Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

• Thiago S. Silva and
• Fernando Coelho

Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

• -cyclization products was attributed to the better overlap between the π-orbital of the enolic carbon atom and the π*-orbital of the complexed olefin terminal carbon. This suggests that, in these cases, the 6-endo-trig cyclizations are under kinetic control. The substrate generality in the methodology

• methylcycloalkanes (94a and 94b) and the terminal olefin 93 (Scheme 37A). Both examples showed perfect regioselectivity for the functionalization of the tertiary C(sp3)–H bond. Mechanistic studies carried out by the authors revealed a strong kinetic isotope effect (KIE = 11.5:1) when a competitive reaction was

Co-crystallization of an organic solid and a tetraaryladamantane at room temperature

• Fabian Rami,
• Jan Nowak,
• Felix Krupp,
• Wolfgang Frey and
• Clemens Richert

Beilstein J. Org. Chem. 2021, 17, 1476–1480, doi:10.3762/bjoc.17.103

• different from inducing two solids to co-crystallize, as the solvent does not have the propensity to form its own crystal lattice at the chosen temperature. Stepping back, one may ask what the difficulties are that usually preclude the formation of co-crystals. The difficulties probably have both kinetic

• that the encapsulation of the guest molecules in the crystals occurs as a kinetic phenomenon [17]. The TAA finds a crystalline arrangement quickly, without full desolvation, and once the crystal lattice has formed, the guest molecule is unable to escape from it, blocking the path to solvent-free

• initially suspected that a slow crystallization, induced by evaporation or diffusion, would make it unlikely to obtain co-crystals, as the long time intervals involved should favor a thermodynamic, rather than a kinetic product. In other words, starting from a solution (I), we expected to find a

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• -Michael reaction, it was possible to reach either cis- or trans-isoindolines, 69 and 70, respectively, from the same precursor 68. The authors proposed that the thermodynamically more stable cis-isomer 69 is formed when TBAF was used. Meanwhile, working under kinetic conditions (DBU as base), trans-isomer

Kinetics of enzyme-catalysed desymmetrisation of prochiral substrates: product enantiomeric excess is not always constant

• Peter J. Halling

Beilstein J. Org. Chem. 2021, 17, 873–884, doi:10.3762/bjoc.17.73

• Peter J. Halling WestCHEM, Dept Pure & Applied Chemistry, University of Strathclyde, Glasgow G1 1XL, Scotland, UK 10.3762/bjoc.17.73 Abstract The kinetics of enzymatic desymmetrisation were analysed for the most common kinetic mechanisms: ternary complex ordered (prochiral ketone reduction); ping

• -pong second (ketone amination, diol esterification, desymmetrisation in the second half reaction); ping-pong first (diol ester hydrolysis) and ping-pong both (prochiral diacids). For plausible values of enzyme kinetic parameters, the product enantiomeric excess (ee) can decline substantially as the

• study if and how the product ee declines at high conversion. Keywords: enantiomeric excess; enzyme; kinetic mechanisms; kinetic parameters; prochiral; Introduction There is great interest in using enzymatic catalysis in the synthesis of homochiral molecules. An early approach was to use

Chiral isothiourea-catalyzed kinetic resolution of 4-hydroxy[2.2]paracyclophane

• David Weinzierl and
• Mario Waser

Beilstein J. Org. Chem. 2021, 17, 800–804, doi:10.3762/bjoc.17.68

• David Weinzierl Mario Waser Institute of Organic Chemistry, Johannes Kepler University Linz, Altenbergerstrasse 69, 4040 Linz, Austria 10.3762/bjoc.17.68 Abstract We herein report a method for the kinetic resolution of racemic 4-hydroxy[2.2]paracyclophane by means of a chiral isothiourea

• -catalyzed acylation with isobutyric anhydride. This protocol allows for a reasonable synthetically useful s-factor of 20 and provides a novel entry to obtain this interesting planar chiral motive in an enantioenriched manner. Keywords: acylation; kinetic resolution; nucleophilic catalysis; paracyclophanes

• out kinetic resolutions of easily accessed racemic precursors [3][4][13][14][15]. 4-Hydroxy[2.2]paracyclophane (2) is one of the commonly used building blocks, which is easily accessible in a racemic manner starting from 1 according to nowadays well-established procedures [16][17][18]. Over the last

Simulating the enzymes of ganglioside biosynthesis with Glycologue

• Andrew G. McDonald and
• Gavin P. Davey

Beilstein J. Org. Chem. 2021, 17, 739–748, doi:10.3762/bjoc.17.64

• includes cellular transport and recycling. A limitation of the model is that it considers only absolute changes to enzyme activity, in which an activity is either off or on, which a kinetic model based on differential-equation-based rate laws [44][45][46][47][48] or stochastic kinetics [49][50] would

• improve upon. Nevertheless, we have shown that the knockouts are able to reproduce the distinct species-specific features and disease states arising from congenital defects of ganglioside biosynthesis. Kinetic models based on the networks described here can be generated in modelling software, using the

[2 + 1] Cycloaddition reactions of fullerene C₆₀ based on diazo compounds

• Yuliya N. Biglova

Beilstein J. Org. Chem. 2021, 17, 630–670, doi:10.3762/bjoc.17.55

• chromatography (HPLC) (methanol/toluene as the eluent) to isolate a reddish-brown powder of methanofullerene 3 in 21% yield (Scheme 4). Similar to photolysis, the thermal rearrangement of kinetic products gives [6,6]-closed isomers that are thermodynamically more stable. After some time, the team of scientists

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• ) and 1 wt % Zn(OAc)2 loading (Table 2, entry 1) [201]. The system resulted in partial selectivity to BHET due to the formation of significant amounts of oligomers, mainly BHET dimers, which increased upon standing. The kinetic of the zinc acetate-promoted process was studied over a range of reaction

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• proline replacements are able to elevate the protein expression speed and yields and improve the thermodynamic and kinetic folding profiles of individual proteins. In this context, fluoroprolines can be viewed as useful tools in the biotechnological toolbox. As a prospect, we envision that proteome-wide

• residue that appear altered in fluoroprolines. The first one to mention is the conformation of the pyrrolidine ring, which exhibits a dynamic transition between several distinct states in a relatively fast kinetic mode (roughly on a GHz scale) [48][49]. For simplicity, two conformations are considered

• preferences should be considered when judging the stability of the folded structures containing fluoroprolines. 2.6 Kinetics of the amide rotation The kinetic stability of the amide conformers generates another important aspect of protein folding. Generally, the amide rotation is considered very slow in

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