Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• bearing linear alkyl groups were transformed into N-acyl amidines 10a–c by copper catalysis. Moreover, good functional group tolerance was observed with a terminal alkene motif (10d). The cyclohexyl-substituted dioxazolone successfully provided the corresponding N-acyl amidine 10e. However, the

• area of medicinal chemistry [93][94][95][96][97]. In 2018, Buchwald and co-workers unveiled the enantioselective synthesis of benzylic amines through the asymmetric Markovnikov hydroamidation of alkenes utilizing diphenylsilane in copper catalysis under mild reaction conditions [98]. Dioxazolones, as

• Synthesis of primary amides via the generation of copper–imidate radical intermediates In a subsequent study, the research group of Son developed a method for the reduction of dioxazolones to synthesize primary amides under mild reducing conditions in copper catalysis (Scheme 10) [103]. The reaction was

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

• electrochemistry and copper catalysis for various organic transformations. Keywords: copper; electrochemistry; radical chemistry; single-electron transfer; sustainable catalysis; Introduction Transition-metal-catalyzed cross-coupling has emerged as an effective method for forming carbon–carbon (C–C) and carbon

• olefin addition reactions [20] conducted by various research groups, contributed to this area of research. Recently, the coupling reactions of C(sp3)-based electrophiles were explored using dual photoredox and copper catalysis, achieving selective radical coupling reactions involving alkyl halides [21

• ’ and Fu’s asymmetric C–N bond cross-coupling reactions by merging photoredox catalysis with copper catalysis [29][30]. Building on the success of photoredox catalysis, electrochemistry has emerged as a complementary and attractive strategy for promoting sustainability of organic synthesis. By offering

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• insights were outlined as well as cycloaddition and aza-Diels–Alder reactions were included. These strategies have gained attention due to their highly atom- and step-economy, one-step multi-bond forming, mild reaction conditions, low cost and easy handling. Keywords: cascade process; copper catalysis

• . Electron-poor and electron-rich aromatic aldehydes gave good results, whereas aliphatic aldehydes gave moderate yields (Scheme 11) [24]. The asymmetric conjugate addition of dialkylzinc and benzaldehyde to unsaturated carbonyls under copper catalysis in the presence of optically pure phosphanes was

• ]quinolinones 42 was achieved via the one-pot reaction of tetronic acid, 5-aminoindazole and arylaldehydes under copper catalysis and ultrasonic irradiation, in acetonitrile as solvent. The mechanism involves a Knoevenagel condensation between the tetronic acid and the arylaldehyde as first step, followed by a

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

• copper catalysis the complex Cu(II)OO-t-Bu was proposed [122]. The difunctionalization of styrenes 175 with trifluoromethyl and peroxy groups was carried out using Togni reagent II (176) as a CF3-group precursor and the metal organic framework Cu3(BTC)2 as a heterogeneous catalyst (Scheme 54) [123]. The

• bisperoxide 190 from styrene 189 is favoured under metalloporphyrin catalysis (Mn(III)-tetra(2,6-dichlorophenyl)porphyrin acetate) in basic media over traditional Kharasch copper catalysis (Scheme 60a). Acrylonitrile 192 was converted into bisperoxide 193 in 55% yield under Cu(OAc)2 catalysis (Scheme 60b) [91

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

• developments and illustrates the influences of copper salt, ligand, and substitution pattern of the substrate on the regioselectivity and stereoselectivity. Keywords: copper-catalysis; copper vinyl allenylidene intermediate; 1,3-enyne; 1,4-enyne; yne-allylic substitution; Introduction Copper is earth

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

• pyrazole synthesis is the synthetic accessibility of hydrazines. To circumvent this limitation, arylboronic acids can be coupled with Boc-protected diimide 23 under copper catalysis to form the hydrazine precursor in situ. Subsequent removal of the Boc groups and cyclocondensation with 1,3-dicarbonyl

• as byproducts in proportions of less than 10%. Copper catalysis opens the unique opportunity to form C–N bonds, e.g., for N-functionalization of pyrazoles in a one-pot fashion. Raghunadh et al. developed a process for the synthesis of 1,3-substituted pyrazoles 76, introducing aryl substituents at

• isolated. However, attempts to carry out the cyclization with phenylhydrazine, Boc-hydrazine, or hydrazine hydrate failed. Alternatively, alkynylation can be achieved through copper catalysis. Glyoxylation of N-methylindole with oxalyl chloride and subsequent Stephens–Castro coupling with phenylacetylene

Negishi-coupling-enabled synthesis of α-heteroaryl-α-amino acid building blocks for DNA-encoded chemical library applications

• Matteo Gasparetto,
• Balázs Fődi and
• Gellért Sipos

Beilstein J. Org. Chem. 2024, 20, 1922–1932, doi:10.3762/bjoc.20.168

• , this approach was applied to the synthesis of N-substituted pyrazoles and poly-substituted isothiazoles [24][25]. Glycine derivatives can be reacted with indoles using copper catalysis or metallophotoredox catalysis [26]. Le et al. reported the use of the same approach for imidazo[1,2-a]pyridines [27

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• combination with electrochemical copper catalysis might allow rapid access to alkylnitriles in a generic fashion (Figure 1C). Herein, we disclose the successful implementation of this strategy and present a mild, practical, and broadly applicable electrophotochemical metal-catalyzed protocol for the direct

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

• Youlong Du,
• Haibo Mei,
• Ata Makarem,
• Ramin Javahershenas,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2024, 20, 212–219, doi:10.3762/bjoc.20.21

• 1 of Table 1, 54% yield product 4a was produced by this reaction in the presence of 10 mol % CuI. These results demonstrate that copper catalysis plays a crucial role in the generation of the desired product 4a. Moreover, we performed this reaction without the addition of tert-butyl nitrite (Scheme

• . Conclusion In summary, a series of new β-trifluoromethyl β-diazo esters have been designed, which are applied for the first time in a cascade reaction through an interrupted esterification with nitrile ylides as the key intermediates under copper-catalysis conditions. Varieties of unsymmetric trifluoromethyl

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

• , employing activated and unactivated alkyl bromides as the halogenation reagents without additional external oxidants. This method features outstanding site selectivity, broad substrate scope, and excellent yields. Keywords: aminoquinolines; C–H bromination; copper catalysis; regioselectivity; Introduction

One-pot nucleophilic substitution–double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives

• Hans-Ulrich Reissig and
• Fei Yu

Beilstein J. Org. Chem. 2023, 19, 1399–1407, doi:10.3762/bjoc.19.101

• carbohydrate mimetics, but the reductive cleavage of the 1,2-oxazine rings to aminopyran moieties did not proceed cleanly with these compounds. Keywords: alkynes; azides; copper catalysis; nucleophilic substitution; 1,2-oxazines; Introduction The concept of click reactions [1][2], in particular, the

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• have been feasible. In 1989, Moriarty was investigating the intramolecular cyclopropanation of 10 under copper-catalysis, presuming that the reaction would proceed through a metallocarbene intermediate [113]. However, a control experiment showed the reaction to also be viable without catalyst, from

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

• incorporation of the SCF3 residue on various molecules has known a tremendous expansion [81][82][83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102][103][104][105][106][107][108][109][110][111][112][113]. Copper catalysis: In 2012, Daugulis and co-workers reported the copper

Synthesis of N-phenyl- and N-thiazolyl-1H-indazoles by copper-catalyzed intramolecular N-arylation of ortho-chlorinated arylhydrazones

• Yara Cristina Marchioro Barbosa,
• Guilherme Caneppele Paveglio,
• Claudio Martin Pereira de Pereira,
• Sidnei Moura,
• Cristiane Storck Schwalm,
• Gleison Antonio Casagrande and
• Lucas Pizzuti

Beilstein J. Org. Chem. 2022, 18, 1079–1087, doi:10.3762/bjoc.18.110

• . All products were fully characterized by HRMS as well as 1H and 13C NMR spectroscopy. Thus, this approach is valuable for promoting the synthesis of N-phenyl-1H-indazoles in a higher yield than that reported in the literature using copper catalysis and the same substrates. This study also prompted the

• yield is lower than that reached using o-brominated arylhydrazones by methods described in the literature, they surpass the yield obtained from the same substrates using copper catalysis. This approach also prompted the synthesis of six novel and interesting N-thiazolyl-1H-indazoles in 12–35% yield

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

• forming CHCl2 radicals [130]. In 2019, the Bao group demonstrated alkyl iodides 20 were suitable radical precursors for the carboazidation reaction (Scheme 32) [131]. Additionally, the authors demonstrated the carboazidation of alkynes 160, a challenging reaction which has only had success under copper

• catalysis [132]. Electron-rich alkyl iodides did not produce the desired product with only perfluorinated and ester-containing alkyl iodides 20 working well. Despite the limited applicability of nucleophiles, the reaction was extremely fast, typically finishing in under 10 minutes. To show the synthetic

Electrocatalytic C(sp³)–H/C(sp)–H cross-coupling in continuous flow through TEMPO/copper relay catalysis

• Bin Guo and
• Hai-Chao Xu

Beilstein J. Org. Chem. 2021, 17, 2650–2656, doi:10.3762/bjoc.17.178

• and sustainable access to 2-functionalized tetrahydroisoquinolines. Keywords: continuous flow; copper; catalysis; dehydrogenative cross-coupling; electrochemistry; Introduction The dehydrogenative cross-coupling of two C–H bonds represents an ideal strategy for the construction of C–C bonds [1][2

• temperatures [3][4][5], prompting the development of mild conditions by merging photoredox catalysis with copper catalysis (Scheme 1B) [8][9]. Notwithstanding of these outstanding achievements, noble metal-based catalysts and chemical oxidants are employed under these photochemical conditions. Organic

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• subsequent stereoselective transformations. In addition, Fimognari’s group [101] utilized copper photoredox catalysts to achieve the N-desulfonylation of benzenesulfonyl-protected N-heterocycles 72 (Scheme 29). In 2019, Xiao’s group [102] observed that under visible light or copper catalysis, cycloketone

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

Synthesis of 6,13-difluoropentacene

• Matthias W. Tripp and
• Ulrich Koert

Beilstein J. Org. Chem. 2020, 16, 2136–2140, doi:10.3762/bjoc.16.181

• –Crafts acylation is then performed in polyphosphoric acid at 140 °C, giving anthraquinone 11 in 53% yield over two steps. Reduction of 11 to the anthracene 9 proceeded smoothly using zinc powder in 1,4-dioxane and aqueous ammonia under copper catalysis [15]. To achieve good yields, it was crucial to

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

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

• similar strategy for radical generations was applied by Glorius and co-workers. They exploited a combination of organophotoredox and copper catalysis to achieve the conversion of carboxylic acids into alkenes using N,N-diaryldihydrophenazine as an organic photocatalyst [46]. Rose bengal (OD15) was also

Copper-catalysed alkylation of heterocyclic acceptors with organometallic reagents

• Yafei Guo and
• Syuzanna R. Harutyunyan

Beilstein J. Org. Chem. 2020, 16, 1006–1021, doi:10.3762/bjoc.16.90

• chiral natural products and bioactive molecules. Hence, this review focuses on the progress made over the past 20 years for heterocyclic acceptors. Keywords: conjugate addition; copper catalysis; heterocyclic Michael acceptor; organometallics; Introduction The copper-catalysed asymmetric addition of

Copper catalysis with redox-active ligands

• Agnideep Das,
• Yufeng Ren,
• Cheriehan Hessin and
• Marine Desage-El Murr

Beilstein J. Org. Chem. 2020, 16, 858–870, doi:10.3762/bjoc.16.77

• Agnideep Das Yufeng Ren Cheriehan Hessin Marine Desage-El Murr Université de Strasbourg, Institut de Chimie, UMR CNRS 7177, 67000 Strasbourg, France Sorbonne Université, Institut Parisien de Chimie Moléculaire, UMR CNRS 8232, 75005 Paris, France 10.3762/bjoc.16.77 Abstract Copper catalysis finds

• -active ligands is itself a much broader area, we shall limit our discussion to copper catalysis with redox-active ligands and the present review aims at providing an overview of the relevant literature on this topic over the last three decades. Review Oxidation: C–O bond formation The central role of

• redox-active ligands opens new venues in copper catalysis by utilizing the efficient electronic interplay between the metal center, the redox-active ligand and the reaction substrate. While such an behavior is a cornerstone in enzymatic reactions, the wide opportunities offered by these bioinspired

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• reactions are discussed. Keywords: C–B bonds; copper catalysis; C–Si bonds; enantioselective reactions; sp3 carbon functionalization; Introduction Transition-metal-catalyzed silylation and borylation are useful transformations [1], widely studied because organosilicon [2][3] and organoboron compounds [4

• scope of this silicon addition to unsaturated lactones using copper catalysis together with NHC ligand L16. The ligand used previously to great advantage by the Hoveyda and Oestreich groups for conjugate additions did not yield high ees for these substrates. The authors designed a new NHC possessing

• . This same research group recently reported on the addition of silyl Grignard reagents to aziridines under copper catalysis [83]. While the use of RMgX led to high chemical yields of the desired products, the corresponding catalytic Cu/zinc reagents gave poor yields (ca. 20%; Scheme 45). A library of

Copper-catalyzed O-alkenylation of phosphonates

• Nuria Vázquez-Galiñanes,
• Mariña Andón-Rodríguez,
• Patricia Gómez-Roibás and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2020, 16, 611–615, doi:10.3762/bjoc.16.56

• /bjoc.16.56 Abstract Copper catalysis allows the direct oxygen alkenylation of dialkyl phosphonates with alkenyl(aryl)iodonium salts with selective transfer of the alkenyl group. This novel methodology proceeds with a wide range of phosphonates under mild conditions and gives straightforward access to

• (alkenyl)iodonium salts, which are air- and moisture-stable, nontoxic and easy to prepare compounds, have become efficient reagents for mild and selective arylation and alkenylation reactions in organic synthesis [16][17][18]. In particular, the use of these hypervalent iodine reagents in copper catalysis