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

• the enantioselective dicarbofunctionalization of olefins, using photoelectrocatalysis with asymmetric copper catalysis (Figure 8) [57]. This asymmetric heteroarylcyanation of arylalkenes 27 via C–H functionalization has a broad substrate scope, including various arylalkenes and heteroarenes, yielding

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• , Ankara 06800, Türkiye 10.3762/bjoc.20.273 Abstract Acenaphthylene-fused heteroarenes with a variety of five- and six-membered heterocycles such as thiophene, furan, benzofuran, pyrazole, pyridine and pyrimidine were synthesized via an efficient Pd-catalyzed reaction cascade in good to high yields (45–90

• total synthesis of the fungal natural product bulgarein. Keywords: acenaphthylene-fused heteroarenes; benzo[j]fluoranthenes; C–H arylation; fluoranthenes; heterocycles; Introduction An important subclass of polycyclic aromatic hydrocarbons (PAHs) [1] is comprised of fluoranthenes, which have been the

• ][27], as well as Friedel–Crafts [28] and Prins-type [29] reactions have been developed to date [2]. However, methods that enable access to the analogous acenaphthylene-fused heteroarenes are less common [30][31][32][33][34][35][36][37][38][39]. In one such study, Würthner and co-workers reported a Pd

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

• arylation precursors 1a–c. Palladium-catalyzed intramolecular direct arylation for synthesizing 8a and 8b and the X-ray crystallographic structure of 8a. Studies on the reaction conditions for 2a from 1a. Pd-catalyzed C–H arylation of heteroarenes. Supporting Information Accession code CCDC 2227450

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• metal-free macrocycles for the C–H arylation of five-membered heteroarenes using aryldiazonium salts, with porphyrin serving as the photoredox catalyst [92]. Control experiments indicated that H2TPP (18), when irradiated with light, gave 80% yield of the C–H arylated product 77 for the reaction of furan

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• corresponding sulfur-containing heteroarenes, only a few methods have been developed (Scheme 1). In 1988, Lee and co-workers reported the synthesis of SR-containing hydrazones in a two-step process (chlorination [65] then reaction with thiols) from readily available aldehyde-derived hydrazones [66]. Wang et al

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

• rearomatization In 2023, Lin and He et al. [72] achieved the challenging dearomatization of heteroarenes through d-orbital electron of the transition-metal center and thus completed the asymmetric substitutions with remote stereoselective control induced by alkynylcopper. A newly electron-rich ligand was

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

• in schemes as H2↑) in the cathodic half-reaction, which will however not be addressed in greater detail in this review. 1.1 Direct anodic oxidation of substrates 1.1.1 C–H bond functionalization. C–H bond carbofunctionalization: CF3 groups can be installed on heteroarenes at a late stage via a TM

• functionalization method where primary, secondary, and tertiary alkyl radicals can be readily generated through the sequential anodic oxidative fragmentation of alkyl carbazates, enabling the functionalization of N-heteroarenes [7]. This transformation is particularly valuable as the cleavage of the C–O bond to

• electro- and photocatalysis can lead to highly precise electron-driven reactions that are otherwise inaccessible [61][62][63][64][65][66][67]. The photoelectrochemical method for the alkylation of C–H heteroarenes using organotrifluoroborates, developed by Xu and coworkers, has demonstrated excellent

Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer

• Mohd Farhan Ansari,
• Atul Kumar Maurya,
• Abhishek Kumar and
• Saravanakumar Elangovan

Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98

• activated by the base dehydrogenates the alcohol to the aldehyde and indoline to indole by acceptorless dehydrogenation. Moreover, C3 alkylation proceeded via BH (Scheme 58). In early 2021, Maji’s group demonstrated an efficient approach for the C-alkylation of methyl N-heteroarenes with primary alcohols

• using a manganese-pincer complex [88]. Various methyl-substituted N-heteroarenes were coupled with several alcohols using Mn1 (2 mol %), t-BuOK (1 equiv) as a base in t-AmOH at 140 °C under argon atmosphere for 24 h to give moderate to excellent yields (53–98%) of the desired C-alkylated N-heteroarene

Mono or double Pd-catalyzed C–H bond functionalization for the annulative π-extension of 1,8-dibromonaphthalene: a one pot access to fluoranthene derivatives

• Nahed Ketata,
• Linhao Liu,
• Ridha Ben Salem and
• Henri Doucet

Beilstein J. Org. Chem. 2024, 20, 427–435, doi:10.3762/bjoc.20.37

• bases in the presence of Pd(OAc)2 as the catalyst (5 mol %) in DMA at 150 °C. This catalyst precursor is known to efficiently promote the direct coupling of 5-membered ring heteroarenes with aryl halides [25]. Cs2CO3 and K2CO3 proved to be totally inefficient bases, while acetate bases gave the desired

• 1,8-dibromonaphthalene, 1,3-dichlorobenzene led to 7,9-dichlorofluoranthene (15) with a yield of 38%. We have previously described the reaction of 1,8-dibromonaphthalene with some heteroarenes such as 2-methylthiophene in the presence of a palladium catalyst for the synthesis of acenaphtho[1,2-d

• ]thiophenes [25]. In these reactions, the C–H bonds at the C2 and C3 positions of the thienyl unit were functionalized. In order to obtain acenaphtho[1,2-c]thiophenes and related compounds that are not easily accessible [33][34][35][36][37][38], we investigated the reactivity of three 5-membered heteroarenes

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• and colleagues achieved a significant breakthrough by sequentially unveiling a series of decarboxylative alkylation reactions involving heteroarenes 22, enamides 24, N-arylglycine derivatives 26, and silyl enol ethers 28 [21][22]. Notably, these transformations were accomplished using only a catalytic

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• carboxylation of acidic arenes and heteroarenes has been reported by Cazin, Nolan and co-workers [90]. In this context, it was found that a combination of [(IPr)CuOH] (3 mol %) with CsOH in THF afforded the best results (Scheme 68), whereas the SIPr, IMes, and SIMes-based NHC–Cu complexes were found to be less

• isomerization-induced alkenylation of electron-rich heteroarenes 187 and 188 utilizing allyl halides as reactants. The same catalyst system was found to effectively promote double-bond migration of the initially formed allylarenes resulting in vinylarene products. This method has been successfully used to

• functionalities, applicability to a wide range of heteroarenes and allyl halides, and high stereoselectivity (Scheme 71). The enantioselective C(sp2)–H allylation of (benz)oxazoles and benzothiazoles with γ,γ-disubstituted primary allyl phosphates catalyzed by NHC–Cu(I) complexes was reported by Ohmiya, Sawamura

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• in functionalizing unactivated C(sp3)–H substrates, including ethers [109][110][111][112][113][114]. In 2018, Wang et al. reported the photocatalytic CDC α-alkylation of N-heteroarenes in acetone solution, using noble-metal Ir as a photocatalyst to induce the reaction (Scheme 41) [115]. Subsequently

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

• enabling controlled bond activations [45]. Regarding the reductive C–C arylation, the application of the xanthene dye rhodamine 6G (Rh-6G) as a catalyst for the reduction of heteroarenes bearing two or three bromine atoms (e.g., 6) under irradiation with green light (λ = 530 nm) gave monosubstituted

Pyridine C(sp²)–H bond functionalization under transition-metal and rare earth metal catalysis

• Haritha Sindhe,
• Malladi Mounika Reddy,
• Karthikeyan Rajkumar,
• Akshay Kamble,
• Amardeep Singh,
• Anand Kumar and
• Satyasheel Sharma

Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• alkenyl heteroarenes [61]. The aza-enolates were trapped with various Michael acceptors such as unsaturated ketones, esters, and amides (Scheme 25) [62]. The authors noted a strong substrate dependence of this process. The trapping reaction worked best with benzoxazole-derived substrate, while thiazole

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• allene 14, giving a boryl diene 16. A Cope rearrangement of the boryl diene 16 followed by transborylation gave the dienyl boronic ester 18 and regenerated the catalyst (Scheme 5). Chang reported the alkoxide-promoted hydroboration of N-heteroarenes with HBpin, the first explicit example of a B‒N/B‒H

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

• ethers and N-heteroarenes by using a novel catalytic system based on sodium iodide (NaI) and triphenylphosphine (PPh3), suggested to function as an electron donor–acceptor (EDA) complex [55][56][57][58][59][60]. Compared to previously reported radical reactions, this novel catalytic system has the key

B–N/B–H Transborylation: borane-catalysed nitrile hydroboration

• Filip Meger,
• Alexander C. W. Kwok,
• Franziska Gilch,
• Dominic R. Willcox,
• Alex J. Hendy,
• Kieran Nicholson,
• Andrew D. Bage,
• Thomas Langer,
• Thomas A. Hunt and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2022, 18, 1332–1337, doi:10.3762/bjoc.18.138

• transborylation (a σ-bond metathesis turnover method) has been used for borane-catalysed reductions of N-heteroarenes [28][29], and the borane-catalysed cyanation of enones [30]. Applying B–N/B–H transborylation to the hydroboration of nitriles would enable the development of a borane-catalysed hydroboration of

Synthesis of α-(perfluoroalkylsulfonyl)propiophenones: a new set of reagents for the light-mediated perfluoroalkylation of aromatics

• Durbis J. Castillo-Pazos,
• Juan D. Lasso and
• Chao-Jun Li

Beilstein J. Org. Chem. 2022, 18, 788–795, doi:10.3762/bjoc.18.79

• of these reagents as late-stage functionalization agents [26][27]. For a trend in reactivity, a more comprehensive scope of arenes and heteroarenes has been explored with the innate trifluoromethylation methodology previously reported by our group [10]. Conclusion In summary, we have successfully

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• summarizing recent relevant literature reports. Keywords: annulation; cyclization; fused indoles; regioselectivity; SEAr; Introduction Over the decades, countless cyclization and annulation reactions of substituted arenes/heteroarenes involving an electrophilic aromatic substitution (SEAr) reaction as the

• or annulation of: (A) substituted arenes/heteroarenes and (B) 3,5-unsubstituted, 4-substituted indoles. Indole C3 regioselective intramolecular alkylation of indolyl allyl carbonates. Indole C3 regioselective Michael-type cyclization in the total synthesis of (−)-indolactam V. Synthesis of azepino

Recent advances and perspectives in ruthenium-catalyzed cyanation reactions

• Thaipparambil Aneeja,
• Cheriya Mukkolakkal Abdulla Afsina,
• Padinjare Veetil Saranya and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 37–52, doi:10.3762/bjoc.18.4

• ruthenium complexes which are efficient as catalysts elevated the scope of this metal in synthetic organic chemistry. For clarity and ease of understanding of the topic, this review is categorized into four sections: cyanation of amines, cyanation of arenes and heteroarenes, photocatalyzed cyanation, and

• such as piperidine, tetrahydroisoquinoline derivatives, and pyrrolidine were also tolerated well in this reaction. The use of the non-toxic and inexpensive acetone cyanohydrin makes this method more advantageous compared to the known methods. 2 Cyanation of arenes and heteroarenes 2.1 Cyanation of

• arenes and heteroarenes using heterogeneous catalysts In 2012, a novel strategy for the 3-cyanation of indole in the presence of Ru(III)-exchanged NaY zeolite (RuY) was reported [36]. In this reaction K4[Fe(CN)6] was utilized as the cyano source in DMF at 110 °C. The Cu(OAc)2 and O2 (1 atm) was found

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

• heteroarenes were all well-tolerated; however, monosubstituted aryl rings suffered from low regioselectivity which is in accordance with HAS-type reactions [138]. In 2020, the Wu group expanded on the radical cyclization chemistry of γ,δ-unsaturated oxime esters, describing a carbonylative cyclization with

Me₃Al-mediated domino nucleophilic addition/intramolecular cyclisation of 2-(2-oxo-2-phenylethyl)benzonitriles with amines; a convenient approach for the synthesis of substituted 1-aminoisoquinolines

• Krishna M. S. Adusumalli,
• Lakshmi N. S. Konidena,
• Hima B. Gandham,
• Krishnaiah Kumari,
• Krishna R. Valluru,
• Satya K. R. Nidasanametla,
• Venkateswara R. Battula and
• Hari K. Namballa

Beilstein J. Org. Chem. 2021, 17, 2765–2772, doi:10.3762/bjoc.17.186

• have always been recognized as the frameworks of interest in organic and medicinal fields. Particularly, aza-heteroarenes have attracted burgeoning interest in the research community owing to their structural and biological significance [1][2][3][4]. The isoquinoline template represents a huge family

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• reagent (N-bromophthalimide) plays a crucial role in achieving the excellent selectivities [43]. The axially chiral biaryl-2-amines, N-heteroarenes [44] and derivatives are ubiquitous structural motifs and have profound applications in biochemistry and asymmetric catalysis [45]. These chiral biaryls can