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

• Transfer Reactions”. The present review will emphasize more recent contributions and, in particular, the application of the extended Grunwald–Winstein equation and kinetic solvent isotope effects to the solvolysis reactions. There is also an appreciable number of reports concerning the corresponding

• from linearity in Arrhenius plots, which with conventional kinetic studies would be masked by a larger random scatter within the different determinations. A precise detailed treatment allowed the “second-order” heat capacities of activation (∆Cp#) to be determined for, among many other substrates

• , methane and benzenesulfonyl chlorides [28]. The magnitude of the ∆Cp# was initially considered to be the most sensitive indicator of the extent of solvent reorganization during the substitution process. Similarly, a very accurate determination of the kinetic solvent isotope effect (ksie) for solvolysis in

DABCO-promoted photocatalytic C–H functionalization of aldehydes

• Bruno Maia da Silva Santos,
• Mariana dos Santos Dupim,
• Cauê Paula de Souza,
• Thiago Messias Cardozo and
• Fernanda Gadini Finelli

Beilstein J. Org. Chem. 2021, 17, 2959–2967, doi:10.3762/bjoc.17.205

• leads to only minor differences in the thermodynamics of the reaction and do not change the qualitative picture. The HAT step carried out with DABCO presents a kinetic barrier of 16.9 kcal·mol−1 in the gas phase while the quinuclidine-catalyzed reaction is predicted to be barrierless as shown in Figure

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• , including kinetic isotope effects and radical trapping, suggested a radical mechanism. The hydroperoxide, in the presence of an iron catalyst, abstracts the hydrogen atom alpha to the heteroatom. The alkyl radical may attack the acrylamide; subsequent intramolecular radical cyclization with the aryl ring

• the synthesis of 1-azaspiro[4.5]decanes 77 (Scheme 13) [89]. The reaction was amenable to both EWGs and EDGs; however, substitution at the ortho-position of the cinnamamide lowered the product yield. Mechanistic experiments suggest the reaction proceeds through a radical reaction. Moreover, kinetic

• radical cyclization with the activated alkene 127. Ring closing with the ortho-carbon of the aryl ring generates aryl radical 128 which was confirmed not to be the rate-determining step by kinetic isotope effect studies. Subsequently, 128 is oxidized by S2O82− and deprotonated to form the desired product

Photophysical, photostability, and ROS generation properties of new trifluoromethylated quinoline-phenol Schiff bases

• Inaiá O. Rocha,
• Yuri G. Kappenberg,
• Wilian C. Rosa,
• Clarissa P. Frizzo,
• Nilo Zanatta,
• Marcos A. P. Martins,
• Isadora Tisoco,
• Bernardo A. Iglesias and
• Helio G. Bonacorso

Beilstein J. Org. Chem. 2021, 17, 2799–2811, doi:10.3762/bjoc.17.191

• -NEt2). The inset shows the first-order kinetic profile. General view for the present study. Synthesis of ((trifluoromethyl)quinolinyl)phenol Schiff bases 3aa–fa. Synthesis of trifluoromethylated quinolinyl-phenol Schiff bases 3bb–be. Photophysical data of derivatives 3aa–fa and 3bb–be ([ ] = 1.50 × 10

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

• axial chiral compounds has been paid much attention [6], and great progress has been made in recent years. For example, many remarkable activities have been undertaken to develop strategies such as dynamic kinetic resolution, atroposelective coupling, cycloaddition, and chirality conversion for the

• (kinetic resolution) in the presence of chiral phosphoric acid CPA 3. In this work, various EWG- and EDG-containing substrates were incorporated, and chiral biaryls 10 were obtained with good to excellent selectivities of 81–93% ee by desymmetrization and 63–96% ee by kinetic resolution. The subsequent

• asymmetric addition reaction of racemic naphthylindole 42 with azodicarboxylate 43 under chiral phosphoric acid catalysis. In the presence of CPA 2, 42 and 43 reacted and underwent dynamic kinetic resolution to afford naphthylindoles 44 with axial chirality in moderate to good yields (50–98%) and high

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• nucleoside analogues. The enantiomerically pure 1,3-oxathiolane core has been an important building block in precursors that result in a defined stereochemistry of the resultant nucleoside product after N-glycosylation. Dynamic kinetic resolution (DKR) is a processes that interconverts a racemic mixture into

• -oxathiolane with Trichosporon laibachii lipase and a kinetic resolution. The synthesis of enantiopure ((R)-5-acetoxy-1,3-oxathiolan-2-yl)methyl benzoate (71) was carried out from the substrates 3a, 1,4-dithiane-2,5-diol (3q), and phenyl acetate via dynamic covalent kinetic resolution. This was a one-pot

• achieved. In 2014, Zhang et al. [64] reported an optimized asymmetric synthesis of 1,3-oxathiolan-5-ones 77 and 78 via dynamic covalent kinetic resolution using hemithioacetal chemistry coupled with a lipase-catalyzed cyclization (Scheme 25). Methyl thioglycolate (3j) was used in the reaction with aldehyde

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

• access to differently sized fragments depending on time and rotation rate. Extended sonication and scission analysis further allowed an estimation of tensile strengths of around 16 MPa for both the BTU and BTP systems. In combination with the high kinetic stability of these SPBs, the applied top-down

• benzenetrispeptide (BTP) motifs [18][19][20]. The resulting amphiphilic character of the materials facilitated a control of the kinetic assembly, which provided access to stable nanostructures on a broad length range (<100 nm–2 µm). While the process enables a good adjustment of the length, it relies on a precise

• ). It is important to note that all obtained fibers remained unchanged over several months after the top-down processing, demonstrating the previously described excellent kinetic stability of these supramolecular aggregates (Figures S15 and S16, Supporting Information File 1) [21]. Inspired by work of

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• transferred between the oxygen atoms after the alkyl migration, making it especially useful in synthetic strategies using these protected intermediates. Additionally, the reaction was found to be useful in the kinetic resolution of a racemic mixture of chiral substrates possessing both alkyl and aryl α

• -xylulose-5-phosphate reductoisomerase (DXR), uses a different mechanism to accomplish the carbon-skeleton rearrangement of its substrate 63 [19]; kinetic isotope effect experiments have excluded an α-ketol rearrangement and instead support a stepwise retro-aldol/aldol sequence for formation of intermediate

• . The catalyst is also capable of kinetic resolution of a mixture of enantiomeric substrates. Al* = 18. BF3-promoted diastereospecific rearrangement of α-ketol 21 to difluoroalkoxyborane 22. In the presence of a gold catalyst and water in 1,4-dioxane, 1-alkynylbutanol derivatives undergo tandem

Copper-catalyzed monoselective C–H amination of ferrocenes with alkylamines

• Zhen-Sheng Jia,
• Qiang Yue,
• Ya Li,
• Xue-Tao Xu,
• Kun Zhang and
• Bing-Feng Shi

Beilstein J. Org. Chem. 2021, 17, 2488–2495, doi:10.3762/bjoc.17.165

• exchange was observed at the ortho-position of 1a with 3.0 equivalents of CD3CO2D under standard conditions (Scheme 5a). Furthermore, a larger value of kinetic isotope effect (KIE = 2.4) was detected (Scheme 5b). These results indicated that the cleavage of C–H bond was most likely involved in the rate

Exfoliated black phosphorous-mediated CuAAC chemistry for organic and macromolecular synthesis under white LED and near-IR irradiation

• Azra Kocaarslan,
• Zafer Eroglu,
• Önder Metin and
• Yusuf Yagci

Beilstein J. Org. Chem. 2021, 17, 2477–2487, doi:10.3762/bjoc.17.164

• at 4.42 ppm and appearance of the new signal at 8.67 ppm corresponding to the triazole moiety confirmed successful click reaction under white LED exposure conditions after 4 h (Figure 3a). Kinetic studies conducted by 1H NMR analysis confirmed that the click reaction between benzyl azide and

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

• maintain due to the conformational lability of the seleniranium ion [52][53][54], this initial problem can be exploited through the addition of an anion-binding catalyst. In this way, the configurational scrambling is used for a dynamic kinetic resolution during the intramolecular nucleophilic opening of

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

• of Tcp in the phase diagram and the UCST is the highest value of Tcp. The cloud-point curve does not exactly match the binodal curve in the overall phase diagram [87]. This difference between cloud-points and the binodal curve is related to kinetic aspects of determining Tcp versus the thermodynamic

On the application of 3d metals for C–H activation toward bioactive compounds: The key step for the synthesis of silver bullets

• Renato L. Carvalho,
• Amanda S. de Miranda,
• Mateus P. Nunes,
• Roberto S. Gomes,
• Guilherme A. M. Jardim and
• Eufrânio N. da Silva Júnior

Beilstein J. Org. Chem. 2021, 17, 1849–1938, doi:10.3762/bjoc.17.126

• , which via a gold catalysis can be triggered to release the drug on specific sites of the target cell in a controlled manner (Scheme 15A) [123]. A proposed catalytic cycle based on kinetic isotopic effect and kinetics data is illustrated in Scheme 15D. At the beginning of the reaction, intermediate III

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

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

• Feng Xiong,
• Bo Li,
• Chenrui Yang,
• Liang Zou,
• Wenbo Ma,
• Linghui Gu,
• Ruhuai Mei and
• Lutz Ackermann

Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

• -position of the reisolated benzhydrazide 1c and product 3ca when the reaction was conducted with the isotopically labeled D2O as cosolvent (Scheme 4c). This observation indicated that the C−H cleavage is irreversible. In accordance with this finding, a kinetic isotope effect (KIE) of kH/kD ≈ 6.1 was

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