All-carbon [3 + 2] cycloaddition in natural product synthesis

• Zhuo Wang and
• Junyang Liu

Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251

•  3A). Trost and co-workers proposed that the catalytic mechanism involves an oxidative addition of palladium(0) into 62 affording the η3-Pd TMM complex A [37] (Scheme 3B). Methyl trimethylsilyl carbonate (64) is formed as side product, which is in equilibrium with carbon dioxide and methyl

• -workers proposed that the catalytic mechanism involves a reaction between phosphine catalyst A and allene 82 to give B and/or C (Scheme 5B). Catalytic [3 + 2] cycloaddition of B and/or C and alkene D gives the cyclic intermediates E and F in an equilibrium state through a 1,2-proton transfer. The loss of

Using multiple self-sorting for switching functions in discrete multicomponent systems

• Amit Ghosh and
• Michael Schmittel

Beilstein J. Org. Chem. 2020, 16, 2831–2853, doi:10.3762/bjoc.16.233

• reversed back to the initial state (Figure 15b). Here, all translocations happen in an off-equilibrium system. Since the kinetic evolution of the lithium pulses was followed by color and luminescence changes of the lithium-sensitive probe 36, the system is suited for a multitude of new applications

• translocation, monitored by distinct emission colors. b) Working principle of the chemical fuel 50. Off-equilibrium lithium pulses generate c) SOS morse signals, and d) sawtooth signals. Adapted with permission from (Ghosh, A.; Paul, I.; Schmittel, M. J. Am. Chem. Soc. 2019, 141, 18954–18957 [61]). Copyright

Dirhamnolipid ester – formation of reverse wormlike micelles in a binary (primerless) system

• David Liese,
• Hans Henning Wenk,
• Xin Lu,
• Jochen Kleinen and
• Gebhard Haberhauer

Beilstein J. Org. Chem. 2020, 16, 2820–2830, doi:10.3762/bjoc.16.232

• G''min. The reciprocal of the frequency where G'' has a minimum approximately corresponds to the breaking/recombination time τb of the reverse micelles, which are self-organized systems that undergo constant scission and recombination processes in a dynamic equilibrium [36]. Therefore, τb is the

• increase in the number of micelles can be explained by the breakup of big branched micelles into plenty of small ones. At elevated temperatures, the micelles can dissolve into surfactant monomers (dynamic equilibrium), which then leads to a decrease in the number of micelles. The relaxation time (τR

Synthesis and investigation of quadruplex-DNA-binding, 9-O-substituted berberine derivatives

• Jonas Becher,
• Daria V. Berdnikova,
• Heiko Ihmels and
• Christopher Stremmel

Beilstein J. Org. Chem. 2020, 16, 2795–2806, doi:10.3762/bjoc.16.230

• enthalpy of the ligand binding (ΔHb) is hardly accessible. Hence, we explain the very low ΔTm values for G4-DNA a2 in the presence of the ligands 4a–e with a very low affinity of these ligands at the melting temperature, which may be caused by the delicate, temperature-dependent equilibrium of the

• . Additional information about the complex formation between the ligands and the quadruplex DNA forms 22AG and a2 was provided by CD spectroscopy. The changes of the CD spectrum of 22AG upon the addition of derivatives 4a–e clearly indicate a shift of the equilibrium between the different quadruplex forms of

• the characteristic CD pattern with a strong positive band at 295 nm and a weak negative one at 260 nm [60]. These observations show that all ligands stabilize preferentially the basket-type quadruplex structure of 22AG. In the case of the G4-DNA a2 the addition of the ligands shifts the equilibrium

Activation of pentafluoropropane isomers at a nanoscopic aluminum chlorofluoride: hydrodefluorination versus dehydrofluorination

• Maëva-Charlotte Kervarec,
• Thomas Braun,
• Mike Ahrens and
• Erhard Kemnitz

Beilstein J. Org. Chem. 2020, 16, 2623–2635, doi:10.3762/bjoc.16.213

• dehydrofluorination product 2,3,3,3-tetrafluoropropene (HFO-1234yf, 1) and the isomerization product 1,1,1,2,2-pentafluoropropane (HFC-245cb, 10b) in a 1:2 ratio (Scheme 2, top) with almost full conversion. The group of Kemnitz previously showed that 1 and 10b can be in an equilibrium when HF is present in the

• equilibrium between 5 and 6, that depends on the amount of HF or HSiEt3 present in the reaction mixture. Additionally, it is conceivable that 14 can further react to form 5 via allylic hydrodefluorination [16]. Therefore, the reactivity of 14 was tested in the presence of ACF and silane in C6D12 or C6D6

Anion exchange resins in phosphate form as versatile carriers for the reactions catalyzed by nucleoside phosphorylases

• Julia N. Artsemyeva,
• Ekaterina A. Remeeva,
• Tatiana N. Buravskaya,
• Irina D. Konstantinova,
• Roman S. Esipov,
• Anatoly I. Miroshnikov,
• Natalia M. Litvinko and
• Igor A. Mikhailopulo

Beilstein J. Org. Chem. 2020, 16, 2607–2622, doi:10.3762/bjoc.16.212

• letter to the editor Kalckar reported for the first time that specific inosine nucleosidase from rat liver catalyzes the reversible reaction “inosine + phosphate ⇌ hypoxanthine + ribose-1-phosphate”: the equilibrium of this reaction in water at pH 6.5 is displaced to the nucleoside synthesis. Moreover

• , he made the very interesting observation that the reaction of hypoxanthine and ribose-1-phosphate reached equilibrium after 20 min at a 70% concentration of inosine and “The synthesis of inosine would probably proceed further if all traces of inorganic phosphate were removed, since with equimolar

• -phosphate buffer, pH 7.4; 45 °C) [41]. It was shown that the N7-isomer formed predominantly at the beginning of the reaction and the ratio of N7- and N9-isomers displaced gradually to the latter getting equilibrium at ca. 1:4.8 ratio after 24 h. Results and Discussion The analysis of the experimental works

Particle size effect in the mechanically assisted synthesis of β-cyclodextrin mesitylene sulfonate

• Stéphane Menuel,
• Sébastien Saitzek,
• Eric Monflier and
• Frédéric Hapiot

Beilstein J. Org. Chem. 2020, 16, 2598–2606, doi:10.3762/bjoc.16.211

• occur over longer times, suggesting that shear, friction, and collision effects did not anymore affect the β-CD particle size and morphology over time. In fact, crystal breaking reduced the particle size up to some critical threshold, as a result of the equilibrium between comminution and aggregation

• . While the deprotonation/protonation equilibrium preferentially takes place at the 2- and 6-positions of the β-CD [29], the alkoxide located on the primary face at the 6-position is more inclined to react with the bulky mesitylenesulfonate group than the alkoxide on the secondary face at the 2-position

Thermodynamic and electrochemical study of tailor-made crown ethers for redox-switchable (pseudo)rotaxanes

• Henrik Hupatz,
• Marius Gaedke,
• Hendrik V. Schröder,
• Julia Beerhues,
• Arto Valkonen,
• Fabian Klautzsch,
• Sebastian Müller,
• Felix Witte,
• Kari Rissanen,
• Biprajit Sarkar and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2020, 16, 2576–2588, doi:10.3762/bjoc.16.209

• anticipated sigmoidal shape of a 1:1 bonded complex (see Figure S5a in Supporting Information File 1). The curve shape suggests a more complex chemical equilibrium that involves more than one chemical process generating heat, taking place in the titration experiment. One process is likely a proton transfer

• ). These results suggest that both ammonium axles form a similar type of equilibrium with NDIC7, where the protonation of the tertiary amine and the complexation in a nonthreaded complex might contribute. When using BArF24− as the counterion for A1, the binding energies increase by 6–8 kJ/mol, which

• . Both compounds exhibit two reversible reduction processes. The lariat ether NDIC7 is not suitable for rotaxane synthesis as it forms a complex equilibrium involving the deprotonation of the secondary ammonium axle and does not form 1:1 pseudorotaxanes. Additionally, the pseudorotaxane is hampered by

Comparative ligand structural analytics illustrated on variably glycosylated MUC1 antigen–antibody binding

• Christopher B. Barnett,
• Tharindu Senapathi and
• Kevin J. Naidoo

Beilstein J. Org. Chem. 2020, 16, 2540–2550, doi:10.3762/bjoc.16.206

• analysis were carried out. These analyses were used to rapidly assess key features of the system, interrogate the dynamic structure of the ligand, and determine the role of glycosylation on the conformational equilibrium. The glycopeptide conformations in solution change relative to the peptide; thus a

• -structure relative to the random coil and the effects of the glycosylation were hypothesized to relate to the conformational properties of the peptides in solution (as opposed to their equilibrium structures in solution) [25]. A comprehensive structural study of the O-glycosylation-induced changes in a

• equilibrium of the peptide backbone near the glycosylated residue for a 15-residue mucin peptide. The APDTRP fragment resembled an S-shaped bend and a clustering of low-energy conformations revealed structural similarities between glycosylated and nonglycosylated peptides [23]. The work by Movahedin et al

NMR Spectroscopy of supramolecular chemistry on protein surfaces

• Peter Bayer,
• Anja Matena and
• Christine Beuck

Beilstein J. Org. Chem. 2020, 16, 2505–2522, doi:10.3762/bjoc.16.203

• a direct measure of the fraction bound and can be used directly to determine the dissociation constant (KD), provided sufficient saturation can be reached [83]. Line broadening occurs due to chemical exchange, that is the interconversion of at least two species in an equilibrium, e.g., the free and

• , a 15N weighting factor of WN = 0.154 was determined [97]. In the case of a two-state equilibrium, signals always shift in a straight line and produce a hyperbolic binding curve [83]. If the signal trajectory is curved, more than one binding site contributes to the chemical shift perturbation. In

• relative intensities of the binary complex in the absence of a stabilizing ligand indicate kinetics of the binding equilibrium in the fast-to-intermediate time regime, resulting in line broadening. In the presence of a stabilizing ligand, a ternary complex consisting of 14-3-3, the peptide and the ligand

Dawn of a new era in industrial photochemistry: the scale-up of micro- and mesostructured photoreactors

• Emine Kayahan,
• Mathias Jacobs,
• Leen Braeken,
• Leen C.J. Thomassen,
• Simon Kuhn,
• Tom van Gerven and
• M. Enis Leblebici

Beilstein J. Org. Chem. 2020, 16, 2484–2504, doi:10.3762/bjoc.16.202

• of the photocatalytic oxidation of thiophenol to phenyl disulfide using a Taylor flow in a microreactor that consists of a capillary tube. By varying the flow rate of the gas and liquid phase and comparing the oxygen concentration in the liquid phase with the equilibrium concentration without a

Conformational preferences of fluorine-containing agrochemicals and their implications for lipophilicity prediction

• Daniela Rodrigues Silva,
• Joyce K. Daré and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2020, 16, 2469–2476, doi:10.3762/bjoc.16.200

• conformational equilibrium of penoxsulam (I, Figure 1). This compound has a 1,2–disubstituted ethane motif that could adopt three main staggered conformations, namely Igg, Iag and Iga (g = gauche and a = anti; see Figure 1), thus we have explored the intramolecular interactions governing its conformational

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• a CPA provided good enantioselectivity (Scheme 20) [69]. The putative mechanism proceeds via a reductive quenching cycle to give α-amino radical 145• after decarboxylation, which is then oxidised further to the imine 146 in the presence of oxygen. Imine 146 is in equilibrium with the enamine

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator

• Poulami Jana,
• Filip Šupljika,
• Carsten Schmuck and
• Ivo Piantanida

Beilstein J. Org. Chem. 2020, 16, 2201–2211, doi:10.3762/bjoc.16.185

• longer incubation times [23][26][27], the time required for reaching equilibrium was checked by repeatedly collecting UV–vis spectra of compound 4 upon the additions of DNA or RNA aliquots to the dye solution in 10 s intervals. The results showed that an incubation period of 180 s proved to be sufficient

• for reaching thermodynamic equilibrium. It should be stressed that all changes in the 330–400 nm range could be attributed dominantly to the NDI chromophore, since absorbance of GCPs in this range is negligible. Absorbance changes of large aromatic chromophores upon DNA or RNA addition can happen for

• calorimetry experiments (ITC), which allowed us to determine all thermodynamic components simultaneously in a single experiment (the equilibrium binding constant (Ka), reaction Gibbs free energy of binding (ΔrG), reaction enthalpy (ΔrH), reaction entropy (ΔrS), and the stoichiometry (n) of the complex formed

Isolation and structure determination of a tetrameric sulfonyl dilithio methandiide in solution based on crystal structure analysis and ⁶Li/¹³C NMR spectroscopic data

• Jürgen Vollhardt,
• Hans Jörg Lindner and
• Hans-Joachim Gais

Beilstein J. Org. Chem. 2020, 16, 2057–2063, doi:10.3762/bjoc.16.172

• in THF solution in fast equilibrium with a further aggregate, which is stable only at low temperatures. Keywords: crystal structure; dilithio sulfonyl methandiide; NMR; solution structure; X-ray analysis; Introduction Functionalized dilithio methandiides I–III (Figure 1) are a fascinating class of

• 6Li NMR spectroscopy of 13C,6Li-2a in [D8]THF [15][51][52][53] had shown an aggregate, 2a-I, which is present in the whole temperature range from 22 °C to −103 °C. The formation of a further equilibrium aggregate, 2a-II, was detected from −50 °C downwards. The equilibrium between the aggregates lies

• –dimer equilibrium. Bonding of the dianionic C atoms 6Li NMR spectroscopy of tetramer 2a-I had revealed a dianionic carbon atom, C1B, carrying two different Li atoms, a bonding situation which is reflected by the two different 6Li,13C coupling constants. It was thus of particular interest to see whether

How and why plants and human N-glycans are different: Insight from molecular dynamics into the “glycoblocks” architecture of complex carbohydrates

• Carl A. Fogarty,
• Aoife M. Harbison,
• Amy R. Dugdale and
• Elisa Fadda

Beilstein J. Org. Chem. 2020, 16, 2046–2056, doi:10.3762/bjoc.16.171

• different N-glycoforms can be represented as a combination of spatial self-contained units, named “glycoblocks”, rather than in terms of monosaccharides and linkages. We find that this approach helps our understanding of N-glycans architecture in terms of equilibrium structures and relative populations and

• found predominantly in an outstretched (66%, cluster 1) conformation, rather than folded over (34%, clusters 1 and 2), see Table S1 in Supporting Information File 1. The addition of a terminal β(1-3)-Gal in the gf N-glycan pushes the equilibrium towards an outstretched (1-6) arm even further, with the

• open conformation populated at 72%, see Table S2 in Supporting Information File 1. Interestingly, in the case of α(1-6) core fucosylated N-glycans, and with double fucosylation as discussed later on, the equilibrium of the (1-6) arm was the exact opposite, with a predominance of the folded conformation

Naphthalene diimide–amino acid conjugates as novel fluorimetric and CD probes for differentiation between ds-DNA and ds-RNA

• Annike Weißenstein,
• Myroslav O. Vysotsky,
• Ivo Piantanida and
• Frank Würthner

Beilstein J. Org. Chem. 2020, 16, 2032–2045, doi:10.3762/bjoc.16.170

• we took advantage of the fluorescence of 3a,b, and 5. Since suspected threading intercalation usually requires longer incubation times, the time required for reaching equilibrium was checked by repeatedly collecting emission spectra upon additions of DNA or RNA aliquots to the dye solution

Design, synthesis and application of carbazole macrocycles in anion sensors

• Alo Rüütel,
• Ville Yrjänä,
• Sandip A. Kadam,
• Indrek Saar,
• Mihkel Ilisson,
• Astrid Darnell,
• Kristjan Haav,
• Tõiv Haljasorg,
• Lauri Toom,
• Johan Bobacka and
• Ivo Leito

Beilstein J. Org. Chem. 2020, 16, 1901–1914, doi:10.3762/bjoc.16.157

• for visualization. An equilibrium likely existed between two conformers where one complex had an additional hydrogen bond and the other included intramolecularly bonded lactate. For the lactate complexes with the larger receptors, whether one dominant conformer or a mixture of two conformers was

Polarity effects in 4-fluoro- and 4-(trifluoromethyl)prolines

• Vladimir Kubyshkin

Beilstein J. Org. Chem. 2020, 16, 1837–1852, doi:10.3762/bjoc.16.151

• , although the exact nature of this interaction (orbital or dipolar) is debatable [82]. Result of this effect though, is that the trans-fluoroproline shifts the equilibrium towards a higher abundance of the trans-amide, while cis-fluoroproline promotes the cis-amide (Figure 8). This was indeed found in the

• influence onto the trans/cis ratio. In contrast, the gauche-effect in fluoroprolines causes a much stronger stabilization of the C4-conformations, as this propagates into stronger effects in the trans/cis equilibrium. In addition, there is a weak but systematic modulation in the trans/cis equilibrium caused

• /cis equilibrium values (Ktrans/cis) were different in 5 compared to the non-fluorinated reference 7. Likewise, the trans/cis equilibrium in 3 is similar to the unsubstituted proline. Conversely, in compound 6, there was a higher content of the C4-endo conformation, a lower trans/cis equilibrium ratio

Tuneable access to indole, indolone, and cinnoline derivatives from a common 1,4-diketone Michael acceptor

• Dalel El-Marrouki,
• Sabrina Touchet,
• Abderrahmen Abdelli,
• Hédi M’Rabet,
• Mohamed Lotfi Efrit and
• Philippe C. Gros

Beilstein J. Org. Chem. 2020, 16, 1722–1731, doi:10.3762/bjoc.16.144

• leading to the formation of the indolone 7 starts with an imine formation between the secondary amine and the nonconjugated carbonyl from the 1,4-diketone. After an imine–enamine equilibrium, an intramolecular 1,4-addition to the Michael acceptor part of the molecule occurs, followed by a prototropy

• , leading to an intermediate enol that, after a keto–enol equilibrium and aromatization, gives the indolone 7. For the indole 6 and the cinnoline 8, the synthesis starts with the protonation of the oxygen atom of the conjugated carbonyl group of the 1,4-diketone, followed by an imine formation between the

• secondary amine and the nonconjugated carbonyl unit. Next, an intramolecular 1,2-addition to the Michael acceptor part of the molecule, previously activated by acid catalysis, takes place (after an imine–enamine equilibrium for the indole pathway), followed by a prototropy, the release of a water molecule

Models of necessity

• Timothy Clark and
• Martin G. Hicks

Beilstein J. Org. Chem. 2020, 16, 1649–1661, doi:10.3762/bjoc.16.137

• become apparent [40]. This is because non-equilibrium structures such as transition states that cannot be described by the conventional Lewis model are passed through during reactions. Quantum chemical methods, often in combination with molecular dynamics, can predict the course of a specific reaction

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• intermediates 13, results in hydroxyisoindolines 11, which can finally tautomerize to aldehydes 2a,b. In the previous report, we have demonstrated the existence of an equilibrium in the course of the transformation of 1a to 2a by trapping isoindole intermediate 4a with N-phenylmaleimide as a dienophile in the

• acid-catalyzed reaction of both aldehydes 1a and 2a [1]. Moreover, as a reverse reaction, the formation of aldehyde 1a was observed in the transformation of aldehyde 2a under similar conditions [1]. However, this equilibrium is obviously influenced by the formation of the dimer-like products. The

• ), and δC= (142.5) showed a considerable line-broadening (coalescence), revealing a partially hindered rotation of the formylphenyl moiety, i.e., the occurrence of a conformational equilibrium has to be taken into account. Even the δHC−N 13C NMR signal remained under the noise level, indicating that the

A dynamic combinatorial library for biomimetic recognition of dipeptides in water

• Florian Klepel and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2020, 16, 1588–1595, doi:10.3762/bjoc.16.131

• library to be under thermodynamic control. Therefore, the equilibrium responds to stimuli such as addition of a template, which would stabilize a suitable receptor and thus amplifies its formation. This strategy has led to the discovery of many artificial receptors [7][8][9][10], with thiolate disulfide

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• intermolecular interactions (NCIs) between aromatic rings (π···π) [58][59] and alkyl and aromatic ring (Csp3–H)···π stackings [59][60][61][62] are widely recognized, from both the experimental and theoretical viewpoint, as a major factor governing the conformational equilibrium, supramolecular assembly and