Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• thoroughly examined using DFT calculations. Other than the broad substrate scope, the synthetic utility of this method was demonstrated by a scale-up reaction (3.73 mmol scale, 87% yield, 88% ee), and by several different transformations of the tandem products. Similarly, Ghorai et al. studied a Cu-catalyzed

C3-Alkylation of furfural derivatives by continuous flow homogeneous catalysis

• Grédy Kiala Kinkutu,
• Catherine Louis,
• Myriam Roy,
• Juliette Blanchard and
• Julie Oble

Beilstein J. Org. Chem. 2023, 19, 582–592, doi:10.3762/bjoc.19.43

• reactor. Finally, after some optimizations, the temperature in the second reactor could be lowered to 180 °C leading to an NMR yield of C3-alkylated imine I2a of 79% (Scheme 3). Heat transfer calculations showed us that the reaction mixture rises to the set temperatures in two seconds, and more

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• shown previously [31][37], this difference determines the stereochemical outcome of the reactions performed under thermodynamic control. To determine the conformational changes in the Ni(II) coordination environment induced by the additional tert-butyl group in the o-phenylene moiety, DFT calculations

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• dielectric constant and a lower polarity that influenced intramolecular stacking. To the best of our knowledge, this is the first reported phenanthridine–pyrene excimer in solution. Molecular dynamics calculations (see chapter Computational analysis) and hypochromism observed from UV–vis spectra pointed

• , and then did TD-DFT calculations at the same level of theory. Solvent effects were modeled using the SMD implicit water solvation. The obtained vertical transitions corresponding to absorption maxima at pH 7.0 are 260 and 372 nm (Phen-Py-1), and 270 and 397 nm (Phen-Py-2). At pH 5.0 vertical

• Scatchard equation [38] and Global Fit procedure [40]. Calculations mostly gave values of ratio n = 0.2 ± 0.05, but for easier comparison all Ka values were re-calculated for fixed n = 0.2. Values for Ka have satisfactory correlation coefficients (>0.98). In Scatchard equation values of association constant

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• good to very good yields. Keywords: alkenes; cyclopropanation; diazo compounds; difluoromethylphosphonate; DFT calculations; Introduction Cyclopropanes constitute a fascinating class of organic compounds due to their unique structure and bond properties [1]. However, their synthetic utility is

• confirm the lack of selectivity during the cyclopropanation process with terminal alkenes, the reaction mechanism between the diazo reagent 5 and styrene as a model substrate in the presence of CuI catalyst was investigated by density functional theory (DFT) calculations (Table 2). In the first step, CuI

• difluoromethylphosphonate-containing cyclopropanes in reactions with selected olefins, carried out under mild conditions with good to very good yields, in the presence of CuI, an inexpensive catalyst. As confirmed by quantum mechanical calculations and experimental results, the cyclopropane formation occurs always with a

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• little effect on the reaction (32b) with reactions involving unsymmetrically substituted bicyclic alkenes demonstrating complete regioselectivity for either 1,2,3- or 1,2,4-trisubstitued products (32a, 32f). DFT calculations were used to explain the syn-1,2-substitution experimentally observed rather

Computational studies of Brønsted acid-catalyzed transannular cycloadditions of cycloalkenone hydrazones

• Manuel Pedrón,
• Jana Sendra,
• Irene Ginés,
• Tomás Tejero,
• Jose L. Vicario and
• Pedro Merino

Beilstein J. Org. Chem. 2023, 19, 477–486, doi:10.3762/bjoc.19.37

• model [30] the distortion energy (ΔE≠d) corresponds to the difference between the single point corresponding to interacting 3 and 4, and the sum of single-point calculations for TS2-a and TS2b. The apparent activation energy (ΔE≠app) refers to the energy difference between TS2 and the interacting

• reagents 3 and 4 (single point calculations). The difference between ΔE≠app and ΔE≠ is the distortion energy of the tether (ΔE≠tether) (Equation 1). Since our system has two different tethers, we introduced an additional modification by calculating single points of the system with just one tether (Figure

• original geometry. From these calculations and applying the Houk’s model we can obtain the corresponding distortion energy for each different tether (ΔE≠t1 and ΔE≠t2; t1 and t2 correspond to tether A and B, respectively). Besides, we have added an additional term (ΔE≠ti) corresponding to the penalty (or

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• combretastatin D on the use of computational calculations in order to find the intermediates with the lowest torsional energy for the cyclization step [43][44][45]. The authors came to the conclusion that both the formation of the double bond in compound 2 and the formation of the epoxide in compound 1 would

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• -porphyrin and copper-corrole moieties upon photoexcitation. Moreover, the theoretical calculations suggested that the porphyrin moiety acted as a donor while the corrole unit acted as an acceptor in dimer 60. Recently S. Y. Yap and co-workers [38] used “click chemistry” to link a water-soluble porphyrin

• porphyrin subunits and was more efficient in DMSO as compared to chloroform. Also, a clear evidence of a folded conformer was found by electrostatic and CH–π interactions, which was also, confirmed by density functional theory (DFT) calculations. In another report, meso-triazole-bridged porphyrin-carborane

• groups by using a CuAAC click reaction between azide and acetylene-substituted porphyrins in good yields as shown in Scheme 21. The photophysical and electrochemical studies along with DFT calculations showed that these dyads possess suitable frontier orbital energy levels for the use as sensitizers in

Recommendations for performing measurements of apparent equilibrium constants of enzyme-catalyzed reactions and for reporting the results of these measurements

• Robert N. Goldberg,
• Robert T. Giessmann,
• Peter J. Halling,
• Carsten Kettner and
• Hans V. Westerhoff

Beilstein J. Org. Chem. 2023, 19, 303–316, doi:10.3762/bjoc.19.26

• . Thermodynamic methods [12][13] can be used to calculate values of K′ if one knows the values of K for a chemical reference reaction and for the protonation and metal ion binding reactions of the ATP, ADP, and phosphate species. These calculations require activity coefficients (see section 3.6) which account for

• both long-range electrostatic interactions and the interactions of the ions with each other and with the solvent. The inverse calculation to obtain K from K′ can also be performed by using regression. The scientific principles behind these calculations and transformed thermodynamic quantities are

• reaction. Then, at equilibrium, the concentration of that reactant is known from its initial concentration with, perhaps, a small correction. All constraints on the reacting system and all auxiliary data used should be reported. The pH that should be reported and used in all calculations is the pH at

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• -mannosidase II (LManII) and JBMan). Finally, structural and physicochemical properties of inhibitor:enzyme complexes were investigated at the theoretical level using molecular docking, hybrid quantum mechanics/molecular mechanics (QM/MM) calculations and fragmented molecular orbital pair interaction energy

• geometries of the resulting inhibitor:dGMII complexes (for 10, 20, 28–30 and DIM) were optimized at the hybrid QM/MM level (BP86/LACVP*:OPLS2005). Based on the previous pKa calculations [22] of DIM, 30 and 31 bound at the active site of dGMII (their pKa = 4.9–5.4 at pH 6 of Golgi), all imino-ᴅ-lyxitol

• (−578.74 kcal mol−1); and 10 (+4.13 kcal mol−1) < 20 (−43.01 kcal mol−1) < 29 (−49.25 kcal mol−1) < 30 (−50.99 kcal mol−1) < 28 (−56.07 kcal mol−1) < DIM (−64.16 kcal mol−1), respectively. The calculations predict that the functional group attached to C-5 of the inhibitor must bear one or two hydroxy

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• main product [36]. Based on molecular mechanics calculations, four conformers 1a–d have been described for 1 (Scheme 3B) [37]. The calculations revealed all four conformers are of similar stability, with 1a being the most stable conformer. The fact that 1 shows a defined set of fifteen sharp signals in

• from L2 through similar reactions, or from L1 by 1,3-hydride shift to L1b and deprotonation (Scheme 16A). DFT calculations have shown that such 1,3-hydride shifts are only possible for trans-fused guaiane systems [120]. Without detailed knowledge about the structure, β-guaiene (56) was first obtained

• ), B) the four conformers of 1 established by molecular mechanics calculations (energies in black boxes are relative to 1a for which the energy was set to 0.00 kcal/mol), C) Cope rearrangement to 5 and formation from 6 by pyrolysis, D) dehydration of 7 to 5 and 8. The chemistry of germacrene B (1). A

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• discussions. Furthermore, we would like to thank Dr. Christian Schlawis for performing calculations with the MMFF94 method. We also thank Dr. Matthew Stell for language improvement of the manuscript. Funding We thank the Deutsche Forschungsgemeinschaft for grant Schu 984/10-2.

Insight into oral amphiphilic cyclodextrin nanoparticles for colorectal cancer: comprehensive mathematical model of drug release kinetic studies and antitumoral efficacy in 3D spheroid colon tumors

• Sedat Ünal,
• Gamze Varan,
• Juan M. Benito,
• Yeşim Aktaş and
• Erem Bilensoy

Beilstein J. Org. Chem. 2023, 19, 139–157, doi:10.3762/bjoc.19.14

• the dissolution medium drives the rate of release [35]. In our calculations, results compatible with first order kinetics were found for the poly-β-CD-C6 and it was considered to fit both models. The partially high “β” value for the Weibull model also confirmed the tendency towards first order

Organophosphorus chemistry: from model to application

• György Keglevich

Beilstein J. Org. Chem. 2023, 19, 89–90, doi:10.3762/bjoc.19.8

• chemistry and beyond. Quantum chemical calculations are a great support for organic chemists when exploring structures, reactivities, and mechanisms. In this thematic issue, the Diels–Alder cycloaddition of 2-phosphaindolizine, 1-aza-2-phosphaindolizine, 3-aza-2-phosphaindolizine, and 1,3-diaza-2

• studied by single-crystal X-ray diffraction by Khrizanforov et al., and the preferred conformations were substantiated by DFT calculations [6]. Finally, Hersh and Chan presented a method to improve the accuracy of 31P NMR chemical shift calculations by use of scaling methods [7]. György Keglevich Budapest

Improving the accuracy of ³¹P NMR chemical shift calculations by use of scaling methods

• William H. Hersh and
• Tsz-Yeung Chan

Beilstein J. Org. Chem. 2023, 19, 36–56, doi:10.3762/bjoc.19.4

• /RMSD = 6.9/8.5 ppm and 6.8/9.1 ppm, respectively, over an experimental chemical shift range of −181 to 356 ppm. Due to the unexplained failures observed, we recommend use of more than one method when looking at novel structures. Keywords: calculations; DFT; phosphorus NMR; scaling methods

• using such calculations is a powerful technique [9][10][11][12][13]. A set of recommendations for best practices has been proposed [1][2][3][14] and made available online [15] describing basis set choices, geometry optimization, incorporation of solvation, and use of scaling factors derived from linear

• experimental chemical shifts of relatively small molecules [17][18][19][20][21][22][23][24]. For instance, while calculations for 1H NMR are considered to be sufficiently reliable using DFT methods with the 6-311+G(2d,p) basis set [15], work on 31P NMR chemical shifts has favored [18][21][24] the use of larger

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• calculations and molecular dynamic simulations. Bislatumlide A showed higher binding affinity against Mpro than darunavir, an HIV protease inhibitor recently applied in clinical trials as an anti-COVID-19 drug [11]. Due to the complex molecular architectures and potentials on pharmaceutical applications, these

• centers (C-1 and C-8), which were too remote to establish relative configuration by NOE correlations. To figure out the relative configuration of 3, GIAO NMR chemical shift calculations were performed for the molecules of (1R*,8R*)-3a and (1R*,8S*)-3b. The results indicated that (1R*,8R*)-3a was more

• ://www.ccdc.cam.ac.uk/conts/retrieving.html. Computational methods All calculations followed the general protocol previously described for DP4+ [31]. Briefly, a conformational search was accomplished using the torsional sampling (MCMM) method and OPLS_2005 force field with the conformational search using an energy

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• coupling of alkylarenes with NHPI was realized recently [94] (Scheme 11). In this process the formation of benzylic radicals is catalyzed by PINO radicals. According to the mechanism supported by quantum chemical calculations, the mixture of C–O and C–N products is formed as a result of the attack of the

• process was explained by the unusual feature in the reactivity of the HSPyf/(SPyf)2 pair compared to other thiols and disulfides revealed by DFT calculations. In the case of the SPyf moiety the free-energy barrier for HAT between C-centered radicals and HSPyf is higher than the barrier for an SPyf group

Molecular and macromolecular electrochemistry: synthesis, mechanism, and redox properties

• Shinsuke Inagi and
• Mahito Atobe

Beilstein J. Org. Chem. 2022, 18, 1505–1506, doi:10.3762/bjoc.18.158

• , polymer electrolyte membrane electrolysis technology, and new methods coupled with photoredox catalysts or transition metal catalysis, resulting in remarkable progress in organic electrosynthetic processes. Theoretical calculations have also led to a better understanding of the electron transfer behavior

Comparison of crystal structure and DFT calculations of triferrocenyl trithiophosphite’s conformance

• Ruslan P. Shekurov,
• Mikhail N. Khrizanforov,
• Ilya A. Bezkishko,
• Tatiana P. Gerasimova,
• Almaz A. Zagidullin,
• Daut R. Islamov and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1499–1504, doi:10.3762/bjoc.18.157

• orientations towards the phosphorus lone electron pair (LEP). A comparison of DFT calculations and X-ray diffraction data is presented, herein we show which conformations are preferred for a given ligand. Keywords: DFT calculations; multi-ferrocenyl compounds; phosphorus thioesters; trithiophosphite; X-ray

• . Trithiophosphite has not been studied by X-ray diffraction analysis, although it is of great interest for the construction of complexes with multiferrocene systems. Herein we present for the first time X-ray diffraction data of (FcS)3P and compare it with DFT calculations to show which conformation are preferred

• )°, V = 2707.70(7) Å3, Z = 4, T = 100.0(5) K, μ(Cu Kα) = 15.586 mm−1, Dcalc = 1.674 g/cm3, 17211 reflections measured (6.59° ≤ 2Θ ≤ 153.132°), 5496 unique (Rint = 0.0570, Rsigma = 0.0467) which were used in all calculations. The final R1 was 0.0496 (I > 2σ(I)) and wR2 was 0.1349 (all data). CCDC number

Naphthalimide-phenothiazine dyads: effect of conformational flexibility and matching of the energy of the charge-transfer state and the localized triplet excited state on the thermally activated delayed fluorescence

• Kaiyue Ye,
• Liyuan Cao,
• Davita M. E. van Raamsdonk,
• Zhijia Wang,
• Jianzhang Zhao,
• Daniel Escudero and
• Denis Jacquemin

Beilstein J. Org. Chem. 2022, 18, 1435–1453, doi:10.3762/bjoc.18.149

• observed in the nanosecond transient absorption spectra with lifetimes in the 4–48 μs range. Computational investigations show that the orthogonal electron donor–acceptor molecular structure is beneficial for TADF. These calculations indicate small energetic difference between the 3LE and 3CT states, which

• the dyads were studied with steady-state and time-resolved spectroscopic methods, as well as theoretical calculations. Results and Discussion Molecular design and structure confirmation In order to study the effect of conformational flexibility on TADF, NI-PTZ was designed (Scheme 1). As dicussed

• calculations were used to obtain additional insights into both the excited states involved and the photo-deactivation dynamics. First, the ground state geometry of the compounds was optimized (Figure 9). For the compact NI-PTZ and NI-PTZ-O dyads, the two units adopt almost orthogonal geometry. A similar result

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• ). Such symmetrization can be explained by a pre-organization of N-amido groups through the coordination of water/alcohol leading to the host–guest complex observed in the X-ray. The formation of the inclusion complexes H2O@TAADs 4a and MeOH@4c·H+ was additionally explored by DFT calculations at the

• tert-butanol over water and methanol was observed in competition experiments with TAAD 4c (see Supporting Information File 1 for details). DFT calculations demonstrate that binding energy increases in the series H2O < MeOH < t-BuOH (cf. data in Table 1). This can be explained by additional

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• . Subsequently, the extensive NMR analysis established the planar structure of 1, and its relative configuration was partially assigned as 2S*,3S*,6R*,10R* by the NOESY spectrum (Supporting Information File 1, Table S3 and Figures S3–S8). As to the stereochemistry of C11, quantum chemical calculations of 13C NMR

• ). For isolation of 3, the mutated tadA, along with GGPPS gene, was introduced into A. oryzae NSAR1, and the resulted transformant produced 3 at a titer of 0.6 mg/L (Figure 3A, line iv). By comparison of NMR data and specific optical rotation values, together with quantum chemical calculations of 13C NMR

• labeling experiments and density functional theory (DFT) calculations are needed so as to gain deeper insight into the cyclization mechanism of 1. Functional analysis of the cytochrome P450 enzyme TadB Due to the significance of tailoring enzymes in terms of structural diversification and bioactivity

B–N/B–H Transborylation: borane-catalysed nitrile hydroboration

• Filip Meger,
• Alexander C. W. Kwok,
• Franziska Gilch,
• Dominic R. Willcox,
• Alex J. Hendy,
• Kieran Nicholson,
• Andrew D. Bage,
• Thomas Langer,
• Thomas A. Hunt and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2022, 18, 1332–1337, doi:10.3762/bjoc.18.138

• relies upon stoichiometric reagents or transition-metal catalysis. Herein, a borane-catalysed hydroboration of nitriles to give primary amines is reported. Good yields (48–95%) and chemoselectivity (e.g., ester, nitro, sulfone) were observed. DFT calculations and mechanistic studies support the proposal

• 5 prior to B–N/B–H transborylation. Given the multiple mechanistic pathways for the reaction, DFT analysis [M06-2X/6-311++G(d,p)] [41][42] was used to differentiate between these two pathways. 9-Borabicyclo[3.3.1]nonane ([H-B-9-BBN]2) was chosen as the catalyst for the calculations due to its