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

• co-workers reported Cu-catalyzed asymmetric electrochemical regiodivergent cross-dehydrogenative coupling of Schiff bases and hydroquinones (Figure 9) [58]. In this approach, a chiral copper complex was used as a Lewis acid catalyst, yielding various synthetic routes for synthesizing chiral amino

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• employing chiral Brønsted acid catalyst (S)-TRIP (118) (Scheme 25). In this approach, the racemic β-formyl amide forms the iminium intermediate that undergoes fast equilibration via the enamine tautomer to form preferentially one enantiomer which then undergoes the acid-catalysed aza-Cope rearrangement

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• , 3,4,5-substituted pyrazoles 5 are formed (Scheme 2) [45]. The Lewis acid catalyst accelerates the reaction via participation in the formation of β-diketonate complexes. Other carbonyl compounds suitable for pyrazole synthesis are 2,4-diketoesters 13. These intermediates can be prepared from diethyl

• pyrazole-4-carboxylates. Shen et al. used Yb(PFO)3 (PFO: perfluorooctanoate), a mild and highly efficient catalyst shown to be effective in the Mannich reaction [94], to synthesize these pyrazoles 65 (Scheme 21) [95]. The Lewis acid catalyst activates and stabilizes the enol tautomer of β-ketoesters

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• . Jung and Shinde, on the other hand, synthetized a supramolecular acid catalyst 14 combining β-cyclodextrins with succinic acid and tested it in a GBB reaction between isatin (15), indazol-3-amine (16) and pentyl isocyanide (17), yielding, after a ring expansion triggered by a retro-aza-ene reaction via

• -substituted products 60 underwent TFA-promoted deprotection which triggered the intramolecular cyclization to furnish the indole moiety in the desired products 61. A control experiment showed that the GBB product 60 was obtained as the sole product in the absence of acid catalyst. Another group developed the

Synthetic applications of the Cannizzaro reaction

• Bhaskar Chatterjee,
• Dhananjoy Mondal and
• Smritilekha Bera

Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120

• potentially useful molecules. Keywords: Cannizzaro reaction; crossed-Cannizzaro; desymmetrization; Lewis acid catalyst; natural products; Introduction The synthesis of functionalized molecules with structural complexity has always been a challenge to synthetic chemists. The Cannizzaro reaction, in its

• proceeded with more than 85% yield in all cases with clean conversion to the products (Scheme 10) [78]. The utility of neutral γ-alumina has been exploited as a polymeric Lewis acid catalyst in the Cannizzaro reaction of similar aromatic aldehydes 16. The conversion to the respective aromatic alcohols 17

Competing electrophilic substitution and oxidative polymerization of arylamines with selenium dioxide

• Vishnu Selladurai and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2024, 20, 1221–1235, doi:10.3762/bjoc.20.105

• mechanism for the formation of oxamide is shown in Scheme 6. Formation of acetanilide in the reaction of aniline and acetonitrile is known to occur in the presence of Lewis acid catalyst Al2O3 [55]. In our case, either SeO2 (Lewis acid) or H2SeO3 (Brønsted acid) may act as acid catalyst to convert aniline

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• 1883 and involves its synthesis from phenylhydrazine and an aldehyde or ketone using an appropriate acid catalyst [8]. In the following years, new processes were developed for the synthesis of indole such as the Castro, Bischler, and Larock synthesis etc. [2][9][10]. Carbonylation reactions represent a

Enhanced reactivity of Li⁺@C₆₀ toward thermal [2 + 2] cycloaddition by encapsulated Li⁺ Lewis acid

• Hiroshi Ueno,
• Yu Yamazaki,
• Hiroshi Okada,
• Fuminori Misaizu,
• Ken Kokubo and
• Hidehiro Sakurai

Beilstein J. Org. Chem. 2024, 20, 653–660, doi:10.3762/bjoc.20.58

• acid catalyst; thermal [2 + 2] cycloaddition; Introduction Chemical functionalization of fullerenes is a fascinating and extensively studied approach, playing a pivotal role in fullerene-based materials science to introduce various characteristic functionalities [1][2][3][4][5][6][7]. Significant

• approaches have diligently explored the details of reaction kinetics, quantitatively elucidating the impact of encapsulated Li+ on the reactivity of the outer fullerene cage as a specialized “encapsulated” Lewis acid catalyst [10][11]. While previous studies have revealed valuable insights, such as

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

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

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

• oxyalkylation product 28. Li and co-workers described the activation of NHPI esters towards SET using a Lewis acid catalyst, allowing for the functionalization of styrene radical acceptors with nucleophiles that do not necessarily engage in hydrogen-bonding interactions, such as electron-rich (hetero)arenes [47

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• chiral phosphoric acid as a Brønsted acid catalyst and Hantzsch ester as the hydrogen source, a series of 3,3-difluoro-substituted 3H-indoles underwent asymmetric transfer hydrogenation under mild reaction conditions, giving the target products with excellent yields and optical purity. Experimental

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

• efficient Lewis acid catalyst (Scheme 10) [50]. In the procedure, oxidative cleavage of one S–N bond and 1,2-sulfur migration afforded π-conjugated 6-substituted 2,3-diarylbenzo[b]thiophenes 16. A plausible mechanism is shown in Scheme 11. The coordination of AlCl3 with the phthalimide/succinimide unit of 1

• -thiolated pyrroles 61 and pyrrolines 62 from propargylic tosylamides 60 and N-thiosuccinimides 1 was described by Gao′s group (Scheme 25) [61]. When AlCl3 as the Lewis acid catalyst and nitromethane as the solvent were used, a series of 3-thiolated pyrrole products 61 were detected, and 3-thiolated

• tetrahydropyrans 88 (Scheme 36) [70]. In this protocol, by controlling acid catalyst (camphorsulfonic acid (CSA) or trifluoromethanesulfonic acid (TfOH)), two different products were achieved and tetrahydrofurans 87 could be converted to tetrahydropyrans 88 by stereoselective rearrangement. In the same year, Zhu

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

• of ethers to obtain symmetric and asymmetric 1,1-bis-indolylmethane derivatives (Scheme 23) [84]. The reaction proceeds through the tandem oxidative coupling of the C–O bond and cleavage of the C–H bond. Fe plays a dual role in catalysing the C–C bond coupling and C–O bond cleavage as Lewis acid

• catalyst. The authors demonstrated that the introduction of the two indoles occurs in two distinct steps, a radical process and a Friedel–Crafts alkylation reaction. Coumarin and flavonoid derivatives are very valuable precursors in drug synthesis. In 2015, Ge et al. developed the regioselective and atom

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

• acetaldehyde, which is hydrolyzed in situ using Amberlyst-15 as an acid catalyst, instead of directly using acetaldehyde allows for higher yields and fewer byproducts. Using mild reaction conditions, it was possible to obtain a variety of functionalized cyclohexene carbaldehydes in good yields and very high

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

• system. Like the classical Friedel–Crafts reaction, the aza-Friedel–Crafts reaction also requires the presence of a Lewis acid catalyst for rate acceleration. The reaction can be very easily modulated by different Lewis acidic metallic compounds which effectively form a coordinate bond by accepting the

• . Stereoselectivity in the products 10/11 was achieved by using the chiral spirocyclic phosphoric acid catalyst P3 which, through H-bonding interactions with the nucleophile and the electrophile, forces the nucleophile to approach the C=N plane from the Re face. In general, enantiocontrol with pyrroles was better

• pyrroles/indoles 4/9 allowing access to 2,3-dihydroisoxazoles 77/78 bearing an all-substituted stereocenter at the C3 position. A dual catalytic activity of the Brønsted acid catalyst was illustrated by the authors which was initiated with a smooth protonation of the OH group in 76 with a subsequnte

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• Clauson–Kaas reaction in a successive cyclization/annulation process from commercially available sulfonamides 14 in the presence of trifluomethanesulfonic acid (TfOH) as Brønsted-acid catalyst. This procedure produces only N-substituted products and preserves other positions open for further

• various substituted anilines, primary arylamides, and sufonylamides 20 and 2,5-DMTHF (2) in the presence of 10 mol % MgI2 etherate in MeCN at 80 °C (Scheme 9a). MgI2 etherate is a main-group Lewis acid catalyst that selectively activates electron-rich aromatic amines. This is a mild, efficient, and highly

• of N-substituted pyrroles using iron(III) chloride as a Lewis acid catalyst. These nitrogen-substituted pyrroles 33 were obtained in 74–98% yields by the reaction between various alkyl-, aryl-, sulfonyl- and aroylamines 32 with 2,5-DMTHF (2) in the presence of 2 mol % FeCl3∙7H2O as catalyst under H2O

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

• nickel Lewis acid catalyst with amino pendant linked NHC complex (Scheme 21). In addition, the authors were able to isolate the bimetallic intermediate structure η2,η1-pyridine–Ni(0)–Al(III) complex 112, as a support for their mechanism for the para-C–H functionalization. They further investigated the

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• analog 26 should also be a reactive dienophile [51], but is a less useful building block, as it reacts twice and the adducts will not be as easily desulfonylated. The dienophile 7 reacts with a wide range of dienes at room temperature, without the need for a Lewis acid catalyst. This is particularly

• give difficulties (Scheme 11a) [42]. The reactivity of the oxy-electrophiles can be enhanced by adding a Lewis acid catalyst such as titanium(IV) isopropoxide [59]. In this way, also epoxides can be smoothly reacted with lithiated dithiins, and both allyl and homoallyl alcohols can thus be prepared in

• alcohol 66 can be lithitated and reacted with a range of electrophiles, even without the need for a Lewis acid catalyst, and good levels of stereoinduction can be achieved. The method was used for the synthesis of a range of hexose sugars, as well as iminosugars (viz 66 → 67 → 68), wherein the piperidine

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• using acyl chloride 6b with an isobutyl side chain is its low volatility in contrast to the highly volatile compound 6a. The aza-Nazarov product 7b was isolated in 61% yield with 20 mol % of AgOTf at 80 °C (Table 1, entry 5). The use of TMSOTf as a Si-based Lewis acid catalyst with 20 mol % loading

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• ethanol). Brønsted acid catalysis by TsOH was also employed in a selective sulfoxidation employing PhI(OAc)2 as oxidant [69]. In this case another mode of catalysis was proposed, including the covalent bonding of the acid catalyst anion and the oxidant with the formation of PhI(OTs)OH as the catalytically

Supramolecular approaches to mediate chemical reactivity

• Pablo Ballester,
• Qi-Qiang Wang and
• Carmine Gaeta

Beilstein J. Org. Chem. 2022, 18, 1463–1465, doi:10.3762/bjoc.18.152

• capsule can catalyze the cyclization of (S)-citronellal forming isopulegol. In this study it was exploited the ability of the resorcinarene capsule to work as a Brønsted acid catalyst, and its aptitude to stabilize cationic intermediates and transition states inside the cavity. Velmurugan, Hu and co

Dienophilic reactivity of 2-phosphaindolizines: a conceptual DFT investigation

• Nosheen Beig,
• Aarti Peswani and
• Raj Kumar Bansal

Beilstein J. Org. Chem. 2022, 18, 1217–1224, doi:10.3762/bjoc.18.127

• acid catalyst, namely ethylaluminum dichloride [13]. Furthermore, when carrying out the reaction of compounds 1 (R1 = Me, R2 = COOMe, COOEt, COOCMe3) with DMB in the presence of the catalyst O-menthoxyaluminium dichloride, generated in situ, complete diastereoselectivity was observed. The DA reactions

Electrochemical Friedel–Crafts-type amidomethylation of arenes by a novel electrochemical oxidation system using a quasi-divided cell and trialkylammonium tetrafluoroborate

• Hisanori Senboku,
• Mizuki Hayama and
• Hidetoshi Matsuno

Beilstein J. Org. Chem. 2022, 18, 1040–1046, doi:10.3762/bjoc.18.105

• : electrochemical oxidation of amides/carbamates yielding α-methoxylated amides/carbamates (Shono oxidation, path c in Scheme 1) followed by the reaction of the isolated α-methoxylated amides/carbamates with arenes in the presence of a Lewis acid catalyst (path e in Scheme 1) [16]. Although the use of CH2Cl2 as a

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• requires the use of a solid acid catalyst [52], apart from the use of high-cost, high-end milling equipment which limits to laboratory scale only. Therefore, developing an operationally simple, environmentally benign protocol, potentially useful for the batch-scale synthesis of aryl halides is highly

• of the solid acid catalyst and the cost of high-end milling instruments are additional considerations for that method [52]. Conclusion In conclusion, we have developed a facile and sustainable mechanochemical route for the catalyst-free halogenation of phenol and aniline derivatives using N