Electron-beam-promoted fullerene dimerization in nanotubes: insights from DFT computations

• Laura Abella,
• Gerard Novell-Leruth,
• Josep M. Ricart,
• Josep M. Poblet and
• Antonio Rodríguez-Fortea

Beilstein J. Org. Chem. 2024, 20, 92–100, doi:10.3762/bjoc.20.10

• the reaction either via singlet excitation or via radical cation formation (Scheme 1). Estimation of the activation barrier for the [2 + 2] cycloaddition when the nanotube acts as a sensitizer is 33.5 ± 6.8 kJ mol−1. This value agrees with computational predictions for the reaction via an excited

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

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

• cycloadditions from bay regions of [N]phenylenes, metal-catalyzed cycloadditions with diphenylacetylene occurred exclusively in the non-bay region, which allowed for straightforward syntheses of curved structures. Moreover, the presence of methyl groups in the structure facilitated the controlled activation of

• -catalyzed formal [2 + 2] cycloaddition reactions but also the emergence of tetracene trimer 86 and tetramer 88 stemming from [2 + 2 + 2] cycloaddition reactions (Scheme 18). It is proposed that an aryne intermediate is formed after thermal activation and that the observed end products are formed from arynes

GlAIcomics: a deep neural network classifier for spectroscopy-augmented mass spectrometric glycans data

• Thomas Barillot,
• Baptiste Schindler,
• Baptiste Moge,
• Elisa Fadda,
• Franck Lépine and
• Isabelle Compagnon

Beilstein J. Org. Chem. 2023, 19, 1825–1831, doi:10.3762/bjoc.19.134

• ) activation functions for each layer. Two dropout layers are interleaved after the first and second hidden layers with a dropout setting of 25% to avoid over-fitting issues. The training objective is a classification task between the 4 monomer categories with a cross-entropy loss function. To account for the

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

• facilitated by the process of photoexcited radical decarboxylation. On the other hand, the copper catalytic cycle involved the capture of alkyl radicals by the copper complex B, the activation of heteroatom-containing substrates 30 by a base-mediated proton transfer, and the subsequent reductive elimination

Trifluoromethylated hydrazones and acylhydrazones as potent nitrogen-containing fluorinated building blocks

• Zhang Dongxu

Beilstein J. Org. Chem. 2023, 19, 1741–1754, doi:10.3762/bjoc.19.127

• activation [108][109][110]. Besides, pyrazolidine and pyrazoline compounds are highly valuable hereocycles which are found in many natural products and bioactive compounds. Among them, CF3-substituted pyrazolidines have already been shown to be highly bioactive [111][112][113]. Thus, Hu et al. chose

Benzoimidazolium-derived dimeric and hydride n-dopants for organic electron-transport materials: impact of substitution on structures, electrochemistry, and reactivity

• Swagat K. Mohapatra,
• Khaled Al Kurdi,
• Samik Jhulki,
• Georgii Bogdanov,
• John Bacsa,
• Maxwell Conte,
• Tatiana V. Timofeeva,
• Seth R. Marder and
• Stephen Barlow

Beilstein J. Org. Chem. 2023, 19, 1651–1663, doi:10.3762/bjoc.19.121

• reducing that for Y = cyclohexyl). Conversely, the combination of a strongly bound dimer and an acceptor with E(SC/SC•−) with the reach of E(1+/0.512), but sufficiently cathodic that ET is very slow, could permit activation of doping by an external stimulus, such as photoexcitation, when desired, for

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

• ATRP relies on the establishment of a reversible activation/deactivation equilibrium reaction between an alkyl halide or halide-like initiator (RX) and a radical species (R·) [43]. During the activation process, the organohalides quickly lose their terminal halogen atoms in the presence of the liganded

• deactivation process. Activation and deactivation reactions are always present throughout the process, and the rate of deactivation must be sufficiently high in order to maintain a low radical concentration to effectively inhibit the termination [44]. The mechanism of ATRP is shown in Scheme 5 [14]. Compared

• 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

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

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

• possibility of through-space interactions with prenyl side chains using DFT calculations. Our calculations show that (i) the unstable secondary carbocation is stabilized by the cation–π interaction from prenyl side chains, thereby lowering the activation energy, (ii) the four-membered ring formation is

• interacts with the secondary carbocation at C10, reducing the activation energy of the first step by approximately 4.7 kcal/mol. Moreover, due to the stabilization of the secondary carbocation-like intermediate IM2, the reaction proceeds stepwise rather than concertedly [7]. It was found that the final

• the stabilization of the intermediate IM2b is greater in path b, the activation energy suggests that path a is more favorable. Generally, the activation energies for terpene cyclization reactions are often below 10 kcal/mol. However, in the case of complex rearrangement reactions involving secondary

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

• and acetic acid (AcOH) as a Brønsted acid, whereas i(a)midation was achieved by using Pd(OAc)2 as catalyst and Cu(OAc)2 as a Lewis acid. A possible mechanism for this chemodivergent C–H activation is depicted in Scheme 16. First, Pd catalyzed the formation of palladacycle I. Oxidative addition of AcOH

• acid organocatalysts were evaluated for sulfenylation on C3, or C2 position of N-heterocycles 115, including indoles, peptides, pyrrole, and 1-methyl-1H-pyrrolo[2,3-b]pyridine. The authors hypothesized a mechanism for the activation of N-sulfanylsuccinimides 1 or 14 by conjugate Lewis base Brønsted

• Lewis base organocatalysts (Scheme 56) [88]. In this procedure, the cyclized products were obtained via the activation of the sulfur electrophile by a Lewis base to generate the thiiranium ion intermediate from the β,γ-unsaturated sulfonyl carboxamide. The attack of the sulfonamide nitrogen atom on this

Cyclization of 1-aryl-4,4,4-trichlorobut-2-en-1-ones into 3-trichloromethylindan-1-ones in triflic acid

• Vladislav A. Sokolov,
• Andrei A. Golushko,
• Irina A. Boyarskaya and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2023, 19, 1460–1470, doi:10.3762/bjoc.19.105

• ; indanones; trichloromethyl group; triflic acid; Introduction Superelectrophilic activation of organic compounds under the action of strong Brønsted and Lewis acids is an effective method for the synthesis of various carbocycles and heterocycles, and polyfunctional compounds (see books [1][2] and reviews [3

• conjugated enones afford O,C-diprotonated forms under superelectrophilic activation conditions. These dications can participate in electrophilic aromatic substitution reactions with arenes ([11] and references therein). Recently, we have shown that the reaction of (E)-5,5,5-trichloropent-3-en-2-one [Cl3CCH

• ). The second protonation of the C=C bond is hampered due to a strong acceptor character of the substituents, contrary to other more donating enones. As a continuation of the research on the electrophilic activation of electron-poor alkenes bearing two electron-withdrawing substituents at the C=C bond

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

• activation to generate an aryl–Cu–NHC species. This is followed by the reaction with NHC–Pd to produce an Ar–Pd(NHC)Cl intermediate through the oxidative addition to Pd(0)NHC. Finally, transmetallation of [(It-Bu)Cu(Ar)] with [(SIPr)Pd(Ar)Cl] followed by reductive elimination leads to biaryl product. No

Consecutive four-component synthesis of trisubstituted 3-iodoindoles by an alkynylation–cyclization–iodination–alkylation sequence

• Nadia Ledermann,
• Alae-Eddine Moubsit and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2023, 19, 1379–1385, doi:10.3762/bjoc.19.99

• nitrogen protection or activation using KOt-Bu in DMSO as a base. Under these conditions, the formation of the terminal (aza)indole anion is the driving force (Scheme 1) [34]. As a consequence, the electrophilic trapping of this intermediate with alkyl halides provides as concise access to N-substituted

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

• cesium cation with the halogen atom and the activation of the Sn–O bond of the stannylene acetal via a pentacoordinated intermediate with the fluoride anion [110]. The acetylation of the secondary alcohol and the deprotection of the primary alcohol with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ

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

• involved in the activation of DDQ by coordinating the carbonyl oxygen atom which leads to an increase in the oxidation activity of DDQ. Subsequently, Li et al. improved the above method, using a mixture of indium and copper salts as a catalyst, NHPI (N-hydroxyphthalimide) as a co-catalyst to achieve the

• . Due to the challenges associated with the activation of C(sp3)–H bonds, this kind of activation strategy has received extensive attention. Huang et al. developed a Cu-catalyzed CDC of unactivated C(sp3)–H ethers with simple ketones under the synergistic effect of CuBr2 and pyrrolidine. By this route

Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• self-aldol condensations, polymerization and Tishchenko-type processes) and stereoselectivity [20]; the activation of acetaldehyde via aminocatalysis, furthermore, suffers from a lack of proper steric hindrance for the enantio-discrimination process. However, some methodologies enabling the use of

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

• addition to alkenes and radical decarboxylation, with many of these being driven by light energy. RLT in alkene functionalization Outside of the realm of C–H activation, RLT has been leveraged to afford complex medicinal scaffolds in alkene difunctionalization. A recent example can be found in the merger

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

• ). Control experiments showed that the reaction failed in the dark at room temperature, and they concluded that blue light activation of the initially-formed EDA complex (analogous to 36) promoted the onset of SET events. As this latter protocol also required two equivalents of ylide 39, the authors proposed

• ]. Computational investigations were conducted to better understand these reactions, and it was determined that the changing alkyl motif (e.g., dimethyl, cyclopentyl, adamantyl) had minimal impact on the activation energy of the fluorination reactions. The reaction coordinate was calculated for Meldrum’s acid

• hard fluoride interacts with the stronger σ-hole. Structural modification of the β-dicarbonyl auxiliary has led to improved outcomes, due to increased ylide stability rather than decreasing activation energies of the fluorination reaction. There are, however, other conflicting pieces of evidence that

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

• generation of reactive intermediates for both oxidative and reductive processes via photon activation of a catalyst. Although this represents a significant step towards chemoselective and, more generally, sustainable chemistry, its efficacy is limited by the energy of visible light photons. Nowadays

• remain inert to direct photoredox activation powered by visible light [12]. Irradiation with UV photons that intrinsically possess higher energy, however, is generally unfavorable due to the high expense and thermal footprint of the reactors. Although most organic molecules directly absorb photons in the

• photoredox catalysts and ii) energy that parallels the energy of UV-driven transformations, but under cheaper, safer conditions and in a more selective manner by indirect substrate activation via a catalyst. These are: a) multi-photon processes that accumulate visible light photon energies for electron

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

• activation of the reaction components through H-bonding engagement with free hydroxy groups of the catalysts also favoring stereoselective addition (see structure 28 in Scheme 8a) [32]. Two years later, the same research group utilized the C1-symmetric catalyst P10 for the functionalization of the C3–H bond

• developed an aza-Friedel–Crafts reaction involving β-naphthols 119 as π-nucleophiles and benzothiazolimines 118 as electrophiles. Chiral squaramide S1-assisted this process affording enantioenriched 1-((benzothiazol-2-ylamino)methyl)naphthalen-2-ols 120 with high chemical yields. The activation of the

• ) [59]. Other catalysts In 2019, Vila, Pedro and co-workers reported a functional group-directed activation of the carbocyclic ring of indoles utilizing cyclic imines as electrophiles. The quinine-derived compound O1 was the catalytic reagent to functionalize the ortho-C–H bond of 4-, 5-, and 6

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

• ][64][65][66][67], we became fascinated in exploring whether photoredox catalysis could be applied for the activation of such unnatural amino acids to expedite the development of completely new synthetic pathways. In particular, 4-dimethylallyltryptophan (DMAT) is of interest for the following reasons

• cyclization event would be triggered using their innate functionality, namely the α-amino carboxylate, through photoredox-mediated oxidative activation and CO2 extrusion, without the need for acid prefunctionalization to the redox-activated ester. Consequently, a technique involving direct generation of α

Synthesis of aliphatic nitriles from cyclobutanone oxime mediated by sulfuryl fluoride (SO₂F₂)

• Xian-Lin Chen and
• Hua-Li Qin

Beilstein J. Org. Chem. 2023, 19, 901–908, doi:10.3762/bjoc.19.68

• the construction of a range of δ-olefin-containing aliphatic nitriles with (E)-configuration selectivity. This new method features wide substrate scope, mild conditions, and direct N–O activation. Keywords: direct N–O activation; E-selectivity; nitrile synthesis; ring-opening cross-coupling; sulfuryl

• ) carbon, which leads to side reactions of the alkyl intermediates [14][19][20]. Besides, most of the C(sp2)–C(sp3) reactions employ organic halides or organometallic reagents [21][22][23], which are not environmentally friendly. Recently, based on the activation effect of O-acyloximes on N–O bonds [24][25

• esters and adopted the pre-acylation activation strategies [39][40][41]. Up to now, only one report employed an oxime for the generation of iminyl radicals to obtain the similar products, in which, substrates were limited to the electron-rich alkenes (Scheme 2b) [42]. On the other hand, sulfuryl fluoride

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

• , diversely functionalized pyridines have been synthesized via C–H activation under transition-metal and rare earth metal catalysis, including C–H alkylation, alkenylation, arylation, heteroarylation, borylation, etc. Recently, metal-free approaches have also been developed for the C–H functionalization of N

• 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

• mechanism involves the coordination of pyridine to the metal center of the cationic catalyst and B(C6F5)3 promotes the ortho-C–H activation (deprotonation) of pyridine to afford pyridyl species 6. Next, the 2,1-migratory insertion of alkene 2 into the metal–pyridyl bond in 6 gives the intermediate 7, which

Eschenmoser coupling reactions starting from primary thioamides. When do they work and when not?

• Lukáš Marek,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2023, 19, 808–819, doi:10.3762/bjoc.19.61

• ) with activation free energies 47 and 59 kJ·mol−1 than from 4-bromo-1,1-dimethyl-1,4-dihydroisoquinolin-3(2H)-one (2b) and N-phenyl-2-bromo(phenyl)acetamide (4a) with activation free energies 78 and 88 kJ·mol−1. These trends fully correspond to a combination of electronic effects (bridging C=O has an

• the ring strain involved in the enthalpy term disfavors it) shows the opposite trend. This means that the activation free energies are decreasing from 47 to 23 kJ·mol−1, respectively. Spontaneous co-catenation (or thiophile-assisted when a P(III) compound is added) extrusion of sulfur from thiirane

• of these isomeric salts have the highest contributions to the overall barrier for Hantzsch reaction pathways because their cyclization through TS4 is very fast (activation free energies 5–15 kJ·mol−1). The overall (relative) energy barriers now decrease in the order 6a > 10a > 15 > 12a, which is