Nucleophilic functionalization of thianthrenium salts under basic conditions

• Xinting Fan,
• Duo Zhang,
• Xiangchuan Xiu,
• Bin Xu,
• Yu Yuan,
• Feng Chen and
• Pan Gao

Beilstein J. Org. Chem. 2024, 20, 257–263, doi:10.3762/bjoc.20.26

• regioselectivity. Significant advancements in the synthesis of arylthianthrenium salts have prompted a growing interest in their utilization as versatile precursors for the conversion of C–H bonds in arenes into C–C/X bonds through transition-metal-catalyzed cross-coupling processes [12][13][14][15][16][17][18][19

• -stage C–H functionalization of arenes, Wickens’s group has introduced an oxidative alkene aziridination strategy that relies on thianthrenation of an alkene under electrochemical conditions [27]. Subsequently, cyclopropanation, [28] aziridination, [29] allylic C–H functionalization, [30][31] transition

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

• important auxiliary group for the proximal C–H activation with the efforts of Daugulis [5] and others [6]. Results from medical research indicated that the introduction of halogen atoms into quinoline motifs has positive effects on their bioactivities, such as antimalarial, antitumor, and so on [7

• quinoline ring of 1a in this reaction. Other competitive site-selective C–H bromination products and multiple brominated products were not observed. Subsequently, the bromination reaction was examined with various catalysts such as CoCl2·6H2O, Ni(OAc)2·4H2O, MnSO4·H2O, CuCl, CuBr, CuCl2, CuBr2, and Cu(OAc)2

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• researchers efficiently conducted palladium-catalyzed C–H activated annulation reactions, involving oxanorbornadiene derivative 26 and aryl bromides including dibromoanthracene 27 [38]. Subsequent aromatization reactions were then carried out, resulting in the successful synthesis of the target POAs with high

• )2C6H3, (c) H), followed by aromatization in acidic conditions, resulted in the formation of three [3]naphthalene regioisomers 43a–c, 44a–c, and 45a–c with excellent yields of up to 94%. The synthesized PAHs 43a, 44a, and 45a with diverse geometries exhibited interesting absorption and emission

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• , C–H insertion products 9 were also observed. Thus, when reacting with indole, the product of carbenoid attack at position 3 (9a) was isolated along with target compound 6a. Introduction of a carbomethoxy group into this position of indole leads to the exceptional formation of the N–H insertion

• product 6b in high yield. The reaction with methyl pyrrole-2-carboxylate resulted in the isolation of only the C–H insertion product 9c in low yield. Similar reaction progress was observed in the case with imidazole, the product N–H insertion was observed only in trace amounts (according to NMR data of

• catalyst for obtaining the product of insertion into the NH bond of the heterocycle. An effort to obtain the N–H insertion product with dibenzoazepine proved fruitless. Instead, the product of insertion into the C–H bond of the activated benzene ring (9z) was isolated in moderate yield. The chemo- and

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

• active natural products. The direct functionalization of C–H bonds in enamides offers a convenient and versatile approach to access a wide range of functionalized enamides. In 2021, Fu and his colleagues successfully developed a novel method for the stereoselective alkylation of enamides 14 using iodine

• and colleagues introduced an interesting metal- and oxidant-free photocatalytic C–H alkylation method for coumarins 18 [17]. The method utilized triphenylphosphine and sodium iodide, along with readily available alkyl N-hydroxyphthalimide esters (NHPIs) 3 as the alkylation reagents (Scheme 10

• functionalized coumarin derivatives and related nitrogen-containing heterocycles, opening up exciting possibilities for their diverse applications in other fields. Similarly, the regioselective photodecarboxylative C–H alkylation of 2H-indazoles and azauracils using NaI/PPh3 as mediators and redox esters 3 was

Charge carrier transport in perylene-based and pyrene-based columnar liquid crystals

• Alessandro L. Alves,
• Simone V. Bernardino,
• Carlos H. Stadtlober,
• Edivandro Girotto,
• Giliandro Farias,
• Rodney M. do Nascimento,
• Sergio F. Curcio,
• Thiago Cazati,
• Marta E. R. Dotto,
• Juliana Eccher,
• Leonardo N. Furini,
• Hugo Gallardo,
• Harald Bock and
• Ivan H. Bechtold

Beilstein J. Org. Chem. 2023, 19, 1755–1765, doi:10.3762/bjoc.19.128

• given in Table 1. Raman spectra of both compounds were acquired off-resonance (Figure 1). Compound 1 presents the main peak at 1609 cm−1 assigned to C=C stretching from the chromophore, a peak of intermediate intensity at 1292 cm−1 assigned to C–H bending and ring stretching, and a less intense peak at

• spectrum being dominated by the peak at 1338 cm−1 (C–N stretching). The peak at 1272 (C–H bending and ring stretching), and the pair of peaks at 1586 and 1624 cm−1 are assigned to the C=C stretching mode [30]. Less intense peaks can be observed at 1186 (C–H bending), 1512 (perylene ring stretching), and

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• NMR spectrum in DMSO-d6 shows the presence of two methylpyrazole moieties (singlet signals of two methyl groups at 3.63 and 3.70 ppm, singlet signals of two CH protons of pyrazole rings at 7.81 and 7.84 ppm), a H–N–C–H fragment with trans-orientation of protons (two doublets at 9.87 and 7.50 ppm, 3J

Effects of the aldehyde-derived ring substituent on the properties of two new bioinspired trimethoxybenzoylhydrazones: methyl vs nitro groups

• Dayanne Martins,
• Roberta Lamosa,
• Talis Uelisson da Silva,
• Carolina B. P. Ligiero,
• Sérgio de Paula Machado,
• Daphne S. Cukierman and
• Nicolás A. Rey

Beilstein J. Org. Chem. 2023, 19, 1713–1727, doi:10.3762/bjoc.19.125

• -withdrawing nitro substituent in hdz-NO2 makes the intramolecular H-bond stronger. Regarding lattice organization, both structures exhibit stacked motifs. In hdz-CH3, the planes were organized by C–H···O non-conventional H-bonds comprising the methoxy groups (Figure 2B). In the columns, there are

• ), it becomes possible to calculate the contribution of each type of intermolecular interaction to the whole profile [44]. In our case, results show that the sum of π···π and C–H···π contacts comprises almost 20% of the Hirshfeld surface for both compounds. The curvedness maps were also plotted over the

• located from the electron density maps and anisotropically refined. C–H hydrogens were ride over the parent carbon with H(Uiso) = 1.2 or 1.5 C (Ueq). N–H and O–H hydrogens were located from the difference maps and isotropically refined using adequate restrains. Disordered nitro group oxygen in hdz-NO2 was

Decarboxylative 1,3-dipolar cycloaddition of amino acids for the synthesis of heterocyclic compounds

• Xiaofeng Zhang,
• Xiaoming Ma and
• Wei Zhang

Beilstein J. Org. Chem. 2023, 19, 1677–1693, doi:10.3762/bjoc.19.123

• AMYs B1 which then were reacted with nucleophiles to form C–H-functionalized pyrrolidines or subjected to the 1,3-dipolar cycloaddition with olefins to afford bicyclic compounds (Scheme 2A and B) [59][60]. We employed cyclic amines for the synthesis of spirooxindole-pyrrolidines 7a or 7b in good

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• of the chemical versatility of the hydroxy moiety (Scheme 15). Site-selective radical C–H activation has been proven to be a useful tool to functionalize relatively inert polymer backbones and upcycling of polymer waste (cf. section 4) [118][119]. Radical chain-end modification as a highly specific

• , such as organic peroxides, hydrogen peroxide, persulfates undergo homolysis of O–O bonds generating radicals that can break C–H bonds followed by a hydrogen abstraction reaction. Phenolic compounds can be oxidized by molecular oxygen in the presence of laccase, and the resulting phenolic radical reacts

C–H bond functionalization: recent discoveries and future directions

• Indranil Chatterjee

Beilstein J. Org. Chem. 2023, 19, 1568–1569, doi:10.3762/bjoc.19.114

• Indranil Chatterjee Department of Chemistry, Indian Institute of Technology Ropar, Nangal Road, Rupnagar, Punjab 140001, India 10.3762/bjoc.19.114 Keywords: C–H bond functionalization; The process of C–H bond functionalization can be defined as the replacement of an activated or nonactivated C−H

• well as famous Noble-prize-winning cross-couplings, therefore approaching another step up towards sustainability. Likewise, a free-radical process is also a classical way to functionalize nonactivated C−H bonds in which site selectivity arises either from the relative strength of the C−H bonds or from

• the abstraction of intramolecular hydrogen atoms. Radical chemistry is a viable alternative to the two-electron process, involving C–H bond functionalization in the absence of any ligand and using low-cost redox-active metals (Fe, Cu, Mn, etc.) rather than heavy metals (Rh, Ir, etc.). Although radical

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

• developed to prepare isoxazole derivatives [10][11][12][13]. However, most of the starting materials for these methods are oximes and hydroximinoyl chlorides [4][13][14][15]. Recently, the sp3 C–H bond functional group transformation of 2-methylquinoline derivatives into isoxazole derivatives has been

• 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

Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials

• Jessica Villegas,
• Bryce C. Ball,
• Katelyn M. Shouse,
• Caleb W. VanArragon,
• Ashley N. Wasserman,
• Hannah E. Bhakta,
• Allen G. Oliver,
• Danielle A. Orozco-Nunnelly and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108

• most streamlined method involves a copper-promoted Pictet–Spengler-type cyclization with glyoxal, with oxidative aromatization at the 8-position (Scheme 1) [30][35]. A recent report suggested a mechanistic role of Cu2+ involving C–H activation [36]; however, it is known that this reaction proceeds

Unraveling the role of prenyl side-chain interactions in stabilizing the secondary carbocation in the biosynthesis of variexenol B

• Moe Nakano,
• Rintaro Gemma and
• Hajime Sato

Beilstein J. Org. Chem. 2023, 19, 1503–1510, doi:10.3762/bjoc.19.107

• hyperconjugative interactions, through-space interactions, and C–H–π interactions, have been intensively investigated by Tantillo and co-workers, who have contributed greatly to revealing the intriguing nature of carbocations [7][19][20]. We have also elucidated various new insights of carbocation chemistry, such

• as the C–H–π interaction between the carbocation intermediate and the Phe residue of terpene cyclase in the biosynthesis of sesterfisherol [21], and the intricated rearrangement reaction mechanism promoted by the equilibrium state of the homoallyl cation and the cyclopropylcarbinyl cation in the

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• functional materials and indispensable synthetic intermediates in drug discovery [31][32][33]. Because of their value, constructing C–S bonds has attracted significant attention via metal-catalyzed cross-coupling reactions and metal-free C–S bond formation [34][35][36][37]. Direct sulfenylation of the C–H

• of aryl sulfides by using the catalyst and the base. A catalytic cycle is shown in Scheme 4. Firstly, electrophilic Pd(TFA)2 generated from Pd(OAc)2 and TFA, which (by C–H functionalization of arene 4) led to intermediate II. Oxidative insertion of intermediate II into the N–S bond of 1 afforded

• intermediate III. Reductive elimination of Pd from III gave product 5 and species IV. Finaly, Pd(II) species were reproduced by ligand exchange to restart the next cycle (Scheme 4). In 2014, Fu and co-workers described a facile method for the C–H thiolation of phenols 7 with 1-(substituted phenylthio

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

• on C1 enhancing its nuceophilicity (Figure 9). The Mulliken charge, obtained from the NBO calculations, was found to be almost double at the C–H atom in the complexed alkyne (−0.294) as compared to the free alkyne (−0.129). Furthermore, as depicted in Figure 10, the HOMO–LUMO energy gap in the NHC–Cu

• and the use of a ketone was necessary to induce C–H functionalization selectivity in preference to C=C functionalization. The products were obtained in moderate to high yields (Scheme 67). 2.6 N–H and C(sp2)–H carboxylation The application of the [(IPr)CuOH] complex as catalyst for the N–H/C(sp2)–H

• effective. This method afforded the products with high selectivity and it could be extended to a variety of substrates, such as benzoxazole, benzothiazole, oxazole, and even acidic hydrocarbons and aniline. Fukuzama and co-workers [91] accomplished the C–H carboxylation of benzoxazole and benzothiazole

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Organic thermally activated delayed fluorescence material with strained benzoguanidine donor

• Alexander C. Brannan,
• Elvie F. P. Beaumont,
• Nguyen Le Phuoc,
• George F. S. Whitehead,
• Mikko Linnolahti and
• Alexander S. Romanov

Beilstein J. Org. Chem. 2023, 19, 1289–1298, doi:10.3762/bjoc.19.95

• identical molecular peak ion and C, H, N values within acceptable deviation of 0.4%. The decomposition temperature (Td, corresponds to 5% weight loss) was measured by thermogravimetric analysis (TGA) indicating excellent thermal stability for 4BGIPN with Td = 425 °C, which is similar to the benchmark

• to ride on their parent atoms with C–H = 0.95–1.00 Å, and Uiso = 1.2–1.5 Ueq (parent atom). All calculations were performed using the SHELXL software and Olex2 graphical user interface [22][23]. 4BGIPN (monoclinic P21), CCDC number 2243340, C60H32N14, monoclinic, space group P21 (no. 4), a = 17.4217

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

• become a major strategy for ether functionalization. This review covers C–H/C–H cross-coupling reactions of ether derivatives with various C–H bond substrates via non-noble metal catalysts (Fe, Cu, Co, Mn, Ni, Zn, Y, Sc, In, Ag). We discuss advances achieved in these CDC reactions and hope to attract

• 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

• significantly different reactivity and chemical selectivity from noble metals (Ru, Rh, Pd). Compared with noble metals, copper catalysts are cheaper and easier to obtain, making Cu more advantageous for industrial applications of C–H functionalization reactions. The Glaser–Hay reaction may be one of the oldest

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• alkyl C–H bond to a high valent iron oxo species, resulting in formation of iron hydroxo and alkyl radical intermediates [15]. Subsequent RLT of the hydroxo ligand to the alkyl radical produces a hydroxylated product, allowing for metabolism and excretion of previously diverse bioactive compounds

• behavior of P450 oxygenases encouraged early work on site-selective C–H functionalization [20]. Throughout their studies, it was found that manganese could perform the same HAT and RLT steps as iron at heme active sites. Groves developed the manganese tetramesitylporphine catalyst V (Scheme 2), which was

• found to be capable of functionalizing specific C–H bonds to numerous functionalities, including C–F [21][22], C–N3 [23], and C–Cl bonds [24][25]. Upon these remarkable observations, methodologies involving manganese–porphyrin catalysts have been developed over the years. These methods take advantage of

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

• 44, from which reductive elimination of iodobenzene would generate 40. In 2021, Sen and Gremaud disclosed a blue LED-mediated formal C–H insertion reaction between iodonium ylides (e.g., 31) and pyrroles (e.g., 45), indoles and furans, producing malonate-substituted heterocycles 46 (Scheme 9) [126

• ]. The authors discounted a free carbene-based C–H insertion because conducting the reaction in the presence of the radical trap phenyl N-tert-butyl nitrone (PBN) and the radical scavenger TEMPO resulted in decreased yields and isolation of their iodonium ylide adducts. Additional kinetic isotope effect

• iodobenzene then generated a strained, cyclopropane-fused bicycle 49 that rearranged into the isolated C–H insertion product 46a. In addition to Neiland’s disclosure of the reactions between iodonium ylides and hydrochloric acid (Scheme 1) [1][102], others have also reported that both strong acids (e.g., TsOH

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

• halides and the coupling products were obtained in good yields (52–74%) (Figure 4B). To suppress the rapid HAT with solvent DMF that yields the dehalogenated product, DMSO was chosen as solvent for the C–H arylation. When applying the catalytic protocol to 2-allyloxy-1,3,5-tribromobenzene, the 5-exo-trig

• for reductive dehalogenations (Figure 8A), C–H arylations and olefinations of aryl halides (Figure 8B) [51]. In addition to the classical conPET mechanism involving the formation of *AQN•−, the authors also confirmed formation of the semiquinone anion AQN-H− via formal addition of a hydrogen atom (e.g

• anion DCA•− generates *DCA•− as a super-reductant capable of reducing aryl bromides and chlorides [52]. Due to minimal overlap in the absorption spectral bands of DCA and DCA•−, a cold-white LED (λ = 410–700 nm) was used for polychromatic irradiation. The protocol for reductive C–H arylations with

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• stereoselectivity is also explained. Keywords: asymmetric; aza-Friedel–Crafts reaction; H-bonding; organocatalysis; stereoselectivity; Introduction The ease of a chemical transformation depends on the thermodynamic instability of a chemical bond owing to its fast cleavage under mild reaction conditions. A C–H

• bond is thermodynamically stable and possesses a high bond dissociation energy opposing the bond to easy chemical transformation. Therefore, harsh reaction conditions and the necessity of an external activator like catalysts are common prerequisites for processes involving C–H bond breaking. Among

• different types of C–H bonds, an aromatic C–H bond is even more inert rendering this type of bond functionalization more difficult. Herewith the term “bond functionalization” is defined as the cleavage of an existing bond with substitution by another bond. Aromatic C–H bond functionalizations have gained

Photoredox catalysis enabling decarboxylative radical cyclization of γ,γ-dimethylallyltryptophan (DMAT) derivatives: formal synthesis of 6,7-secoagroclavine

• Alessio Regni,
• Francesca Bartoccini and
• Giovanni Piersanti

Beilstein J. Org. Chem. 2023, 19, 918–927, doi:10.3762/bjoc.19.70

• Hz, 1H)], strongly indicating that this product is not the desired structure 6’ but the eight-membered cycloalkene structure 6, shown in Scheme 2. Based on these results and previous reports on the benzylic and allylic C–H bond functionalization enabled by metallaphotoredox catalysis [86], we propose

• a tentative mechanism (Figure 2). First, the radical cation I was generated via the oxidation of indole 5 by the excited Ir-based photocatalyst, followed by sequential regioselective proton transfer on the benzylic dimethylallyl unit C–H bond of the C4 side-chain, thereby generating II. Here, the

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

• of several methods for the synthesis of functionalized pyridines or their integration into an organic molecule, new methodologies for the direct functionalization of pyridine scaffolds have been developed during the past two decades. In addition, transition-metal-catalyzed C–H functionalization and

• rare earth metal-catalyzed reactions have flourished over the past two decades in the development of functionalized organic molecules of concern. In this review, we discuss recent achievements in the transition-metal and rare earth metal-catalyzed C–H bond functionalization of pyridine and look into

• the mechanisms involved. Keywords: C–H functionalization; heterocycles; pyridine; rare earth metal; transition-metal-catalyzed; Introduction Pyridine, one of the most important azaheterocyclic scaffolds, is found in a diverse range of bioactive natural products, pharmaceuticals, and functional