Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• -attached ketyl radical B are generated under photoredox NHC catalysis under visible-light irradiation. The 5-exo-trig radical cyclization of the alkene-tethered iminyl radicals A furnished a dihydropyrrole-derived radical coupled with the NHC group attached ketyl radical B. This approach features readily

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• deprotection, afforded enal 42. To avoid the chemoselectivity issues in the subsequent allylic oxidation and radical cyclization steps, enal 42 was converted to 43 by reduction of the aldehyde and protection of the resultant diol with Ph2SiCl2. Allylic oxidation of 43 with 44 [37] afforded the enone in 22

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• relies on a non-photocatalysis approach. Results and Discussion Retrosynthetic analysis of (+)-aglacin B Based on the retrosynthetic analysis shown in Scheme 1, both C8′–C8 and C7–C1 bonds in (+)-aglacin B (2) could be constructed in one-step from the β-bromo acetal 5 by a Ni-promoted tandem radical

• cyclization, and a subsequent acetal reduction under acidic conditions then can complete the total synthesis of this molecule. The cyclization precursor 5 could be prepared from the primary alcohol 6 through transforming functional groups of the alkyl chain and installing an allyl group. It was envisioned

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• polycyclic products in a highly diastereo- and enantioselective manner [45]. The polyene substrates were designed to facilitate a radical cyclization process, with alternating electron-poor and electron-rich olefins so as to enable polarity matching of the olefins and radical intermediates. With this design

• photoenzymatic transformation developed by the Hyster group, α-chloroamides were converted to enantioenriched 5-, 6-, 7-, and 8-membered lactams through an enantioselective radical cyclization followed by a diastereoselective HAT, producing contiguous stereocenters [75]. In the subsequent year, the same group

• reported intramolecular Giese-type radical cyclization reactions involving unstabilized alkyl radicals generated from alkyl iodides (Scheme 8) [34]. The generation of unstabilized, nucleophilic alkyl radicals from alkyl iodides was more challenging than the generation of more electrophilic alkyl radicals

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• and aldehyde 37, which was prepared with 9 steps from commercially available (+)-citronellol, underwent a Reformatsky-type radical addition under the conditions of Et3B/air/Bu3SnH to deliver aldol product [16]. Dehydration of the secondary alcohol gave (E)-38. The HAT radical cyclization [17] of 38 in

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• available has prevented its practical use, and synthesis methods for tricyclic-PGDM methyl ester are required. Based on the utilization of oxidative radical cyclization for the stereoselective construction of the cyclopentanol subunit with three consecutive stereocenters, we describe an asymmetric total

• synthesis of tricyclic-PGDM methyl ester in 9 steps and 8% overall yield. Keywords: asymmetric total synthesis; oxidative radical cyclization; tricyclic prostaglandin D2 metabolite methyl ester; Introduction Prostaglandins (PGs), a family of hormone-like lipid compounds, are ubiquitous natural products

• used as a powerful method for synthesizing complex natural products [20][21]. We envisaged that the A-ring in 4 could be constructed from the alkene-substituted β-keto ester precursor A via a bioinspired oxidative radical cyclization (Scheme 1D). Herein, we report the full details of our efforts to

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• and co-workers introduced an intramolecular radical cyclization strategy to synthesize highly luminescent tetraceno[6]helicenone and its aza analogue 76 [90] (Table 26). The incorporation of a carbonyl group into the helicene backbone substantially enhanced fluorescence quantum yields and red-shifted

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

• -free synthetic method for 3,3-disubstituted oxindoles via 1,2-alkylarylation of activated alkenes with alcohols [4]. N-Arylacrylamides and simple alcohols were employed as substrates, proceeding through an oxidative radical cyclization mechanism. The standard reaction conditions involved the use of an

• demonstrated that both primary and secondary alcohols were compatible substrates (7a, 7f). The proposed reaction mechanism involves oxidative radical cyclization. Initially, TBHP undergoes homolytic cleavage to generate a tert-butoxy radical, which then forms an α-hydroxy carbon radical. This radical

• quinolinone products. Beyond electrochemical protocols, photochemical activation – particularly visible-light photoredox catalysis – has become a powerful and sustainable strategy for generating carbon radicals under mild conditions. In 2023, Fan’s group discovered a radical cyclization of N-arylacrylamides

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

• bridge cycle [36][37]. The excellent diastereoselectivity in this radical cyclization was further rationalized by DFT calculations, which suggests an energy discrepancy of the hydrogen atom transfer process from different faces of the resulting α-hydroxyl radical. Final reduction of the ketone and amide

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

• salts and TEMPO as the radical initiator/oxidant couple that promoted the intramolecular radical cyclization of suitable 1,3-dicarbonyl Ugi adducts 54 and 55 (Scheme 45) [108][109]. The stabilization of the enol in the 1,3-dicarbonyl Ugi adduct allows single-electron transfer (SET) with the anion

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

• of our ongoing interest in radical cyclization reactions [22][23][24][25][26], we report here a sustainable and efficient protocol for synthesizing difluoromethylated and aryldifluoromethylated polycyclic imidazoles via visible-light-promoted cyclization of unactivated alkene-containing imidazoles

• intermediate D via intramolecular radical cyclization. A single-electron-transfer (SET) process then occurred between the radical B and the radical D, resulting in the generation of cationic intermediate E, difluoroacetate anion and PhI. Finally, the product 3a was obtained after the deprotonation by

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

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

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

• oxidized to [Co(III)]+ at the anode, while MeOH undergoes cathodic reduction to form MeO− and H2. The MeO− then deprotonates the carbamate, and the resulting conjugated base is oxidized by the cobalt–salen complex [Co(III)]+, generating an amide radical. This amide radical initiates radical cyclization to

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

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; isocyanide; radical addition; radical cyclization; Introduction Carbon monoxide is a very important C1 resource in both synthetic and industrial chemistry and is not only capable of reacting with a variety of active species such as carbon cations, carbon anions, and carbon radicals (Figure 1

• isocyanides forms boron-substituted imidoyl radical intermediates and rapid β-scission then causes elimination of the substituents on the nitrogen (Scheme 12) [53]. Radical cyclization via formation of imidoyl radical species In the former chapter, we discussed 1,1-addition reactions of typical element

• imidoyl radicals will be possible by introducing an unsaturated group at an appropriate position in the isocyanide molecule, since intramolecular reactions are generally 103 times faster than intermolecular reactions. This chapter discusses the intramolecular radical cyclization reactions of isocyanides

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

Harnessing the versatility of hydrazones through electrosynthetic oxidative transformations

• Aurélie Claraz

Beilstein J. Org. Chem. 2024, 20, 1988–2004, doi:10.3762/bjoc.20.175

• point of view, the authors proposed the formation of N-pyridyl radical 18 through the anodic oxidation of in situ-generated anion 17. Subsequent radical cyclization, second anodic cyclization and deprotonation yielded the fused heterocycle 16. Similarly, Youssef and Alajimi disclosed the electrochemical

• produced hydrazones 29. After deprotonation, the authors proposed that the carboxylate anion underwent SET anodic oxidation/decarboxylation/radical cyclization sequence to form radical intermediates 34. Subsequent second anodic oxidation and deprotonation yielded the desired heteroaromatic 5-membered rings

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

• 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

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

• organic dye Mes–Acr–MeClO4 as photocatalyst (Scheme 5). They demonstrated intermolecular radical cyclization of o-hydroxybenzoic acid derivatives with terminal alkynes to afford flavone derivatives. Here, functionally diverse flavonoids were synthesized in moderate to excellent yield by reacting various

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

• 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

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• partners. The scope of the protocol was further expanded to a radical cyclization/aminocarbonylation cascade reaction yielding the bis-carbonylated α-keto amide 26h in 31% yield. 2.1.2 C(sp3)–X activation: The generation of alkyl radicals using alkyl halides as precursors proves very challenging due their

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• common synthetic route to ergot alkaloids, providing an advantageous synthetic method for this class of natural products. Further studies on the utility of the decarboxylative radical cyclization and their applications are currently being investigated in our laboratory. (a) Transformations of DMAT to

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• refluxing acetonitrile for 6 h. It underwent a radical cyclization in refluxing benzene for 20 h to give rise to a nine-membered phostone thieno[2,3-d]pyrimidine-fused 2-hydroxy-1,2-oxaphosphonane 2-oxide 46 as a potential inhibitor after the deprotection of the benzyl group in the presence of DABCO in

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• construction of the 8-membered ring from an appropriate cyclopentane precursor. The proposed strategies include metathesis, Nozaki–Hiyama–Kishi (NHK) cyclization, Pd-mediated cyclization, radical cyclization, Pauson–Khand reaction, Lewis acid-promoted cyclization, rearrangement, cycloaddition and biocatalysis

• precursor. The proposed strategies include metathesis, Nozaki–Hiyama–Kishi (NHK) cyclization, Pd-mediated cyclization, radical cyclization (including SmI2), Pauson–Khand reaction, Lewis acid-promoted cyclization, rearrangement, cycloaddition, and biocatalysis. In particular, the purpose will focus on the

• by a vinyl ketone (compound 135) or a butenolide (compound 137) moiety dramatically influenced the outcome of the reaction and no cycloadduct was observed in both cases (Scheme 27). 4 Radical cyclization (including SmI2) Introduced by Kagan more than four decades ago, samarium diiodide (SmI2) has