A resorcin[4]arene hexameric capsule as a supramolecular catalyst in elimination and isomerization reactions

• Tommaso Lorenzetto,
• Fabrizio Fabris and
• Alessandro Scarso

Beilstein J. Org. Chem. 2022, 18, 337–349, doi:10.3762/bjoc.18.38

• [20] or hydrogen bonding units. In the latter case, a key role is played by the resorcin[4]arene 1 as a one-step multigram synthesis product, that spontaneously self-assembles in wet apolar solvents like chloroform or benzene forming a hexameric structure [21] thanks to the formation of a seam of

• nano-environment provided by the capsule [45]. Moreover, all reactions were also tested i) using 4-n-hexylresorcinol (2) as a molecular unit able to provide the same hydrogen bonding properties of the resorcin[4]arene but lacking the formation of the cavity ii) in the presence of the capsule with an

• of the substrate. The reaction was repeated with 2 as a hydrogen bonding unit and with acetic acid (4) as a comparable Brønsted acid observing in both cases that the formation of 1,1-diphenylethylene was negligible (Figure 2E and F, Table 2, entries 3 and 4). Further control experiments with the

A Se···O bonding catalysis approach to the synthesis of calix[4]pyrroles

• Qingzhe Tong,
• Zhiguo Zhao and
• Yao Wang

Beilstein J. Org. Chem. 2022, 18, 325–330, doi:10.3762/bjoc.18.36

• noncovalent forces, hydrogen bonding interactions play a central role in noncovalent catalysis [2] while halogen bonding interactions have lately been exploited as a new tool to catalyze a diverse array of reactions [3][4][5]. In addition, nonclassical interactions such as anion–π [6][7][8][9][10][11] as well

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• environment inside the container. The containers include supramolecular structures self-assembled through metal/ligand interactions or hydrogen bonding and open-ended covalent structures such as cyclodextrins and cavitands. Challenges and prospects for the future are also provided. Keywords: confinement

• , directing groups are introduced to the substrates covalently to achieve site-selective C–H bond activation, which prospered greatly in the past decades [7][8][9]. Template regulation is also introduced to locate reactive centers in a noncovalent way through hydrogen bonding [10][11][12]. Even though

• that apart from molecular containers, other designed moieties could also be used to anchor the substrate through hydrogen-bonding interactions [10][11][12]. In 2019, the Fujita group reported the site-selective oxidations of linear diterpenoids with the help of cage host A (Figure 9) [70]. The linear

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• derivative in good yield, albeit with a considerable diminishment in the ee (Scheme 4). Based on the literature reports and the stereochemical outcome, a plausible transition state is proposed, as shown in Figure 2. The activation of nitrosobenzene was achieved by the intramolecular hydrogen-bonding of the

Diametric calix[6]arene-based phosphine gold(I) cavitands

• Gabriele Giovanardi,
• Andrea Secchi,
• Arturo Arduini and
• Gianpiero Cera

Beilstein J. Org. Chem. 2022, 18, 190–196, doi:10.3762/bjoc.18.21

• devised a new family of triphosphine calix[6]arene gold(I) complexes (Figure 1c) [30]. These cavitands are able to form (pseudo)rotaxane species, by threading viologen-based guests, with a conformational control operated by the sulfonamido hydrogen-bonding donor domain [31][32]. Furthermore, their

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• bifunctional hydrogen-bonding catalyst would activate both CPD via a tertiary amino group of a quinuclidine moiety acting as a base via anion-binding, and an oxindole through the squaramide or thiourea moieties of the catalyst as hydrogen bond donors (Figure 1) [29][30][31][32]. Therefore, squaramide and

Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction

• Irina Kuznetcova,
• Felix Bacher,
• Daniel Vegh,
• Hsiang-Yu Chuang and
• Vladimir B. Arion

Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15

• challenge and practical synthesis is still missing in the literature. Its accessibility may enrich the arsenal of available tools for enzyme inhibitor design by increasing the number of hydrogen bonding donor and acceptor groups at the same side of the backbone, which may result in a tight binding with

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• methanol lead to the simple two molecule formulation of the SN2 process for the hydrolysis being an oversimplification. The observation that the small molecule H2O is in bulk a liquid at room temperature requires a dynamic situation where water molecules are to a large extent associated by hydrogen-bonding

Biological properties and conformational studies of amphiphilic Pd(II) and Ni(II) complexes bearing functionalized aroylaminocarbo-N-thioylpyrrolinate units

• Samet Poyraz,
• Samet Belveren,
• Sabriye Aydınoğlu,
• Mahmut Ulger,
• Abel de Cózar,
• Maria de Gracia Retamosa,
• Jose M. Sansano and
• H. Ali Döndaş

Beilstein J. Org. Chem. 2021, 17, 2812–2821, doi:10.3762/bjoc.17.192

• intramolecular hydrogen-bonding interactions (Figure 2). Additional steric hindrance in conformer B, compared to conformer A (as found in L1-Ni complexes), raises the energy of the latter. Thus, in L3-M complexes, only one set of signals was expected in the NMR spectra. Due to the high number of possible

• complexes. Blue and yellow surfaces represent the solvent accessible surface of ligands with a probe radius of 1.4 Å. Hydrogen atoms not involved on hydrogen–bonding interactions are omitted for clarity. Synthetic route for the preparation of L1-M, L2-M and L3-M complexes. Antibacterial and antituberculosis

Recent advances in the asymmetric phosphoric acid-catalyzed synthesis of axially chiral compounds

• Alemayehu Gashaw Woldegiorgis and
• Xufeng Lin

Beilstein J. Org. Chem. 2021, 17, 2729–2764, doi:10.3762/bjoc.17.185

• asymmetric bromination reaction afforded monobrominated biaryls with excellent enantioselectivities up to 99% ee (Scheme 4). The experimental and computational studies showed that the highly organized hydrogen-bonding network between a substrate, a chiral phosphoric acid catalyst (CPA 3), and a brominating

• (Brønsted acidity/basicity, hydrogen-bonding units, and counter-anions toward metals) [48][49]. In 2019, Shi, Lin, and co-workers achieved an enantioselective synthesis of axially chiral quinoline-derived biaryl atropisomers via Pd-catalyzed C–H olefination of 8-phenylquinoline (11) using a novel chiral

• nucleophilic addition reactions using isatin-derived imines 50 as electrophiles was reported by Tan, Shi and co-workers in 2020. Enantioenriched 3,3'-bisindoles with a biologically essential chiral 3-aminooxindole unit can be readily prepared by these methods. CPA 9 utilizes hydrogen bonding to activate both

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• proceeds via initial enamine formation from the aldehyde and catalyst. The coordination of the nitroalkene via hydrogen bonding with the (thio)urea moiety will bring it in the vicinity of the enamine from the re-face. The major enantiomer of the Michael adduct (S,S)-10 is formed via re-attack on the

• this case, the nitroalkene could not be activated by hydrogen bonding via the (thio)urea moiety, however, it is also probably less sterically hindered (Figure 3a). The DFT calculated transition states support this analysis. The transition state TS-major-re-SR-cat leading to the major stereoisomer of

Adjusting the length of supramolecular polymer bottlebrushes by top-down approaches

• Tobias Klein,
• Franka V. Gruschwitz,
• Maren T. Kuchenbrod,
• Ivo Nischang,
• Stephanie Hoeppener and
• Johannes C. Brendel

Beilstein J. Org. Chem. 2021, 17, 2621–2628, doi:10.3762/bjoc.17.175

• coupled to a UV detector and a multiangle laser light scattering detector (AF4–MALLS technique) to estimate the apparent structure length and the length distribution of the SPBs. Results and Discussion The general structure of the tested BTP and BTU is depicted in Figure 1 [19][20]. While the hydrogen

• bonding moieties are either urea-based or peptide-based (i.e., phenylalanine) units, the dodecyl chains act as hydrophobic shields to induce the amphiphilic assembly in water and prevent the surrounding water from interfering with the hydrogen bonds in the interior [29]. Attaching a hydrophilic PEO chain

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• compounds; however, in order to comply with the requirements of a mini review, additions of amines and amides only will be included. 1. Non-covalent bonding organocatalytic aza-Michael reactions Organocatalysts catalyzing aza-MRs through mainly hydrogen bonding include cinchona alkaloids, squaramide

• formed Michael adduct (Scheme 1) [25]. The proposed catalytic cycle involved generation of the active complex through hydrogen bonding between catalyst and aniline followed by interaction with chalcone via π–π stacking of aromatic rings and hydrogen bonding leading to the Michael adduct. Likewise, Lee et

• appears that in this case, both activation mechanisms, namely through hydrogen bonding and iminium ion formation are operating. Using the same chiral cinchona-based primary-tertiary diamine as catalyst (cat. 11), Zhai et al. developed a highly efficient intramolecular enantioselective aza-Michael addition

Cryogels: recent applications in 3D-bioprinting, injectable cryogels, drug delivery, and wound healing

• Luke O. Jones,
• Leah Williams,
• Tasmin Boam,
• Martin Kalmet,
• Chidubem Oguike and
• Fiona L. Hatton

Beilstein J. Org. Chem. 2021, 17, 2553–2569, doi:10.3762/bjoc.17.171

• intermolecular hydrogen bonding changes, leading to variations on how hydrated the cryogel is, triggering a volume phase transition [34][35]. Changes in solubility can be described by the upper critical solution temperature (UCST) and lower critical solution temperatures (LCST). The UCST is the temperature at

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• furylmercurials 91 via syn-addition of acetylene, which on carbonylation yielded the furan-containing carbonyl compound 92 (Scheme 30) [83]. It was proposed that initially mercuration of acetylene bonds via mercurinium like ions or π-complex takes place. Then the structure was stabilized through hydrogen bonding

Base-free enantioselective S_N2 alkylation of 2-oxindoles via bifunctional phase-transfer catalysis

• Mili Litvajova,
• Emiliano Sorrentino,
• Brendan Twamley and
• Stephen J. Connon

Beilstein J. Org. Chem. 2021, 17, 2287–2294, doi:10.3762/bjoc.17.146

• synthesis of a potent CRTH2 receptor antagonist. Keywords: alkylation; base-free; cinchona alkaloids; CRTH2 antagonist; hydrogen-bonding; oxindole; phase-transfer catalysis; Introduction The 2-oxindole scaffold is an important motif present in a myriad of natural products. Among 2-oxidole derivatives, 3,3

• investigation by evaluating, as a model alkylation, the phase-transfer-catalysed benzylation of substrate 5 under ‘classical’ basic reaction conditions using cinchona alkaloid-based catalysts capable of hydrogen-bonding as a control element [33][34][35][36][37][38][39][40]. As expected, the ester group α to the

Halides as versatile anions in asymmetric anion-binding organocatalysis

• Lukas Schifferer,
• Martin Stinglhamer,
• Kirandeep Kaur and
• Olga García Macheño

Beilstein J. Org. Chem. 2021, 17, 2270–2286, doi:10.3762/bjoc.17.145

• , the regulation of membrane potentials is one of such applications, in which the transport of chloride anions is facilitated by noncovalent hydrogen bonding interactions (Figure 1a) [6]. Noncovalent interactions are in fact one of the essential factors for the molecular recognition in enzymatic

• anion coordination and supramolecular chemistry [7][8][9][10][11], this field of research has attracted more attention within the past two decades. Immense efforts were made to identify small molecules that are able to productively bind anions via noncovalent hydrogen bonding, from which cationic

• spherical halides [10]. The key to hydrogen bonding of the halide anion resides in the polarized N–H bonds of these (thio)urea units, which have since served as a benchmark in the design and development of anion receptor catalysts [12][13][14]. Consequently, other synthetic anion receptors have been

(Phenylamino)pyrimidine-1,2,3-triazole derivatives as analogs of imatinib: searching for novel compounds against chronic myeloid leukemia

• Luiz Claudio Ferreira Pimentel,
• Lucas Villas Boas Hoelz,
• Henayle Fernandes Canzian,
• Frederico Silva Castelo Branco,
• Andressa Paula de Oliveira,
• Vinicius Rangel Campos,
• Floriano Paes Silva Júnior,
• Rafael Ferreira Dantas,
• Jackson Antônio Lamounier Camargos Resende,
• Anna Claudia Cunha,
• Nubia Boechat and
• Mônica Macedo Bastos

Beilstein J. Org. Chem. 2021, 17, 2260–2269, doi:10.3762/bjoc.17.144

• ). Additionally, the analysis of the interactions between IMT and the enzyme BCR-Abl-1 shows hydrogen bonds with Glu305, Thr334, Met337, and Asp400 (hydrogen bonding energy = −8.97 a.u.) and steric interactions with Glu305, Thr334, Met337, Ile379, and Asp400 (steric binding energy = −193,658 a.u.), in agreement

• with the interactions found for IMT in the 3PYY crystal. The analysis of the inhibitor complexes 2c and 2g and BCR-Abl-1 showed interactions similar to those described for IMT (Figure 4a). Thus, compound 2c presented hydrogen-bonding interactions with Asp400 and Leu383 (hydrogen bonding energy of −1.31

• a.u.) and steric interactions with Glu301, Glu305, Val308, Met309, Leu373, Ile379, and Asp400 (steric interaction energy = −151.683 a.u.) (Figure 4b). Similarly, compound 2g showed a hydrogen-bonding interaction with Asp400 (hydrogen bonding energy = −2.62 a.u.) and steric interactions with Lys290

Photoredox catalysis in nickel-catalyzed C–H functionalization

• Lusina Mantry,
• Rajaram Maayuri,
• Vikash Kumar and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2021, 17, 2209–2259, doi:10.3762/bjoc.17.143

• computational studies highlight the involvement of hydrogen bonding assistance during the radical addition to olefine. The proposed reaction mechanism has two synergistic catalytic cycles, namely a photocatalytic cycle and a nickel catalytic cycle (Figure 23). The photoexcitation of the ketone PC 96 results in

Constrained thermoresponsive polymers – new insights into fundamentals and applications

• Patricia Flemming,
• Alexander S. Münch,
• Andreas Fery and
• Petra Uhlmann

Beilstein J. Org. Chem. 2021, 17, 2123–2163, doi:10.3762/bjoc.17.138

• thermoresponsive behavior of polymers is governed by oriented polymer–polymer interactions, such as hydrogen bonding or electrostatic interactions. As a function of temperature, these attractive interactions are formed and contribute to phase separation (T < UCST) or are increasingly destabilized and allow

• between the chains themselves and with the solvent including structuring effects in hydrogen bonding solvents, and polyelectrolyte brushes, whose behavior is additionally determined by long-range Coulomb interactions [114][116]. The main difference between classical and nonclassical polymer brushes is the

• , UCST type behavior is generally governed either by strong hydrogen bonding or by attractive electrostatic interactions [51][52][55]. UCST resulting from strong hydrogen bonding interactions. Increasing interest is focussed on nonionic polymers in water, whose UCST behavior is based on hydrogen bonding

Enantioenriched α-substituted glutamates/pyroglutamates via enantioselective cyclopropenimine-catalyzed Michael addition of amino ester imines

• Zara M. Seibel,
• Jeffrey S. Bandar and
• Tristan H. Lambert

Beilstein J. Org. Chem. 2021, 17, 2077–2084, doi:10.3762/bjoc.17.134

• ) improved the reactivity somewhat but was detrimental to enantioselectivity (Table 1, entry 4), while changing the relative stereochemistry of the hydroxy substituent resulted in an inactive catalyst (8, entry 5 in Table 1). Likewise, catalysts such as 9 lacking a hydrogen-bonding substituent were not

Asymmetric organocatalyzed synthesis of coumarin derivatives

• Natália M. Moreira,
• Lorena S. R. Martelli and
• Arlene G. Corrêa

Beilstein J. Org. Chem. 2021, 17, 1952–1980, doi:10.3762/bjoc.17.128

• amines enables both the formation of an imine ion with the enone and activation of the hydroxycoumarin by hydrogen bonding [41]. Despite the long reaction time (3 days), the desired products 3 were obtained with good to excellent yields and moderate enantiomeric excesses (Scheme 9). A new organocatalyst

• proposed transition state includes activations of the enone via an iminium ion and the coumarin by hydrogen bonding. A series of optically active polycyclic pyranocoumarin derivatives 37 was obtained in high yields with excellent enantioselectivities (up to 97% ee) (Scheme 12). Kowalczyk and Albrecht

• discussed above, the organocatalysts may also proceed by noncovalent activation, in which a hydrogen bond or an ion pair is formed. A broad variety of mono- and bifunctional chiral hydrogen-bonding organocatalysts has been developed, in special using cinchona alkaloid derivatives [52]. In this sense, Lin

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• latter strategy can be divided into the conjugation of amine groups onto ONs still attached to the solid support, or onto ONs in solution after cleavage from the solid support. The C-5 position of the pyrimidine ring has in general been the most used attachment point since it is not involved in hydrogen

• bonding and is facing the major groove upon duplex formation [27]. An illustrative approach that allowed the exploration of the 5-position of the pyrimidine ring as attachment site involved the use of 5-methoxycarbonylmethyl-2'-deoxyuridine and 5-trifluoroethoxycarbonyl-2’-deoxycytidine building blocks in

Development of N-F fluorinating agents and their fluorinations: Historical perspective

• Teruo Umemoto,
• Yuhao Yang and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2021, 17, 1752–1813, doi:10.3762/bjoc.17.123

• shown in Scheme 40, the 18-2 pyridinium series proved to be effective fluorinating agents for a wide range of substrates. Moreover, an extremely high ortho-selectivity was observed in the fluorination of phenol. This could be attributed to a hydrogen-bonding interaction between the sulfonate anion and

Chemical approaches to discover the full potential of peptide nucleic acids in biomedical applications

• Nikita Brodyagin,
• Martins Katkevics,
• Venubabu Kotikam,
• Christopher A. Ryan and
• Eriks Rozners

Beilstein J. Org. Chem. 2021, 17, 1641–1688, doi:10.3762/bjoc.17.116

• and diagnostics that depend on Watson–Crick hydrogen bonding to natural nucleic acids. An unexpected discovery of early studies was that the triplex-forming PNAs built of pyrimidine monomers formed a 2:1 PNA–DNA–PNA strand-invasion triplex instead of the expected 1:1 PNA–dsDNA triplex (c.f., Figure 2A

• features [42]. The hydrogen bonding between PNA and RNA backbones is most likely the reason behind the >10-fold higher stability PNA–dsRNA triplexes [28][29][30][31] (compared to PNA–dsDNA) that favor structures having the ideal interphosphate distance of ≈6 Å. In contrast, the interphosphate distances in

• –C triplets than J when binding to dsRNA, which was suggested to be a combined effect of improved van der Waals contacts, base stacking, hydrogen bonding, and reduced dehydration energy [98]. Replacement of three Js with Ls increased the binding affinity of a PNA 8-mer ≈4-fold [98]. In addition, the