Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

Transition-metal-free synthesis of arylboronates via thermal generation of aryl radicals from triarylbismuthines in air

• Yuki Yamamoto,
• Yuki Konakazawa,
• Kohsuke Fujiwara and
• Akiya Ogawa

Beilstein J. Org. Chem. 2024, 20, 2577–2584, doi:10.3762/bjoc.20.216

• with halogen or triflate groups. Recently, transition-metal-catalyzed direct borylation of arenes via C–H bond activation has been reported, although the design of the substrate and ligands is somewhat complicated [16][17][18][19][20][21][22]. Since the complete removal of catalyst-derived metal

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• the potential for chemical non-innocence of fluorinated alcohol solvents in NGT catalysis. Keywords: aziridination; electrochemistry; H-bond activation; hypervalent iodine; nitrene transfer; Introduction Hypervalent iodine reagents find widespread application in selective oxidation chemistry due to

• the generality of H-bond activation of iminoiodinanes for direct aziridination, albeit with modest efficiency for some substrates. The impact of the iminoiodinane structure on the efficiency of HFIP-promoted direct aziridination was next investigated (Scheme 3). For this purpose, cyclopentene was

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

• palladium-catalyzed direct intermolecular arylation, followed by a direct intramolecular arylation step. As the C–H bond activation of several benzene derivatives remains very challenging, the preparation of fluoranthenes from 1,8-dibromonaphthalene via Suzuki coupling followed by intramolecular C–H

• reported [39][40]. The synthesis of fluoranthenes from 1,8-dibromonaphthalene via a double C–H bond activation of the arene used as coupling partner remains limited to specific arenes featuring an activated C–H bond. Consequently, we also investigated the access to fluoranthenes from 1,8-dibromonaphthalene

• , carbonyl or nitrile. Using the appropriate arenes, this synthetic route enables the desired functional groups to be introduced at positions 7 to 10 of fluoranthenes. The second method involves a Suzuki coupling followed by an intramolecular C–H bond activation step, and provides access to specific

Lewis acid-promoted direct synthesis of isoxazole derivatives

• Dengxu Qiu,
• Chenhui Jiang,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2023, 19, 1562–1567, doi:10.3762/bjoc.19.113

• the Lewis acid to realize the sp3 C–H-bond activation of nitrogen heterocycles to synthesize isoxazole derivatives. Results and Discussion At the outset of this study, we chose the reaction of 2-methylquinoline (2a) with phenylacetylene (1a) in the presence of AlCl3 (3 equiv) and sodium nitrite (10

• oxide E [23], which can be converted to the desired isoxazole with 1a through a 1,3-dipolar cycloaddition. Conclusion In conclusion, we have developed an efficient and concise synthesis of isoxazole nitrogen heterocycles by direct C–H-bond activation of methyl heteroaromatics. The method avoids using

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

• overcome the shortcomings of the above coupling reactions, organic chemists have envisaged the construction of C–C bonds directly through C–H bond activation [5]. Fortunately, scientists have used various transition metals as catalysts to realize the activation of various types of C–H bonds, and have

• unique catalytic behavior [89]. However, there are only a few examples of cobalt catalysis in CDC reactions. Limited by the activity of Co catalysts, there are few examples of Co-catalyzed reactions involving ether C(sp3)–H bond activation. The Co-catalyzed C(sp3)–C(sp3) CDC of glycine and peptide

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

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

• also found to have a higher catalytic activity for the ortho-alkylation of pyridines with styrenes to give the linear alkylated products (5b,c, Scheme 2). Further, the authors proposed that the C–H bond activation could be the rate limiting step based on kinetic isotope experiments (KIE). The proposed

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

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

• functionalization of C(sp2) and C(sp3) centers with SCF3, SeCF3, or OCH2CF3 groups among others, by C–H bond activation. The scope and limitations of these transformations are discussed in this review. Keywords: C–H bond activation; emergent fluorinated groups; homogeneous catalysis; organofluorine chemistry

• retrosynthetic disconnections. In this context, a strong interest from the scientific community was shown towards the challenging synthesis of fluorinated molecules by transition-metal-catalyzed C–H bond activation [44][45][46][47][48][49][50], allowing the functionalization of complex molecules and even for

• (e.g., SCF3, SeCF3, SCF2CO2Et, OCH2CF3) by transition-metal-catalyzed C–H bond activation (Scheme 1). The review will be organized in two main parts, dedicated to the construction of a C–SCF2R/SeCF3 and C–OCH2CF3 bond. This review does not aim to be exhaustive and key examples were carefully chosen to

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• review paper exploring several procedures of C–H bond activation for the functionalization of N-oxides [12] and in 2019, Dongli Li and co-workers analyzed heterocyclic N-oxides with regard to their usefulness in synthesis of organic drug molecules and catalysis [13]. Many review papers have been

Mechanochemical halogenation of unsymmetrically substituted azobenzenes

• Dajana Barišić,
• Mario Pajić,
• Ivan Halasz,
• Darko Babić and
• Manda Ćurić

Beilstein J. Org. Chem. 2022, 18, 680–687, doi:10.3762/bjoc.18.69

• dynamics of the formation of cyclopalladated intermediates In-I, LAG reactions of Pd(OAc)2 with L6–8 and TsOH were performed using 25 µL of MeCN as a liquid additive in a molar ratio of 1:1:1 (Ln/Pd(OAc)2/TsOH). In situ Raman monitoring of C–H bond activation was possible for L6 and L7, while in the case

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• , directing groups are introduced to the substrates covalently to achieve site-selective C–H bond activation, which prospered greatly in the past decades [7][8][9]. Template regulation is also introduced to locate reactive centers in a noncovalent way through hydrogen bonding [10][11][12]. Even though

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

•  2a). Suga and co-workers reported an electrochemical approach for P–H bond activation promoted by this reactive species, leading to the synthesis of several phosphacycles [24] (Figure 2b). Concomitantly with the development of our work, some photocatalytic strategies for DABCO activation emerged. Li

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

• and quinones through a dual H-bond activation mode to form the intermediate I-3, and aromatization with central-to-axial chirality transfer occurs to afford the axially chiral phenylindoles in good yield (76–92%) with good to excellent enantioselectivity (88–96% ee, Scheme 8a). The position and

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• by treatment with PCC/Celite in dichloromethane (DCM). Finally, treatment with a catalytic amount of CF3SO3H provided the corresponding anthracenes 30a–c in good yields (57–75%) [40]. Metal-catalyzed C–H bond activation In 2016, Hong’s group developed a synthetic strategy to generate substituted

• converted to the substituted anthracenes 109 and 110 by varying the acidic workup procedures. In addition, they prepared 9-chloro-10-phenylanthracene (112) in good yield (87%) through diol 111 [59]. Synthesis of substituted benzo[a]anthracene and dibenzoanthracene derivatives Metal-catalyzed C–H bond

• activation In 2009, Liang et al. reported an efficient and highly regioselective route to construct substituted tetracyclic benz[a]anthracene derivatives 115 (Scheme 26) [60]. For this purpose, the authors developed an efficient palladium-catalyzed tandem C–H activation/bis-cyclization reaction of

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

• synthetic methodologies is the C–H bond activation process that enables a straightforward access to several important and innovative compounds [14][15][16][17][18]. In the last few years, metals such as ruthenium [19][20][21], rhodium [22][23][24], palladium [25][26][27], and iridium [28][29][30] have been

• widely applied as catalysts for this matter, including in the synthesis of bioactive substances. Although catalysts based on these metals, are known to be efficient in C–H bond activation reactions affording the products in good yields and mild conditions, they are also known to be usually expensive

A recent overview on the synthesis of 1,4,5-trisubstituted 1,2,3-triazoles

• Pezhman Shiri,
• Ali Mohammad Amani and
• Thomas Mayer-Gall

Beilstein J. Org. Chem. 2021, 17, 1600–1628, doi:10.3762/bjoc.17.114

• . Later, carboxylate-ligand-assisted C–H bond activation takes place through a concerted metalation–deprotonation transformation to produce the next intermediate. Finally, the corresponding product 142 is formed by a reductive elimination process, along with the regeneration of the active catalytic

• '. The isocyanide is inserted into intermediate 158' to achieve intermediate 159'. A 1,2,3-triazole C–H bond activation occurs using palladium, which subsequently undergoes a reductive elimination process to afford final product 154. Likewise, the Pd(0) species is reformed for the next cycle [64]. The

Prins cyclization-mediated stereoselective synthesis of tetrahydropyrans and dihydropyrans: an inspection of twenty years

• Asha Budakoti,
• Pradip Kumar Mondal,
• Prachi Verma and
• Jagadish Khamrai

Beilstein J. Org. Chem. 2021, 17, 932–963, doi:10.3762/bjoc.17.77

• enantioselectivity varied with the polarity of the solvent. The optimization study disclosed that the enantioselectivity increases with the decrease of the polarity of the solvent (Scheme 68). Yu and co-workers reported a novel segment-coupling Prins cyclization involving sequential benzylic/allylic C–H bond

• activation via DDQ oxidation, followed by nucleophilic attack of an unactivated olefin to obtain all-cis-trisubstituted Prins products with high stereochemical precision [111]. A single-electron transfer (SET) mechanism was proposed for the above transformation (Scheme 69). A SET from an arene or alkene to

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

• catalysis and photochemistry. Where transition metal catalysis provides one strategy for C–H bond activation, transition-metal-free photochemical C–H fluorination can provide a complementary selectivity via a radical mechanism that proceeds under milder conditions than thermal radical activation methods

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

• last decade particular attention has been focused on two modern fields, C–H bond activation, and visible-light-induced photocatalysis. Couplings through C–H bond activation involve the use of non-prefunctionalized substrates that are directly converted into more complex molecules, without the need of a

• , isolated in moderate to good yields. A possible gram scale-up synthesis was also accomplished. Within the mechanistic cycle, after initial vinylic C–H bond activation and insertion of CO into the C–Pd bond, the acylpalladium intermediate is converted into its conjugated analog under DABCO assistance

• features when working with biological systems. Thus, a variety of functionalized purines nucleosides that are potentially of great importance in medicinal chemistry were obtained in good yields. In contrast to C(sp2)–H bonds, C(sp3)–H bond activation is much more challenging. Inspired by the potential of

In silico rationalisation of selectivity and reactivity in Pd-catalysed C–H activation reactions

• Liwei Cao,
• Mikhail Kabeshov,
• Steven V. Ley and
• Alexei A. Lapkin

Beilstein J. Org. Chem. 2020, 16, 1465–1475, doi:10.3762/bjoc.16.122

• : https://github.com/sustainable-processes/Pd-catalysed_C-H_activation_reaction_prediction. Results and Discussion Computational approach to rationalise reactivity in Pd-catalysed C–H bond activation reactions Chemical reactivity is simultaneously influenced by many factors including catalysts, reactants

Synthesis of esters of diaminotruxillic bis-amino acids by Pd-mediated photocycloaddition of analogs of the Kaede protein chromophore

• Esteban P. Urriolabeitia,
• Pablo Sánchez,
• Alexandra Pop,
• Cristian Silvestru,
• Eduardo Laga,
• Ana I. Jiménez and
• Carlos Cativiela

Beilstein J. Org. Chem. 2020, 16, 1111–1123, doi:10.3762/bjoc.16.98

• literature [52][53][54][55][56][57][58][59]. The styryl fragment bonded to an oxazolone ring has not been characterized previously by X-ray methods, but it shows internal bond distances and angles similar to those found in related 2-styrylimidazolone species [60]. C–H Bond activation processes on (Z)-4

• ], did not produce the expected cyclobutanes or gave only very low conversions (<5%) after long reaction times (96 h). As this reactivity was poor, it was decided to attempt the reaction using Pd complexes as templates [28][29][30]. The first step in this process was to study the C–H bond activation in

• factors, namely the presence of bulky CF3 and NO2 groups in ortho positions of the starting oxazolones 2e and 2i, and the strongly deactivating effect of the two groups on the C–H bond activation process. The reactions were usually carried out using 0.6 mmol of the starting material 2. In this respect, it

Bipyrrole boomerangs via Pd-mediated tandem cyclization–oxygenation. Controlling reaction selectivity and electronic properties

• Liliia Moshniaha,
• Marika Żyła-Karwowska,
• Joanna Cybińska,
• Piotr J. Chmielewski,
• Ludovic Favereau and
• Marcin Stępień

Beilstein J. Org. Chem. 2020, 16, 895–903, doi:10.3762/bjoc.16.81

• measurements show that helicene-like boomerangs may be usable as circularly polarized luminescent materials. Keywords: donor–acceptor systems; double C–H bond activation; helicenes; pyrroles; Introduction Nanographenes and other polycyclic aromatics as well as their heterocyclic analogues are typically

• disadvantage may be obviated by transition-metal-mediated double C–H bond activation [22][23], which is functionally equivalent to conventional oxidative coupling reactions, and has become a powerful synthetic tool with a rapidly growing scope of use [24][25][26]. However, in the field of π-conjugated

• (NDA) and naphthalenemonoimide (NMI) moieties. The double C–H bond activation initially used palladium(II) acetate in acetic acid as the coupling system. The subsequent screening revealed, however, that a catalytic coupling could be also achieved in the presence of silver(I) carbonate as the

Synthesis of C₇₀-fragment buckybowls bearing alkoxy substituents

• Yumi Yakiyama,
• Shota Hishikawa and
• Hidehiro Sakurai

Beilstein J. Org. Chem. 2020, 16, 681–690, doi:10.3762/bjoc.16.66

• equilibrium between the Pd(IV) intermediates through C–H bond activation. Keywords: buckybowl; C70; rearrangement through C–H bond activation; Introduction The study of buckybowls, the bowl-shaped π-conjugated aromatic hydrocarbons corresponding to the fragments of fullerenes, pioneered by the works on

• succeeded in synthesizing three different alkoxy-substituted C70-fragment buckybowls 5a–c. In particular, 5c was not an intended molecule, but was formed unexpectedly through the rearrangement through the Pd-catalyzed C–H bond activation reaction. The X-ray crystal structure analysis of 5a–c clearly