CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• environment will be scrutinized. The chapter will summarize kinetic studies and concomitant theoretical investigations on the cations formation and stability data as well as synthetic perspectives offered by the studied carbenium ions. Any discussion of the results coming from the ionization of perfluorinated

• )-substituted carbenium ion 48. Surprisingly, a relatively low kinetic effect (kH/kCF3 = 54, in TFA) was observed by comparing the solvolysis rate of tosylates 21f and 56f. For p-OMe derivatives 21a and 56a, kH/kCF3 = 2.5 (HFIP) was obtained. These ratios are very small compared to typical kH/kCF3 ratios in the

• )carbenium ion. Further studies were conducted by Lenoir and Dahn to shed light on the mechanism of the solvolysis of CF3-substituted diazoalkane derivatives (Figure 10a) [144]. They measured an inverse kinetic isotope effect of kH/kD = 0.25 for the solvolysis of 217a in dioxane/H2O 60:40 in the presence of

¹⁹F NMR as a tool in chemical biology

• Diana Gimenez,
• Aoife Phelan,
• Cormac D. Murphy and
• Steven L. Cobb

Beilstein J. Org. Chem. 2021, 17, 293–318, doi:10.3762/bjoc.17.28

• thermodynamic equilibrium binding constants (K) and kinetic rates of association (kon) and dissociation (koff) in protein–ligand binding events [37]. In order to achieve this, they analysed the binding of four different proline-rich peptides to a 5-FTrp-labelled Src homology 3 (SH3) recognition protein domain

• enthalpic and entropic contributions to their transitions. In addition, 19F NMR saturation transfer experiments allowed a convenient estimate of the kinetic rates at which the various species interconvert. This study by Prosser et al. nicely illustrates how quantitative and detailed thermodynamic and

• kinetic information for complex systems can be obtained by 19F NMR. Another rapidly expanding and particularly challenging area of research where 19F NMR has found new applications is in the field of intrinsically disordered proteins (IDPs). IDPs play a key role in cell signalling and regulation processes

Diels–Alder reaction of β-fluoro-β-nitrostyrenes with cyclic dienes

• Savva A. Ponomarev,
• Roman V. Larkovich,
• Alexander S. Aldoshin,
• Andrey A. Tabolin,
• Sema L. Ioffe,
• Jonathan Groß,
• Till Opatz and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2021, 17, 283–292, doi:10.3762/bjoc.17.27

• investigated. A series of novel monofluorinated norbornenes was prepared in up to 97% yield. The reaction with 1,3-cyclohexadiene permits the preparation of monofluorinated bicyclo[2.2.2]oct-2-enes. The kinetic data of the reactions with 1,3-cyclopentadiene and 1,3-cyclohexadiene were used to calculate

• , whereas in the absence of a strong EWG, the ratio was about 1:1 (3a). However, in contrast to CPD derivatives, the major products formed in the reaction with CHD have exo-configuration. To gain deeper insights into the reaction, we carried out some kinetic studies to evaluate and compare the reactivities

• of CHD and CPD in the reactions with model nitrostyrene 1h (Scheme 4). All the kinetic runs were performed using a ≈43–49 molar excess of the diene in o-xylene (1:1) to provide pseudo-first order conditions. Conversions (F) of 1 were measured by 1H NMR spectroscopy. The reactions were found to

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• the kinetic reactivity of difluorocyclopropanes and lowering the temperature required for the rearrangement. Furthermore, another effect of the geminal substitution was a weakening of the bond opposite to the CF2 fragment by 8–10 kcal/mol. Dolbier et al. studied the thermal rearrangements of 2,2

Insight into functionalized-macrocycles-guided supramolecular photocatalysis

• Minzan Zuo,
• Krishnasamy Velmurugan,
• Kaiya Wang,
• Xueqi Tian and
• Xiao-Yu Hu

Beilstein J. Org. Chem. 2021, 17, 139–155, doi:10.3762/bjoc.17.15

• comprehensive investigation of the kinetic and thermodynamic aspects relating to the host–guest interactions and photochemical transformation efficiency of the substrate [10][11]. Thus, this review highlights the supramolecular photocatalytic substrate transformation involving various stoichiometric host–guest

• to determine the kinetic rates of the forward and reverse reactions. Instead, the supramolecular photochemical transformation efficiency is calculated via quantum yield and reaction velocity experiments. In addition, the thermodynamic and kinetic functions of the supramolecular systems can be

• various photocatalytic reactions, there are still several issues to be addressed: 1) To develop supramolecular photocatalytic systems, it is critical to have a thorough understanding of the photochemical and photophysical aspects of the reactions, such as the kinetic equilibrium constants, the reaction

Molecular basis for protein–protein interactions

• Brandon Charles Seychell and
• Tobias Beck

Beilstein J. Org. Chem. 2021, 17, 1–10, doi:10.3762/bjoc.17.1

• perfect geometry to form the capsid irreversibly [80]. However, this approach is too simplistic and does not take into consideration kinetic traps where capsid formation cannot be completed due to a lack of assembly units. As a result, the use of assembly simulations and mathematical calculations shows

• three generalisations [81]. Firstly, errors and kinetic traps are minimised by weak interactions of the assembly units. The weak interactions result in nucleation, the second generalisation, where the initiation of capsid formation is minimised. This in return reduces the kinetic trap. Finally, the

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• ). Thus, under kinetic control, the reaction would lead to the formation of XII. However, as will be commented on later in the discussion, the experimental results clearly show the sole formation of compound 15 (Table 1), which arises from hydrolysis of an intermediate related to the complex XV. Thus, we

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

On the mass spectrometric fragmentations of the bacterial sesterterpenes sestermobaraenes A–C

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2020, 16, 2807–2819, doi:10.3762/bjoc.16.231

• the fragmentation reactions, is comparably cheap, and can often easily be introduced, e.g., into C,H-acidic positions, a drawback of deuterium usage lies in possible kinetic isotope effects [21]. Also MS/MS-based techniques have been used to study the fragmentations of terpenes [26][27][28], but

• data interpretation may be hampered by kinetic isotope effects. Nevertheless, at the current stage it cannot be excluded that such experiments could demonstrate the need for a refinement of the fragmentation mechanisms for certain fragment ions presented here. We will continue our investigations on

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

• ]. Solid-state kinetic models We then tried to define a kinetic model for the synthesis of β-CDMts. The commonly used solid-state kinetics models considered in this study were described by Khawam and Flanagan [31], and make use of an adapted version of the conversion fraction α, that we defined as the

• mechanically assisted synthesis of mono- and poly-β-CD mesitylene sulfonate (β-CDMts). Variation of the physical properties of the β-CD particles against grinding time. Supporting Information Supporting Information File 540: Determination of α, solid-state kinetic models and general procedure for the

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

• between the catechol ring of the crown ether and aromatic moieties of the secondary ammonium ion contribute to the complex formation [22][23][24][25]. Over the last 25 years, a detailed understanding of the thermodynamic and kinetic properties of crown ether/ammonium complexes has developed enabling the

• electrochemical analytical tools, e.g., cyclic voltammetry (CV), exhibit great potential to investigate the kinetic and thermodynamic parameters of the switching processes [32][33]. Although various redox-active crown ethers have been described [14][21][34], they are not commonly implemented into crown ether

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

• biomolecules with KDs in the µM range fall, the line shape and signal intensity do not directly correlate with fraction bound. It is possible to extract the kinetic interconversion rates from a full line shape analysis. The KD can then be calculated from the ratio of the on and off rate (KD = koff/kon

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

• intrinsic kinetics. This would reduce the reactor size and downstream the processing costs while increasing the safety. The design considerations for microreactors that aim at large-scale chemical synthesis are significantly different from the lab-on-a-chip concept. While gathering intrinsic kinetic data

Computational tools for drawing, building and displaying carbohydrates: a visual guide

• Kanhaya Lal,
• Rafael Bermeo and
• Serge Perez

Beilstein J. Org. Chem. 2020, 16, 2448–2468, doi:10.3762/bjoc.16.199

• an essential part of the research process, data visualisation allows not only to communicate experimental results but also is a crucial step in the integration of multiple data derived resources, such as thermodynamics and kinetic analysis, glycan arrays, mutagenesis, etc. Data visualisation remains

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

Synthesis of 1,4-benzothiazinones from acylpyruvic acids or furan-2,3-diones and o-aminothiophenol

• Ekaterina E. Stepanova,
• Maksim V. Dmitriev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2020, 16, 2322–2331, doi:10.3762/bjoc.16.193

• possibly mean, that BTA 3a was the kinetic product. Unfortunately, conduction of the reaction at −40 °C (Table 2, entry 5) did not increase the BTA 3a yield. Thus, we found two approaches to the target BTA 3a. These two approaches could be used as interchangeable in the synthesis of BTAs 3. The furandione

Azo-dimethylaminopyridine-functionalized Ni(II)-porphyrin as a photoswitchable nucleophilic catalyst

• Jannis Ludwig,
• Julian Helberg,
• Hendrik Zipse and
• Rainer Herges

Beilstein J. Org. Chem. 2020, 16, 2119–2126, doi:10.3762/bjoc.16.179

• ) does not catalyze the reaction either (Figure S6, Supporting Information File 1). Thus, it should be obvious that any catalytic effect, if detected, must be due to the DMAP unit. In our kinetic experiments, the following compounds were used as catalysts or reference compounds: record player 1 in the

• effect of the electron poor porphyrin should be weak. There are eight bonds between the porphyrin β-position and the pyridine ring including one meta-phenyl connection attenuating the through-bond conjugation. A closer look at the kinetic data in Table 1 (sample I, II, and VII) might give an explanation

• of catalyst (see Scheme 3) at 25 °C in THF-d8) to yield 7. For details see Tables S4 and S5 in Supporting Information File 1. DMAP (2), azopyridine trans-4, record player trans- and cis-1 and Ni-porphyrin 8 were used in kinetic experiments. Pseudo-first order rate constants (k) of the Henry reaction

Synergy between supported ionic liquid-like phases and immobilized palladium N-heterocyclic carbene–phosphine complexes for the Negishi reaction under flow conditions

• Edgar Peris,
• Raúl Porcar,
• María Macia,
• Jesús Alcázar,
• Eduardo García-Verdugo and
• Santiago V. Luis

Beilstein J. Org. Chem. 2020, 16, 1924–1935, doi:10.3762/bjoc.16.159

• kinetic plots for this model reaction are represented in Figure 1. The NHC–Pd catalyst 4a showed a rather reduced activity (less than 10% after two hours), while the catalyst bearing isopropyl moieties at the aromatic ring (4b) displayed a significant increase in the catalytic activity, reaching 67% yield

Synthesis, docking study and biological evaluation of ᴅ-fructofuranosyl and ᴅ-tagatofuranosyl sulfones as potential inhibitors of the mycobacterial galactan synthesis targeting the galactofuranosyltransferase GlfT2

• Marek Baráth,
• Jana Jakubčinová,
• Zuzana Konyariková,
• Stanislav Kozmon,
• Katarína Mikušová and
• Maroš Bella

Beilstein J. Org. Chem. 2020, 16, 1853–1862, doi:10.3762/bjoc.16.152

• –10 mM. Interestingly, while compound 1bα showed a dose-dependent inhibitory effect in this experiment, compound 3a did not (Table 2). Although the crude system that we used in the enzymology experiments precludes precise kinetic characterization of the studied inhibitors on the target enzyme, GlfT2

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

• displacement in the opposite direction (C4-exo or up pucker). Unsubstituted proline does not have a distinct preference towards either form, and the transition between them occurs in a relatively fast kinetic mode (barrier 10–13 kJ mol−1) [64][65]. The 2-CH multiplicity in the 1H NMR spectrum is indicative of

One-pot synthesis of isosorbide from cellulose or lignocellulosic biomass: a challenge?

• Isaline Bonnin,
• Raphaël Mereau,
• Thierry Tassaing and
• Karine De Oliveira Vigier

Beilstein J. Org. Chem. 2020, 16, 1713–1721, doi:10.3762/bjoc.16.143

• particular, in situ kinetic studies by spectroscopic methods [31] correlated to computational chemistry approaches [32] might reveal specific interaction between reactants and catalysts as well as solvent effects at work in such a complex system that should provide an understanding of the underlying reason

• for the observed unique kinetics, yields and selectivity in these one-pot reactions. In addition, such in-depth fundamental mechanistic and kinetic studies should enable determining the key structural parameters of the catalytic platform that govern its efficiency hence supporting the design of novel

Models of necessity

• Timothy Clark and
• Martin G. Hicks

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

• by a theory associating heat with motion [2]. The discovery of Brownian motion by Robert Brown in 1827 [3], followed far later by Einstein’s paper on the molecular kinetic theory of heat in 1905 [4], showed that temperature was directly linked to molecular movement. In contrast to the common picture

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

• (Figure S10, Supporting Information File 1). This behavior does not contradict the ITC measurements and can be attributed to the kinetic isotope effect. Although, D-bonding is generally stronger than H-bonding, its contribution to the peptide–peptide binding can be weakened by even stronger competitive

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

In silico rationalisation of selectivity and reactivity in Pd-catalysed C–H activation reactions

• Liwei Cao,
• Mikhail Kabeshov,
• Steven V. Ley and
• Alexei A. Lapkin

Beilstein J. Org. Chem. 2020, 16, 1465–1475, doi:10.3762/bjoc.16.122

• on the reaction path. In this case, the intermediates are likely to be close to, and resemble, transition states. Due to that, their relative energy of formation can be translated to relative reaction kinetic barriers and thus be used, as the first approximation, to predict distributions of the final

• and the appropriate mechanism, but also provides information for further kinetic studies and process development, thus contributing to the development of robust new chemical transformations. An approximate energy map for the electrophilic aromatic substitution mechanism. Schematic representation of