Synthesis of organic liquid crystals containing selectively fluorinated cyclopropanes

• Zeguo Fang,
• Nawaf Al-Maharik,
• Peer Kirsch,
• Matthias Bremer,
• Alexandra M. Z. Slawin and
• David O’Hagan

Beilstein J. Org. Chem. 2020, 16, 674–680, doi:10.3762/bjoc.16.65

• difluorocarbene addition to alpha-fluorostyrenes [13]. This used the extraordinary useful method for the generation of difluorocarbene from the Ruppert–Prakash (TMSCF3) reagent [14]. DFT analysis suggests the lowest energy conformer of aryl α,β,β-trifluorocyclopropane 7 orients the C–F bond perpendicular to the

• properties significantly, however, we were interested in assessing the energy required for the bispirocyclohexane ring to adopt an axial rather than the lower energy equatorial arrangement. For 11a, the lowest energy conformer found was a rotamer around the central C–C bond linking the cyclohexane rings, but

• an essentially isoenergetic conformer is that found in the X-ray crystal structure. The first conformers where the terminal bispirocyclohexane ring lies axial are significantly higher in energy (ΔG = +1.25 kcal/mol−1 and ΔG = +1.19 kcal/mol−1) than the equatorial conformers as illustrated in Figure 3

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• performed using SPARTAN Version 5.11. Conformational searches of 36 were carried out using Monte Carlo method within MMFF94 force field, and the AM1 semiempirical method [72] was used to optimize the global minimum conformer. The geometry of the most abundant minimum energy conformer was successively

• . Once the lowest energy conformer was calculated, the three principal moments of inertia (Ixx, Iyy, Izz) and normalized principal moments of inertia, npr1 (Ixx/Izz) and npr2 (Iyy/Izz) were determined and plotted on a triangular graph with the vertices (0,1), (0.5,0.5) and (1,1) representing a perfect

• rod, disc and sphere, respectively. Chemical structure of representative approved drugs containing a spirocyclic moiety. Top: Selected NOE contacts from NOESY 1D spectra of compound 36; bottom: low energy conformer of 36, Z rotamer, using ab initio calculation at the HF/3-21G* level. PCA plot

Synthesis of 4-(2-fluorophenyl)-7-methoxycoumarin: experimental and computational evidence for intramolecular and intermolecular C–F···H–C bonds

• Vuyisa Mzozoyana,
• Fanie R. van Heerden and
• Craig Grimmer

Beilstein J. Org. Chem. 2020, 16, 190–199, doi:10.3762/bjoc.16.22

• Gaussian 09W (Rev C.01) at the B3LYP/6-311G level. Geometry optimization and calculation of NMR parameters for TMS and CCl3F at the same level provided reference chemical shifts for 1H, 13C, and 19F. The chemical shifts for the lowest energy structure (Φ = 65.3°) and the most unstable conformer (Φ = 5

• calculated 13C NMR chemical shifts for both the optimized and least-stable DFT-generated conformations, the RMSD values were found to be 8.84 ppm and 8.79 ppm, respectively. The RMSD value for the calculated 1H NMR chemical shifts of the optimized conformer was found to be substantially smaller (RMSD = 0.14

• ppm) than that for the least-stable conformer (RMSD = 0.57 ppm). The theoretical coupling constants at the same 24 geometries from geometry scan for coumarin 6 were obtained using the same functional and level of theory (B3LYP/6-311G). The coupling constants (F···C or F···H) for selected nuclei of

Synthesis, liquid crystalline behaviour and structure–property relationships of 1,3-bis(5-substituted-1,3,4-oxadiazol-2-yl)benzenes

• Afef Mabrouki,
• Malek Fouzai,
• Armand Soldera,
• Abdelkader Kriaa and
• Ahmed Hedhli

Beilstein J. Org. Chem. 2020, 16, 149–158, doi:10.3762/bjoc.16.17

• cycle at 126 °C for compound 4b. Typical diffractogram observed for compound 2b at 398 K. Typical diffractogram observed for compound 4a at 411 K. Conformer of lowest energy of compounds: 4c, conformation A, (a) front view, (a’) top view, (a”) side view; 4b, conformation B, (b) front view, (b’) top view

Synthesis and characterization of bis(4-amino-2-bromo-6-methoxy)azobenzene derivatives

• David Martínez-López,
• Amirhossein Babalhavaeji,
• Diego Sampedro and
• G. Andrew Woolley

Beilstein J. Org. Chem. 2019, 15, 3000–3008, doi:10.3762/bjoc.15.296

• performed for any of the species, the following calculations were performed: To ensure that the conformation shown in Figure 2 was the thermodynamically most stable arrangement around the azo moiety, free energies for two alternative arrangements – conformer 2: with both bromine atoms on the same side of

• the N–N double bond and conformer 3: with a bromine atom in the position of the methoxy group that H-bonded with the azonium proton (see Supporting Information File 1) – were calculated for each compound at 298.15 K. Both alternate conformers were predicted to have higher energies in vacuo (conformer

• 2: 1.1 kJ/mol for the 6-membered ring and 2.2 kJ/mol for the 5-membered ring; conformer 3: 20 kJ/mol for the 6-membered ring and 19 kJ/mol for the 5-membered ring). Thus, conformer 2 was slightly higher in energy than conformer 1 and should be populated at room temperature. However, we did not carry

Regioselectivity of glycosylation reactions of galactose acceptors: an experimental and theoretical study

• Enrique A. Del Vigo,
• Carlos A. Stortz and
• Carla Marino

Beilstein J. Org. Chem. 2019, 15, 2982–2989, doi:10.3762/bjoc.15.294

• (Figure 2). After a full conformational search with MM3, the lower-energy structures were submitted to optimization with B3LYP/6-311+G**, and then, single-point calculations with M06-2X/6-311+G** (Figure S1 and Table S1, Supporting Information File 1). After calculations for each low-energy conformer and

Pigmentosins from Gibellula sp. as antibiofilm agents and a new glycosylated asperfuran from Cordyceps javanica

• Soleiman E. Helaly,
• Wilawan Kuephadungphan,
• Patima Phainuphong,
• Mahmoud A. A. Ibrahim,
• Kanoksri Tasanathai,
• Suchada Mongkolsamrit,
• Janet Jennifer Luangsa-ard,
• Souwalak Phongpaichit,
• Vatcharin Rukachaisirikul and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2968–2981, doi:10.3762/bjoc.15.293

• File 1. ECD theoretical calculations TDDFT-ECD was used to perform theoretical ECD calculations. Conformational searches for the investigated compounds were first performed with a MMFF94S force field and an energy window of 10 kcal/mol using Omega2 software [54][55]. Each resulting conformer was then

Two new aromatic polyketides from a sponge-derived Fusarium

• Mada Triandala Sibero,
• Tao Zhou,
• Keisuke Fukaya,
• Daisuke Urabe,
• Ocky K. Karna Radjasa,
• Agus Sabdono,
• Agus Trianto and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2019, 15, 2941–2947, doi:10.3762/bjoc.15.289

• conformational isomers within 35 kcal/mol from the minimum energy conformer. The next optimizations were performed at the M06-2X/6-31G(d) level of theory and solvation effects were included using the PCM solvation model (DMSO). Frequency calculations were carried out at the same level of theory to confirm the

Acid-catalyzed rearrangements in arenes: interconversions in the quaterphenyl series

• Sarah L. Skraba-Joiner,
• Carter J. Holt and
• Richard P. Johnson

Beilstein J. Org. Chem. 2019, 15, 2655–2663, doi:10.3762/bjoc.15.258

• quaterphenyls are unavailable in the literature but these values and other estimates for relative energies can be predicted by theory. Starting with the lowest energy conformer for each quaterphenyl, we first computed heats of formation using the T1 method [39]. Predicted values (Supporting Information File 1

Effect of ring size on photoisomerization properties of stiff stilbene macrocycles

• Sandra Olsson,
• Óscar Benito Pérez,
• Magnus Blom and
• Adolf Gogoll

Beilstein J. Org. Chem. 2019, 15, 2408–2418, doi:10.3762/bjoc.15.233

• calculated in MacroModel 9.9 with the OPLS3e force field, CHCl3 as solvent and dielectric constant 9.1 [48][49]. Redundant conformer elimination in MacroModel was used to reduce the number of conformations to 10–20 structures [50]. Synthesis Synthesis of 6-methoxyindan-1-one (3) Compound 2 (2.523 g, 14.0

• reaction (Figure S47, Supporting Information File 1). The differences in ring strain between the E- and Z-isomers show an exponential correlation to the linker length. Conformer ensembles for the macrocyclic stiff stilbene diethers 1a–d. Dihedral angles between the two aromatic rings are given in

Synthesis and anion binding properties of phthalimide-containing corona[6]arenes

• Meng-Di Gu,
• Yao Lu and
• Mei-Xiang Wang

Beilstein J. Org. Chem. 2019, 15, 1976–1983, doi:10.3762/bjoc.15.193

• ]. The observation of the single set of proton and carbon resonance signals of 3 indicated the presence of the conformer with high symmetry or most likely a mixture of conformers which underwent very fast interconversion relative to the NMR time scale. In comparison to diethyl terephthalate, a

Synthesis, enantioseparation and photophysical properties of planar-chiral pillar[5]arene derivatives bearing fluorophore fragments

• Guojuan Li,
• Chunying Fan,
• Guo Cheng,
• Wanhua Wu and
• Cheng Yang

Beilstein J. Org. Chem. 2019, 15, 1601–1611, doi:10.3762/bjoc.15.164

• dichroism (CD) spectroscopy. The first fraction showing negative CD signals was assigned to the Sp conformer and the second fraction showing positive CD signals was assigned to the Rp conformer. Aggregation behaviors of the enantiopure chiral pillar[5]arene derivatives were investigated by adding water into

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• determined, no predominant conformer was found. As shown in Figure 3A and B both tripeptides indicate a fully flexible conformation. Corzana et al. suggested for the C- and N-protected, glycosylated ʟ-serine residue an extended conformation without intramolecular hydrogen bond between the amide proton of

2,3-Dibutoxynaphthalene-based tetralactam macrocycles for recognizing precious metal chloride complexes

• Li-Li Wang,
• Yi-Kuan Tu,
• Huan Yao and
• Wei Jiang

Beilstein J. Org. Chem. 2019, 15, 1460–1467, doi:10.3762/bjoc.15.146

• suggests that the conformational interconversion is slow at this temperature and only one conformer is predominant in the solution at 298 K. However, the exact conformer cannot be assigned because the two conformers have the same number of peaks. In contrast, H3 of 2 are broadened even at room temperature

• between the amide NH protons and the pyridine nitrogen atoms in 2, which pre-organizes the cavity for molecular recognition. How would this affect the binding affinity of 2? To answer this question, molecular modelling was performed. Only conformer I of 1 was used for the molecular modelling but both

Efficient resolution of racemic crown-shaped cyclotriveratrylene derivatives and isolation and characterization of the intermediate saddle isomer

• Sven Götz,
• Andreas Schneider and
• Arne Lützen

Beilstein J. Org. Chem. 2019, 15, 1339–1346, doi:10.3762/bjoc.15.133

• these studies an intermediate saddle conformer could also be isolated and characterized by 1H and 13C NMR spectroscopy. The HPLC separation method was further developed in order to allow investigations on the racemization behavior of the cyclotriveratrylene derivative. Keywords: chiral resolution

• the intermediate saddle conformer. Results and Discussion Synthesis and chiral resolution of 1 and isolation of the saddle isomer The synthesis of (rac)-1 was accomplished according to the already mentioned protocol by Rousseau and co-workers (Scheme 3) [60] although it should be noted here that

• corresponds to the saddle conformer and is marked with 1-S. a) 1H NMR spectrum of the neat crown isomers of (rac)-1 in CD3OD (400 MHz, 298 K); b) 1H NMR spectrum in CD3OD (400 MHz, 298 K) of a sample of (rac)-1 after heating it to 200 °C in DMSO and quenching the solution by pouring it into an ice water

Robust perfluorophenylboronic acid-catalyzed stereoselective synthesis of 2,3-unsaturated O-, C-, N- and S-linked glycosides

• Madhu Babu Tatina,
• Xia Mengxin,
• Rao Peilin and
• Zaher M. A. Judeh

Beilstein J. Org. Chem. 2019, 15, 1275–1280, doi:10.3762/bjoc.15.125

• perflurophenylboronic acid to the allylic acetate moiety of glucal 1a induces polarization (structure I) and leads to the formation of an allyloxycarbenium ion (structure II) in the preferred 4H3 conformation. Addition of the nucleophiles to C1 from the α-face gives the lower energy half-chair conformer and results in

• the observed α-selectivity of the 2,3-unsaturated glycosides III (Figure 4) [22]. However, the addition of the nucleophiles from the β-face gives the higher energy twist-boat conformer. Conclusion We developed a robust perfluorophenylboronic-acid-catalyzed protocol for the synthesis of a broad range

Bambusuril analogs based on alternating glycoluril and xylylene units

• Tomáš Lízal and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2019, 15, 1268–1274, doi:10.3762/bjoc.15.124

• CD3CN showed two sets of signals (Figure 3) which were assigned to the calculated conformers. Conformer 1a-1 possesses a plane of symmetry, therefore, is characterized by single signals of methyl (H6), methine (H5) and aromatic (H1 and H3) protons. Contrary, 1a-2 is characterized by two signals for each

• in favor of 1a-1 which remained constant at even lower temperature. By application of the Boltzmann distribution to the conformer population, we have calculated that 1a-1 is more stable by 0.13 kcal mol−1 than 1a-2. Conformer 1a-1 is preferred probably due to its higher symmetry. Diastereomer 1b was

• reflecting the presence of conformers 1b-2 and 1b-1. However, the ratio of these conformers is 82:1 in favor of 1b-1 which translates to the energy difference of 2.04 kcal mol−1. Stabilization of the 1b-1 conformer can be attributed to the intramolecular hydrogen bonding interaction between the oxygen atom

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• from C-1 to C-10 and the 1,11-cyclisation featuring the unusual syn-SN2’ attack. Combining various aspects of the initial cyclisation, the proposed conformer of cation D may also rationalise the reduced selectivity of HcS by its positioning of OPP−. Providing access to labelled isotopomers of its

Halogen bonding and host–guest chemistry between N-alkylammonium resorcinarene halides, diiodoperfluorobutane and neutral guests

• Fangfang Pan,
• Mohadeseh Dashti,
• Michael R. Reynolds,
• Kari Rissanen,
• John F. Trant and
• Ngong Kodiah Beyeh

Beilstein J. Org. Chem. 2019, 15, 947–954, doi:10.3762/bjoc.15.91

• two Br− counterions are covered by the bent hexyl “arms”. In 1&DIOFB_B, the two DIOFB molecules link the two hex-NARBrs using the diametrically opposed Br− anions. The average RXB of these XBs is 0.98. In this second conformer, a space was created between the hosts, thus the hexyl groups bend inwards

Strong hyperconjugative interactions limit solvent and substituent influence on conformational equilibrium: the case of cis-2-halocyclohexylamines

• Camila B. Francisco,
• Cleverton S. Fernandes,
• Ulisses Z. de Melo,
• Roberto Rittner,
• Gisele F. Gauze and
• Ernani A. Basso

Beilstein J. Org. Chem. 2019, 15, 818–829, doi:10.3762/bjoc.15.79

• -iodocyclohexylamine (I) by dynamic NMR and theoretical calculations. The experimental data pointed to an equilibrium strongly shifted toward the ea conformer (equatorial amine group and axial halogen), with populations greater than 90% for F, Cl and Br in both dichloromethane-d2 and methanol-d4. Theoretical

• preference for the ea conformer in cis-2-halocyclohexylamines, being strong enough to restrain the shift in the equilibrium due to other factors such as steric repulsion or solvent effects. Keywords: conformational equilibrium; cyclohexane derivatives; dynamic NMR; hyperconjugation; principal component

• cause some effect on the conformational equilibrium. Freitas and co-workers have demonstred this effect on trans-1,2-dihalocyclohexanes [12], where the diequatorial repulsion between the bulky halogens make the diaxial conformer more stable. Similarly, in trans-2-halocyclohexanols the OH–X interaction

Influence of per-O-sulfation upon the conformational behaviour of common furanosides

• Alexey G. Gerbst,
• Vadim B. Krylov,
• Dmitry A. Argunov,
• Maksim I. Petruk,
• Arsenii S. Solovev,
• Andrey S. Dmitrenok and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2019, 15, 685–694, doi:10.3762/bjoc.15.63

• –H5 defining the conformation of the exocyclic C4–C5 bond was set either to +60°, −60° or 180°. The only exception was the sulfated mannoside 1s, where 3JH4-H5 was very small suggesting low contribution of the 180° conformer. The starting conformation of the propyl aglycon was always chosen as follows

• Information File 1). Examination of these conformations revealed that these deviations were due to unfavorable orientation of the 2-OH and 3-OH hydroxy groups. In these cases re-optimization of the high-energy conformer was performed to ensure that energy would converge to the minimum. Table 4 shows the

• SO3− group at O5, due to its size, tends to have trans-orientation to C(3) (see Figure 2). In the case of galactose 3, however, the situation is more complex. This saccharide in its furanoside form has increased conformational flexibility around the C4–C5 bond, because for its lowest energy conformer

Conformational signature of Ishikawa´s reagent using NMR information from diastereotopic fluorines

• Laize A. F. Andrade,
• Lucas A. Zeoly,
• Rodrigo A. Cormanich and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2019, 15, 506–512, doi:10.3762/bjoc.15.44

• dipole moments and, consequently, the conformer populations are expected to change with the solvent polarity [29]. Indeed, the 1H NMR outcomes in C6D12 (dielectric constant ε = 2.2), CDCl3 (ε = 4.8) and C5D5N (ε = 12.4) solutions are informative on the rotation of H–C2–C1–F and conformational equilibrium

• 1C is not expected when the solvent varies, because of their similar molecular dipole moments. In turn, the populations of conformer 1A are not prone to increase by increasing the solvent polarity, because of their smaller molecular dipole moments compared to 1B and 1C. So, the observed changes in

• . Because conformer 1Ac is of very high energy and, therefore, non-populated (Table 2), the larger 3JH,F(1) SSCC in Table 1 is likely to correspond to 3JH,F(pro-R), while the smaller one corresponds to 3JH,F(pro-S). Since the large 3JH,F(pro-R) SSCC is practically insensitive to solvent changes, while 3JH,F

Computational characterization of enzyme-bound thiamin diphosphate reveals a surprisingly stable tricyclic state: implications for catalysis

• Ferran Planas,
• Michael J. McLeish and
• Fahmi Himo

Beilstein J. Org. Chem. 2019, 15, 145–159, doi:10.3762/bjoc.15.15

• between the lowest energy conformer and the typical V-conformation of enzyme-bound ThDP [48] is 4.2 kcal/mol. Interestingly, the lowest energy structure also adopts a V-shape, but one in which thiazolium ring is perpendicular to the pyrimidine ring (see Supporting Information File 1 for an optimized

Synthesis, biophysical properties, and RNase H activity of 6’-difluoro[4.3.0]bicyclo-DNA

• Sibylle Frei,
• Adam K. Katolik and
• Christian J. Leumann

Beilstein J. Org. Chem. 2019, 15, 79–88, doi:10.3762/bjoc.15.9

• ) surprisingly showed only one single low energy region in the Southern area of the pseudorotational cycle. The minimal energy conformer of nucleoside 7 adopted a C2’-endo furanose conformation (P = 160°) and a twist-boat orientation of the carbocyclic unit (Figure 3b). Hence, the angle γ took up a synclincal

• arrangement and the 5’-hydroxy group a pseudoaxial orientation. Again, the spacing between the 5’-oxygen and the equatorial aligned fluorine atom Fa of 2.61 Å corresponded to the sum of their van der Waals radii. Interestingly, this distance was shorter in the minimal conformer of nucleoside 7 than in the

• (left) and 6b (right). a) Potential energy profile versus pseudorotation phase angle of nucleoside 7 and b) its minimal energy conformer. CD spectra of ON1–4 with complementary a) DNA, and b) RNA. Total strand conc. 2 μM in 10 mM NaH2PO4, 150 mM NaCl, pH 7.0. Hydrolysis products of the RNase H

A simple and effective preparation of quercetin pentamethyl ether from quercetin

• Jin Tatsuzaki,
• Tomohiko Ohwada,
• Yuko Otani,
• Reiko Inagi and
• Tsutomu Ishikawa

Beilstein J. Org. Chem. 2018, 14, 3112–3121, doi:10.3762/bjoc.14.291

• groups at 3- and 5-positions. The most stable conformer 2A contains a hydrogen bond between the OH group at 5 position and the carbonyl group at 4 position. The overall conformation is sensitive to the direction of the OH group at 3 position. The OH isomer at 3 position (2B) was significantly

• . The relative energies of all isomeric oxyanions are shown in Figure 4. All the monoanions (anions 2A) derived from the stable neutral conformer 2A were more stable than those (anions 2B) from the conformer 2B. Among the oxyanions at the OH group at 3 position (3-anions), we calculated the species (3