Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• ) catalyst is then regenerated at the Pt cathode. Protonation of D gives intermediate E, and subsequent deprotonation at the anode yields the target compound 35a. N-Arylalkenes: difluoroalkyl/trifluoroalkyl radicals While the majority of radical cyclizations involve hydrocarbon-based radicals, the

Synthesis of pyrrolo[3,2-d]pyrimidine-2,4(3H)-diones by domino C–N coupling/hydroamination reactions

• Ruben Manuel Figueira de Abreu,
• Robin Tiedemann,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2025, 21, 1010–1017, doi:10.3762/bjoc.21.82

• . Keywords: alkynes; catalysis; cyclizations; domino reactions; heterocycles; Introduction Pyrimidines and purines are one of the most important heterocyclic compounds with prevalent biological functions. Both are found in nucleosides and their corresponding polymeric DNA and RNA, and hence are vital for

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

• reactions [7][8], the exploration of enamides’ nucleophilic reactivity has only gained momentum in recent years. Inspired by pioneering work from various research groups [9][10][11][12][13][14][15], the potential of enamides in nucleophilic reactions has become recognized. Among them, enamide cyclizations

• have attracted considerable attention due to their promise in the total synthesis of alkaloids [16]. Notably, these valuable compounds can be employed as efficient synthons in enamide–alkyne cycloisomerization, [n + m] cycloadditions, pericyclic reactions, and radical cyclizations. A comprehensive

• review of these advancements up until 2015 has already been documented [16]. In this review, recent breakthroughs of these enamide cyclizations will be surveyed from the viewpoint of natural product synthesis. Leveraging the enamide–alkyne cycloisomerization cyclizations, Lycopodium alkaloids

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

• for the time-controlled palladium-catalyzed divergent synthesis of silacycles [43]. Metal-free temperature-controlled regiodivergent borylative cyclizations of enynes [45]. Nickel-catalyzed switchable site-selective alkene hydroalkylation by temperature regulation [46]. Copper-catalyzed

Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• involvement of a fluorescent intermediate in the cascade synthetic process. Keywords: cascade reactions; copper-catalyzed three-component coupling; gold-mediated 6-endo hydroamination; tandem cyclizations; tetrahydroisoquinoline alkaloids; Introduction The bis-tetrahydroisoquinoline (THIQ) alkaloid family

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

• purities (Scheme 3). Sparr and co-workers developed an atroposelective synthesis for tetra-ortho-substituted biaryls 11 by non-canonical polyketide cyclizations [21]. This work was based on an earlier report of the team on the aldol cyclization of naphthyl-substituted unsaturated ketoaldehydes [22]. The

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

• example. This review discusses different examples involving IEDADA reactions and other cyclizations, with a special focus on the mode of action of the organocatalysts, and aims to show the synthetic applicability of the formed cyclic derivatives. The three non-covalent organocatalysts which will be

• carbamate group by interaction with the oxygen atom of the phosphoryl group. Although recently Rana and co-workers published a review article covering catalytic asymmetric transformations of azadienes [16], there is still room for this review which only focuses on non-covalent organocatalyzed cyclizations

• the field, other dienes bearing two nitrogen atoms in their structure such as 1,3-azadienes or azo-alkenes are also included. On the contrary, asymmetric cyclizations involving aza-ortho-quinone intermediates and in situ-formed 1-azadienes were excluded as they have been discussed in other recent

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• as Meldrum’s acid and 1,3-dimethylbarbituric acid were used as the nucleophiles, the yne-allylic substitution products underwent further intramolecular cyclizations to give the spiro-cyclic products in high yields (Scheme 31, 30a–f). The generation of products likely begins with an α-attack on the

• formal [4 + 1] and [4 + 2] cyclizations were carried out through substitution by an alkynyl copper-driven dearomatization/rearomatization/cyclization/isomerization process (Scheme 40). Li, Yu and Liu et al. [78] achieved the asymmetric catalyzed dearomative [4 + 1] spiroannulation of nonfunctionalized 1

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• performance. In their contribution “Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs”, Moutayakine and Burke described a new synthetic route for the synthesis of 10,11-dihydro-5H-dibenzo[b,e][1,4]diazepinone (DBDAP

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

• research [11][12], particularly focusing on innovative approaches to synthesize natural or bioactive compounds [13]. In the carboamination of alkenes, amides are used in photoredox cyclizations under proton-coupled electron transfer (PCET) conditions [14][15][16][17]. An alternative method to generate N

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

• previous report on N-alkenylamide cyclizations. B) An overview of the present work. Calculated mechanism for the cyclization of amide 3a optimized at the B3LYP/ 6-31+G(d,p) level of theory with SDDall used for iodine. Solvent effects were considered using the CPCM model. All ΔG values are in kcal·mol−1

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

• aza-Wacker cyclizations under acidic conditions, which are expected to proceed via radical cations generated by single-electron oxidation of alkenes. Keywords: alkene; aza-Wacker cyclization; electrochemistry; radical cation; sulfonamide; Introduction Activating bench-stable substrates is the first

• the difference in such reactivities are intramolecular cyclizations (Scheme 1). A radical cyclization generates a five-membered ring with a less-stable primary radical, while a six-membered ring with a secondary cation is obtained through ionic cyclization. When such intramolecular cyclizations are

• expected to proceed via radical cations, there are several interpretations of the mechanisms involved, since radical and ionic cyclizations are both possible. In this context, electrochemical and photochemical aza-Wacker cyclizations have provided interesting models for mechanistic discussion (Scheme 2

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• . Iterative Pictet–Spengler cyclizations: saframycin A and jorunnamycin A Saframycin A (5) was isolated from Streptomyces lavendulae, and a number of related alkaloid families such as safracins and renieramycins have been identified from both soil and marine microorganisms [89][90]. These natural product

Ring opening of photogenerated azetidinols as a strategy for the synthesis of aminodioxolanes

• Henning Maag,
• Daniel J. Lemcke and
• Johannes M. Wahl

Beilstein J. Org. Chem. 2024, 20, 1671–1676, doi:10.3762/bjoc.20.148

• ). The corresponding protecting group (PG) was thought to control the conformation of the 1,4-biradical 2, which is known to be important for efficient Norrish–Yang cyclizations [27][28]. Furthermore, the PG was deemed crucial for the development of further functionalizations of the azetidinols (vide

• chosen as a preferred solvent because it is known to facilitate Norrish–Yang-cyclizations and allows simple analysis by nuclear magnetic resonance (NMR) spectroscopy [10]. Our results are summarized in Table 1. When p-toluenesulfonyl (Ts) was used as a PG at nitrogen, azetidine 3a was obtained in 81

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• transformations in a single reactor, reducing the number of steps and the amount of waste with consequent benefits of cost and environmental impact [42][43]. Representative examples of relevant N-fused heterocycles. Different acid-catalyzed six-membered ring cyclizations. Substrate scope for the assembly of

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• recent discovery of the aridacins, which transforms a 2E-cis-eunicellane into a 6/7/5-tricyclic diterpene via a cytochrome P450 [12]. Coincidentally, these reactive skeletons also provide chemists the ability to access synthetically challenging scaffolds with simple electrophilic cyclizations. With

• epoxide 9, but the similar reaction with 2 yields gersemienol 8. Isolation yields are provided. (B and C) Results of DFT calculations on the protonation-induced cyclizations of 1 and 2. The energies of the cationic intermediates (italicized values) are not on the same energy scale as for the substrates

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• of the substituent located at carbon C3 of the chromone moiety and also on the type of nucleophile employed. Keywords: cyclizations; 1,3-dicarbonyl compounds; domino reactions; heterocycles; regioselectivity; silyl enol ethers; Introduction Domino reactions (also called cascade or tandem reactions

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• -workers [22][23]. Recently, Jacobsen reported asymmetric Prins cyclizations with HCl solutions [24]. Hence, all the described hydrochlorinations are racemic or diastereoselective reactions. Review Polar hydrochlorination reactions To comprehend polar hydrochlorination reactions, a solid understanding of

Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• of acyl-CoA: cholesterol acyltransferase [4]. In this mini-review, we focus on the fungal meroterpenoids biosynthesis, especially terpenonid cyclizations and post-cyclization modifications, which mostly contribute to the skeletal diversity. Several terpenoid cyclases and αKG-dependent dioxygenases

• Aspergillus oryzae, will be also introduced. Review Standard reactions of fungal meroterpenoid biosynthesis The skeletal diversity within this group of compounds arises from polyketide synthesis, prenyl transfer, terpenoid cyclizations, and post-cyclization modifications [5]. In these reactions, terpenoid

• cyclizations and post-cyclization modifications are especially important in fungal meroterpenoid biosynthesis, contributing to the structural diversity of this class of compounds. Fungal meroterpenoid cyclases (CYCs) are seven-membrane-spanning transporter-like enzymes that regulate the conformations of

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• attack of the oxygen atom of the ester group on the benzyl bromide residue prevails, with the cleavage of the arylidene succinimide fragment involved in further non-selective processes. The causes of the failed cyclizations in the last two cases can be summarized as follows. The intermediates obtained

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• of parameters with which to control reactivity. In this perspective, we provide an overview of the different mechanisms for radical reactions involving NHPI esters, with an emphasis on recent applications in radical additions, cyclizations and decarboxylative cross-coupling reactions. Within these

• [119] (Scheme 37A). Recently, Lumb and co-workers showcased the use of NHPI esters in key radical cyclizations, allowing the synthesis of diverse dibenzocyclooctadiene lignans [55] (Scheme 37B). A Ru-catalyzed cyclization was employed to construct the quaternary stereocenter in taiwankadsurin A

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

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

• ], Friedel–Crafts acylation [12], radical cascade reactions [2][13], and photoinduced radical cyclizations [14][15][16][17]. However, these methods often suffer from drawbacks such as harsh reaction conditions and the requirement of transition-metal catalysts. Although photocatalyzed cyclization reactions

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• introduced in 2017, followed by carbon nanotubes in 2019. Consistent with expectations from theory, anion–π catalysis on carbon allotropes generally increases with polarizability. Realized examples reach from enolate addition chemistry to asymmetric Diels–Alder reactions and autocatalytic ether cyclizations

• catalysis; electromicrofluidics; enolate addition; ether cyclizations; fullerenes; Introduction Anion–π catalysis was introduced ten years ago [1]. The idea is to stabilize anionic transition states on electron-deficient, π-acidic aromatic surfaces (Figure 1A). The true beginning is arguably in 2015

• catalysis. Moreover, epoxide opening polyether cyclizations are among the most impressive cascade reactions in nature [71][72][73]. Best known is the hypothetical cascade XII in the biosynthesis of brevetoxin B [74]. It affords eleven fused ethers by violating the Eschenmoser–Dunitz–Baldwin guidelines [75

Synthetic approach to 2-alkyl-4-quinolones and 2-alkyl-4-quinolone-3-carboxamides based on common β-keto amide precursors

• Yordanka Mollova-Sapundzhieva,
• Plamen Angelov,
• Danail Georgiev and
• Pavel Yanev

Beilstein J. Org. Chem. 2023, 19, 1804–1810, doi:10.3762/bjoc.19.132

• reductive cyclizations of o-nitrobenzoyl ketones [57][58], enamines [59][60], or isoxazoles [61]. The scope of these reductive cyclizations is limited by the availability of the necessary intermediates and has remained largely underexplored, especially with regard to 4-quinolones with long-chain