Study of the interaction of 2H-furo[3,2-b]pyran-2-ones with nitrogen-containing nucleophiles

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2025, 21, 556–563, doi:10.3762/bjoc.21.44

• ). Apparently, for the realization of the presented condensation, the nucleophilicity of the aromatic amines is not sufficient. Wherein, the type of substituent in the aroyl fragment of furanone 1 doesn’t influence the result of this reaction. Thus, enamines 4 can be synthesized only using active aliphatic

• unsubstituted hydrazine. So, reflux of furanone 1a with hydrazine monohydrochloride in EtOH for 8 h resulted in a complex mixture of products (Scheme 5a). Taking into account the fact that the nucleophilicity of hydrazine is higher than for arylhydrazines and similar to alkylamines we tested the conditions

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• the regioselective glycosylation produced products 24:25 in a 4:1 ratio in 61% yield. Aglycon transfer was also observed in the reaction producing 26 in 15% yield. The predominance of product 24 also indicates towards a higher nucleophilicity of the C-4 position of the glucoside acceptor 26

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• electrophilic amination reaction afforded sulfonamides 5aa, 5ba, 5da, and 5ea with moderate yields. However, no amination product was detected with tert-butyl 3-(benzylsulfinyl)propanoate (4c). This result suggests that aliphatic β-sulfinyl esters may not possess sufficient nucleophilicity to react with the

Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF₅- and CF₃SF₄-containing [2]staffanes

• Jón Atiba Buldt,
• Wang-Yeuk Kong,
• Yannick Kraemer,
• Masiel M. Belsuzarri,
• Ansh Hiten Patel,
• James C. Fettinger,
• Dean J. Tantillo and
• Cody Ross Pitts

Beilstein J. Org. Chem. 2024, 20, 3134–3143, doi:10.3762/bjoc.20.259

• dramatic change in bicyclopentyl radical philicity would arise after incorporation of the second BCP unit. In addition to charge models, we evaluated global reactivity indices (ω: electrophilicity index [70] and N: nucleophilicity index [71]) within the conceptual density functional theory (CDFT) framework

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• . The level of this chemoselectivity was dependent on the iodane ligand: OPiv was more selective for aminofluorination than OAc, which was proposed to be due to differences in basicity and nucleophilicity (Scheme 10). Detailed mechanistic studies were carried out using multinuclear NMR spectroscopy

• and N-bromosuccinimide (NBS), which promoted the intramolecular bromolactonisation of unsaturated acids 68. The authors investigated the oxidation using a variety of ortho-substituted iodobenzenes. Increasing the nucleophilicity of the groups at the ortho-substituted positions of iodobenzene gave

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• nature of X− [45][46]. Anions like tetrafluoroborate, hexafluorophosphate, and trifluoromethanesulfate are commonly used in DAIS due to their good solubility and weak nucleophilicity. If the two aryl groups (Ar1 and Ar2) in DAIS are different, they are termed unsymmetric diaryliodonium salts 3. The

• factors like steric hindrance. The ring opening proceeded smoothly when nucleophiles with higher nucleophilicity are used yielding up to 99% of the desired products 43. The N-arylation of amino acid esters 44 was established with the utility of substituted phenyl(anisyl)iodonium triflate salts 45 (Scheme

• therapeutics, particularly in antibody–drug conjugates (ADCs). Cysteine (Cys) holds a special place in this context due to the distinctive nucleophilicity of its thiol side chain. The cysteine thiol group offers a reactive handle for site-selective modifications, allowing for the attachment of various

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• . These limitations suggest that a more viable approach to employing FLPs as catalysts for CO2-related reactions could involve their use in CO2 activation [7][18][19]. In particular, the capture of CO2 by FLPs enhances the electrophilicity of the CO2 carbon atom and the nucleophilicity of one of the CO2

Anion-dependent ion-pairing assemblies of triazatriangulenium cation that interferes with stacking structures

• Yohei Haketa,
• Takuma Matsuda and
• Hiromitsu Maeda

Beilstein J. Org. Chem. 2024, 20, 2567–2576, doi:10.3762/bjoc.20.215

• closure with aniline requires a base as reported by Laursen et al. [26], whereas 2,6-dimethylaniline in this study was reacted without the use of a base. This can be explained by the high nucleophilicity of 2,6-dimethylaniline, though it is sterically hindered. As counteranions affect ion-pairing

Photoredox-catalyzed intramolecular nucleophilic amidation of alkenes with β-lactams

• Valentina Giraldi,
• Giandomenico Magagnano,
• Daria Giacomini,
• Pier Giorgio Cozzi and
• Andrea Gualandi

Beilstein J. Org. Chem. 2024, 20, 2461–2468, doi:10.3762/bjoc.20.210

• , Via Gobetti 85, 40129 Bologna, Italy 10.3762/bjoc.20.210 Abstract The direct nucleophilic addition of amides to unfunctionalized alkenes via photoredox catalysis represents a facile approach towards functionalized alkylamides. Unfortunately, the scarce nucleophilicity of amides and competitive side

• •] = +2.09 V vs SCE) [55][56]. The *PC+ species can oxidize the unsaturated lactam, thereby producing the corresponding radical cation intermediate A. The low stabilization by amide-bond resonance of the cyclic four-membered β-lactam [57][58] ensures a good nucleophilicity of the nitrogen atom to efficiently

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• proton abstraction from DMSO to produce 3 as main product. It was thought that the increase of steric hindrance caused a reduction in nucleophilicity and an increase in basicity in the generated triphenylmethyl anion species, in comparison to the diphenylmethyl anion species. To elucidate the mechanism

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• have also been used to predict the Mayr–Patz nucleophilicity parameter N, which estimates the nucleophilicity of a nucleophile based on experimentally measured kinetic data. The MLR models are used to predict N for more than 1200 nucleophiles, enabling the prediction of N for further nucleophiles [98

Heterocycle-guided synthesis of m-hetarylanilines via three-component benzannulation

• Andrey R. Galeev,
• Maksim V. Dmitriev,
• Alexander S. Novikov and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2024, 20, 2208–2216, doi:10.3762/bjoc.20.188

• amines with different nucleophilicity, namely benzylamine (primary alkylamine), morpholine (secondary alkylamine) and aniline (aromatic amine). We first examined the reaction of 1,2,4-oxadiazole-1,3-diketone 1a (σm/σp 0.463/0.575, which is quite close to the constants of the CO2Me group, so a successful

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

• base in the Knoevenagel reaction and as a component for ring formation. Cyclization is completely regioselective when arylhydrazines are used; with methylhydrazine, the ratio is greater than 10:1. In addition to malononitrile, derivatives with reduced nucleophilicity (X = CO2R) are also tolerated in

• chlorides furnishes alkynones 104 under mild reaction conditions [124][125]. Without isolation alkynones 104, hydrazines react directly by Michael addition–cyclocondensation, affording 1,3,5-trisubstituted pyrazoles 102 and 103 with remarkable regioselectivity (Scheme 37) [126][127]. The nucleophilicity of

• stabilization of the secondary nitrogen atom attenuates the nucleophilicity on the secondary nitrogen, furnishing regioisomeric product 103. This latter inverse regioselectivity is typical for arylhydrazines, and due to a lower overall nucleophilicity, often forcing conditions for the cyclocondensation are

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• , Parr and Yang developed a now widely used index of nucleophilicity from robust electron population methods such as NBO analyses, referred to as the Fukui index (f-) [44]. The larger the Fukui index, the greater the nucleophilicity, and is thus inversely proportional to the partial charge. Our

• stabilization, nucleophilicity would dictate regioselectivity outcomes. This also implies that the favorable NCIs and chelation are stronger driving forces towards transition-state energy partitioning than nucleophilicity alone. These results suggest chelation is a highly plausible driving force for

• support the claim made by Alam and Keeting that a tight ion pair drives N1-selectivity when electron-withdrawing groups that can coordinate the cation are present at the 3-position. When 3-cyanoindazole is employed and no bidentate coordination is possible with N2, the nucleophilicity of N1 drives the

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

• its nucleophilicity and improving its orientation. Furthermore, Ser105 formed a strong hydrogen bond also with benzaldehyde, making it a better electron acceptor. Interestingly, also the imine intermediate showed strong interaction with Thr40 and Ser105 residues, so becoming a good electrophile for

• nucleophilicity. In their second work about this topic, Prasad et al. synthesized 5-(3”-alkyl/arylamino-1”-azaindolizin-2”-yl)-2’-deoxyuridines 31 as new base-modified fluorescent nucleosides with high Stokes’ shift, potentially useful for investigating nucleic acid structure and functions. The authors

• their reduced nucleophilicity. Also the synthesis of a bis-imidazo[1,2-a]pyridine scaffold was achieved in 43% yield from the pseudo-para-substituted bis-aldehyde, using the same conditions, but longer reactions times (6 days). Following the same approach, the authors also developed a one-pot protocol

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• solubility issues of metal fluoride salts, safety issues with hydrogen fluoride, poor nucleophilicity [79], and side reactivity as a base [75][79], a few elegant examples of nucleophilic benzylic C(sp3)–H fluorination have been reported. Metal catalysis Fluoride sources have been used in combination with

• the ionic liquid 1-ethyl-3-methylimidazolium trifluoromethanesulfonate ([emim][OTf]) for the fluorination of phthalides at the benzylic position (Figure 37) [95]. It was considered that the zwitterionic nature of the ionic liquid served two purposes. Firstly, to enhance the nucleophilicity of fluoride

• dissolve caesium fluorides and facilitate an electrochemical benzylic C(sp3)–H fluorination of triphenylmethane (Figure 39) [97]. The authors suggested that PEG complexed the metal ion, increasing the nucleophilicity of the fluoride ion. Product 23 was achieved in 85% isolated yield after a small

Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones

• Pooja Goyal,
• Akhil K. Dubey,
• Raghunath Chowdhury and
• Amey Wadawale

Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136

• -covalent catalysis via bifunctional hydrogen-bonding organocatalysts. The C-4 nucleophilicity of pyrazolin-5-ones was also explored in enantioselective reactions with α,β-unsaturated carbonyl compounds through covalent catalysis with chiral amine-based catalysts; however, it has achieved limited success

Predicting bond dissociation energies of cyclic hypervalent halogen reagents using DFT calculations and graph attention network model

• Yingbo Shao,
• Zhiyuan Ren,
• Zhihui Han,
• Li Chen,
• Yao Li and
• Xiao-Song Xue

Beilstein J. Org. Chem. 2024, 20, 1444–1452, doi:10.3762/bjoc.20.127

• DFT calculations for predicting key properties of organic molecules such as BDE, nucleophilicity, and electrophilicity [48][49][50][51][52][53][54][55][56][57][58][59][60]. Recently, applications of the Elastic Net model with Avalon fingerprints [55] and the deployment of artificial neural network

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• various hydrocarbons in good yield. Alcohols containing electron-deficient arenes delivered a comparably lower yield (i.e., 62b–d, 52–63%), probably because of the lower nucleophilicity of the alcohols. Halogen atoms present in the p-position of alcohols were tolerated well and provided a decent yield

Computation-guided scaffold exploration of 2E,6E-1,10-trans/cis-eunicellanes

• Zining Li,
• Sana Jindani,
• Volga Kojasoy,
• Teresa Ortega,
• Erin M. Marshall,
• Khalil A. Abboud,
• Sandra Loesgen,
• Dean J. Tantillo and
• Jeffrey D. Rudolf

Beilstein J. Org. Chem. 2024, 20, 1320–1326, doi:10.3762/bjoc.20.115

• . Scaffold exploration of the eunicellane skeleton During protonation-induced cyclization of 1 and 2, the C6–C7 alkene showed higher nucleophilicity than either of the other two double bonds likely due to the unique conformation of the eunicellane skeleton. This selective reactivity was further supported

Domino reactions of chromones with activated carbonyl compounds

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1256–1269, doi:10.3762/bjoc.20.108

• %. Employment of dienes derived from 1,3-diketones (R3 = Me, Ph) proved to be unsuccessful, presumably due to the lower nucleophilicity of these dienes as compared to those derived from β-ketoesters (R3 = Oalkyl). Substituents located at carbon C-4 of the diene (R1) were generally tolerated as well. In fact

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• was instead not investigated, due to low SciFinder® score (Figure 3). The nucleophilicity of 4 provides useful support for its ring bromination towards 4b, resulting in an excellent isolated yield of 89%. Moreover, the intermediacy of 4b is advantageous for obtaining 4c, thus avoiding the selectivity

Mild and efficient synthesis and base-promoted rearrangement of novel isoxazolo[4,5-b]pyridines

• Vladislav V. Nikol’skiy,
• Mikhail E. Minyaev,
• Maxim A. Bastrakov and
• Alexey M. Starosotnikov

Beilstein J. Org. Chem. 2024, 20, 1069–1075, doi:10.3762/bjoc.20.94

• similar rearrangement of the other arylhydrazones 12b–h strongly depends on the aryl substituent. Indeed, the 2,4-dinitrophenylhydrazones 12b,e, and h did not undergo recyclization even under drastic conditions, apparently due to a low nucleophilicity of the hydrazone anion (Table 1, entries 2, 5, and 8

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• to the electrophilicity parameter E, the nucleophilicity parameter N, and a nucleophile-dependent slope parameters [27]. The nucleophilicity parameter N, as proposed by Mayr, provides a dependable estimation of the reactivity of a given nucleophile, such as an alkene in our case (Figure 1

• differences among alkenes. As demonstrated in the case of methylcyclopentene (Figure 1), the nucleophilicity of the exo-double bond is higher compared to the internal double bond. The higher energy of exo-alkenes compared to internal alkenes is well known and attributed to a less-effective hyperconjugation of

• of a single report concerning the catalytic asymmetric hydrochlorination of alkenes. Hence, this represents another important challenge for the future. Mayr’s nucleophilicity parameters for several alkenes. References for each compound can be consulted via the database. Hydride affinities relating to

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

• , probably due to decomposition by the high temperature used in the protocol. Furthermore, the use of the less reactive TosMIC as isocyanide did not furnish the expected product; only the formamide product was isolated from the chromatographic column, which may be due to the lower nucleophilicity of this