Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• fluoride product (Table 1, entry 9). Although representing a considerable drop in efficiency compared to using 1.25 equiv of BT-SCF3, this observation provides an interesting insight into the reaction mechanism (vide infra). Changing the solvent from DCM to THF or MeCN resulted in no significant change in

• , replacing the benzylamine coupling partner with phenylalanine methyl ester provided dipeptide 5t in 67% yield (Scheme 3b). With the scope of the deoxyfluorination process established, our attention turned to an investigation of the reaction mechanism (Scheme 4). As demonstrated in our previous work

Ortho-ester-substituted diaryliodonium salts enabled regioselective arylocyclization of naphthols toward 3,4-benzocoumarins

• Ke Jiang,
• Cheng Pan,
• Limin Wang,
• Hao-Yang Wang and
• Jianwei Han

Beilstein J. Org. Chem. 2024, 20, 841–851, doi:10.3762/bjoc.20.76

• -positions to the ester group were all well-tolerated (Table 3). To gain further insights into the reaction mechanism, we conducted control experiments. Given the utility of diaryliodonium salts in radical chemistry, we introduced 2 equivalents of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) or 2 equivalents

• tested in the reaction under the standard conditions, however, product 3aa was not obtained. Based on the literature known results and the experimental evidences [35][36], we proposed a plausible reaction mechanism (Scheme 2b). The reaction started with the formation of radical intermediate A from

• protocol enables the efficient formation of two chemical bonds in one pot, representing a valuable tool for the synthesis of polycyclic benzocoumarins. Our ongoing research endeavours are dedicated to explore the detailed reaction mechanism with the ultimate aim of broadening the scope and applicability of

Palladium-catalyzed three-component radical-polar crossover carboamination of 1,3-dienes or allenes with diazo esters and amines

• Geng-Xin Liu,
• Xiao-Ting Jie,
• Ge-Jun Niu,
• Li-Sheng Yang,
• Xing-Lin Li,
• Jian Luo and
• Wen-Hao Hu

Beilstein J. Org. Chem. 2024, 20, 661–671, doi:10.3762/bjoc.20.59

• [32][33][34][35][36][37][59][60][61][62], upon the loss of dinitrogen. The radical I further adds to the terminal position of 1,3-butadiene (2a) to produce hybrid allylPd radical II, which would exist in equilibrium with π-allyl complex III. Following the classical Tsuji–Trost reaction mechanism, a

HPW-Catalyzed environmentally benign approach to imidazo[1,2-a]pyridines

• Luan A. Martinho and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2024, 20, 628–637, doi:10.3762/bjoc.20.55

• report from the literature [24] a plausible reaction mechanism is shown in Scheme 6. It involves the nucleophilic attack of the aminopyridine 1 to the HPW-activated carbonyl compound 2, followed by iminium ion formation (iii) and [4 + 1] cycloaddition with the isocyanide. A 1,3-hydrogen shift yields the

• scale-up of the HPW-catalyzed GBB reaction (5.0 mmol) between 2-aminopyridine (1a), 4-nitrobenzaldehyde (2a) and cyclohexyl isocyanide (3) in EtOH under μw heating. Plausible reaction mechanism for the HPW-catalyzed GBB reaction. Optimization of the reaction conditions.a Comparison of reaction

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• , rendering this protocol applicable for the chemoselective conversion of aromatic aldehydes to corresponding bis(indolyl)methanes in the presence of aliphatic aldehydes and ketones [81]. The proposed reaction mechanism for this protocol is showcased in Scheme 5. At the beginning of the reaction, the bromide

• electron-withdrawing substituents. The reaction mechanism is based on the activation of the carbonyl group by molecular I2, through the formation of a halogen bond, which lowers the LUMO of the carbonyl moiety, increasing its electrophilicity, and thus allowing the addition of the indole group (Scheme 7

• excellent yields (85–98%) in a more facile manner. The reaction mechanism is similar to other halogen-bond donor catalysts (Scheme 14). While the broad substrate scope is a crucial benefit of this approach, the use of a toxic solvent and the slow reaction rates were some of the drawbacks that would need to

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• Stern–Volmer constant (Ksv = 1146 M−1 with acid vs Ksv = 603 M−1 without acid). The reaction mechanism continues with the fragmentation of 33 into radical 34. From radical 34 the annulation reaction initiates via intermolecular radical addition, resulting in the formation of intermediate 35. After

Synthesis of spiropyridazine-benzosultams by the [4 + 2] annulation reaction of 3-substituted benzoisothiazole 1,1-dioxides with 1,2-diaza-1,3-dienes

• Wenqing Hao,
• Long Wang,
• Jinlei Zhang,
• Dawei Teng and
• Guorui Cao

Beilstein J. Org. Chem. 2024, 20, 280–286, doi:10.3762/bjoc.20.29

• 4aa [35] was isolated in 62% yield (Scheme 4). On the basis of the transformation of 3aa to 4aa, a tentative reaction mechanism is proposed. As shown in Scheme 5, the spiropyridazine-benzosultam 3aa was firstly oxidized to intermediate A. Next, an aziridine was formed with the hydrolysis of the amide

• regioselectivity. Comparision of previous work with this work. The effects of substituent groups on the [4 + 2] annulation reaction. Reaction conditions: 1 (1.0 mmol), 2 (1.5 mmol), Et3N (2.0 mmol), MeCN (10.0 mL), 25 °C, 2.0 h. Gram-scale synthesis of 3aa. The transformation of 3aa. The reaction mechanism of the

Unveiling the regioselectivity of rhodium(I)-catalyzed [2 + 2 + 2] cycloaddition reactions for open-cage C₇₀ production

• Cristina Castanyer,
• Anna Pla-Quintana,
• Anna Roglans,
• Albert Artigas and
• Miquel Solà

Beilstein J. Org. Chem. 2024, 20, 272–279, doi:10.3762/bjoc.20.28

• into the corresponding bis(fulleroid) product after 4 h of reaction (Figure S1 in Supporting Information File 1). Importantly, the observation of this intermediate represents an experimental proof of the proposed reaction mechanism. Confirmation that only one unit of 1a reacted with C70 in the reaction

•  1), unveiled the following reaction mechanism: initially, an oxidative coupling of the two alkyne moieties of our model 1a leads to the formation of INT 1, as previously reported [33]. This step, with a Gibbs energy barrier of 25.7 kcal·mol−1, is the rate-determining step for this process. Next, INT

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

• . Control experiments. Proposed reaction mechanism. Scale-up synthesis. Optimization of reaction conditions.a Supporting Information Supporting Information File 8: Experimental details and spectral data. Funding We gratefully acknowledge the financial support from the National Natural Science Foundation

Comparison of glycosyl donors: a supramer approach

• Anna V. Orlova,
• Nelly N. Malysheva,
• Maria V. Panova,
• Nikita M. Podvalnyy,
• Michael G. Medvedev and
• Leonid O. Kononov

Beilstein J. Org. Chem. 2024, 20, 181–192, doi:10.3762/bjoc.20.18

• structure and the reaction mechanism are the keys to understanding chemical reactivity and selectivity [65][66][67]. In the area of carbohydrate chemistry, a lot of efforts are devoted to finding relationships between the fine details of molecular structures of both glycosylation partners (glycosyl donor

Tandem Hock and Friedel–Crafts reactions allowing an expedient synthesis of a cyclolignan-type scaffold

• Viktoria A. Ikonnikova,
• Cristina Cheibas,
• Oscar Gayraud,
• Alexandra E. Bosnidou,
• Nicolas Casaretto,
• Gilles Frison and
• Bastien Nay

Beilstein J. Org. Chem. 2024, 20, 162–169, doi:10.3762/bjoc.20.15

• photooxygenation, Hock rearrangement and Friedel–Crafts reaction, which is supposed to proceed through aldehyde 3 (see further discussion below on the reaction mechanism). To complete this exploratory work, we envisaged to add an external aromatic nucleophile to the reaction mixture, namely 1,3,5-trimethoxybenzene

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

• gram-scale preparation was carried out using 1a, that afforded the desired product in 96% yield (Scheme 4, reaction 4). To gain more insight into the reaction mechanism, several control experiments were carried out (Scheme 5). On one hand, the failure of substrates 10–15 to participate in the reaction

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• generalizing the elucidated reaction mechanism to other [2 + 2] CA–RE reactions involving TCNE and TCNQ as electrophiles might be difficult. They emphasized the significance of considering a pre-equilibrium state of the charge-transfer complexes between the alkynes and alkenes and mentioned that the

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• derivatives. UV–vis spectra of substrates; [1a] 0.33 M, [2a] 0.11 M. Selected works for the construction of dihydropyrido[1,2-a]indolones and current methodology. Substrate scope of the cascade reaction. Radical trapping experiment. Plausible reaction mechanism. Optimization of reaction conditions.a

Photoinduced in situ generation of DNA-targeting ligands: DNA-binding and DNA-photodamaging properties of benzo[c]quinolizinium ions

• Julika Schlosser,
• Olga Fedorova,
• Yuri Fedorov and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 101–117, doi:10.3762/bjoc.20.11

• presence of the corresponding radical scavengers. As there is no obvious reaction mechanism for the direct formation of C-radicals upon irradiation of 3f it is proposed that the reaction of the initially formed hydroxyl radicals with the benzoquinolizinium 3f leads to the formation of the C-centered

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

• 20 Å) and a time step of 0.144 fs. We used the metadynamics technique to analyze the dimerization reaction mechanism [28][29][30]. The collective variable (CV) considered for the exploration of the free-energy surface was the coordination number of nine C atoms of one C60 (those that are involved in

Identification of the p-coumaric acid biosynthetic gene cluster in Kutzneria albida: insights into the diazotization-dependent deamination pathway

• Seiji Kawai,
• Akito Yamada,
• Yohei Katsuyama and
• Yasuo Ohnishi

Beilstein J. Org. Chem. 2024, 20, 1–11, doi:10.3762/bjoc.20.1

• strongly support our previous observation that AvaA7 showed a preference for NADPH as a cofactor [13][29]. In addition, CmaA6 could be an attractive target for understanding the reaction mechanism of ATP-dependent diazotase. CmaA6 could also be an ancestor for generating useful biocatalysts to synthesize

Construction of diazepine-containing spiroindolines via annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates

• Xing Liu,
• Wenjing Shi,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1923–1932, doi:10.3762/bjoc.19.143

• and proceeds through a by base-promoted annulation reaction of α-halogenated N-acylhydrazones and isatin-derived MBH carbonates. The reaction mechanism of this formal [4 + 3] annulation includes the in situ generated allylic ylide, nucleophilic substitution, Michael additon, and elimination processes

• cyclic 1,2-diazepine ring and the methylene unit is connected to the 3-positon of the oxindole moiety. On the basis of the current results and previous works [54][55][56][57][58][59][60][61], a reaction mechanism for the formation of the spiro[indoline-3,5'-[1,2]diazepines] has been proposed and is

• elimination of a proton and the Lewis base. Obviously, the spiro compounds 5 and 7 are formed by a similar reaction mechanism. Additionally, the method was applied to a gram-scale reaction of α-halogenated p-toluenesulfonylhydrazone 6c and MBH nitrile of isatin 2c under the standard conditions (Scheme 6). The

Controlling the reactivity of La@C₈₂ by reduction: reaction of the La@C₈₂ anion with alkyl halide with high regioselectivity

• Yutaka Maeda,
• Saeka Akita,
• Mitsuaki Suzuki,
• Michio Yamada,
• Takeshi Akasaka,
• Kaoru Kobayashi and
• Shigeru Nagase

Beilstein J. Org. Chem. 2023, 19, 1858–1866, doi:10.3762/bjoc.19.138

• 3a was confirmed by the SC-XRD analysis, which showed that the addition site of addendum was indeed at the C10 position of La@C2v-C82 (Figure 5). The La@C2v-C82 anion can act as an electron donor and a nucleophile. To confirm the reaction mechanism, charge density and the p-orbital axis vector (POAV

• , the C10, C14, and C18 atoms have larger spin densities (C10: 0.032, C14: 0.023, C18: 0.030) [34][35] than the C1 and C2 atoms (C1: 0.002, C2: 0.016) in La@C2v-C82 (Figure 6b). These results suggest that the reaction mechanism involving the electron transfer from the La@C2v-C82 anion to benzyl bromide

• derivatives followed by the radical coupling reaction is more plausible for the formation of the corresponding adducts rather than the SN2 reaction mechanism of the La@C2v-C82 anion with benzyl bromide derivatives. Conclusion The reaction of La@C2v-C82 anion with benzyl bromide derivatives 1 at 110 °C

Substituent-controlled construction of A₄B₂-hexaphyrins and A₃B-porphyrins: a mechanistic evaluation

• Seda Cinar,
• Dilek Isik Tasgin and
• Canan Unaleroglu

Beilstein J. Org. Chem. 2023, 19, 1832–1840, doi:10.3762/bjoc.19.135

• reaction mechanism of the presented method was studied on model reactions by electrospray-ionization time-of-flight (HRESI–TOF) mass spectral analysis in a timely manner. The analytical results indicated that the observed azafulvene-ended di- and tripyrrolic intermediates are responsible for the formation

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

• symmetry. The stereochemistry of the products was confirmed by X-ray crystal structure and NMR analysis. The reaction mechanism shown in Scheme 11 suggests that a semi-stabilized AMY 16 generated from the reaction of glycine and arylaldehydes undergoes a [3 + 2] cycloaddition with 14a via the favorable

• olefinic oxindoles to replace maleimides, the reactions gave spiro[indoline-tetrahydropyrrolothiazole] products 30 in 55–70% with greater than 4:1 dr [76]. The reaction mechanism suggests that the reaction of cysteine with arylaldehydes gives N,S-acetals 27 which convert to AMYs 28 after decarboxlyation

• -oriented synthesis (DOS) [82][83][84][85][86][87][88]. The work presented in this paper may also be helpful to understand the reaction mechanism and stereoselectivity of semi-stabilized N–H-type AMYs. We hope the new development for 1,3-dipolar cycloaddition chemistry can be used for the synthesis of

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

• . It was found that the desired product could be obtained in 87% yield (Scheme 4). Next, some control experiments were carried out to study the reaction mechanism. We found that the reaction of compound 3a could not be inhibited by TEMPO and BHT under the standard conditions. Therefore, it is assumed

• atmosphere, 90 °C, 24 h. Reaction substrate scope of quinolines. Conditions: 1a (0.1 mmol, 1 equiv), 2 (0.2 mmol, 2 equiv), AlCl3 (0.3 mmol, 3 equiv), NaNO2 (1 mmol, 10.0 equiv), DMAc (1.0 mL), N2 atmosphere, 90 °C, 24 h. Gram scale reaction. Control experiments and possible reaction mechanism. Optimization

Synthesis of 5-arylidenerhodanines in L-proline-based deep eutectic solvent

• Stéphanie Hesse

Beilstein J. Org. Chem. 2023, 19, 1537–1544, doi:10.3762/bjoc.19.110

•  2, entry 5). This observation demonstrates the positive role of proline on the reaction mechanism but clearly indicates that it is not sufficient. In fact, the exact role of DES in this reaction is still not clear as ʟ-proline may act as a catalyst via an iminium pathway as previously described [21

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

• offer many valuable insights from a fundamental organic chemistry perspective. The terpene cyclization cascade generally involves a multistep domino-type reaction. Therefore, it is challenging to reveal the detailed reaction mechanism solely by an experimental method. To address this issue

• 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

• aspects. First, this cyclization cascade involves a prenyl side chain that do not participate in the cyclization cascade. This type of terpene compounds has already been reported, such as santalene, bergamotene, mangicol, etc. The idea that the reaction mechanism changes due to differences in the prenyl

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

• 102 were obtained in moderate to excellent yields with good to excellent enantioselectivities (Scheme 42) [76]. It should be noted that the authors did not define the exact role of the organocatalyst in the reaction mechanism. Transition-metal-free C–H sulfenylation of electron-rich arenes 103 by N