Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• ]. Although quite important in all organocatalytic processes, there are specific organocatalysts which activate reactants through non-covalent interactions such as hydrogen bonding. These interactions are crucial to obtain high enantioselectivity in the reaction. The 1-azadienes possess an electronegative

• covered in this review are hydrogen-bond donors such as thioureas and squaramides, Brønsted bases such as tertiary amines, and Brønsted acids such as chiral phosphoric acids. As depicted in Figure 4, a bifunctional squaramide is able to activate both an α,β-unsaturated imine through hydrogen bonding with

• Michael addition product was obtained with low diastereoselectivity. The mechanism is described in Scheme 4: the bifunctional squaramide activates the azadiene through hydrogen bonding while the malononitrile is deprotonated by the tertiary amine present in the backbone of the catalyst, establishing

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• second-sphere interactions with a multipoint hydrogen-bonding pattern enhance CO2 reduction in organic solvents, improving stability, facilitating proton transfer, reducing energy barriers, and increasing selectivity [20]. Apart from advances in synthetic methodologies [2][21][22][23], the exploration of

• active groups for a variety of substrates, making their use as supramolecular organocatalysts based on bifunctional activation mechanism (hydrogen-bonding/Lewis basicity) highly promising. At the same time, additional functional groups that are required for the catalysis can be easily installed on the

• addition of furan-based silyloxydiene synthons to a variety of achiral aldehydes using four different calix[4]pyrrole macrocycles (3, 4, 11, and 12) as organocatalysts (Figure 3) [38]. These calixpyrrole macrocycles acted as hydrogen-bond donors, activating substrate aldehydes through hydrogen-bonding

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• combining the indole moiety with the 1,5-disusbtituted tetrazole pharmacophore could increase the non-covalent interactions, including π–π stacking, hydrogen bonding, and hydrophobic interactions. This combination may improve the pharmacodynamic profile, providing a solid foundation for developing compounds

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• the hydrogen bonding by the primary- or secondary-alcohol groups, as confirmed by theoretical analyses. This structure was consistent with a previously reported X-ray crystal structure analysis of the complex structure comprising α-CD, polyion, and Li+ or Cd2+ [45]. Regarding the small rotaxane

• , or 24 methylene units as the axle component. The results revealed that the weakened hydrogen bonding and hydrophobic interaction by PMα-CD was the key to the formation of rotaxane molecules with an odd number of wheel components as well as their much lower yields than the native-CD-based rotaxanes

• component, is not so easy because of the strong hydrogen bonding between the CD units. Beckham and Zhao reported that an increase in the molecular weight of the axle polymer caused a decrease in the coverage ratio, although the coverage ratio in the same molecular weight polymer could not be controlled at

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• porphyrins Nonplanar porphyrins are known to form supramolecular assemblies [6], either through hydrogen-bonding networks or through π–π interactions. Examples of this can be seen in the trapping of Keggin-type heteropolyoxometalate (POM) through nonplanar Mo(V)–porphyrin complexes [58], or porphyrin

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• presence of a strong-electron donating substituent, e.g., a -OCH3 on the benzene ring attached to the carbonyl center has a more pronounced effect on the UV-protection abilities (4bb, 4cb, 4eb and 4fb) since it increases the electron density on the carbonyl center, and hence the hydrogen bonding between

Deciphering the mechanism of γ-cyclodextrin’s hydrophobic cavity hydration: an integrated experimental and theoretical study

• Stiliyana Pereva,
• Stefan Dobrev,
• Tsveta Sarafska,
• Valya Nikolova,
• Silvia Angelova,
• Tony Spassov and
• Todor Dudev

Beilstein J. Org. Chem. 2024, 20, 2635–2643, doi:10.3762/bjoc.20.221

• hydrogen bonding, although generally not dominant, can influence the complex formation as well [5]. Cyclodextrins form inclusion complexes with polar and non-polar substances of various aggregate states. This incredible versatility, combined with the enhanced stability against oxidation, as well as

• enlarging the aperture (“open” configuration). In the “open” configuration, the primary hydroxy groups are not involved in the intramolecular hydrogen-bonding interactions with neighboring OH groups. Relatively weak hydrogen bonds are formed between the secondary hydroxy groups at the wider/lower rim of the

• water molecules and the CD host system: β-CD hydration is dominated by water–water hydrogen bonding interactions rather than water–CD interactions. In contrast, the interactions between water guests and the cavity walls are more significant at α-CD and γ-CD, favoring a consecutive water release process

Applications of microscopy and small angle scattering techniques for the characterisation of supramolecular gels

• Connor R. M. MacDonald and
• Emily R. Draper

Beilstein J. Org. Chem. 2024, 20, 2608–2634, doi:10.3762/bjoc.20.220

• may be assumed to provide an in situ environment. While D2O is chemically identical to H2O, it does exhibit differences in properties including density, viscosity, hydrogen-bond strength, a more pronounced hydrophobic effect. As hydrogen bonding and hydrophobicity are critical to hydrogel

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

• File 1). As a crystallization solvent, three CHCl3 molecules were located between the 2,6-dimethylphenyl units by forming hydrogen bonding with Cl− with C(–H)···Cl− distances of 3.36, 3.36, and 3.37 Å. A similar arrangement of the counteranions was observed for 2+-BF4− and 2+-PF6−, with the BF4− and

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• , halogen bonding [I1···Br1 = 3.0610(5) Å, 80% of Σr, and C8–I1···Br1 = 171.67(9)°] and hydrogen bonding were found [H2···Br1 = 2.7991(4) Å, 95% of Σr, C2···Br1 = 3.545(4) Å, 100% of Σr and C2–H2···Br1 = 136.1(2)°]. On the other axis, no ortho proton is present, so only XB is observed [I1···Br1 = 3.2023(5

• ). Halogen bonding dimer found in the crystal structure of 7Br. Ellipsoids are shown at 50% probability (carbon: grey, nitrogen: blue, oxygen: red, bromine: orange, iodine: purple) and hydrogen atoms are shown in standard ball-and-stick model (white). Halogen and hydrogen bonding is indicated dashed. 1H NMR

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

• the asymmetric addition of organoboron reagents to imines (Scheme 3). An intermolecular hydrogen bonding between a non-rigid organocatalyst and a non-rigid substrate was shown to play a key role in assembling a configurationally stable transition structure. As a result, this approach unveiled the

Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines

• Michał Błauciak,
• Dominika Andrzejczyk,
• Błażej Dziuk and
• Rafał Kowalczyk

Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198

• catalysis with hydrogen bonding units has been essential for achieving high reactivity and enantioselectivities [21][22]. Additionally, the reactivity of the nucleophilic addition is influenced by substitutions near the electron-poor double bond. This approach requires 30 mol % of catalyst and a reaction

• proved ineffective in facilitating the Michael addition of bisthiomalonates to conjugated ketones, whereas DABCO enabled the formation of desired products under mild conditions [30]. However, reports of highly stereoselective protocols utilizing hydrogen bonding catalysis have mainly focused on

• -based catalytic system for the highly stereoselective addition of various bisthiomalonates to chalcones and dienones [29]. While recognizing the potential for greater selectivity enhancement and time savings with ball milling, hydrogen-bonding catalysis was effective only with aromatic enones, yielding

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• iminoiodinanes for the metal-free aziridination of unactivated olefins. 1H NMR and cyclic voltammetry (CV) studies indicate that hydrogen-bonding between HFIP and the iminoiodinane generates an oxidant capable of direct NGT to unactivated olefins. Stereochemical scrambling during aziridination of 1,2

• at 5.52 ppm with a FWHM = 56.6 Hz (Scheme 4a). This resonance was broader and more downfield than that of free HFIP in CD3CN (5.41 ppm with FWHM = 5.0 Hz), suggesting a hydrogen bonding interaction between HFIP and 2c, and similar observations were also reported for the hydrogen bonding between HFIP

• (denoted by asterisk *) of HFIP in the presence of iminoiodinane 2c suggesting hydrogen bonding observed in 1H NMR spectra (CD3CN) of: 8.0 mM 2c with no HFIP (blue line), 8.0 mM 2c with 32 mM HFIP (green line), 4.0 mM of 4-(trifluoromethyl)benzenesulfonamide with 32 mM HFIP (purple line), only 32 mM HFIP

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• adsorbed onto the support surface through weaker intermolecular forces, such as van der Waals forces and hydrogen bonding. Ionic catalysts form ionic bonds or those that can be ionised under immobilisation conditions. Encapsulation involves physically trapping the catalyst within the pores or cavities of

• catalyst can easily leach into the solution as it reaches equilibrium between the absorbed species on the surface and the solubilised species. To improve the stability of the supported catalyst, it is important to modify the catalyst and support to enable hydrogen bonding. This method can also bring the

• organocatalyst [113], reactants [114], product [115] or solvent [116] can significantly impact catalytic activity. These interactions often manifest in various forms of adsorption: physisorption, involving forces like van der Waals interactions and hydrogen bonding, or chemisorption, which may involve ionic or

Solvent-dependent chemoselective synthesis of different isoquinolinones mediated by the hypervalent iodine(III) reagent PISA

• Ze-Nan Hu,
• Yan-Hui Wang,
• Jia-Bing Wu,
• Ze Chen,
• Dou Hong and
• Chi Zhang

Beilstein J. Org. Chem. 2024, 20, 1914–1921, doi:10.3762/bjoc.20.167

• substrate 1c may act as an electrophilic center, forming a C–O bond with the alkenyl group to give the isochromen-1-one oxime product 2c'. When wet HFIP was used as the solvent, the reaction followed a different pathway. HFIP, a strong hydrogen bonding donor [26][27][28], interacts with the amide moiety of

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

• . Sashidhara et al. reported no conversion, while Liu et al. reported a 58% yield of the GBB product, postulating the ability of ethylene glycol to function as an activator (through hydrogen bonding) and a facilitator of proton transfer. After this discovery, ethylene glycol has never been employed in GBB

• significantly more active than 9, owing to higher rigidity and the correct position of the ortho H atoms in close proximity to the σ-holes on the I atom. The authors demonstrated that hydrogen bonding between H in ortho position of 8 and both O atom of aldehyde and N atom of imine significantly increased the

Supramolecular assemblies of amphiphilic donor–acceptor Stenhouse adducts as macroscopic soft scaffolds

• Ka-Lung Hung,
• Leong-Hung Cheung,
• Yikun Ren,
• Ming-Hin Chau,
• Yan-Yi Lam,
• Takashi Kajitani and
• Franco King-Chi Leung

Beilstein J. Org. Chem. 2024, 20, 1590–1603, doi:10.3762/bjoc.20.142

• stronger fatigue effect was observed in the photoisomerization of DA7 and DA6, this might be attributed to stabilization through hydrogen bonding and a favored cyclized-isomer in polar solvents. The increased alkyl linker length of DA10 and DA11 provided an improved photostability compared to DA7 and DA6

Regio- and stereochemical stability induced by anomeric and gauche effects in difluorinated pyrrolidines

• Ana Flávia Candida Silva,
• Francisco A. Martins and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2024, 20, 1572–1579, doi:10.3762/bjoc.20.140

• systems [5]. This conformational preference is attributed to an electrostatic gauche effect, where an attractive NH2+∙∙∙Fδ− interaction reinforces the well-known hyperconjugative gauche effect. Additionally, NH∙∙∙F hydrogen bonding has been proposed to play a role in stabilizing conformers of certain 3

• delocalization is considered to be secondary [7]. However, stabilization via intramolecular hydrogen bonding does not seem to significantly impact the conformational stability of 3-fluoropiperidine. In this context, the cis-conformer, with the axial fluorine atom facing the N-hydrogen atom, is either equally or

• only slightly more stable than the other three conformers in both the gas phase and implicit water [4]. Hence, it appears that strong intramolecular interactions, and not only hydrogen bonding, govern the orientation of the fluorine atom in the F‒C‒C‒N fragment, favoring the cis-isomer of 3

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

• assembly) activates the pyrazol-5-one 2a through hydrogen bonding and forms the corresponding enol. Simultaneously, the enol form of the pyrazol-5-one attacks the Re-face of the α,β-unsaturated ketone 1b to provide the intermediate 5 (Scheme 5), which after hydrolysis leads to product ent-3ba'. In situ

Selectfluor and alcohol-mediated synthesis of bicyclic oxyfluorination compounds by Wagner–Meerwein rearrangement

• Ziya Dağalan,
• Muhammed Hanifi Çelikoğlu,
• Saffet Çelik,
• Ramazan Koçak and
• Bilal Nişancı

Beilstein J. Org. Chem. 2024, 20, 1462–1467, doi:10.3762/bjoc.20.129

• compounds by changing their metabolic stability, hydrogen bonding ability, lipophilicity, solubility, bioavailability, conformation and general structure [1][2][3][4]. About 20% of commercially available drugs contain fluorine, and this ratio is estimated to increase further [5][6]. Among organofluorines

Synthesis and physical properties of tunable aryl alkyl ionic liquids based on 1-aryl-4,5-dimethylimidazolium cations

• Stefan Fritsch and
• Thomas Strassner

Beilstein J. Org. Chem. 2024, 20, 1278–1285, doi:10.3762/bjoc.20.110

• blocked at the C2 position [33]. The use of a substituent at the C2 position was found to have a strong influence on the properties of these ionic liquids due to changes in the hydrogen-bonding network. Here, we investigate the properties of TAAILs based on the 1-aryl-4,5-dimethylimidazolium cation. It is

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

• P21/c [49]. It adopts a transoid geometry around the oxamide C–C bond with nearly 180° torsion angle. This provides the molecule with a planar geometry. It shows intermolecular hydrogen bonding between the amide O and NH moieties. (Figure S35, Supporting Information File 1). Oxamide 9 crystallized in

• a monoclinic crystal system in the space group P21/c. The structure was similar to the structure of oxamide 3 (Figure 2). The hydrogen of the NH unit was concealed by the oxygen atoms of the C=O and OMe units. Consequently, it did not engage in intermolecular hydrogen bonding. Due to the planar

• . It crystallized in a triclinic crystal system in the space group P−1. It was structurally similar to the other oxamides 3 and 9. It showed an intramolecular hydrogen bonding between the NH and the carbonyl group of the methoxy ester. A layer-by-layer packing was observed in the crystal structure

Structure–property relationships in dicyanopyrazinoquinoxalines and their hydrogen-bonding-capable dihydropyrazinoquinoxalinedione derivatives

• Tural N. Akhmedov,
• Ajeet Kumar,
• Daken J. Starkenburg,
• Kyle J. Chesney,
• Khalil A. Abboud,
• Novruz G. Akhmedov,
• Jiangeng Xue and
• Ronald K. Castellano

Beilstein J. Org. Chem. 2024, 20, 1037–1052, doi:10.3762/bjoc.20.92

• 73019, United States 10.3762/bjoc.20.92 Abstract Presented here is the design, synthesis, and study of a variety of novel hydrogen-bonding-capable π-conjugated N-heteroacenes, 1,4-dihydropyrazino[2,3-b]quinoxaline-2,3-diones (DPQDs). The DPQDs were accessed from the corresponding weakly hydrogen

• -bonding dicyanopyrazinoquinoxaline (DCPQ) suspensions with excess potassium hydroxide, resulting in moderate to good yields. Both families of compounds were analyzed by UV–vis and NMR spectroscopy, where the consequences of hydrogen bonding capability could be assessed through the structure–property

• studies. Conversion of the DCPQs into hydrogen-bonding capable DPQDs results in modulation of frontier MO energies, higher molar extinction coefficients, enhanced crystallinity, and on-average higher thermal stability (where in some cases the 5% weight loss temperature is increased by up to 100 °C

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

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

• following mechanism (Scheme 30B): Initially, the terminal palladium species H, formed through the hydropalladation of terminal or internal alkenes (upon chain walking), coordinates to NCS via hydrogen bonding (I). Subsequent oxidation takes place to yield a Pd(IV) species (J), which then undergoes reductive

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

• substituted by two mesogenic cholesteryl groups (Figure 6) [28]. Due to strong hydrogen bonding between the pyridyl moiety and the N–H of the hydrazone, tweezers 5 predominantly exist in the closed E-form in a CD2Cl2 solution (E/Z-isomer ratio of 91:9). Upon protonation of the pyridyl group, a complete

• PtCl2 preorganizes the tweezers in a closed conformation with the two hydrogen-bonding-recognition sites in proximity. A significant increase in the binding affinity toward all anions and in particular for dihydrogen phosphate (log K = 3.5) was obtained. More recently, Álvarez and co-workers reported

• luminescence properties of the system could then be regulated by closing/opening but also by the addition of Cl− that could form hydrogen bonding with the amide function of the spacer between the switching and the functional units. The WLA has also been applied to obtain switchable molecular tweezers for