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

• , and benzamide, however, no relevant competitive oxidation peak was observed with only Cu(OAc)2. These results indicate that Cu(II) intermediate 5 was generated. Based on the mechanistic studies, the authors suggested plausible reaction mechanisms (Figure 4). First, the Cu(II) catalyst coordinates with

• substrate 1 in the presence of a base to form Cu(II) complex 5, which undergoes anodic oxidation to generate Cu(III) intermediate 6. Carboxylate-assisted C–H activation of the benzamide subsequently leads to the formation of Cu(III) species 7. Metalation of the terminal alkyne 2, followed by reductive

• features of electrochemical copper catalysis. Scheme and proposed mechanism for Cu-catalyzed alkynylation and annulation of benzamide. Scheme and proposed mechanism for Cu-catalyzed asymmetric C–H alkynylation. Scheme for Cu/TEMPO-catalyzed C–H alkenylation of THIQs. Scheme and proposed mechanism for Cu

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• that, up to 24 hours, this method shows some degree of functional group tolerance, as the amido and carboxylic acid functionalities of benzamide and benzoic acid, were left untouched, and the starting materials were finally fully recovered. 1-Bromo-4-nitrobenzene (8a) and 3-chlorophenol were used to

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

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• nonmetallic reagents as an attractive alternative is less developed. In 2014, Antonchick and Manna firstly reported the synthesis of a series of 3,4-diaryl-substituted isoquinolinone derivatives through oxidative annulation between alkynes and benzamide derivatives using iodobenzene as a catalyst and

• using 2-alkenylbenzamide derivatives as substrates (Scheme 1). Results and Discussion We began by exploring the reaction of N-methoxy-2-(prop-1-en-2-yl)benzamide (1a) with PISA (1.5 equiv) in anhydrous acetonitrile at room temperature under argon atmosphere. 4-Methylisoquinolinone 2a was the sole

• % yield. Additional experiments were then carried out using N-methoxy-2-(prop-1-en-2-yl)benzamide with different substituents R2. Both electron-donating (methyl, alkoxy, dimethylamino) and electron-withdrawing substituents (fluoro, chloro, trifluoromethyl) were well tolerated on the phenyl ring and gave

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

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

• bifunctional amide nucleophiles (Scheme 1e). Results and Discussion Our studies here focused on the development of hypervalent iodine-catalyzed amide and alkene coupling reaction [53][54][55]. In this case, we started with styrene (1) and benzamide (2) as the standard substrates. Using iodotoluene A as the

• reaction designs. Time studies of the amide and alkene coupling. a) Iodoarene time studies: styrene (1), para-substituted iodoarenes, LiBF4, and benzamide (2). b) Li salt time studies: styrene (1), iodoanisole, Li salts, and benzamide (2). c) Alkene time studies: para-substituted styrenes, iodotoluene A

• , LiBF4, and benzamide (2). d) Benzamide time studies: styrene (1), iodotoluene A, LiBF4, and para-substituted benzamides. Amide substrate scope studies. a) Standard conditions: styrene (0.25 mmol), iodotoluene (20 mol %), LiBF4 (100 mol %), Selectfluor (150 mol %), amide (400 mol %), MeNO2 (0.25 M), rt

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• , and benzamide 1c (Table 4). Under standard conditions (2.5 mol % [JPhosAu(NCCH3)]SbF6, 0.05 M alkene in DCM) benzamide and carbamate hydroamination were too slow to measure, so the reactions were done with 55 μL MeOH promoter but still only an estimated rate constant was obtained for 1c (14

• % conversion after 24 h, estimated t1/2 = 96 h, kobs = 1.4 × 10−6 s−1). With 55 μL MeOH in DCM, the relative rates for each substrate are 3,850:50:1 with urea 1a > carbamate 1b > benzamide 1c. The analogous toluene sulfonamide substrate 1d did not react on measurable timescales at room temperature (no product

• by identifying a more Lewis acidic gold. To determine whether benzamide (1c) cyclization could be made efficient with appropriate combination of ligand and MeOH we surveyed rates with (PhO)P(o-biphenyl)2AuOTf (4a) and JackiephosAuNTf2 (6a, Table 5). Benzamide rates remain slow but gains can be

Catalytic multi-step domino and one-pot reactions

• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2024, 20, 254–256, doi:10.3762/bjoc.20.25

• -aminopyrazoles with azlactones under solvent-free conditions, through subsequent elimination of a benzamide molecule in a superbasic medium, is described by the Fisyuk group [13]. A further facile one-pot process toward a new series of copper(II) benzo[f]chromeno[2,3-h]quinoxalinoporphyrin analogues is described

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

• reaction of 8-aminoquinoline amides using activated and unactivated alkyl bromides as the bromine source (Scheme 1, reaction 4). Results and Discussion At the beginning of this investigation, N-(quinolin-8-yl)benzamide (1a) and ethyl bromoacetate (2a) were selected as model substrates to screen the

• highly efficient C5-bromination protocol has been established. Having identified the optimal reaction conditions for the bromination of N-(quinolin-8-yl)benzamide (1a) with ethyl bromoacetate (2a) (Table 1, entry 12), we next examined the substrate scope and limitations of our method with an array of 8

• substrates containing substituents on the quinoline ring. For example, the 6-OMe-substituted quinoline derivative N-(6-methoxyquinolin-8-yl)benzamide (4) underwent bromination at the C5 position to give 5 in nearly quantitative yield (Scheme 4, reaction 1). Subsequently, we attempted to apply this method to

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

New one-pot synthesis of 4-arylpyrazolo[3,4-b]pyridin-6-ones based on 5-aminopyrazoles and azlactones

• Vladislav Yu. Shuvalov,
• Ekaterina Yu. Vlasova,
• Tatyana Yu. Zheleznova and
• Alexander S. Fisyuk

Beilstein J. Org. Chem. 2023, 19, 1155–1160, doi:10.3762/bjoc.19.83

• ) under solvent-free conditions, through subsequent elimination of a benzamide molecule in a superbasic medium (t-BuOK/DMSO). The fluorescent properties of the synthesized compounds were studied. 4-Arylpyrazolo[3,4-b]pyridin-6-ones luminesce in the region of 409–440 nm with a quantum yield of 0.09–0.23

• (Table 1). For compound 3a, the possibility of benzamide elimination was studied. The benzamide fragment is a poor leaving group; however, in a superbasic medium, we were able to eliminate this group in compound 3a. In order to select optimal synthesis conditions, we heated compound 3a in DMSO at

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

• -promoted trifluoromethylthiolation of benzamide derivatives 1 at the ortho-position by C–H bond activation [114]. Indeed, using a bidentate directing group (amide derived from the 8-aminoquinoline), the mono- and difunctionalized compounds were obtained when Cu(OAc)2 (0.5 equiv) and the toxic and volatile

• catalysts for such functionalization. In 2013, the group of Daugulis described the copper-catalyzed ortho-2,2,2-trifluoroethoxylation of a 3-trifluoromethylated benzamide derived from 8-aminoquinoline, giving the corresponding product in 73% yield [149]. The group of Baidya showed that the dehydrogenative

• 2,2,2-trifluoroethoxylation of benzamide with another bidentate directing group was also possible in the presence of Cu(OAc)2 and hexamethyldisilane [163]. Using N,N- and N,O-bidentate directing groups, the construction of C(sp2)–OCH2CF3 bonds by C–H bond activation was also reported using Ni [164] and

NaI/PPh₃-catalyzed visible-light-mediated decarboxylative radical cascade cyclization of N-arylacrylamides for the efficient synthesis of quaternary oxindoles

• Dan Liu,
• Yue Zhao and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2023, 19, 57–65, doi:10.3762/bjoc.19.5

• synthesis of (±)-physovenine and (±)-physostigmine alkyl analogues exhibiting inhibitory activity against acetylcholinesterase and butyrylcholinesterase [30][78][79][80][81][82][83][84]. Subsequently, we expanded the scope of this protocol to include a benzamide derived acrylamide 1r. The expected six

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

• (−)-α-bisabolol. The optimized synthetic route includes a new purification method for isolating (−)-7-amino-7,8-dihydrobisabolene in enantiomerically pure form via recrystallization of its benzamide derivative. The key intramolecular aza-Prins reaction forms the characteristic 3-azabicyclo[3.3.1]nonane

• ultimately found success with the benzamide derivative 5, which could be prepared from the mixture of 4 and its C7-epimer in 93% yield upon treatment with benzoyl chloride. Recrystallization of the resulting mixture of diastereomeric amides from cyclohexane improved the dr from 83:17 to 95:5 (as determined

• organic co-solvent), and slow decomposition occurred under acidic conditions at elevated temperatures. Alternative methods to cleave the benzamide using sodium peroxide [11] or triethyloxonium tetrafluoroborate [12] were also unsuccessful, giving either no reaction or significant decomposition

Synthesis of novel [1,2,4]triazolo[1,5-b][1,2,4,5]tetrazines and investigation of their fungistatic activity

• Anna V. Korotina,
• Svetlana G. Tolshchina,
• Rashida I. Ishmetova,
• Natalya P. Evstigneeva,
• Natalya A. Gerasimova,
• Natalya V. Zilberberg,
• Nikolay V. Kungurov,
• Gennady L. Rusinov,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2022, 18, 243–250, doi:10.3762/bjoc.18.29

• characteristic singlet of H(4) of the pyrazolyl substituent in the region of 6.38–6.41 ppm in the 1H NMR spectrum. A small amount of N-(6-(4-bromo-3,5-dimethylpyrazol-1-yl)-1,2,4,5-tetrazin-3-yl)benzamide, as a byproduct, was isolated from the reaction mixture, the structure of the latter was confirmed by the

• been found. All the above-mentioned results demonstrate good prospects for finding new antifungal drugs in this class of compounds. X-ray structure of N-(6-(4-bromo-3,5-dimethylpyrazol-1-yl)-1,2,4,5-tetrazin-3-yl)benzamide. Chemical structures of [1,2,4]triazolo[4,3-b][1,2,4,5]tetrazine (a), [1,2,4

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

• [13], as well as Ir-catalyzed intramolecular dehydrative cross-coupling of 2-(pyrrolidine-1-yl)benzamide [14]. Another approach to compounds of type 1 that relies on a cascade formation of the pyrimidine and pyrrole rings have found much wider application (see Scheme 1B). One of its variations

Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2021, 17, 2668–2679, doi:10.3762/bjoc.17.181

• activated derivatives (intramolecular Friedel–Crafts acylation) [29][30][31] found wide application here. In a different approach, a total synthesis of dengibsin (1a) was accomplished by Wang and Snieckus in 15 steps by means of a directed remote metalation [32], using a benzamide residue as the directing

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• intramolecular aza-MR by using phase-transfer catalysts. Alkenylated benzamide was used as the substrate in this reaction. The resulting compounds were found to be useful intermediates for the synthesis and development of benzodiazepine-receptor agonists [47]. In 2018, Sallio et al. worked on the same reaction

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

•  34B and 34C) [170]. The new method presented broad scope in the construction of tetrasubstituted carbon centers from methylenes to access a wide range of spiro N-heterocyclic oxindoles in excellent yields, including diamine, benzamide, and spirothiazole scaffolds. The high potential of the reaction

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• carboxylate-assisted C−H cleavage to deliver copper(II) intermediate A. Next, the copper(III) carboxylate species B is generated. Thereafter, a facile base-assisted ligand exchange is followed by reductive elimination to afford the alkynylated benzamide D. Finally, the desired isoindolone 3 is formed via an

Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects

• Shivani Gulati,
• Stephy Elza John and
• Nagula Shankaraiah

Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• copper salt, acting as both, the catalyst for C–H activation and the oxidizing agent, was also required. The reaction occurred at higher temperatures (60 °C) compared to other dual catalytic systems. A wide variety of benzamide substrates bearing different functional groups such as alkyl, phenyl, halogen

• perfluoroalkyl benzoic acid derivatives. A plausible mechanism for the perfluoroalkylation of N-(quinolin-8-yl)benzamides is proposed in Figure 34. First, C–H activation of the benzamide substrate with copper produces a cyclometalated complex. Meanwhile, perfluoroalkyl radicals are generated by electron transfer

Installation of -SO₂F groups onto primary amides

• Jing Liu,
• Shi-Meng Wang,
• Njud S. Alharbi and
• Hua-Li Qin

Beilstein J. Org. Chem. 2019, 15, 1907–1912, doi:10.3762/bjoc.15.186

• and Discussions Initially, benzamide (1a) was selected as model substrate to test the feasibility of this proposed N-fluorosulfonylation reaction in the presence of Cs2CO3 in DMSO under SO2F2 atmosphere (balloon) at 50 °C, and excitingly, the desired product benzoylsulfamoyl fluoride (2a) was obtained

A metal-free approach for the synthesis of amides/esters with pyridinium salts of phenacyl bromides via oxidative C–C bond cleavage

• Kesari Lakshmi Manasa,
• Yellaiah Tangella,
• Namballa Hari Krishna and
• Mallika Alvala

Beilstein J. Org. Chem. 2019, 15, 1864–1871, doi:10.3762/bjoc.15.182

• intermediate A. The attack of the ortho-position of the pyridinium moiety by the nucleophilic oxygen of intermediate A is then proposed to generate cyclic oxazolopyridine intermediate B [42][43]. The intermediate B then undergoes a rearrangement to afford N-alkylated benzamide 3 via a C–C bond cleavage with