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

Entry to new spiroheterocycles via tandem Rh(II)-catalyzed O–H insertion/base-promoted cyclization involving diazoarylidene succinimides

• Alexander Yanovich,
• Anastasia Vepreva,
• Ksenia Malkova,
• Grigory Kantin and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2024, 20, 561–569, doi:10.3762/bjoc.20.48

• consequence, the significantly greater nucleophilicity of the nearest α-carbon atom. When an attempt was made to generate an anion from compound 25 under the action of a stronger base (t-BuOK/THF, 0 °C) in order to effect spirocyclization, only the formation of a complex multicomponent mixture was observed

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

Ligand effects, solvent cooperation, and large kinetic solvent deuterium isotope effects in gold(I)-catalyzed intramolecular alkene hydroamination

• Ruichen Lan,
• Brock Yager,
• Yoonsun Jee,
• Cynthia S. Day and
• Amanda C. Jones

Beilstein J. Org. Chem. 2024, 20, 479–496, doi:10.3762/bjoc.20.43

• localized due to the strong competitive carbonyl resonance donation of the non-attacking nitrogen. Weaker competitive donation from the more electronegative oxygen, and the less electron-donating phenyl, would lead to decreasing nucleophilicity, respectively, for the carbamate and benzamide attacking

• groups as measured by rates of Michael addition [52]. This suggests that in fact nitrogen nucleophilicity alone is not the most relevant factor since sulfonamides react much slower in hydroamination. Sulfonamide N–H bonds are significantly more acidic than urea, amide and carbamate N–H bonds (16.1 versus

• -centered while being C-centered in analogous anions alpha to sulfonamides [51]. Sulfonamides are known to protonate at nitrogen [31]. Gold coordination to carbonyls would be predicted to retain N-centered nucleophilicity, while gold coordination to the sulfonamide nitrogen would not. Sulfonamides are less

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• ), the basicity of which must obviously be higher than that of the starting heterocycle 5. To this end, we conducted a series of experiments on its oxidative amination by varying the reaction conditions (time, temperature, addition of n-butyllithium to increase the nucleophilicity of amines), and

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

• substituent in meta position (R2 = F, Cl, Br, OMe) was present (12f–i), as expected from the increased nucleophilicity of the carbon involved in the intramolecular Friedel–Crafts reaction. In the para position, R3 = Br and CO2Me were tested and showed good results, to give 12j and 12k with more than 70

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

• ) in Scheme 5, Scheme 6 and the Experimental section). There are some features of this cyclization. The electron-poor enones 2l,m are unreactive and do not give rise to the corresponding indanones due to the low nucleophilicity of the nitro-substituted aromatic ring. On the other hand, the electron

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

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

• to changes in an ylide’s UV–vis absorption profile, or to its overall basicity or nucleophilicity, both of which could lead new and unexpected reactivity. The first example that specifically invoked electron donor–acceptor complexes of iodonium ylides was reported in 2018 by Wang and co-workers [122

• also have improved the nucleophilicity of the carbanion (see 52, Figure 11), facilitating the initial metallocarbene forming event. In 2019, Takemoto et al. investigated ortho-groups as a means to enhance the stability and solubility of ylide precursors, and they envisioned how blocking one of iodine’s

Linker, loading, and reaction scale influence automated glycan assembly

• Marlene C. S. Dal Colle,
• Manuel G. Ricardo,
• Nives Hribernik,
• José Danglad-Flores,
• Peter H. Seeberger and
• Martina Delbianco

Beilstein J. Org. Chem. 2023, 19, 1015–1020, doi:10.3762/bjoc.19.77

• ]. We wondered whether different glycan sequences were more sensitive to the linker structure. Less reactive donors might highlight differences in the linker nucleophilicity [25]. The aggregation of the growing glycan chains is conceivable to be connected to linker flexibility [18]. The efficiency of UV

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

• in 83 and the enantioregulation was achieved by BINOL-derived chiral phosphoric acid P22. An amine functionality was crucial in the isoxazole ring to enhance the nucleophilicity of the adjacent carbon atom. In addition, the amine hydrogen forms an H-bond with the catalyst along with another hydrogen

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

• expensive reagents and also has numerous applications in other areas of research. In this study, it was discovered that amines with less nucleophilicity also produced good yields of the product. In contrast, for the reaction with polyaromatic amines, THF was found to be the best solvent because these

Sulfate radical anion-induced benzylic oxidation of N-(arylsulfonyl)benzylamines to N-arylsulfonylimines

• Joydev K. Laha,
• Pankaj Gupta and
• Amitava Hazra

Beilstein J. Org. Chem. 2023, 19, 771–777, doi:10.3762/bjoc.19.57

• condensation of aromatic aldehydes and sulfonamides (Scheme 1a) [3][5][6][7][8]. Because of the poor nucleophilicity of sulfonamides, the condensation reactions generally require harsh reaction conditions involving the use of strong acids, elevated temperature, and metal catalysts. Other methods include a non

• corresponding N-heterocycles 4c–f were obtained in good to moderate yield. However, the reaction with 2-aminophenol did not give the corresponding cyclized product 4g. This could be possibly due to the poor nucleophilicity of the ortho-OH group in 2-aminophenol thereby restricting the intramolecular

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• . Such a change in the reaction selectivity could be explained by the influence of a higher nucleophilicity of the examined alkylamines in comparison with benzylamine. Then, we tried to involve less nucleophilic amines to the proposed approach. For these, we examined a reaction of APBTT 1a with aniline

• nucleophilicity of the amine. Then, we examined the proposed approach to PBTAs by involving bulky nucleophilic compounds 16a–d to the reaction with APBTT 1a. Unexpectedly, product 17a was formed instead of the anticipated PBTA C (Scheme 20). Compound 17a was formed in good isolated yields (60–70%) and was

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• polymerization, we suppose that a rapid termination and chain transfer reaction occurs during the MeOx polymerization. According to the chain transfer mechanism introduced by Litt et al., MeOx acts as a base and abstracts a proton from the polymer side chain [45]. Due to the slightly increased nucleophilicity

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• alkoxides exhibit strong σ-donating properties, given the high nucleophilicity of the alkoxide moiety. Moreover, the beneficial effect of molecular σ-donating additives on the yields and selectivities of iron-mediated cross-coupling reactions had already been reported in the literature. Nakamura thus

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

• group of intermediate 8 is expected to be more nucleophilic than that of intermediate 28 given the fact that allylsilanes possess a significantly higher nucleophilicity than vinylsilanes [69]. Therefore, the electron richness of the nucleophilic alkene appears to be an important parameter in addition to

• though the nucleophilicity of the allylsilane is expected to be low due to the presence of the electron-withdrawing acyl chloride functionality (pathway II, Scheme 8a). The subsequent lactam formation in intermediate 35 would give the final product 7. While general reactivity considerations and the