Caryolene-forming carbocation rearrangements

• Quynh Nhu N. Nguyen and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2013, 9, 323–331, doi:10.3762/bjoc.9.37

• encountered in the very first step involving carbocations. We were unable to locate a minimum for B in a productive conformation, despite the fact that alternative conformers of this secondary carbocation had been found to be involved in pathways to pentalenene and presilphiperfolanol [18][19][20][21][22

• a hybrid of the tertiary cation C and a resonance structure with two 4-membered rings [22]. We performed a conformational search for C to assess whether other conformers lacking this close contact were possible, but all starting geometries examined in which the two methyl groups pointed to the same

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• to 58% ee) (Scheme 5) [16]. The enantiofacial differentiation can be explained through the formation of the complexed conformers by the coordination of the organolithium and the chiral ligand, which will react with the double bond in an intramolecular syn-addition to form benzyllithium derivatives 15

• . These secondary α-carbamoyloxybenzyllithiums are configurationally stable and can be trapped. The authors assume that the problem of these enantioselective carbolithiations is due to the interconversion of the conformers, formed by coordination of n-BuLi and the chiral ligand, being too slow, and that

Synthesis of 5-(ethylsulfonyl)-2-methoxyaniline: An important pharmacological fragment of VEGFR2 and other inhibitors

• Miroslav Murár,
• Gabriela Addová and
• Andrej Boháč

Beilstein J. Org. Chem. 2013, 9, 173–179, doi:10.3762/bjoc.9.20

• VEGFR2 receptor has been solved by X-ray crystallography and is available in the Protein Data Bank (PDB: 1Y6A). The complex 1Y6A contains the intracellular tyrosine kinase domain of the VEGFR2 receptor, which accommodates two conformers of the AAZ ligand [5]. Compound 5 is an important precursor for the

The diketopiperazine-fused tetrahydro-β-carboline scaffold as a model peptidomimetic with an unusual α-turn secondary structure

• Francesco Airaghi,
• Andrea Fiorati,
• Giordano Lesma,
• Manuele Musolino,
• Alessandro Sacchetti and
• Alessandra Silvani

Beilstein J. Org. Chem. 2013, 9, 147–154, doi:10.3762/bjoc.9.17

• -turn conformation. The synthesis is based on a diastereoselective Pictet–Spengler condensation to give the THBC core, followed by an intramolecular lactamization to complete the tetracyclic THBC-DKP fused ring system. The presence of conformers bearing the intramolecular thirteen-membered hydrogen bond

• interatomic distance dα between the terminal Cα5 atom and the benzyl oxygen of the Cbz (which emulates the Cα1 atom), assuming a value dα < 7 Å as a probe of a generic reverse turn. Results are reported as the number of conformers that meet the geometric requirements. The most frequently observed is the 5→3 H

• -bond (H-bond A), which is related to a classical γ-turn around these residues, and a 5→1 H-bond (H-bond B), which can be identified as an α-turn (this conformation is present in four conformers for compound 1a). Inspection of the global minima showed the α-turn conformation only for compound 1a. For

The β-cyclodextrin/benzene complex and its hydrogen bonds – a theoretical study using molecular dynamics, quantum mechanics and COSMO-RS

• Jutta Erika Helga Köhler and
• Nicole Grczelschak-Mick

Beilstein J. Org. Chem. 2013, 9, 118–134, doi:10.3762/bjoc.9.15

• started with such manually constructed models and their AM1 optimisations. Step 1: Our four β-CD models are conformers; all the hydrogen bonds of each rim are oriented in the same direction. We named them BCDO23lO6l, BCDO23rO6l, BCDO23lO6r and BCDO23rO6r, referring to their manually constructed hydrogen

• molecular structures with COSMO-RS on DMOL, BP/SVP or BP/TZVP level of approximation. Our trial to optimise the β-CD complexes with BP/TZVP failed: not always but in several cases, here, for example, the benzene guest was expelled for the BCDbenzeneO23lO6r conformers. Now, however, the current version of

• , 290, 280, and 273 K for 500 ps each, and their release of the guest was analysed from these trajectories. Results and Discussion AM1 Calculations The four conformers of empty β-CD The BCDO23rO6l structure turned out to be the lowest energy conformer, also having the lowest dipole moment of only 0.5618

Theoretical study on β-cyclodextrin inclusion complexes with propiconazole and protonated propiconazole

• Adrian Fifere,
• Narcisa Marangoci,
• Stelian Maier,
• Adina Coroaba,
• Dan Maftei and
• Mariana Pinteala

Beilstein J. Org. Chem. 2012, 8, 2191–2201, doi:10.3762/bjoc.8.247

• be subjected to PM3 calculations, without any constraints, to obtain the heats of formation and to compare the stability of the conformers. Looking at Figure 2 it is obvious that all structures are stable since, in all cases, negative binding energies were obtained. It can also be observed that the

Antifreeze glycopeptide diastereomers

• Lilly Nagel,
• Carsten Budke,
• Axel Dreyer,
• Thomas Koop and
• Norbert Sewald

Beilstein J. Org. Chem. 2012, 8, 1657–1667, doi:10.3762/bjoc.8.190

• (Figure 1) [16]. The difference in configuration at Cβ of the threonine residue seems to reduce the propensity for β-strand formation. In the φ/ψ-energy map the conformers PPII and β-strand are very close, and the energy barrier is quite low, facilitating the transition between the conformers [31][32

Synthesis and evaluation of new guanidine-thiourea organocatalyst for the nitro-Michael reaction: Theoretical studies on mechanism and enantioselectivity

• Tatyana E. Shubina,
• Matthias Freund,
• Sebastian Schenker,
• Timothy Clark and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2012, 8, 1485–1498, doi:10.3762/bjoc.8.168

• (Figure 1), gas-phase DFT, MP2 and DFT-D with van der Waals correction predict 7a to be more stable than 7b by between 1.8 and 7.4 kcal·mol−1 (Figure 1). The MP2 and DFT-D energies agree very well. The two other conformers, 7c and 7d, are less stable than 7a/7b at all levels employed and were therefore

• flexible. On the other hand, modification of the guanidine moiety by introducing a rigid aza-heterocycle (1,5,7-triazabicyclo[4.4.0]dec-5-ene (TABD)) gave promising results. For the modified 7-TABD catalyst, we found only two conformers that differ by ca. 6–8 kcal·mol−1 (Figure 5). Assuming that the first

• performed with the ORCA program [85]. Optimized geometries of four conformers of catalyst 7. Energies are in kcal·mol−1, B3PW91/6–31G(d) (first entry), DFT-PCM (second entry), MP2/6–311++G(d,p)// B3PW91/6–31G(d) (third entry), DFT-D (fourth entry). Bond lengths are in Å. Complexes (CatN1–CatN5) between

Organocatalytic asymmetric addition of malonates to unsaturated 1,4-diketones

• Sergei Žari,
• Tiiu Kailas,
• Marina Kudrjashova,
• Mario Öeren,
• Ivar Järving,
• Toomas Tamm,
• Margus Lopp and
• Tõnis Kanger

Beilstein J. Org. Chem. 2012, 8, 1452–1457, doi:10.3762/bjoc.8.165

• configuration of the product 3a was determined by a comparison of the experimental and calculated vibrational circular dichroism (VCD) spectra. DFT calculations (method B3PW91/6-311G**) of a series of conformers of compound 3a with R-configuration were performed. Calculations of harmonic vibrational frequencies

• were carried out for all favored conformers to verify their stability. The Boltzmann distribution of the Gibbs energy showed that one conformation out of six is dominant (84%). The experimental and calculated IR spectra match well in the range 1500–1800 cm−1 (both experimental and calculated spectra

Cation affinity numbers of Lewis bases

• Christoph Lindner,
• Raman Tandon,
• Boris Maryasin,
• Evgeny Larionov and
• Hendrik Zipse

Beilstein J. Org. Chem. 2012, 8, 1406–1442, doi:10.3762/bjoc.8.163

• (120) and 601 (120Me) conformations. Some of these conformations are eliminated on geometry optimizations at DFT level, but the final low-energy window of 10 kJ/mol for "good" structures still contains 139 (120) and 94 (120Me) structures (after the elimination of mirror-image conformers). A reliable

• calculation of Boltzmann-averaged thermochemical data and the identification of the best conformers thus requires frequency calculations and MP2 single point calculations for all of these structures. It should be added that the energetically best structure varies on moving from Etot(DFT) to H298(DFT) to H298

A macrolactonization approach to the total synthesis of the antimicrobial cyclic depsipeptide LI-F04a and diastereoisomeric analogues

• James R. Cochrane,
• Dong Hee Yoon,
• Christopher S. P. McErlean and
• Katrina A. Jolliffe

Beilstein J. Org. Chem. 2012, 8, 1344–1351, doi:10.3762/bjoc.8.154

• unreacted cyclic peptide (retention time = 34.0 min) and ● is a peak attributed to hydrolysis of both the cyclic peptide ester bond and Cbz protecting group (LCMS m/z = 902 [M + H]+). Structures and lowest-energy conformers of 24 (left) and 25 (right) obtained using Macromodel. Hydrogen bonding is

Restructuring polymers via nanoconfinement and subsequent release

• Alan E. Tonelli

Beilstein J. Org. Chem. 2012, 8, 1318–1332, doi:10.3762/bjoc.8.151

• , crystallization of c- or p-PETs into the all-trans conformation proceeds rapidly from preponderantly gauche± –O–CH2–, trans –CH2–CH2– and gauche –CH2–O– bond conformers through facile counter rotations about the –O–CH2– and –CH2–O– bonds, requiring only a very modest amount of swept-out volume [17][52][69]. Thus

The preferred conformation of erythro- and threo-1,2-difluorocyclododecanes

• Yi Wang,
• Peer Kirsch,
• Tomas Lebl,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2012, 8, 1271–1278, doi:10.3762/bjoc.8.143

• by using a combination of 19F{1H} NMR spectroscopy, computational studies and, in the case of the threo isomer, X-ray structural analysis. In the lowest energy conformers for both diastereoisomers the vicinal C–F bonds are located corner/edge, rather than edge/edge. These structures avoid placing a C

• to conformational analysis by 19F NMR and X-ray structural analyses. A computational study was also carried out to explore the relative energies of the candidate edge/edge and edge/corner conformers. Results and Discussion Synthesis The synthetic route to erythro- (5a) and threo-1,2

• a transition state. This may arise as a result of desolvation for this isomer. Computational study In order to explore conformer energies further, a theoretical study MP2/6-311+G(2d,p)//B3LYP/6-311+G(2d,p)+ZPE) [16] was carried out to assess relative ground-state energies of candidate conformers

Conformational analysis, stereoelectronic interactions and NMR properties of 2-fluorobicyclo[2.2.1]heptan-7-ols

• Fátima M. P. de Rezende,
• Marilua A. Moreira,
• Rodrigo A. Cormanich and
• Matheus P. Freitas

Beilstein J. Org. Chem. 2012, 8, 1227–1232, doi:10.3762/bjoc.8.137

• Discussion The hydroxy group of the 2-fluorobicyclo[2.2.1]heptan-7-ols undergoes rotation, giving rise to the stable conformers (energy minima) of the potential energy surfaces (PES) in Figure 2, which were obtained by computing the relative energies of 5–8 upon scanning of the H–O–C–C(CF) dihedral angle (θ

• density (ρ) and its Laplacian () in the bond critical point (BCP) referring to the F∙∙∙HO intramolecular HB (HBCP), and the integrated properties on the H(O) atoms of the conformers of 5. Calculated F,H(O) SSCC for 5–8, and the corresponding terms contributing to the overall J (FC, Fermi contact; SD, spin

Formation of smectic phases in binary liquid crystal mixtures with a huge length ratio

• Nadia Kapernaum,
• Friederike Knecht,
• C. Scott Hartley,
• Jeffrey C. Roberts,
• Robert P. Lemieux and
• Frank Giesselmann

Beilstein J. Org. Chem. 2012, 8, 1118–1125, doi:10.3762/bjoc.8.124

• each molecular structure was minimized by molecular modelling with the semiempirical method MOPAC/AM1 for the most extended conformers. The phase diagram of the binary mixture system PhP16/2PhP. The layer spacing obtained by SAXS-measurements in the SmA phase at T = Tc is plotted against the mole

Control over molecular motion using the cis–trans photoisomerization of the azo group

• Estíbaliz Merino and
• María Ribagorda

Beilstein J. Org. Chem. 2012, 8, 1071–1090, doi:10.3762/bjoc.8.119

• position (trans-I form), or placed next to it (trans-II). Similarly, motion of the aromatic rings accompanying the photoisomerization process can also lead to several cis conformers (cis-I and cis-II). The electronic nature and steric bulk of the substituents of the aromatic rings can be a key factor in

Toward unidirectional switches: 2-(2-Hydroxyphenyl)pyridine and 2-(2-methoxyphenyl)pyridine derivatives as pH-triggered pivots

• Christina Tepper and
• Gebhard Haberhauer

Beilstein J. Org. Chem. 2012, 8, 977–985, doi:10.3762/bjoc.8.110

• repulsive interaction between the free electron pairs of the nitrogen and the oxygen atoms, should be the more stable one (Scheme 1). A protonation of the nitrogen inverts the relative energies of the two conformers. Due to the internal hydrogen bridge the conformer of 4 having a dihedral angle of 0° is the

• is to transform the enantiomeric conformers with a dihedral angle of about 150° into diastereomers that are different in energy. Due to the energetic gap between the diastereomers there will be an excess of one in solution. As the majority of the switches will now rotate in one direction (e.g

• the switching process proceed in both cases unidirectionally at the molecular level. Unidirectionality of the switching process As already mention above, the whole switching process (sum of all molecular processes) becomes unidirectional if the enantiomeric conformers with a dihedral angle of about

Synthesis and anion recognition properties of shape-persistent binaphthyl-containing chiral macrocyclic amides

• Marco Caricato,
• Nerea Jordana Leza,
• Claudia Gargiulli,
• Giuseppe Gattuso,
• Daniele Dondi and
• Dario Pasini

Beilstein J. Org. Chem. 2012, 8, 967–976, doi:10.3762/bjoc.8.109

• . Preliminary conformational structures were optimized by using the semiempirical PM3 method [38]. The geometries were then subjected to further refinement by using DFT B3LYP/6-31G(d) methods. In order to locate conformers having the minimum energy, the structures obtained by preliminary optimization were then

Synthesis of functionalized macrocyclic derivatives of trioxabicyclo[3.3.0]nonadiene

• Sabine Leber,
• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2012, 8, 738–743, doi:10.3762/bjoc.8.83

• principal structures). This will also be the case for the derivatives described below. The splitting of several signals in the NMR spectra may be ascribed to the presence of mixtures of diastereoisomers and conformers. Reduction Several methods were attempted for the reduction of the nitro groups in 8 and

An easy α-glycosylation methodology for the synthesis and stereochemistry of mycoplasma α-glycolipid antigens

• Yoshihiro Nishida,
• Yuko Shingu,
• Yuan Mengfei,
• Kazuo Fukuda,
• Hirofumi Dohi,
• Sachie Matsuda and
• Kazuhiro Matsuda

Beilstein J. Org. Chem. 2012, 8, 629–639, doi:10.3762/bjoc.8.70

• one-pot α-glycosylation method was effectively applied. The synthetic GGPL-I isomers were characterized with 1H NMR spectroscopy to determine the equilibrium among the three conformers (gg, gt, tg) at the acyclic glycerol moiety. The natural GGPL-I isomer was found to prefer gt (54%) and gg (39

• %) conformers around the lipid tail, while adopting all of the three conformers with equal probability around the sugar position. This property was very close to what we have observed with respect to the conformation of phosphatidylcholine (DPPC), suggesting that the Mycoplasma glycolipids GGPLs may constitute

• , each of them is allowed to have three staggered conformers of gg (gauche-gauche), gt (gauche-trans) and tg (trans-gauche) (Figure 3). In solution and also in self-contacting liquid-crystalline states, these conformers are thought to equilibrate with each other. In this study, we calculated time

Enantioselective supramolecular devices in the gas phase. Resorcin[4]arene as a model system

• Caterina Fraschetti,
• Matthias C. Letzel,
• Antonello Filippi,
• Maurizio Speranza and
• Jochen Mattay

Beilstein J. Org. Chem. 2012, 8, 539–550, doi:10.3762/bjoc.8.62

• ]+ complexes whose large enantioselectivity (ρ = 16.9 ± 2.8) must be essentially promoted by substantial differences in the relevant reaction pathway [49]. Indeed, from the computational analysis performed on catharanthine (T), two families of conformers resulted as stable from the study performed in vacuum as

• . Amidoresorcin[4]arene YS. Catharanthine and vindoline, monomers constituting the anticancer vinblastine and the analogous vincristine. Stable conformers of catharanthine. Global minima of (a) [VS∙H∙T]+ and (b) [VR∙H∙T]+ complexes. Guests studied in [47]. Selected nucleosides. Example of molecular logic gate

Fifty years of oxacalix[3]arenes: A review

• Kevin Cottet,
• Paula M. Marcos and
• Peter J. Cragg

Beilstein J. Org. Chem. 2012, 8, 201–226, doi:10.3762/bjoc.8.22

• bind such species. In common with other calix[n]arenes, oxacalix[3]arenes containing free OH groups are conformationally mobile, leading to cone and partial-cone conformers (Figure 6). Without lower-rim substituents there is free rotation of each phenolic unit through the macrocyclic annulus; however

• cone (8%) and partial-cone (68%) conformers, and the only isolated product with Cs2CO3 was the partial-cone conformer (75%) [28]. The X-ray structure of the partial-cone conformer (Figure 7), reported by Cragg, shows one pyridyl group to be included within the macrocyclic cavity and the remaining two

• analogue was, in both the cone (77% vs 24% E) and partial-cone (42% vs 6% E) conformers [29]. In a wider study, Yamato determined extraction data for 17a with n-BuNH3+ picrate (98% E cone vs 93% E partial-cone), iBuNH3+ picrate (48% E cone vs 37% E partial-cone) and t-BuNH3+ picrate (35% E cone vs 14% E

The interplay of configuration and conformation in helical perylenequinones: Insights from chirality induction in liquid crystals and calculations

• Elisa Frezza,
• Silvia Pieraccini,
• Stefania Mazzini,
• Alberta Ferrarini and
• Gian Piero Spada

Beilstein J. Org. Chem. 2012, 8, 155–163, doi:10.3762/bjoc.8.16

• ) calculations, and with the prediction of the twisting ability of conformers, by the surface chirality (SC) method [29]. Results and Discussion HTP measurement The propensity of a dopant to induce a helical organization in the liquid-crystalline matrix is measured by its helical twisting power, which is defined

• this issue we performed a computational study at different levels: Single-molecule DFT calculations were carried out to evaluate energy and geometry of all the conformers of 1 and 2, and the SC method was used to estimate their twisting ability. Conformational analysis by DFT For each of the side

• chains in position 1 and 12 of cercosporin and phleichrome, three conformational states are possible, which are shown in Figure 2, where the same notation as in [31] is used. This makes a total of six conformers for each molecule, which are labeled according to the state of each side chain; thus, for

Laterally substituted symmetric and nonsymmetric salicylideneimine-based bent-core mesogens

• Sonja Findeisen-Tandel,
• Wolfgang Weissflog,
• Ute Baumeister,
• Gerhard Pelzl,
• H. N. Shreenivasa Murthy and
• Channabasaveshwar V. Yelamaggad

Beilstein J. Org. Chem. 2012, 8, 129–154, doi:10.3762/bjoc.8.15

• , which is significantly shorter than the molecular length Lcalc = 5.5 nm estimated by molecular models. The difference may be caused by a deviation of the molecular configuration from that assumed in the model calculations (e.g., by another bending angle or a high proportion of gauche conformers), or by

Computational evidence for intramolecular hydrogen bonding and nonbonding X···O interactions in 2'-haloflavonols

• Tânia A. O. Fonseca,
• Matheus P. Freitas,
• Rodrigo A. Cormanich,
• Teodorico C. Ramalho,
• Cláudio F. Tormena and
• Roberto Rittner

Beilstein J. Org. Chem. 2012, 8, 112–117, doi:10.3762/bjoc.8.12

• isomerization around the α [H–O–C–C(=O)] and β [C(X)–C–C–C(OH)] torsional angles (Figure 1), giving the energy minima obtained at the B3LYP/aug-cc-pVDZ level depicted in Table 1. Flavonol itself (X = H) exhibits two stable conformers, with the most stable one having the hydroxy hydrogen directed toward the

• conformers, in which those with the hydroxy hydrogen directed toward the carbonyl oxygen (A and B) are significantly more stable than the other two conformers (Table 1); clearly, the intramolecular HB O–H···O=C plays the determinant role for the conformational isomerism of 2'-fluoroflavonol, as confirmed by

• than in the remaining conformers (Table 1) provide evidence that fluorine lone pairs in C are involved in intramolecular HB O–H···F–C instead of contributing to the resonant structure with C=F+. HB involving fluorine as a proton acceptor when bonded to carbon is unusual [4], but it has been shown to be