion-containing tetraalkylammonium salts as the supporting electrolytes (Table 1, entries 5–7) with Et4N–BF4 providing the highest yield of the desired product 6a. The anodic decarboxylation/cyclization reaction was similarly efficient when the

• facilitated the cyclization, and the 6-membered heterocycles 6h,i could be obtained in 27% and 18% yield, respectively. In addition to sulfonamides, carbamates such as N-Boc and benzamide are also suitable as nucleophiles for the anodic decarboxylation/cyclization reaction. However, the corresponding 2

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

• -aza-Prins cyclization reaction of homoallylic amines with disulfides and DMSO under copper catalysis, where DMSO acts as a solvent and a formaldehyde source at the same time (Scheme 13) [48]. This protocol represents a versatile method for the construction of oxygen-containing heterocycles, in which

• these examples, even if the whole process is performed in one-pot, the reaction needs two steps: the generation of the Ugi (or Passerini) adduct and then the post-cyclization reaction. Interestingly, Peshkov et al. showed that when phenyl glyoxal is used instead of ethyl glyoxylate, a pyrrolone

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• reactions of 2-methylquinolines with 3,5-di-(tert-butyl)-1,2-benzoquinone [1] and benzophenones with o-chloranil [15]. The norcaradiene derivatives 5, formed in the next step by the intramolecular cyclization reaction of 4, undergo thermal isomerization into 2,3-dihydrotropolones 6. The formation of 2

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

• model reaction was proposed (Scheme 6). First, 1a was acidified to form p-methylbenzenesulfinic acid A, and A was reduced by HI to form p-tolyl hypoiodothioite B, which then reacted with A to form the thiosulfonate C. 3a undergoes a cyclization reaction to form 3aa in an acidic environment. Compound B

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

• , Palestine 10.3762/bjoc.21.15 Abstract An efficient and eco-friendly approach for synthesizing difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles was established via a visible-light-promoted radical cyclization reaction. This method employed the readily accessible and inexpensive

• CF2HCO2H or PhCF2COOH, along with benzimidazoles bearing unactivated alkenes and PhI(OAc)2 as substrates, and proceeded without the need of any base, metal catalyst, photocatalyst or additive. In total, 24 examples were examined, and all of them successfully underwent cyclization reaction to produce the

• groups have reported the direct difluoromethylation/cyclization reaction of benzimidazoles with alkenes for the syntheses of difluoromethylated tricyclic benzimidazoles to date. For example, in 2023, Chen and co-workers pioneered an electrochemical approach for the difluoromethylation and cyclization

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

• reactions, particularly in controlling the high reactivity and selectivity of radical intermediates [13][14]. Early studies on copper-mediated radical reactions, such as Julia’s work on radical cyclization reaction [15], along with advancements in dimerization [16][17], oxidative cleavage [18][19], and

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

• catalyst C43 leads to allene intermediate Int-41. The enantiospecific intramolecular enamine–aldol cyclization and further dehydration provide the enantioenriched heterobiaryl product 189. The 5-endo-dig-cyclization reaction of N-pyrroloalkynylanilines 190 catalyzed by SPINOL-derived CPA C44 was utilized

• 219oa (84%, 92% ee). The unique combination of photochemistry and Brønsted acid-catalysis by CPA (R)-C23 was utilized in the cyclization reaction of cinnamates 220 forming N-arylquinolones 221 (Scheme 65) [95]. Optimized reaction conditions led to the formation of products 221 in remarkable yields with

Intramolecular C–H arylation of pyridine derivatives with a palladium catalyst for the synthesis of multiply fused heteroaromatic compounds

• Yuki Nakanishi,
• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2024, 20, 3256–3262, doi:10.3762/bjoc.20.269

• palladium catalyzed C–H arylation to pyridine derivatives. The cyclization reaction proceeded in a moderate to excellent yield when an appropriate phosphine ligand was employed. The reaction is expected to be useful for the synthesis of functional materials, and bioactive molecules in a facile manner

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

• acid activates both the enol form of the azlactone and the α,β-unsaturated imine, facilitating the asymmetric [4 + 2] cyclization reaction. The authors proposed the formation of intermediate B which subsequently undergoes an isomerization to give the chiral dihydropyridinone derivative 49. An

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• -indole system 10, in a two-step reaction: Ugi-azide followed by a cyclization reaction catalyzed by AuCl3, in good to high yields [21]. In 2019, Salahi et al. synthesized the series of tetrazole-indoles 15 via an Ugi-azide reaction in moderate to high yields [22]. It is noteworthy that none of the

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

• ) [42][43]. Another I-MCR for forming pyrroles is the in situ formation reaction of the zwitterion III, known as Huisgens 1,4-dipole. The latter is formed by the reaction of imines with acetylenedicarboxylates and can be trapped by an isocyanide through a [4 + 1] cyclization reaction to synthesize

HFIP as a versatile solvent in resorcin[n]arene synthesis

• Hormoz Khosravi,
• Valeria Stevens and
• Raúl Hernández Sánchez

Beilstein J. Org. Chem. 2024, 20, 2469–2475, doi:10.3762/bjoc.20.211

• limitation, we analyzed the mechanism underlying the formation of resorcin[n]arenes. The first step of the cyclization reaction is a hydroxyalkylation involving various cationic intermediates [69]. Hence, we hypothesized that any factor enhancing the rate of the first step by stabilizing carbocations will

• -substitued resorcinols are notoriously difficult to engage in the cyclization reaction towards resorcin[n]arenes since the nucleophilic character of the attacking aromatic carbon is diminished. Specifically, there is no literature information on 2-chlororesorcinol or 2-iodoresorcinol being used in this

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• variants. A) Access of clavam derivatives by intramolecular photoredox reaction of alkenes. B) Clavulanic acid and its derivatives. C) Construction of the oxacepham scaffold by radical cyclization. Tentative mechanism for the photo-cyclization reaction. Preparation of alkenyl β-lactam derivatives for the

Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols

• Smaher E. Butt,
• Konrad Kepski,
• Jean-Marc Sotiropoulos and
• Wesley J. Moran

Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209

• . Optimized structures are shown for the cyclization transition states (hydrogen atoms are omitted for clarity and bond lengths are given in Å). Scope of cyclization reaction. Reactions of di- and trisubstituted alkene substrates. Optimization of cyclization reaction. Supporting Information Supporting

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• )AuCl was applied with a catalyst loading of 2 mol %, activated by an equal amount of the DAI salt. Due to solubility issues, the reaction had to be performed in methylene chloride instead of chloroform. The gold-catalyzed cyclization reaction (Scheme 2) was followed via 1H NMR spectroscopy (Figure 3

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• radical, which induces 5-exo cyclization. The following hydrogen abstraction, intramolecular ionic cyclization, and hydrolysis during chromatography on silica gel affords the cyclic amide in good yield. They further applied this radical cyclization reaction as a key step in the synthesis of (±)-α-kainic

• isocyanates In the case of o-alkenyl isocyanides, it has already been described that the 5-exo cyclization reaction proceeds selectively, yielding nitrogen-containing 5-membered cyclic products. In sharp contrast, when the photoirradiated reaction of ortho-alkynyl isocyanides was carried out, we found that an

• in which phosphorus-centered radicals generated from diarylphosphine oxides by Mn(OAc)3-assisted oxidation [94] or the photoredox system [95][96][97] were used in the radical cyclization reaction of 2-isocyanobiaryls (Scheme 24). Yadav and Sigh et al. reported the direct synthesis of 6-sulfonylated

Electrochemical radical cation aza-Wacker cyclizations

• Sota Adachi and
• Yohei Okada

Beilstein J. Org. Chem. 2024, 20, 1900–1905, doi:10.3762/bjoc.20.165

• chromatography (hexane/ethyl acetate) gave the corresponding ring compounds. Cyclic voltammograms for aryl sulfonamides. Radical and ionic intramolecular cyclizations. Electrochemical and photochemical aza-Wacker cyclizations. Scope of electrochemical aza-Wacker cyclization. Reaction conditions: the alkene (0.20

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

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

• -toluenesulfonic acid-mediated hydrolysis led to the cyclization reaction yielding the steroidal 17-spiro derivatives. The procedure was applied to synthesize drospirenone (Figure 1) and extended to build the spirolactone 23 from DHEA, a key intermediate toward the popular diuretic spironolactone (Scheme 7). 17

• process, the carbonyl group at C-17 was stereoselectively attacked by α-lithio-α-methoxyallene at −78 °C to produce allene 25. A further cyclization reaction was induced by potassium tert-butoxide in the presence of catalytic dicyclohexyl-18-crown-6. The final 17-spirodihydro-(2H)-furan-3-one 27 was

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

• reaction [6][7], and Gabbaï yet another in a different cyclization reaction [8][9], among other catalytic chalcogen bonding activation examples [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29]. In contrast, we have reported recently some redox-active Te-based catalysts

• enabling the activation of small yet highly relevant organic substrates. For example, Huber and co-authors recently designed a Te-based catalyst in an indole Michael addition reaction [1][2][3][4][5]. Pale and Mamane utilized another Te-based catalyst in an electrophilic bromine-mediated cyclization