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

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

6’-Fluoro[4.3.0]bicyclo nucleic acid: synthesis, biophysical properties and molecular dynamics simulations

• Sibylle Frei,
• Andrei Istrate and
• Christian J. Leumann

Beilstein J. Org. Chem. 2018, 14, 3088–3097, doi:10.3762/bjoc.14.288

• variation of the pseudorotation phase angle P at the range of the maximum puckering amplitude νmax and was visualized in the pseudorotation wheel (Figure 3a). The two low energy regions appeared in the Southern hemisphere. The lowest energy conformer was associated with the furanose unit in a C2’-endo

• orientation and the six-membered ring in a twist-boat conformation (Figure 3b). Approximately 1 kJ/mol higher in energy was the second conformer where the furanose unit adopted a C3’-exo arrangement and the cyclohexene unit a half-chair conformation (Figure 3c). The C(5’) hydroxy group adopted in both

• conformers a pseudoaxial position. Consequently, the torsion angle γ was aligned in a +sc arrangement (C2’-endo conformer: 64°; C3’-exo conformer: 83°). The distance between the fluorine atom and the C(5’) oxygen was 3.3 Å in the C2’-endo conformer and 2.9 Å in the C3’-exo conformer. These two conformers

Dispersion-mediated steering of organic adsorbates on a precovered silicon surface

• Lisa Pecher,
• Sebastian Schmidt and
• Ralf Tonner

Beilstein J. Org. Chem. 2018, 14, 2715–2721, doi:10.3762/bjoc.14.249

• reflected in the Lewis structure is the tilting of the molecule upon adsorption leading to a chair-like conformer bending over the dimer rows on the surface [7]. Starting from this precovered surface (i.e., decorated with one adsorbate in the unit cell), we now investigate the adsorption of a second

Calixazulenes: azulene-based calixarene analogues – an overview and recent supramolecular complexation studies

• Paris E. Georghiou,
• Shofiur Rahman,
• Abdullah Alodhayb,
• Hidetaka Nishimura,
• Jaehyun Lee,
• Atsushi Wakamiya and
• Lawrence T. Scott

Beilstein J. Org. Chem. 2018, 14, 2488–2494, doi:10.3762/bjoc.14.225

• determinations were made on the possible major conformations, based upon those previously defined in reference [20]. Three distinct conformations (saddle, cone and 1,2-alternate) shown in Figure 2, were generated. Significantly, whereas for 3 which was based upon its X-ray structure, a partial cone conformer

• Table 2 with the saddle conformer (Figure 2c) having the lowest energy. Nevertheless, when subjected to geometry optimizations with the individual respective TRAX salt guests, the saddle conformer opened up to generate and accommodate each of the guests in typical “guest-in-cone” structures, as can be

Tetrathiafulvalene – a redox-switchable building block to control motion in mechanically interlocked molecules

• Hendrik V. Schröder and
• Christoph A. Schalley

Beilstein J. Org. Chem. 2018, 14, 2163–2185, doi:10.3762/bjoc.14.190

• -cation dimer (TTF●+)2. However, the Coulombic repulsion in this six-fold charged complex destabilizes the radical-cation dimer and the system converts into a second stable co-conformation in which both dihydroxynaphthalene units are inside the cavity of the wheel. To achieve this conformer, two types of

Calix[6]arene-based atropoisomeric pseudo[2]rotaxanes

• Carmine Gaeta,
• Carmen Talotta and
• Placido Neri

Beilstein J. Org. Chem. 2018, 14, 2112–2124, doi:10.3762/bjoc.14.186

• presence of a less abundant conformer of 1. The nature of this minor conformer can be inferred by the work of Reinhoudt and co-workers which showed [41] that the conformations preferentially adopted by calix[6]arene hexaethers are the cone and 1,2,3-alternate ones. In accordance, 2D COSY and HSQC spectra

• of 1 at 233 K clarified that this minor conformer was the cone one through the presence of an AX system at 3.35/4.42 ppm (COSY), which correlates with a carbon resonance at 29.1 ppm (HSQC), related to syn-oriented Ar rings (cone conformation). The coalescence temperature of the methylene protons was

D-Fructose-based spiro-fused PHOX ligands: synthesis and application in enantioselective allylic alkylation

• Michael R. Imrich,
• Jochen Kraft,
• Cäcilia Maichle-Mössmer and
• Thomas Ziegler

Beilstein J. Org. Chem. 2018, 14, 2082–2089, doi:10.3762/bjoc.14.182

• and 93:7 β:α, respectively (Table 1, entries 1 and 2) to a β:α ratio of 66:34 (Table 1, entry 9). These ratios can be explained by the mechanism of the Ritter reaction. The oxocarbenium ion 9 exists as an equilibrium of two conformer half-chair forms 9a and 9b (Scheme 5). Theoretical investigations of

• substituted cyclic oxocarbenium ions showed for oxocarbenium ions with electronegative substituents that two positions from the ring oxygen the conformer with this substituent in an axial position is favored. This can be explained by a through space electrostatic interaction of the partially negatively

• charged substituent and the positively charged ring. With the axial substituent these charges are closer together and the conformer is preferred [36][37][38]. By application of these assumptions to our system, we suggest that 9a should be the main conformer. A second argument for the dominance of 9a is

A pyridinium/anilinium [2]catenane that operates as an acid–base driven optical switch

• Sarah J. Vella and
• Stephen J. Loeb

Beilstein J. Org. Chem. 2018, 14, 1908–1916, doi:10.3762/bjoc.14.165

• + can be protonated to yield [8-HDB24C8]7+ in two different co-conformations A and B. b) The partial 1H NMR spectrum (500 MHz, 298 K, CD3CN) of [8-HDB24C8]7+ shows key resonances for both co-conformations A (red) and B (blue). See Scheme 1 for labelling; atoms of co-conformer B are labelled with a prime

Host–guest complexes of conformationally flexible C-hexyl-2-bromoresorcinarene and aromatic N-oxides: solid-state, solution and computational studies

• Rakesh Puttreddy,
• Ngong Kodiah Beyeh,
• S. Maryamdokht Taimoory,
• Daniel Meister,
• John F. Trant and
• Kari Rissanen

Beilstein J. Org. Chem. 2018, 14, 1723–1733, doi:10.3762/bjoc.14.146

• conformer space in these simulations, no constraints were enforced on either N-oxide or acetone molecules. The low energy structures obtained from these OPLS-2005 searches were then further analysed using DFT-based techniques [45][46][47]. The resulting optimised geometries of the 3@BrC2, 3@BrC3 and 3@BrC6

The phenyl vinyl ether–methanol complex: a model system for quantum chemistry benchmarking

• Dominic Bernhard,
• Fabian Dietrich,
• Mariyam Fatima,
• Cristóbal Pérez,
• Hannes C. Gottschalk,
• Axel Wuttke,
• Ricardo A. Mata,
• Martin A. Suhm,
• Melanie Schnell and
• Markus Gerhards

Beilstein J. Org. Chem. 2018, 14, 1642–1654, doi:10.3762/bjoc.14.140

• binding motifs. However, distinct differences were found between the two methods: While B3LYP-D3 predicted the OH–E conformer as the most stable complex SCS-CC2 gave OH–P as the lowest minimum (cf. Table S1 in Supporting Information File 1). This is in contrast to our results of diphenyl ether–alcohol

A conformationally adaptive macrocycle: conformational complexity and host–guest chemistry of zorb[4]arene

• Liu-Pan Yang,
• Song-Bo Lu,
• Arto Valkonen,
• Fangfang Pan,
• Kari Rissanen and
• Wei Jiang

Beilstein J. Org. Chem. 2018, 14, 1570–1577, doi:10.3762/bjoc.14.134

• exchange is now slow on the NMR timescale (Figure S7c in Supporting Information File 1). Only two signals for the aromatic protons of the host are observed, suggesting that ZB4 predominantly exists as either conformer I or IV in the complex 10+@ZB4. However, it has been not clear which one ZB4 adopts

• . Fortunately, a single crystal suitable for X-ray diffraction could be obtained by slow evaporation of the solution of 10+ and ZB4 in a mixture of CH2Cl2 and CH3CN. The crystal structure clearly shows that conformer I (Figure 1d) is the selected conformation by guest 10+. TA4 shows a large amplitude of

• conformer III (C2h symmetry) [37] to be the most favored conformation for all complexes. Obviously the conformational network of ZB4 shows no response to the electronic substituents on the guests. This is quite different from TA4. In addition, there has been a linear free energy relationship between

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• in the presence of NaH or n-BuLi (Figure 5) [46]. Conformational analysis of calixarene-diphosphite ligands revealed that presence of sterically hindered groups led to the formation of the predominantly cone-conformer. In order to check whether calix[4]arene-diphosphite ligands may also serve as

London dispersion as important factor for the stabilization of (Z)-azobenzenes in the presence of hydrogen bonding

• Andreas H. Heindl,
• Raffael C. Wende and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2018, 14, 1238–1243, doi:10.3762/bjoc.14.106

• [12] and show reversible isomerization from the thermally stable E- to the Z-isomer upon irradiation with UV light. The metastable Z-azobenzene re-isomerizes to the E-conformer either thermally or upon irradiation with visible light [13][14]. Interestingly, the thermal stability of azobenzene isomers

• are possible for the stabilization of Z-azobenzenes 4–7. To estimate the influences of those effects, a conformer distribution analysis was performed to identify low-lying conformations of the corresponding (Z)-azobenzenes. The energetically favored conformers found (within 1.5 kcal mol−1 for 4 and 5

• kcal mol−1 for 5–7, respectively, relative to the lowest energy conformer) were then re-optimized at the B3LYP/6-31G** [26][27][28][29] level of theory with and without D3(BJ) [30][31] dispersion correction (gas phase) (conformations of one enantiomer of each diastereomer of 4 were analyzed. The

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

• Kartik Temburnikar and
• Katherine L. Seley-Radtke

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

• various conformers of the permethylated furanosyl oxocarbenium intermediate revealed that the E3 conformer with the C5'–OMe oriented over the positively charged furanosyl ring (Figure 6C) has a large stabilizing effect due to C5'–O5 dipole interactions. In addition, the C2' pseudoequatorial methoxy and C3

• ' pseudoaxial methoxy groups further stabilize the intermediate in E3 conformer, thereby favoring the E3 confomer over the 3E. In the case of an anomeric phenyl group (Ph, Figure 6C), stabilization of the positive charge (C=O+) through conjugation, via parallel alignment, helps to overcome the unfavorable

• steric interactions between the C2'–OMe and the Ph group [81]. Because E3 is the favored conformer, an inside attack of the nucleophile (H−) results in an α orientation in the final product, which is evident from the the synthesis of 1 (OBn-substituted Pseudouridine, Figure 6D). Despite the greater

Syn-selective silicon Mukaiyama-type aldol reactions of (pentafluoro-λ⁶-sulfanyl)acetic acid esters with aldehydes

• Anna-Lena Dreier,
• Andrej V. Matsnev,
• Joseph S. Thrasher and
• Günter Haufe

Beilstein J. Org. Chem. 2018, 14, 373–380, doi:10.3762/bjoc.14.25

• conformer A, conformer B should be favored. Assisted by the chloride, this species is deprotonated forming the condensation product 4h with an (E)-configured double bond. Obviously, this formal dehydration is possible only in the presence of electron-donating para-substituents in the benzaldehyde. In order

¹⁵N-Labelling and structure determination of adamantylated azolo-azines in solution

• Sergey L. Deev,
• Alexander S. Paramonov,
• Tatyana S. Shestakova,
• Igor A. Khalymbadzha,
• Oleg N. Chupakhin,
• Julia O. Subbotina,
• Oleg S. Eltsov,
• Pavel A. Slepukhin,
• Vladimir L. Rusinov,
• Alexander S. Arseniev and
• Zakhar O. Shenkarev

Beilstein J. Org. Chem. 2017, 13, 2535–2548, doi:10.3762/bjoc.13.250

• observed by NMR spectroscopy in DMSO solution (≈10:7). Interestingly, for 15a, the major conformer corresponds to a rotameric state with a screened N1 atom, but in the major conformer of 15b, the N2 atom of the heterocycle is screened. Notably, similar structural disorder was previously observed in the

A permutation approach to the assignment of the configuration to diastereomeric tetrads by comparison of experimental and ab initio calculated differences in NMR data

• Przemysław J. Boratyński

Beilstein J. Org. Chem. 2017, 13, 2478–2485, doi:10.3762/bjoc.13.245

• shieldings (Equation 3). The geometries for tetrads 1–3 were also reoptimized using the 6-311G+(2d,p) basis set and the GIAO calculation was redone using mPW1PW91 functional and the same basis set as recommended by Tantillo [3] where Ej is the relative energy of conformer j, σij is isotropic shielding for

• atom i in conformer j. An example of scoring of all permutations based on 13C NMR data for tetrad 1 is shown in Table 2 (for all data, see Supporting Information File 1). For all the compounds comparison of the 13C NMR data identified the permutations corresponding to proper configuration assignment