Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• benzamides with terminal alkynes, 5-exo-dig aza-cyclization of 2-alkynylbenzamides as well as reductive cascade annulation of o-alkynylbenzamides. Pyrroles and imidazoles were formed efficiently via electrochemical annulation of alkynes with enamides and tandem Michael addition/azidation/cyclization of

• annulation of benzamides and terminal alkynes was established for the synthesis of isoindolones by Ackermann in 2019 (Scheme 8) [207]. After screening the reaction carefully, the optimum conditions were presented as following: a mixture of benzamide 22 (0.25 mmol), alkyne 23 (0.50 mmol), NaOPiv (0.25 mmol

• tandem C–H indolization of 2-alkynylanilines with 3-functionalized indoles. The electrochemical and copper-catalyzed annulation of benzamides and terminal alkynes formed isoindolones in high yields. Isoindolinone could be also afforded via electrochemical 5-exo-dig aza-cyclization of 2-alkynylbenzamides

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• diaryliodonium salts under photoredox conditions has been proposed for the first time. The suggested procedure allows preparing a broad range of benzamides using both symmetric and unsymmetric diaryliodonium salts under mild conditions. A plausible mechanism for the reaction and the selectivity of aryl transfer

• (in case of unsymmetrical iodonium salts) were studied. Keywords: arylation; benzamides; diaryliodonium salts; isonitriles; photoredox; Introduction Amides represent a crucial and ubiquitous structural motif in essential biomolecules including proteins and peptides [1], as well as in a wide array of

• of benzamides (Scheme 1A) [6]. Over the years, the basic reaction has been modified to imply various metal-containing catalysts [7][8][9][10][11][12][13][14][15][16][17][18], metal-free transformations that employ heteroarenes under harsh conditions [19], or using diazonium salts as arylating agents

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

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

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

• toxic chemical oxidants and releasing hydrogen gas as the sole byproduct. Various benzamides 1 and terminal arylalkynes 2 bearing electron-rich or electron-withdrawing groups provided the desired products 3 with high chemoselectivities. However, terminal alkynes with alkyl substituents did not yield the

• directed C–H amination of benzamides with secondary amine electrophiles independently (Figure 11) [61]. In 2023, De Sarkar and Baidya reported the Cu-catalyzed electrocatalytic azidation of N-arylenamines, followed by denitrogenative annulation for quinoxaline synthesis (Figure 12) [62]. Only 0.5 mol

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

• % yield, respectively. The related reaction is also carried out with amides of non-pyridine derivatives terephthal- and benzamides to afford multiply fused heterocyclic compounds in 81% and 89% yields, respectively. Keywords: intramolecular C–H arylation; multiply fused heterocycles; palladium acetate

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• and co-workers reported a mild, metal free-synthesis of fluorobenzoxazepines 30 in 2016 (Scheme 13) [37]. Using 1-fluoro-3,3-dimethylbenziodoxole (12) and 4 Å molecular sieves, a range of benzamides 29 were successfully cyclised in good yields. The sustainability of the reaction was improved by

• up to 95% within a short time-frame of 10 minutes. Treatment of N-(2-phenylallyl)benzamides with 10 equivalents of BF3·Et2O, iodobenzene, m-CPBA in dichloromethane (DCM) at 0 °C resulted in the formation of the oxazoline product (Scheme 21). DFT calculations indicated several steps in the mechanism

• corresponding chlorinated dihydro-[1,3]-oxazines 50 in good to excellent isolated yields [49]. When various substituted N-(2-phenylallyl)benzamides (52) were tolerated, it led to the formation of chlorinated 2-oxazolines 51 in good to excellent yields. When BF3 was used as the halogen source in the author’s

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

• annulation of benzamides and allenes [47]. This method demonstrated excellent functional group tolerance, yielding a broad range of C–N axially chiral compounds with good yields and enantioselectivities. The practicality of this strategy was further demonstrated by a decagram-scale synthesis and the LSF of

• complex compounds (Scheme 35). In addition, Niu and coworkers reported a similar work on a cobalt-electrocatalyzed atroposelective C–H annulation of benzamides with acetylenes [48]. 1.3.3 Ni-assisted anodic oxidation: Apart from cobalt, nickel complexes have also been applied in anionic oxidations and

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

• cyclization of para-substituted benzamides and chloro- (7b), bromo- (7c), phenyl- (7d), and methoxy- (7e) derivatives were all isolated in moderate yields. The ortho-substituted derivatives 7f, 7g, and 7h were also successfully prepared. Alkylamides were found to be ambiguous substrates as the acetamide 7i

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

• positive charge was likely built up on the olefin prior to the nucleophilic addition. On the other hand, the electronic nature of the para-substituted benzamides had little impact on the overall reaction rate as both electron-rich and electron-deficient benzamides proceeded with similar kinetic profiles

• . All the kinetic plots are shown in Figure 1. With the optimized conditions and kinetic information in hand, we turned our attention to the amide substrate scope. In this case, both electron-rich and -deficient benzamides proceeded to the desired products in reasonable yields and high

• regioselectivities (Figure 2, products 4–7). Concurring with our kinetic data, the electronic nature of the amide bears little impact on the overall reaction rate and in this case, on the final yields as well. Similarly, ortho- and meta-substituted benzamides with halogen functionalities could also generate the

Copper-promoted C5-selective bromination of 8-aminoquinoline amides with alkyl bromides

• Changdong Shao,
• Chen Ma,
• Li Li,
• Jingyi Liu,
• Yanan Shen,
• Chen Chen,
• Qionglin Yang,
• Tianyi Xu,
• Zhengsong Hu,
• Yuhe Kan and
• Tingting Zhang

Beilstein J. Org. Chem. 2024, 20, 155–161, doi:10.3762/bjoc.20.14

• -aminoquinoline amides, and the results are illustrated in Scheme 2. A wide variety of 8-aminoquinoline amides with different substitutions efficiently participated in this mild and versatile bromination. Benzamides with both electron-donating groups (3ba–ca) and electron-withdrawing groups (3da–fa) were well

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts

• Nils Clamor,
• Mattis Damrath,
• Thomas J. Kuczmera,
• Daniel Duvinage and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2024, 20, 12–16, doi:10.3762/bjoc.20.2

• optimized conditions in hand, the substrate scope was explored. The variations of amides are outlined in Scheme 2. Switching from valeramide to benzamide as a substrate gave a more advantageous yield of 85% of 2b. We tested para-substituted benzamides in the reaction to further assess the diversity of

• % yields. para-Amino- and boronic acid-substituted benzamides did not react. While meta-bromo-substituted benzamide gave 2j in 84% yield, ortho-bromination resulted in a diminished yield of 2k (55%). We obtained 3,5-disubstituted N-acyl carbazoles 2l and 2m in 91% and 88% yields. The same disubstitution

• with electron-donating methoxy groups gave product 2n in a diminished output of 56% yield. Other electron-rich 2,4,6-trimethyl- and 3,4,5-trimethoxy-substituted benzamides gave 2o in 91% and 2p in 69% yield. In an experiment at a larger scale (1 mmol), 2o was still generated in 81%, which underscores

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

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

• the products. Furthermore, this method shows good functional group tolerance, because various aromatic amines, benzamides, and sulfonamides were successfully used as substrates in these transformations. In this study, it was found that the reactions of aromatic amines bearing electron-withdrawing

• ). This reaction has been successfully used for common amines using acetic acid and water, but benzylamines and benzamides show no reaction under aqueous conditions. In the case of amino acid ester hydrochlorides, the reaction to give pyrrole can be carried out without the need for the two-phase

• solvent-free conditions or in microwave-assisted reactions to synthesize various N-substituted pyrrole derivatives. Because of the high functional group tolerance of this method, various primary aliphatic/aromatic amines, benzamides, and sulfonamides have been used successfully as substrates in these

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• and benzamides with azabenzonorbornadienes [78]. Interestingly, the dehydration step occurred smoothly with an aza-leaving group rather than the more common oxa-leaving group discussed above. In 2013, the Radhakrishnan laboratory reported the Rh-catalyzed domino ring-opening coupling reaction of

Transition-metal-catalyzed C–H bond activation as a sustainable strategy for the synthesis of fluorinated molecules: an overview

• Louis Monsigny,
• Floriane Doche and
• Tatiana Besset

Beilstein J. Org. Chem. 2023, 19, 448–473, doi:10.3762/bjoc.19.35

• catalysis reported by He and Pan [137]. Palladium-catalyzed (ethoxycarbonyl)difluoromethylthiolation reaction of 2-(hetero)aryl and 2-(α-aryl-vinyl)pyridine derivatives reported by Besset [138]. Pd(II)-catalyzed trifluoromethylselenolation of benzamides derived from 5-methoxy-8-aminoquinoline reported by

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• (trifluoromethanesulfonic acid), and the N-acyliminium cation was proposed to be protonated with the super acidic TfOH to form a dicationic species, which was shown by computational studies to be crucial for the success of this transformation. In a later study, the same research group showed that benzamides 2 bearing an

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• halichonic acid B in 10 steps starting from commercially available (−)-α-bisabolol (3). An important intermediate in our route was (−)-7-amino-7,8-dihydrobisabolene (4), which was prepared in enantiomerically pure form following recrystallization of a diastereomeric mixture of the corresponding benzamides. A

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• -methylaminobenzamides 72, 76 and N-methyl-2-(3-bromopropylamino)benzamides 79 via the P–C bond formation as the crucial step. N-(3-Chloropropyl)-2-methylaminobenzamides 72 and 76 and N-methyl-2-(3-bromopropylamino)benzamides 79 were first treated with phosphorus trichloride followed by intramolecular cyclization in the

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

The PIFA-initiated oxidative cyclization of 2-(3-butenyl)quinazolin-4(3H)-ones – an efficient approach to 1-(hydroxymethyl)-2,3-dihydropyrrolo[1,2-a]quinazolin-5(1H)-ones

• Alla I. Vaskevych,
• Nataliia O. Savinchuk,
• Ruslan I. Vaskevych,
• Eduard B. Rusanov,
• Oleksandr O. Grygorenko and
• Mykhailo V. Vovk

Beilstein J. Org. Chem. 2021, 17, 2787–2794, doi:10.3762/bjoc.17.189

• on PIFA-initiated oxidative 5-exo-trig cyclization of 2-(3-butenyl)quinazolin-4(3Н)-ones, in turn prepared by thermal cyclocondensation of the corresponding 2-(pent-4-enamido)benzamides. The products obtained have a good natural product likeness (NPL) score and therefore can be useful for the design

• - or ultrasound-assisted reaction of 2-aminobenzonitrile and alkenoyl chlorides [56]. We have found that substrates 7 can be obtained efficiently by a two-step reaction sequence commencing from acylation of anthranilamides 8 with α-allylacetyl chloride 9 leading to benzamides 10. These intermediates

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• nature of their α-C–H also proved viable under slightly modified reaction conditions, as was reported by Hashmi in 2019 (Scheme 25) [68]. In a recent publication, the group of Martin enabled an intermolecular alkylation of α-amino C–H bonds of benzamides 31 with unactivated alkyl halides 40 [72]. In this

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197