Mechanochemical synthesis of unsymmetrical salens for the preparation of Co–salen complexes and their evaluation as catalysts for the synthesis of α-aryloxy alcohols via asymmetric phenolic kinetic resolution of terminal epoxides

• Shengli Zuo,
• Shuxiang Zheng,
• Jianjun Liu and
• Ang Zuo

Beilstein J. Org. Chem. 2022, 18, 1416–1423, doi:10.3762/bjoc.18.147

• the unsymmetrical salens with zinc, copper, and cobalt was studied and the chiral Co–salen complex 2f was obtained in 98% yield. Hydrolytic kinetic resolution (HKR) of epichlorohydrin with water catalyzed by complex 2f (0.5 mol %) was explored and resulted in 98% ee, suggesting complex 2f could serve

• with regard to conformational differences, for instance, oligosalen [14], macrocyclic oligosalen [15], and polymeric salen [16]. Jacobsen and co-workers reported the first synthesis of α-aryloxy alcohols through the phenolic kinetic resolution (KR) of terminal epoxides using a Co–salen catalyst [17

• were explored as well. Furthermore, we present the hydrolytic kinetic resolution (HKR) of epichlorohydrin with water using Co–salen complexes 2, and α-aryloxy alcohols were synthesized by the 2f catalytic system through the asymmetric ring opening of epichlorohydrin and phenols. Results and Discussion

On drug discovery against infectious diseases and academic medicinal chemistry contributions

• Yves L. Janin

Beilstein J. Org. Chem. 2022, 18, 1355–1378, doi:10.3762/bjoc.18.141

• miniaturization to undertake fast screening campaigns of very large chemical libraries using targets and/or phenotypic-based assays. – The development of structural sciences providing very precise ideas on the kinetic, thermodynamic or on the mode of interactions of chemicals with their biochemical targets. Which

Cyclodextrin-based Schiff base pro-fragrances: Synthesis and release studies

• Attila Palágyi,
• Jindřich Jindřich,
• Juraj Dian and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2022, 18, 1346–1354, doi:10.3762/bjoc.18.140

• stability towards hydrolysis. Kinetic studies of the imine hydrolysis by NMR For the kinetic studies of the hydrolysis of imino-CDs, we selected the pro-fragrance 3d made from the most common aldehyde – benzaldehyde. The release of the benzaldehyde (2d) was studied by 1H NMR spectroscopy. Aqueous 0.1 M

• that CD-based pro-fragrances combine a chemical barrier, as the aldehydes are linked to the CD via imine bond, and a physicochemical (supramolecular) barrier, as we established that aldehydes formed inclusion complexes in aqueous solution with β-CD. We confirmed from the NMR kinetic study of the imine

• 1H, 150.04 MHz for 13C) and Varian UNITYINOVA 400 (399,95 MHz for 1H and 100,58 MHz for 13C) spectrometers. For the kinetic studies, the 1H NMR spectra were acquired on a Varian VNMRS 300 spectrometer (300 MHz for 1H). DMSO-d6 and D2O were used as the solvents. The chemical shift values (δ) are given

Make or break: the thermodynamic equilibrium of polyphosphate kinase-catalysed reactions

• Michael Keppler,
• Sandra Moser,
• Henning J. Jessen,
• Christoph Held and
• Jennifer N. Andexer

Beilstein J. Org. Chem. 2022, 18, 1278–1288, doi:10.3762/bjoc.18.134

• concentrations of substrate, the different kinetic preferences of PPK1 and PPK2 can be observed. The implications of these results for the application of PPKs in chemical synthesis and as enzymes for ATP regeneration systems are discussed. Keywords: ATP regeneration; biocatalyst; ePC-SAFT; polyp; PPK

• substrate bonds (Figure 2e) [17]. Apart from the structures, the kinetic preference of either polyP synthesis (NTP usage) or NTP synthesis (polyP degradation) has been described to be a characteristic feature of PPK1 and PPK2(-I), respectively (Figure 2a). This is supported by analysis of the kinetic

• cholerae is very similar to the one from E. coli with 82% similarity (64% identity) on the amino acid level; however, it was described to show kinetic preferences of a PPK2 [20]. While the PPK2 from P. aeruginosa catalyses both synthesis and usage of ATP with kinetic preference for ATP synthesis, the

Ferrocenoyl-adenines: substituent effects on regioselective acylation

• Mateja Toma,
• Gabrijel Zubčić,
• Jasmina Lapić,
• Senka Djaković,
• Davor Šakić and
• Valerije Vrček

Beilstein J. Org. Chem. 2022, 18, 1270–1277, doi:10.3762/bjoc.18.133

• kinetic and thermodynamic control of the acylation reaction. Results and Discussion It was shown that the reaction between the pyrimidine anion (uracil, thymine, or 5-fluorouracil) and FcCOCl in N,N-dimethylformamide (DMF) proceeded in a full regiospecific mode [19]. In the purine series, however, the

Enantioselective total synthesis of putative dihydrorosefuran, a monoterpene with an unique 2,5-dihydrofuran structure

• Irene Torres-García,
• Josefa L. López-Martínez,
• Rocío López-Domene,
• Manuel Muñoz-Dorado,
• Ignacio Rodríguez-García and
• Miriam Álvarez-Corral

Beilstein J. Org. Chem. 2022, 18, 1264–1269, doi:10.3762/bjoc.18.132

• stereoselective kinetic resolution of allenol 3 via lipase AK-catalyzed acetylation [15]. In this way, unaltered, (−)-hydroxyallene 3 could be separated from (+)-acetyl derivative 9 through standard column chromatography (Scheme 3). Enantiomeric excesses of (−)-3 and (+)-9 were determined by chiral HPLC analyses

Experimental and theoretical studies on the synthesis of 1,4,5-trisubstituted pyrrolidine-2,3-diones

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Nguyen Ngoc Tri,
• Luc Van Meervelt,
• Nguyen Tien Trung and
• Wim Dehaen

Beilstein J. Org. Chem. 2022, 18, 1140–1153, doi:10.3762/bjoc.18.118

• proposed based on computational results and the main product is formed favorably following the PES via the lowest ΔG# pathway in both the gas-phase and an ethanol solvent model. DFT calculations showed that kinetic selectivity is more significant than thermodynamic selectivity for forming main products

• , the reaction pathway starting from 4a through IS3 and finally yielding 10ab-v2 is a more favorable one in both thermodynamic (ΔG) and kinetic (ΔG#) aspects (red and black lines) in comparision with going through IS5 to achieve the 10ab product. For the reaction originating from 4a’, passing through

• IS5 and finally forming product 10ab is the most preferred pathway, and even more favorable than both directions from 4a to yield 10ab-v2. Hence, the reaction routes to obtain 10ab-v2 are thermodynamically favorable, while yielding 10ab is under kinetic control. In order to better evaluate the

Understanding the competing pathways leading to hydropyrene and isoelisabethatriene

• Shani Zev,
• Marion Ringel,
• Ronja Driller,
• Bernhard Loll,
• Thomas Brück and
• Dan T. Major

Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97

• . We show that there is a great thermodynamic preference for hydropyrene and hydropyrenol formation, and hence most likely in the synthesis of the isoelisabethatriene products kinetic control is at play. Keywords: diterpenes; enzyme mechanism; quantum mechanics; terpene synthases; thermodynamic and

• kinetic control; Introduction Terpenes constitute a ubiquitous class of natural molecules that are synthesized by terpene synthases (TPS). TPS generate a plethora of terpenes employing rich carbocation chemistry from a very limited number of substrates, known as geranyl pyrophosphate (GPP), farnesyl

• on the mechanistic details of the HP and IE pathways using computational methods in the gas phase. Gas-phase studies have been crucial in understanding terpene chemistry [10][11][12][13][14][15][16][17][18][19][20][21][22]. This work sheds light on the thermodynamic and kinetic parameters of the

Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple

• Alexander S. Filatov,
• Olesya V. Khoroshilova,
• Anna G. Larina,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77

• revealed that the cycloaddition reactions are under kinetic control and belong to the class of inverse electron demand 1,3-DC reactions. We believe that the outcome of this work will serve as a basis for developing synthetic approaches to other bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• [41][42][43]. Crystal structures of COXs The structural basis for the di-peroxide formation reaction by COXs has been substantially elucidated by electron paramagnetic resonance (EPR), kinetic analysis, X-ray crystallography, and mutagenesis experiments [24][44][45]. The structural analyses of

• . Catalytic residue in the cyclooxygenase reaction The formation of a tyrosyl radical during the catalytic cycle was proved by EPR and kinetic analyses [59][60][61]. Moreover, chemical and molecular biology analyses and a mutagenesis experiment identified the position of the tyrosyl radical. Treatment of the

• , including kinetic, UV–vis absorption, and EPR analyses of FtmOx1 wild type and its Y68F, Y74F, Y140F, and Y224F variants [70]. Their results revealed that the Y68F variant did not accumulate the initial tyrosyl radical and the formation of verruculogen was significantly decreased, while the Y224F variant

Inductive heating and flow chemistry – a perfect synergy of emerging enabling technologies

• Conrad Kuhwald,
• Sibel Türkhan and
• Andreas Kirschning

Beilstein J. Org. Chem. 2022, 18, 688–706, doi:10.3762/bjoc.18.70

• water can be improved by using RF heating (Scheme 6) [43]. Thus, nickel-coated iron carbide NP (FeC-Ni) was developed to drastically reduce the overpotential at 20 mA/cm2 (≈200 mV for OER). This kinetic enhancement corresponds to a temperature increase of 200 °C, although the actual temperature only

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• heteroleptic aggregates are quite different. While in the former often a step-by-step attachment of the different ligands to the metal centers under kinetic control is dominating, the formation of dynamic aggregates relies on effective self-sorting protocols under thermodynamic control [24]. In its initial

• catalytic machinery was due to kinetic and not thermodynamic reasons (Figure 19). While the concept of increased liberation of an organocatalyst (ILC) has been demonstrated in other dynamic nanomechanical systems as well [99], a particular highlight was recently realized with a catalytic nanorotor that was

Shift of the reaction equilibrium at high pressure in the continuous synthesis of neuraminic acid

• Jannis A. Reich,
• Miriam Aßmann,
• Kristin Hölting,
• Paul Bubenheim,
• Jürgen Kuballa and
• Andreas Liese

Beilstein J. Org. Chem. 2022, 18, 567–579, doi:10.3762/bjoc.18.59

• can be modelled as a Michaelis–Menten rate expression. The Michaelis–Menten equation was used to fit the reaction rates at different substrate concentrations for different pressures in Figure 8. The resulting kinetic parameters are listed with 95% confidence intervals in Table 3. The influence of

• were kept constant and only the pressure was varied, resulting in the reactions rates shown in Figure 10 (left). By rearranging the rate expression and inserting the previously calculated kinetic parameters, the inhibition constant was calculated (Figure 10 (right)). The change in molar volume

• introduced by the coupling of pyruvate to the enzyme was calculated by using the exponential fit. The calculated value is −12.9 ± 5.5 mL/mol (the values at 50 MPa and 89 MPa were considered as outliers and not included in the calculation). Kinetic studies of the immobilized aldolase show an increase in

BINOL as a chiral element in mechanically interlocked molecules

• Matthias Krajnc and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2022, 18, 508–523, doi:10.3762/bjoc.18.53

• is formed preferentially under kinetic control (er = 67:33, total yield 23%). Interestingly, employing (R)-15 together with (rac)-19 gave a significantly lower diastereoselectivity (er = 56:44), albeit at slightly increased yield (33%). Similarly, the reaction of the chiral isomannide-based

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban

• Martin Vrbický,
• Karel Macek,
• Jaroslav Pochobradský,
• Jan Svoboda,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46

• material were practically the same as the one of the starting material in all cases. Further, the separation via kinetic resolution in the final reaction step was also examined. The course of the re-esterification was stopped at a conversion of ca 50% and the de values were determined. Unfortunately, no

Menadione: a platform and a target to valuable compounds synthesis

• Acácio S. de Souza,
• Ruan Carlos B. Ribeiro,
• Dora C. S. Costa,
• Fernanda P. Pauli,
• David R. Pinho,
• Matheus G. de Moraes,
• Fernando de C. da Silva,
• Luana da S. M. Forezi and
• Vitor F. Ferreira

Beilstein J. Org. Chem. 2022, 18, 381–419, doi:10.3762/bjoc.18.43

• reaction mechanisms: free radical autoxidation, cation radical autoxidation, and thermal intersystem crossing (ISC), using 18O2 labeling, spin-trapping, spectroscopic, mass spectrometric, kinetic, and computational techniques. After several experiments, the obtained results have demonstrated that the 2

Regioselectivity of the S_EAr-based cyclizations and S_EAr-terminated annulations of 3,5-unsubstituted, 4-substituted indoles

• Jonali Das and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2022, 18, 293–302, doi:10.3762/bjoc.18.33

• highly nucleophilic indole C3 as the peri position, with the latter being often more nucleophilic than the former. Noteworthy is that the kinetic preference for ring-closure onto the C5 position may be a more dominating factor than the higher nucleophilicity of the C3 position (or vice versa). Due to

• –j was performed by converting them into the corresponding acid chloride, followed by treatment with AlCl3 in refluxing 1,2-dichloroethane (DCE) (Scheme 10B). The reactions furnished indole 4,5-fused indanones 29g–j as the only detectable cyclized products. The authors noted that the kinetic

New advances in asymmetric organocatalysis

• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 240–242, doi:10.3762/bjoc.18.28

• Waser employed an isothiourea catalyst for esterification-mediated kinetic resolution of paracyclophane derivatives with planar chirality [19]. Parida and Pan showed that a Michael reaction coupled with an acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones can produce a

Trichloroacetic acid fueled practical amine purifications

• Aleena Thomas,
• Baptiste Gasch,
• Enzo Olivieri and
• Adrien Quintard

Beilstein J. Org. Chem. 2022, 18, 225–231, doi:10.3762/bjoc.18.26

• contrast, use of Lewis basic solvents such as DMF considerably accelerate the decarboxylation kinetic (Table 1, entry 3) with the recovery of the free amine after 24 hours. However, this solvent is not convenient given its high boiling point making difficult it’s separation from the purified amine

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• degree of variability for the generation of small libraries, in our case of Cyl-1 derivatives. Chiral allylic alcohols are easily accessible, either via kinetic resolution of racemic alcohols [46][47], asymmetric catalysis [48], or from chiral pool materials, such as threitol 1 [49]. Using the last

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

• (Table 2). As the racemate of 3a was obtained in a higher diastereomeric ratio (6.3:1) we applied kinetic and thermodynamic conditions for the epimerisation of it (Table 2, entries 1 and 2, respectively). Unfortunately, in both cases the diastereomeric ratio decreased and the amount of more stable syn

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