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The chiral, triangular-shape hexaimine macrocycles (trianglimines), bearing bulky alkynyl or aryl substituents were synthesized and studied by means of experimental and theoretical methods. The macrocyclization reactions are driven by the extraordinary stability of the trianglimine ring and provided products with high yields. Electrostatic repulsion between imine nitrogen atoms and the substituents forced an anti conformation of the aromatic linkers. Although the DFT-optimized structure of 7 is D3 symmetrical, in the crystal, the macrocycle adopts a bowl-like molecular shape. The macrocycle self-assembles into tail-to-tail dimers by mutual interdigitation of aromatic moieties. In contrast, macrocycle 8 adopts a rigid pillararene-like conformation. The nature of the substituent significantly affects the electronic properties of the linker. As a result, unexpectedly high exciton Cotton effects are observed in the electronic circular dichroism (ECD) spectra. The origin of these effects was subject of an in-depth study.

Gold-catalyzed imination/Mannich reaction cascades on readily available 3-en-1-ynamides enable the diastereoselective synthesis of 1,5-iminoamino compounds in a one-pot operation. The reactions work well with diversified 3-en-1-ynamides, aldehydes and anilines with good to excellent diastereoselectivities. Our control experiments indicate gold-catalyzed aminations of 3-en-1-ynamides to yield α-imino allylgold intermediates that react subsequently with iminiums to implement the Mannich reactions stereoselectively. The reactions proceed with anti-selectivity for those 3-en-1-ynamides bearing acyclic alkenes whereas syn-selectivity is seen for their cycloalkene-based analogues. An open-transition state can satisfactorily rationalize these observed stereoselectivities based on an antiperiplanar conformation.

Hydrothermal reactions of 1,4-bis(imidazol-1-yl)benzene (bimb) and either 5-hydroxyisophthalic acid (HO-H2ip) or 5-methoxyisophthalic acid (MeO-H2ip), as well as transition metal salts, gave rise to six new coordination polymers: [Zn2(bimb)(H2O)(HO-ip)2]n (1), [Zn(bimb)(MeO-ip)]n·(H2O)n (2), [Mn2(bimb)2(HO-ip)2]n (3), [Mn2(bimb)2(H2O)2(MeO-ip)2]n (4), [Cu2(bimb)2(MeO-ip)2]n·(H2O)3n (5), and [Co(bimb)(H2O)(MeO-ip)]n·(DMF)0.5n·(H2O)n (6). Their structures have been defined by single-crystal X-ray diffraction analyses, IR spectra, elemental analyses and thermogravimetric analyses. Complex 1 is a 2D coordination network consisting of μ-oxygen-bridged dinuclear ZnII units, whereas 2 is an interdigitating 2D layer. ZnII ions in 1 and 2 have a distorted tetrahedral geometry, and two independent HO-ip and two bimb moieties in the dinuclear unit of 1 form π···π stacking interactions. Complexes 3 and 4 are 2D layers consisting of dinuclear MnII carboxylate units; bimb in an anti conformation serves as an exo-bidentate ligand in 3, whereas in 4 it acts as a terminal ligand, filling void space. Bis-monodentate MeO-ip in 5 connects CuII ions into a 3D coordination network, whereas MeO-ip in 6 bridges between two CoII ions to form a 2D layer, with the strong hydrogen bonds between water molecules of the adjacent 2D layers generating a 2D supramolecular bilayer. The dinuclear MnII units in 3 and 4 are well separated by organic ligands, and make up the basic magnetic units. Temperature-dependent magnetic susceptibility analyses show the existence of antiferromagnetic interaction in 3 and 4.

Unlike π-electron chromophores, the peralkylated n-tetrasilane σ-electron chromophore resembles a chameleon in that its electronic spectrum changes dramatically as its silicon backbone is twisted almost effortlessly from the syn to the anti conformation (changing the SiSiSiSi dihedral angle ω from 0 to 180°). A combination of UV absorption, magnetic circular dichroism (MCD), and linear dichroism (LD) spectroscopy on conformationally controlled tetrasilanes 1-9, which cover fairly evenly the full range of angles ω, permitted a construction of an experimental correlation diagram for three to four lowest valence electronic states. The free chain tetrasilane n-Si4 Me10 (10), normally present as a mixture of three enantiomeric conformer pairs of widely different angles ω, has also been included in our study. The spectral trends are interpreted in terms of avoided crossings of 1B with 2B and 2A with 3A states, in agreement with SAC-CI calculations on the excited states of 1-7 and conformers of 10.

International audience; Cyanoacetaldehyde (NC-CH2CH=O) and its isomer, cyanovinylalcohol (NC-CH=CH-OH), as possible components of the interstellar medium, comets, or planetary atmospheres, exist in equilibrium in the gas phase, although the latter compound is very much in the minority (2%). The recording and analysis of the gas-phase infrared spectrum of the former compound within the 4000-500 cm(-1) spectroscopic range and the potential presence of the latter isomer, which could be vital for their detection in these media, are reported. CCSD(T) and G4 high-level ab initio methods, as well as density functional theory calculations, predict the existence of two stable rotamers of cyanoacetaldehyde. The global minimum has a structure with an unusual O-C-C-C dihedral angle (150°) that falls between the antiperiplanar (180°) and anticlinal forms (120°). The second rotamer, which is about 4.0 kJ mol(-1) less stable in terms of free energy, has a planar structure that corresponds to the synperiplanar form (O-C-C-C dihedral angle: 0°). The absorption vibrational bands of the two aldehyde rotamers that are present in the mixture lead to a spectrum with a very complex structure in the region of deformation movements, in which several low-intensity bands overlap. A complete and unambiguous assignment of the experimental spectrum has been achieved by using the calculated harmonic and anharmonic vibrational frequencies.

The present study addresses the conformational preferences and the mechanism of decarboxylation of levodopa (LD). LD is used to increase dopamine concentrations in the treatment of Parkinson's disease. LD crosses the protective blood-brain barrier, where it is converted into dopamine by the process of decarboxylation. Molecular dynamics simulation has been carried out at the DFT/6-31++G level of theory to identify the global minimum structure of LD. Conformational preferences of the amino acid side chain of LD has been investigated at the B3LYP/6-311++G** level of theory. Fourier transform analysis has been performed to identify the origin of the rotational barriers. Electrostatic dipole moment and bond interactions underlie the observed potential energy barriers for rotation of the amino acid side chain of LD. The vital biological process of decarboxylation of LD has been examined in the gas phase and in aqueous solution. Without the presence of water, there is only one possible route for the decarboxylation of LD. In this concerted mechanism, a proton transfer and breakage of the C10C18 bond, take place simultaneously (E# = 73.2 kcal/mol). In solution, however, two possible decarboxylation routes are available for LD. The first involve the formation of a zwitterionic intermediate (E# = 72.4 kcal/mol). The zwitterionic form of LD have been localized using explicitly bound water molecules to model short-range solvent effects and self-consistent reaction field polarized continuum model to estimate long-range solvent interactions. The second route involve the formation of a cyclic structure in which a water molecule acts as a bridge linking the anticarboxylic hydrogen and -position carbon atom (E# = 59.8 kcal/mol). Natural bond orbital (NBO) analysis reveals that the conformational and overall stability of the amino acid side chain is facilitated by the antiperiplanar interactions between the phenyl moiety CH and CC bonds and CX bonds of the amino acid side chain. However, much of the major donor-acceptor interactions is of the lone pair type and is localized within the amino acid side chain itself. Results of the present work reveal that NBO data reflect nicely and identify clearly reaction coordinates at the transition species.

The mechanism and origin of high E selectivity in the modified Julia olefination of aromatic aldehydes have been explored by computational and experimental means. Reversibility of addition and hence selectivity of the formation of sulfinate 5 is very variable and depends on the nature of the sulfone substrate. However, in all cases, elimination occurs through a concerted antiperiplanar and synperiplanar mechanism for sulfinates anti-5 and syn-5, respectively. Both syn and anti diastereomeric pathways thus lead preferentially to the (E)-alkene. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Three new one-dimensional (1D) chain metal–nitroxide complexes {[Cu(NIT4Py)2(suc)(H2O)]·3H2O}n (1), {[Cd(NIT4Py)2(suc)(H2O)]·[Cd(NIT4Py)2(suc)(H2O)2]·3H2O}n (2), and {[Zn(NIT4Py)(glu)(H2O)]·H2O}n (3) [NIT4Py = 2-(4′-pyridyl)-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3-oxide, suc = succinate anion and glu = glutarate anion] were synthesized and structurally characterized. Single-crystal X-ray analyses indicate that the three complexes crystallize in neutral 1D chains in which the metal-nitroxide units are linked by flexible dicarboxylate anions. The succinate anions only adopt trans configuration in complexes 1 and 2, whereas the glutarate anion has gauche/anti conformation in complex 3. Magnetic measurements show that complex 1 exhibits weak antiferromagnetic interactions between the copper ions and the nitroxides.

The equal molar reaction of Cu(BF4)2·3H2O with the ditopic, bis(pyrazolyl)methane ligand p-[CH(pz)2]2C6H4 (Lp) where pz is a pyrazolyl ring, in methanol produces [Cu(μ-Lp)(CH3OH)](BF4)2·(CH3OH)0.62 (1) and a similar reaction in water/methanol yields [Cu(μ-Lp)(CH3OH)]2(SiF6)(BF4)2·(CH3OH)2 (2). The water/ethanol solvent system yields both [Cu2(μ-Lp)(H2O)6](SiF6)2·(H2O)4 (3) and [Cu(μ-Lp)(H2O)](BF4)2·(CH3CH2OH)2 (4), and if the ratio of Cu(BF4)2·3H2O and Lp is changed to 2:1, only 3 forms. Recrystallization of the solid formed from the reaction of THF solutions of Cu(BF4)2·3H2O with Lp from DMSO yields [Cu2(μ-Lp)(DMSO)6](BF4)4·(DMSO)2·C6H6·(H2O)0.5 (5) and a recrystallization of compound 1 from DMSO yields [Cu2(μ-Lp)(DMSO)6](BF4)4·(DMSO)2·C6H6 (6). Complexes 1, 2, and 4 are coordination polymers in which the N4O-coordinated, square-pyramidal copper(II) ions are oriented in an anti conformation withrespect to the phenylene spacer of Lp. Complexes 3, 5 and 6 are dinuclear with N2O3-coordinated, square-pyramidal copper(II) ions again oriented in an anti configuration with respect to the bridging Lp. The square pyramidal geometries show axial elongation, a result of pseudo Jahn–Teller electronic effects. In the cases of the coordination polymers, the axially coordinated solvent molecule is lost at low temperatures upon heating of the crystals. The three compounds in each structural type have nearly the same overall configurations. Cooperative effects of O–H···F, O–H···O and C–H···F hydrogen bonding interactions organize the supramolecular structures and influence the crystal packing of complexes 1–4. The C–H···F interactions have metrics that indicate they are unusually strong, due to the enhanced polarization of the C–H bond and charge assistance from the anionic fluorine atom.

A Cu(2+)-templated, multinuclear, nonfluorescent, anti-[3]pseudorotaxane was synthesized on a fluorophoric axle. The Cu(2+)-templated [3]pseudorotaxane was characterized by the electrospray ionization mass spectroscopy (ESI-MS), UV/Vis and EPR spectroscopy, and single-crystal X-ray data. The ESI-MS showed peaks that support the formation of [3]pseudorotaxane. The UV/Vis spectrum of [3]pseudorotaxane in CH(3)CN showed a characteristic d-d band of a Cu(2+) complex at 650 nm. Further, the X-band in the EPR spectrum of [3]pseudorotaxane suggested a distorted square-pyramidal geometry of Cu(2+). Importantly, formation of the [3]pseudorotaxane was confirmed by the single-crystal X-ray structural analysis, which showed that one fluorophoric axle was threaded into two Cu(2+) macrocyclic wheels (MC-Cu(2+)) with an anti conformation. The UV/Vis and fluorescence titration experiments were carried out to follow the solution-state formation of [3]pseudorotaxane by MC-Cu(2+) and fluorophoric axle in CH(3)CN. In both studies, the sigmoidal curve fit supported the formation of 1:2 complex of the fluorophoric axle and MC-Cu(2+) complex. Secondly, the release of the fluorophoric axle from the nonfluorescent [3]pseudorotaxane through the formation of a [2]pseudorotaxane was demonstrated by titrating a solution of the [3]pseudorotaxane with a stronger bidentate chelating ligand, such as 1,10-phenanthroline (Phen). Substitution of the fluorophoric axle from the [3]pseudorotaxane with about 100% efficiency was achieved by the addition of approximately two equivalents of Phen, and the formation of a Phen-threaded [2]pseudorotaxane was established by ESI-MS of the resulting solution and a single-crystal X-ray study. Axle substitution was also confirmed by a fluorescence titration experiment, which showed a step-wise recovery of the fluorescence intensity of the fluorophoric axle. The association constants for the formation of the [3]- and [2]pseudrotaxanes were calculated from the fluorescence and UV/Vis data. In addition, 2,2'-bipyridine (BPy), which is a relatively weaker bidendate chelating ligand compared to Phen, showed an inefficient and incomplete axle substitution of the [3]pseudorotaxane, although BPy previously showed the formation of [2]pseudrotaxane with the MC-Cu(2+) wheel in solution and ESI-MS studies. In this context, the formation of a BPy-threaded [2]pseudrotaxane was further established by single-crystal X-ray diffraction study.

Group 12 and silver(I) tetramethyl-m-benziporphodimethene (TMBPDM) complexes with phenyl, methylbenzoate, or nitrophenyl groups as meso substituents were synthesized and fully characterized. The dimeric silver(I) complex displays an unusual η(2),π coordination from the β-pyrrolic C=C bond to the silver ion. All of the complexes displayed a close contact between the metal ion and the inner C(22)-H(22) on the m-phenylene ring. The downfield chemical shifts of H(22) and large coupling constants between Cd(II) and H(22) strongly support the presence of an agostic interaction between the metal ion and inner C(22)-H(22). Crystal structures revealed that the syn form is the predominant conformation for TMBPDM complexes. This is distinctively different from the exclusive anti conformation observed in m-benziporphyrin and tetraphenyl-m-benziporphodimethene (TPBPDM) complexes. Evidently, intramolecular hydrogen-bonding interactions between axial chloride and methyl groups stabilize syn conformations. Unlike the merely syn conformation observed in the solid-state structures of TMBPDM complexes that contain an axial chloride, in solution these complexes display highly solvent- and temperature-dependent syn/anti ratio changes. The observation of dynamic (1)H NMR spectroscopic scrambling between syn and anti conformations from the titration of chloride ion into the solution of the TMBPDM complex suggests that axial ligand exchange is a likely pathway for the conversion between syn and anti forms. Theoretical calculations revealed that intermolecular hydrogen-bonding interactions between the axial chloride and CHCl(3) stabilizes the anti conformation, which explains the increased ratio for the anti form when dichloromethane or chloroform was used as the solvent.

A remote 4J(F,H) coupling (FC(α)C(O)NH) of up to 4.2 Hz in α-fluoro amides with antiperiplanar arrangement of the CF and the CO bonds (dihedral angle FCCO ca. 180°) confirms that previous NMR determinations, using the XPLOR-NIH procedure, of the secondary structures of β-peptides containing β3hAla(αF) and β3hAla(αF2) residues were correct. In contrast, molecular-dynamics (MD) simulations, using the GROMOS program with the 45A3 force field, led to an incorrect conclusion about the relative stability of secondary structures of these β-peptides. The problems encountered in NMR analyses and computations of the structures of backbone-F-substituted peptides are briefly discussed.

The antidepressant drug tetramezine [1,2-bis-(3,3-dimethyldiaziridin-1-yl)ethane] consists of two bridged diaziridine moieties with four stereogenic nitrogen centers, which are stereolabile and, therefore, are prone to interconversion. The adjacent substituents at the nitrogen atoms of the diaziridines moieties exist only in an antiperiplanar conformation, which results in a coupled interconversion. Therefore, three stereoisomers exist (meso form and two enantiomeric forms), which epimerize when the diaziridine moieties are regarded as stereogenic units due to the coupled interconversion. Here, we have investigated the epimerization between the meso and enantiomeric forms by dynamic gas chromatography. Temperature-dependent measurements were performed, and reaction rate constants were determined using the unified equation of chromatography implemented in the software DCXplorer. The activation barriers of the epimerization were found to be ΔG≠ = 100.7 kJ mol−1 at 25°C and ΔG≠ = 104.5 kJ mol−1 at 37°C, respectively. The activation enthalpy and entropy were determined to be ΔH≠ = 70.3 ± 0.4 kJ mol−1 and ΔS≠ = −102 ± 2 J mol−1 K−1. Chirality, 2011. © 2010 Wiley-Liss, Inc.

A study of the infrared and Raman spectra of some vicinal dihalogeno-ethanes, -propanes and -butanes with predominant antiperiplanar orientation in the straight chain and branched series, reveals that the two C-Hal stretching frequencies occur characteristically as a more or less strongly coupled pair: an intense Raman band (νs) and a strong infrared active mode of vibration (νas) at lower frequencey. The C-Hal frequencies of the gauche conformations are weakly coupled. The position of the bands and the difference Δν = νs − νas are functions of the chemical/geometrical structure in the vicinity of the C-Hal bonds. Empirical rules are presented by which the C-Hal frequencies or, in strongly coupled systems, the average frequency of anti as well as of gauche forms can be predicted with fair accuracy.

The reaction of the title cyclic complex (1) with sodium amalgam in THF resulted in the expected cleavage of the Fe—Fe bond to afford bis-sodium salt (Me2SiSiMe2) [η5-C5H4Fe (CO)2Na]2 (4). The latter was not isolated and was used directly to react with MeI, PhCH2Cl, CH3C(O)Cl, PhC(O)Cl, Cy3SnCl (Cy = cyclohexyl) or Ph3SnCl to afford corresponding ring-opened derivatives (Me2SiSiMe2) [η5-C5H4Fe (CO)3R]2 [5, R=Me; 6, R = PhCH2; 7, R = CH3C(O); 8, R = PhC (O); 9, R = Cy3Sn or 10, R = Ph3Sn]. The crystal and molecular structures of 10 were determined by X-ray diffraction analysis. The molecule took the desired anti conformation around the Si—Si bond. The length of the Si—Si bond is 0.2343(3) nm, which is essentially identical to that in the cyclic structure of 1 [0.2346(4) nm]. This result unambiguously demonstrates that the Si—Si bond in the cyclic structure of 1 is not subject to obvious ring strain.

The (1)H, (13)C and (15)N NMR studies have shown that the E and Z isomers of pyrrole-2-carbaldehyde oxime adopt preferable conformation with the syn orientation of the oxime group with respect to the pyrrole ring. The syn conformation of E and Z isomers of pyrrole-2-carbaldehyde oxime is stabilized by the N-H...N and N-H...O intramolecular hydrogen bonds, respectively. The N-H...N hydrogen bond in the E isomer causes the high-frequency shift of the bridge proton signal by about 1 ppm and increase the (1)J(N, H) coupling by approximately 3 Hz. The bridge proton shows further deshielding and higher increase of the (1)J(N, H) coupling constant due to the strengthening of the N-H...O hydrogen bond in the Z isomer. The MP2 calculations indicate that the syn conformation of E and Z isomers is by approximately 3.5 kcal/mol energetically less favorable than the anti conformation. The calculations of (1)H shielding and (1)J(N, H) coupling in the syn and anti conformations allow the contribution to these constants from the N-H...N and N-H...O hydrogen bondings to be estimated. The NBO analysis suggests that the N-H...N hydrogen bond in the E isomer is a pure electrostatic interaction while the charge transfer from the oxygen lone pair to the antibonding orbital of the N-H bond through the N-H...O hydrogen bond occurs in the Z isomer.

The acylation of lithium (±)-spiro-γ-lactone enolate 5 by the O-protected methyl (−)-(S)-lactate or the O-protected methyl (+)-(S)-mandelate occurs through enantio-differentiating reactions. The (S,S)-enolate 5 is the most reactive with the lactate whereas the (R,R)-enolate 5 selectively reacts with the mandelate. According to theoretical calculations at the B3LYP/6-31G(++)(d,p) level of theory of 40 intermediates of this Claisen condensation, the experimental results are compatible with a previous chelation of the ester by an auxiliary cation lithium arising from the medium. The addition reaction occurs through a chelation process mediated by the counterion of the enolate. More stable tetrahedral intermediates including two lithium cations result from an antiperiplanar transition state. These results clearly demonstrate that the presence of a second lithium cation (the first lithium cation is solvated by di-isopropylamine and the second one is solvated by a THF molecule or a di-isopropylamide anion) stabilizes the tetrahedral intermediate and is compatible with an antiperiplanar transition state according to the Felkin–Anh model. Copyright © 2010 John Wiley & Sons, Ltd.

In connection with study of chiral derivatizing agents (CDAs) for NMR determination of absolute configuration of organic compounds, factors controlling the conformational preference between syn- and anti-forms in α-substituted α-fluorophenylacetic acid methyl ester (FC(X)(Ph)COOMe) model systems were theoretically investigated. Substituents X at the stereogenic carbon atom were X = H, CCH and CH3, the electronic and steric properties of which were significantly different from each other. The model system with X = CCH and that with X = CH3 were found to be possible candidates for fluorine-containing CDAs. The syn conformation is stable compared with the anti one by 0.7 kcal mol−1 for the ester with X = CCH. On the other hand, the anti conformation is stable compared with the syn one by 0.5 kcal mol−1 for the ester with X = CH3. Both natural bond orbital (NBO) analysis and deletion of selected orbitals based on the donor–acceptor NBO scheme were adopted for semi-quantitative estimation of factors responsible for the conformational preference as well as a qualitative inspection of occupied canonical molecular orbitals (MOs). It was shown that [σ–(σ* + π*)(CO)] and [σ–σ*(Ph) and π(Ph)–σ*] hyperconjugations are the main factors controlling the conformational preferences between the syn and anti conformations. Other types of effects such as electrostatic effects were also investigated. The role of the fluorine atom was also clarified. Copyright © 2009 John Wiley & Sons, Ltd.

Sonogashira coupling of diacetyl 5-ethynyl-2′-deoxyuridine with diacetyl 5-iodo-2′-deoxyuridine gave the acylated ethynediyl-linked 2′-deoxyuridine dimer (3 b; 63 %), which was deprotected with ammonia/methanol to give ethynediyl-linked 2′-deoxyuridines (3 a; 79 %). Treatment of 5-ethynyl-2′-deoxyuridine (1 a) with 5-iodo-2′-deoxyuridine gave the furopyrimidine linked to 2′-deoxyuridine (78 %). Catalytic oxidative coupling of 1 a (O2, CuI, Pd/C, N,N-dimethylformamide) gave butadiynediyl-linked 2′-deoxyuridines (4; 84 %). Double Sonogashira coupling of 5-iodo-2′-deoxyuridine with 1,4-diethynylbenzene gave 1,4-phenylenediethynediyl-bridged 2′-deoxyuridines (5; 83 %). Cu-catalyzed cycloisomerization of dimers 4 and 5 gave their furopyrimidine derivatives. One-electron addition to 1 a, 3 a, and 4 gave the anion radical, the EPR spectra of which showed that the unpaired electron is largely localized at C6 of one uracil ring (17 G doublet) at 77 K. The EPR spectra of the one-electron-oxidized derivatives of ethynediyl- and butadiynediyl-linked uridines 3 a and 4 at 77 K showed that the unpaired electron is delocalized over both rings. Therefore, structures 3 a and 4 provide an efficient electronic link for hole conduction between the uracil rings. However, for the excess electron, an activation barrier prevents coupling to both rings. These dimeric structures could provide a gate that would separate hole transfer from electron transport between strands in DNA systems. In the crystal structure of acylated dimer 3 b, the bases were found in the anti position relative to each other across the ethynyl link, and similar anti conformation was preserved in the derived furopyrimidine–deoxyuridine dinucleoside.

The molecular structure of methyl trifluoroacetate (CF3C(O)OCH3) has been determined in the gas phase from electron-diffraction data supplemented by ab initio (MP2) and DFT calculations using different basis sets. Experimental data revealed an anti conformation with a dihedral angle θ (CCOC) = 180°. Quantum mechanical calculations indicate the possible existence of two conformers, differing by a rotation about the C(O)O bond. The global minimum represents a Cs-symmetric structure in which the CF3 group has the anti orientation with respect to the CH3 group, but there is another potential minimum, much higher in energy, representing a Cs-symmetric structure with a cis conformation. The preference for the anti conformation was studied using the total energy scheme and the natural bond orbital (NBO) partition scheme. Additionally, the total potential energy has been deconvoluted using a six-fold decomposition in terms of a Fourier-type expansion, showing that the electrostatic and steric contributions are dominant in stabilizing the anti conformer. Infrared spectra of CF3C(O)OCH3 were obtained for the gaseous and liquid phases, while the Raman spectrum was recorded for the liquid phase. Harmonic vibrational frequencies and a scaled force field have been calculated, leading to a final root mean-square deviation of 9 cm−1 when comparing experimental and calculated frequencies. Copyright © 2009 John Wiley & Sons, Ltd.

The molecular orbital INDO method is used for the calculation of long-range NMR proton-proton coupling constants between H1, and protons of the base and between the protons of the furanose ring in purine and pyrimidine nucleosides. The computations show that the couplings between H1, and the protons of the base are negligible in the purine nucleosides and are very sensitive to the torsion angle about the glycosidic bond in pyrimidine nucleosides. For uridine and its derivatives the calculated J1, 5 are in agreement with experiment for an anti conformation of these compounds. For α- and β-pseudouridines, J1, 6 is important and may be large for anti as well as syn conformations. The long-range couplings between the protons of the furanose ring vary little with the puckering of the sugar.

Hydrothermal treatment of aqueous mixtures of copper(II) halides and 3,3′-bipyridine (3,3′-bpy) has afforded the coordination polymers [CuCl(3,3′-bpy)]n (1) and [Cu2Br2(3,3′-bpy)]n (2), which were analyzed via single crystal X-ray diffraction, infrared spectroscopy, and elemental analysis. The structure of 1 consists of two-dimensional (2-D) layers constructed from the linkage of castellated one-dimensional (1-D) [CuCl]n stepped chains through anti-conformation 3,3′-bpy tethers. Compound 2 presents a related 2-D sheet motif, albeit built from infinite 1-D [Cu2Br2]n ladders strutted by 3,3′-bpy ligands in anti conformation. In both cases neighboring 2-D sheets stack into 3-D via weak C–H···halogen interactions.

Polysulfonylamines. CLXXXIII. Novel Solid-State Aspects of Di(arenesulfonyl)amines: Silver(I) Di(4-iodobenzenesulfonyl)amide, a Layer Compound Displaying Structure-Directing Ag–I–C Motifs, and Di(4-fluorobenzenesulfonyl)amine Monohydrate, a Column Structure Exhibiting Intracolumnar Water Chains and Intercolumnar C–H···F–C Hydrogen Bonds Low-temperature X-ray structures are reported for (4-I–C6H4SO2)2NAg (1, triclinic, , Z′ = 1) and (4-F–C6H4SO2)2NH·H2O (2, orthorhombic, Pna21, Z′ = 2). Whereas metal di(arenesulfonyl)amides usually display folded anions (C–S···S′–C′ synperiplanar) and crystallize in lamellar layers, compound 1 has an extended anion (C–S···S′–C′ antiperiplanar) and forms non-lamellar striated layers in which the ions are connected by Ag–N/Ag–O bonds in one dimension and by Ag–I–C interactions, C–I···O halogen bonds and weak π/π ring interactions in the other dimension. The silver ion adopts a trigonal-bipyramidal pentacoordination comprising two long axial Ag–O bonds (259 and 261 pm), one short Ag–N bond (228 pm) and two structure-determining Ag–I bonds (289 and 294 pm, Ag–I–C 107 and 109°). An analysis of Ag···I–C contacts < 340 pm extracted from the Cambridge Structural Database (25 structures, 63 contacts) reveals that the Ag–I–C angles lie between 90 and 110° for contacts < 300 pm, whereas for longer interactions, the directionality rapidly becomes weaker; this result is in keeping with the electrophile/nucleophile model for interactions involving halogen atoms bonded to carbon. In the structure of compound 2, a dimer of two independent water molecules is repeated via glide planes to give a chain in which water 1 acts as a difunctional hydrogen bond donor and water 2 as a difunctional acceptor. The extended disulfonylamine molecules are connected to water 1 by N–H···O(w), to water 2 by O(w)–H···O=S bonds. The resulting supramolecular polymer is a square column that is reinforced by C–H···O=S hydrogen bonds and π/π interactions and bears four one-dimensional sets of fluorine atoms at the vertices. Dense packing of these columns causes all the fluorine atoms to segregate into parallel tunnels and to form short C–H···F–C intercolumnar contacts strongly suggestive of weak hydrogen bonding (H···F 240–250 pm, C···F 328–346 pm, C–H···F 137–148°).

A model compound was de- signed to study the relative orientation of enol silane and carbonyl moieties in the Mukaiyama aldol reaction.The cyclization must proceed with either a synclinal or an antiperiplanar orienta- tion of the aldehyde with respect to the enol silane.These two orientations lead to diastereomeric products, thus allow- ing for unambiguous correlation be- tween product configuration and transi- tion-state geometry.As steric bias is minimal, the product distribution should reflect the intrinsic preferences for reactant geometry in the transition state.Cyclizations of the model com- pound showed a modest preference for reaction via an antiperiplanar (open transition state) orientation of reac- tants in the presence of a wide range of Lewis acids (TiCl4, SnCl4, SnCl2, BF3·OEt2, TMSBr, trityl perchlorate, EtAlCl2) and triflic acid.The cycliza- tions promoted by tin(II) salts were syn-selective and dependent on the nature of the counterion.Fluoride ion promoted reactions were anti-selective and were independent of the nature of the cation.

To further study the preference of the antiperiplanar (ap) conformation in α-fluoro-amide groups, two β-peptides, 1 and 2, containing a (2-F)-β3hAla and a (2-F)-β2hPhe residue, have been synthesized. Their NMR-solution structures in CD3OH were determined and compared with those of non-F-substituted analogs, 3 and 4a. While we have found in a previous investigation (Helv. Chim. Acta2005, 88, 266) that a stereospecifically introduced F-substituent in the central position of a β-heptapeptide is capable of ‘breaking’ the 314-helical structure by enforcing the FCCO ap-conformation, we could now demonstrate that the same procedure leads to a structure with the unfavorable ca. 90° FCCO dihedral angle, enforced by the 314-helical folding in a β-tridecapeptide (cf.1; Fig. 4). This is interpreted as a consequence of cooperative folding in the longer β-peptide. A F-substituent placed in the turn section of a β-peptidic hairpin turn was shown to be in an ap-arrangement with respect to the neighboring CO bond (cf.2; Fig. 7). Analysis of the non-F-substituted β-tetrapeptides (with helix-preventing configurations of the two central β2/β3-amino acid residues) provides unusually tight hairpin structural clusters (cf.3 and 4a; Figs. 8 and 9). The skeleton of the β-tetrapeptide H-(R)β3hVal-(R)β2hVal-(R)β3hAla-(S)β3hPhe-OH (4a) is proposed as a novel, very simple backbone structure for mimicking α-peptidic hairpin turns.

Irradiation of 9-(arylmethoxymethyl)anthracenes 3 leads either to a cyclomer and cyclodimer mixture (3a 4a,5a), to selectively formed dimers (3b 5b), or a selectively formed cyclomer (3c 4c). The [4π+4π]cyclodimerization is under the conditions used a regioselective head-to-tail process. In the crystals of the dimers 5a,b, the sidechains are attached in an antiperiplanar position related to the CC bonds generated in the dimerization. In solutions, however, the structures consist of three rotamers the equilibration of which was studied by temperature-dependent NMR spectra. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

The 1JC--H coupling constants in conformationally constrained sulfoxides, bissulfoxides, sulfoxide-sulfones, and sulfilimines derived from 2-benzylidene-1,3-dithiane and 2-(2,2-dimethylpropylidene)-1,3-dithiolane were measured by means of HMQC and HSQC NMR experiments and the Perlin effects were calculated. The type and the relative configuration of S==X groups (X= O, NTos) in these compounds have a strong influence on the magnitude of coupling constants for axial and equatorial C--H bonds, respectively. Axial S==O bonds give rise to a stereoelectronic effect on antiperiplanar axial C--H bonds. The resultant weakening of the respective C--H bonds leads to a smaller coupling constant than for a respective equatorial C--H bond. Equatorial S==O groups have an influence on beta-C--H bonds through a homoanomeric effect. Here, the axial C--H bond is weakened and a smaller coupling constant is measured. Sulfilimine groups show similar effects to sulfoxide groups.

To compare the crystalline-state conformations of MαNP acid esters with those existing in the solution state, X-ray crystallographic analyses of 22 MαNP esters and two MαNP acids were carried out. It was found that all 27 conformers observed in the solid state have structures in which the 2-CH3 group and the 2′-H of the naphthyl group are synperiplanar and are almost always located in the same plane. In addition, the CH3–O7–C2–C1 moiety in all cases has an antiperiplanar structure within the MαNP plane. From further analyses, 22 conformers adopt the so-called syn structure, in which the O7–C2–C1–O6 moiety is synperiplanar. On the other hand, the remaining five conformers have the so-called anti structure. With regard to the rotational conformation around C1″–O5, all conformers have structures similar to the synperiplanar conformation. In the so-called syn conformers, the interatomic distance d(H8′–O6) is distributed between 2.48 A and 2.96 A, while the distance d(H8′–O7) varies between 2.26 A and 2.56 A, indicating the weak bifurcated hydrogen bond between O6–H8′–O7 as the intramolecular stabilizing force. The crystalline-state conformations of MαNP esters are thus similar to those in solution as determined by 1H NMR spectroscopy, implying that the intramolecular forces make a dominant contribution to the conformations of MαNP esters. The X-ray crystallographic analyses of MαNP acids indicated that the O6–H(acid)–O7 bifurcated hydrogen bond also serves as an intermolecular force to stabilize the so-called syn conformation. A similar bifurcated hydrogen bond [O6–H(alcohol)–O7] was observed in a MαNP ester containing a tertiary alcohol group. It should be emphasized that despite the existence of the so-called syn and anti conformations in the crystalline state, the absolute configurations of all MαNP esters determined here by X-ray crystallography all agree with those obtained by the 1H NMR anisotropy method.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

The thermodynamic functions ΔH and ΔS, were computed along the dihedral angle (x) of conformational change for a few selected single rotors: YCH2CH2Y and YCH2OH. The computations were carried out at the B3LYP/6–31G(d,p) level of theory, with 5° increments in x, under very tight optimization condition. The entropy function, S(x), was generated for the full range (0° to 360°) of internal rotation and was subjected to functional analysis. We found the general rule that S(x) had critical points at or near the critical points of ΔH(x); therefore, (dS/dx) vanished for all critical points (minima and transition states) of ΔH(x). However, the entropy derivative also vanished at certain characteristic conformations that were not manifested on the potential energy or enthalpy function. These geometries were classified as “latent minima” or “latent critical points.” The conformational entropy change was related to the relative information (I/I180) of the same state, where the reference state was chosen to be the anti conformation (x = 180°). According to the relationship ln(I/I180) = −ΔS/R, information accumulation was observed in the case of 1,2-disubtituted ethane and information depletion occurred in the case of fluoromethanol and ethyl alcohol. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007

A new and high-yielding method for the regioselective preparation of 4-deoxy- and 2,4-dideoxy-2-acetamido-β-D-threo-hex-3-enopyranosides has been developed. The process involves a simultaneous activation–elimination of the OH-4 group of β-D-talopyranosides and 2-acetamido-2-deoxy-β-D-talopyranosides, mediated by the NaH/N,N′-sulfuryldiimidazole system at –30 °C. The same reaction applied on the analogous β-D-galactopyranosides takes place without any regioselectivity, affording mixtures of hex-3- and hex-4-enopyranosides. In the case of the methyl 2,3,6-tri-O-benzyl-α-D-talo- and α-D-galactopyranosides, the corresponding 4-O-imidazylates can be isolated by quenching the reactions at –30 °C. Upon warming these crude products to room temperature, the α-talo-4-O-imidazylate gives the corresponding hex-3-eno derivative in very high yield, but its α-galacto analogue gives the hex-4-enopyranoside enol ether in poor yield. The different regiochemical outcome between the talo and the galacto series has been attributed to the stereoelectronic effect exerted, exclusively in talo-configured compounds, by the axially disposed C-2 electronegative substituent, which selectively accelerates the breaking of the antiperiplanar C(3)–H bond. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Diastereomeric meso- and d,l-bis(bicyclopropylidenyl) (5) were obtained upon oxidation with oxygen of a higher-order cuprate generated from lithiobicyclopropylidene (4) in 50 and 31 % yield, respectively. Their perdeuterated analogues meso-[D(14)]- and d,l-[D(14)]-5 were obtained along the same route from perdeuterated bicyclopropylidene [D(8)]-3 (synthesized in six steps in 7.4 % overall yield from [D(8)]-THF) in 20.5 % yield each. Dehalogenative coupling of 1,1-dibromo-2-cyclopropylcyclopropane (6) gave a mixture of all possible stereoisomers of 1,5-dicyclopropylbicyclopropylidene 16 in 69 % yield, from which (Z)-cis-16 was separated by preparative gas chromatography (26 % yield). The crystal structure of meso-5 looks like a superposition of the crystal structures of two outer bicyclopropylidene units (3) and one inner s-trans-bicyclopropyl unit, whereas the two outer cyclopropyl moieties adopt a gauche orientation with respect to the cyclopropane rings at the inner bicyclopropylidene units in (Z)-cis-16. Birch reduction with lithium in liquid ammonia of meso-5 and d,l-5 gave two pairs of diastereomeric quatercyclopropanes trans,trans-(R*,S*,R*, S*)-17/cis,trans-(R*,S*,R*,R*)-18 and trans,trans-(R*,S*,S*,R*)-19/cis,trans-(R*,S*,S*,S*)-20 in 97 and 76 % yield, respectively, in a ratio 9:1 for every pair. The latter diastereomer was also obtained as the sole product by Birch reduction of (Z)-cis-16 in 96 % yield. Under the same conditions, tetradecadeuterio analogues trans,trans-[D(14)]-(R*,S*,R*,S*)-17/cis,trans-[D(14)]-(R*, S*,R*,R*)-18 (8:1) and trans,trans-[D(14)]-(R*,S*,S*,R*)-19/cis,trans-[D(14)]-(R*,S*,S*,S*)-20 (12:1) were prepared from meso-[D(14)]-5 and d,l-[D(14)]-5 in 37 and 63 % yield, respectively. Reduction of meso-5 with diimine gave the cis,cis-quatercyclopropane (S*,S*,R*,R*)-21 as the main product (58 % yield) along with the cis,trans-diastereomer (S*,S*,R*,S*)-18 (29 % yield). Thus, five of the six possible diastereomeric quatercyclopropanes were obtained from meso-5, d,l-5, and (Z)-cis-16. The X-ray crystal structure analyses of trans,trans-(R*,S*,R*,S*)-17 and cis,cis-(S*,S*,R*,R*)-21 revealed for the both an unusual conformation in which the central bicyclopropyl unit adopts an s-trans-(antiperiplanar) orientation with phi=180.0 degrees , and the two terminal bicyclopropyl moieties adopt a synclinal conformation with phi=49.8 and 72.0 degrees , respectively. In solution the vicinal coupling constants (3)J(H,H) in trans,trans-(R*,S*,R*,S*)-[D(14)]-17, trans,trans-(R*,S*,S*,R*)-[D(14)]-19, trans,cis-(R*,S*,R*,R*)-[D(14)]-18 and trans,cis-(R*,S*,S*,S*)-[D(14)]-20 were found to be 4.1, 4.7, 5.9 and 5.9 Hz, respectively. This indicates a predominance of the all-gauche conformer in (R*,S*,R*,S*)-17 and a decreasing fraction of it in this sequence of the other diastereomers.

Four novel cadmium(II) coordination polymers, [Cd3(TCMB)2(4,4-bipy)(H2O)16]n (1), [Cd3(TCMB)2(bpe)(H2O)13]n (2), [Cd3(TCMB)2(bpe)2(H2O)4]n (3), and [Cd3(TCMB)2(dpp)2(H2O)3]n (4), [TCMB = 1,3,5-tris(carboxymethoxy)benzene, 4,4-bipy = (4,4-bipyridine), bpe = 1,2-bis(4-pyridyl)ethane, dpp = 1,3-bis(4-pyridyl)propane] have been hydrothermally synthesized by the self-assembly of the flexible tripodal acid TCMB and Cd(OAc)2·2H2O with pyridyl-containing ligands possessing different flexibilities. Single-crystal X-ray diffraction analysis reveals that the four polymers exhibit novel frameworks due to diverse coordination modes and different conformations of the flexible TCMB as well as pyridyl-containing ligands. Complex 1 shows a unique twofold parallel interpenetrating 2D honeycomb network structure with an unusual 63 topology, in which two different large hexagonal rings are arranged alternately, with extraordinarydimensions of ca. 22.172(6) × 12.947(2) A (A) and 17.233(2) × 12.947(2) A (B) based on the distances of the atoms at the opposite positions of the rings. Complex 2 is almost isostructural to complex 1, except that the bidentate bpe ligands bridge the cadmium centers in an anti conformation, rendering the network more flexible. Complex 3 features a 3D network with one of the scarce eight-connected (46, 614, 88)(43)2 topologies based on the rare CdI2-type layer constructed from secondary building units (SBUs) of rare [Cd3(CO2)4]2- isosceles triangle cadmium clusters. Complex 4 possesses distorted CdI2-type layers constructed from unprecedented ten-connected Cd3 clusters which are linked by more flexible dpp ligands in a trans-gauche (TG) conformation in (4,4) networks, leading to another 3D framework of the unusual (418, 624, 83)(43)2 topology. Such an arrangement represents the highest connected topology presently known for the frameworks. Among them, complex 1 displays photoluminescent properties at 460 nm due to the ligand-to-metal charge transfer (LMCT).

Dithia-(dithienylethena)phane derivatives, composed of dithienylethene moieties and benzene bridges, were synthesized by a coupling reaction of the corresponding bis(chloromethyl)benzene with bis(mercaptomethyl)dithienylethene under high-dilution conditions. The products exhibit photochromic properties upon irradiation with ultraviolet and visible light. The photocyclization and cycloreversion quantum yields were determined, and a relationship between the photocyclization quantum yield and distance between the reactive carbon atoms of the phane derivatives established. The ortho isomer has a high efficiency in photocyclization due to its fixation in the photo-active anti conformation and short distance between the two reactive carbon atoms. The thermal stability of these photochromic compounds has been studied and the ortho isomer found to show thermal irreversibility. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

NMR and CD data have previously shown the formation of the T(4) tetraloop hairpin in aqueous solutions, as well as the possibility of the B-to-Z transition in its stem in high salt concentration conditions. It has been shown that the stem B-to-Z transition in T(4) hairpins leads to S (south)- to N (north)-type conformational changes in the loop sugars, as well as anti to syn orientations in the loop bases. In this article, we have compared by means of UV absorption, CD, Raman, and Fourier transform infrared (FTIR), the thermodynamic and structural properties of the T(4) and A(4) tetraloop hairpins formed in 5'-d(CGCGCG-TTTT-CGCGCG)-3' and 5'-d(CGCGCG-AAAA-CGCGCG)-3', respectively. In presence of 5M NaClO(4), a complete B-to-Z transition of the stems is first proved by CD spectra. UV melting profiles are consistent with a higher thermal stability of the T(4) hairpin compared to the A(4) hairpin. Order-to-disorder transition of both hairpins has also been analyzed by means of Raman spectra recorded as a function of temperature. A clear Z-to-B transition of the stem has been confirmed in the T(4) hairpin, and not in the A(4) hairpin. With a right-handed stem, Raman and FTIR spectra have confirmed the C2'-endo/anti conformation for all the T(4) loop nucleosides. With a left-handed stem, a part of the T(4) loop sugars adopt a N-type (C3'-endo) conformation, and the C3'-endo/syn conformation seems to be the preferred one for the dA residues involved in the A(4) tetraloop.

The β-heptapeptides H-βhVal-βhAla-βhLeu-βhAla(Xn)-βhVal-βhAla-βhLeu-OH 3–7 with central 3-amino-2-fluoro-, 3-amino-2,2-difluoro-, or 3-amino-2-hydroxybutanoic acid residues (βhAla(Xn)) of like and unlike configuration were subjected to a detailed NMR analysis in MeOH solution. For the geminal difluoro and for the F- and OH-substituted derivatives of u-configuration (see 5, 4, and 7, resp.), 14-helices were found, i.e., with axial disposition of the hetero atoms on the helix. The two compounds containing the central l-configured β-amino acid moieties (see 3 and 6) are not helical over the full lengths of the chains; they have ‘quasi-helical’ termini and a central turn consisting of a ten-membered H-bonded ring (Fig. 2, d and e). Quantum-mechanical calculations with l- and u-AcNH-CHMe-CHF-CONH2 confirm the observed preference for a conformation with antiperiplanar arrangement of the FC and the CO bond. The calculated energy difference between the observed ‘non-helical’ geometry of this moiety and a hypothetical helical one is 6.4 kcal/mol (Fig. 3).

Phenazopyridine hydrochloride (1), a drug in clinical use for many decades, and some derivatives were studied by one- and two-dimensional 1H, 13C and 15N NMR methodology. The assignments, combined with DFT calculations, reveal that the preferred protonation site of the drug is the pyridine ring nitrogen atom. The chemoselective acetylation of phenazopyridine (2) and its influence on the polarization of the azo nitrogen atoms were evidenced by the 15N NMR spectra. Molecular calculations of the phenazopyridines 2–4 show that the pyridine and phenyl groups are oriented in an antiperiplanar conformation with intramolecular hydrogen bonding between the N-b atom and the C-2 amino group preserving the E-azo stereochemistry. Copyright © 2004 John Wiley & Sons, Ltd.

1,3-Dipolar cycloaddition reactions of N-methyl-C-arylnitrones with N-phenyl- or N-methylmaleimide were studied. The reaction of p-dimethylamino-, 4-benzyloxy-3-methoxy-, p-nitro- and p-chloro-substituted phenylnitrones with N-phenylmaleimide gave cis and trans cycloadducts but that of the corresponding phenylnitrones with N-methylmaleimides only the cis adducts in the case of p-dimethylamino and 4-benzyloxy-3-methoxy substitution. All cis adducts attain a biased conformation whereas the trans forms are shown (by 1H NMR at 233 K and 13C NMR at 208 K) to be mixtures of two invertomers, namely o-(N-lone pair antiperiplanar to 3H; minor) and i-conformations (3H-C-C-3aH dihedral angle close to 90°; major). PM3 and DFT calculations at the B3LYP/6–31G(d) level of theory prove qualitatively that these two conformers of the trans adduct are of comparable stability and represent energy minima.

Lithium tellurophosphinite [Ph2PTe][Li(TMEDA)1.33(THF)1.33] (4), ditellurophosphinate, [Ph2PTe2][Li(THF)3.5(TMEDA)0.25] (5), and selenotellurophosphinate [Ph2P(Se)Te][Li(THF)2(TMEDA)] (6) complexes have been prepared from the insertion/oxidation reactions of lithiated secondary phosphanes with elemental chalcogens and characterised by X-ray crystallography. Compounds 4−6 contain no tellurium−lithium bonding interactions in the solid state, instead existing as ion-separated species with THF/TMEDA-solvated lithium cations. Reaction of dilithiated primary phosphanes with more than three equivalents of elemental selenium gives [{(c-C6H11)P(Se)(SeLi)}2·2TMEDA] (7) via a phosphorus-phosphorus coupling reaction. Solid state characterisation of 7 reveals the organo groups in the tetradentate tetraselenohypodisphosphinate ligand to be in an anti conformation to one another and each lithium atom to be coordinated by two selenium atoms, one from each of the diselenophosphinate groups. Multinuclear NMR spectroscopic data are consistent with retention of the solid-state structures of 4−7 in solution. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Hexaethylbenzene adopts a conformation with the ethyl groups perpendicular to the aromatic ring and oriented in a fully alternated up-down arrangement. The synthesis, stereochemistry and rotational barriers of systems possessing two polyethylaryl rings in spatial proximity (e.g., decaethylbiphenyl, octaethylbiphenylene) are reviewed. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

The preparation of (S)-β2,2,3-amino acids with two Me groups in the α-position and the side chains of Ala, Val, and Leu in the β-position (double methylation of Boc-β-HAla-OMe, Boc-β-Val-OMe, and Boc-β-Leu-OMe, Scheme 2) is described. These β-amino acids and unlabelled as well as specifically 13C- and 15N-labelled 2,2-dimethyl-3-amino acid (β2,2-HAib) derivatives have been coupled in solution (Schemes 1, 3 and 4) to give protected (N-Boc, C-OMe), partially protected (N-Boc/C-OH, N-H/C-OMe), and unprotected β2,2- and β2,2,3-hexapeptides, and β2,2- and β2,2,3-heptapeptides 1–7. NMR Analyses in solution (Tables 1 and 2, and Figs. 2–4) and in the solid state (2D-MAS NMR measurements of the fully labelled Boc-(β2,2-HAib)6-OMe ([13C30, 15N6]-1e; Fig. 5), and TEDOR/REDOR NMR investigations of mixtures (Fig. 6) of the unlabelled Ac-(β2,2-HAib)7-OMe (4) and of a labelled derivative ([13C4,15N2]-5; Figs. 7–11, and 19), a molecular-modeling study (Figs. 13–15), and a search in the Cambridge Crystallographic Data Base (Fig. 16) allow the following conclusions: i) there is no evidence for folding (helix or turn) or for aggregation to sheets of the geminally dimethyl substituted peptide chains in solution; ii) there are distinct conformational preferences of the individual β2,2- and β2,2,3-amino acid residues: close to eclipsing around the C(O)C(Me2(CHR)) bond (τ1,2), almost perfect staggering around the C(2)C(3) ethane bond (τ2,3), and antiperiplanar arrangement of H(C3) and H(N) (τ3,N; Fig. 12) in the solid state; iii) the β2,2-peptides may be part of a turn structure with a ten-membered H-bonded ring; iv) the main structure present in the solid state of F3CCO(β2,2-HAib)7-OMe is a nonfolded chain (>30 A between the termini and >20 A between the N-terminus and the CH2 group of residue 5) with all CO bonds in a parallel alignment (±10°). With these structural parameters, a simple modelling was performed producing three (maybe four) possible chain geometries: one fully extended, two with parallel peptide planes (with zick-zack and crankshaft-type arrangement of the peptide bonds), and (possibly) a fourth with meander-like winding (D–G in Figs. 17 and 18).

The crystal structures of 32 derivatives of 4-isopropyl-5,5-diphenyl-1,3-oxazolidin-2-one (A and 1–31) are presented (Fig. 2 and Tables 1–3). In all but four structures, the Me2CH group is in a disposition that mimick a Me3C group (Figs. 3–5). The five-membered ring shows conformations from an envelope form with the Ph2C group out of the plane containing the other four atoms to the twist form with the twofold axis through the CO group (Fig. 6, and Table 2). In the entire series, the Me2CH and the neighboring trans Ph group are approximately antiperiplanar (average torsion angle 155°). The structural features are used to interpret the previously observed reactivity behavior of the diphenyl-oxazolidinone derivatives. The practical advantages of the title compound over classical Evans auxiliaries are outlined (Figs. 1 and 7, and Scheme 2): high crystallinity of all derivatives, steric protection of the CO group in the ring, excellent stereoselectivities in reactions of its derivatives, and safe preparation and easy recovery of the auxiliary.

The C(2) isotropic chemical shift values in solid-state CP/MAS 13C NMR spectra of conformational polymorphs Form I (δ 28.5) and III (δ 22.9) of (1S,4S)-sertraline HCl (1) were correlated with a γ-gauche effect resulting from the respective 162.6° antiperiplanar and 68.8° (+)-synclinal C(2) C(1) N CH3 torsion angles as measured by X-ray crystallography. The similarity of the solution-state C(2) chemical shifts in CD2Cl2 (δ 22.8) and DMSO-d6 (δ 23.4) with that for Form III (and other polymorphs having C(2) C(1) N CH3 (+)-synclinal angles) strongly suggests that a conformational bias about the C(1) N bond exists for 1 in both solvents. This conclusion is supported by density functional theory B3LYP/6-31G(d)-calculated relative energies of C(1) N rotameric models: (kcal) 0.00 [73.8 °C(2) C(1) N CH3 torsion angle], 0.88 (168.7°), and 2.40 (−63.4°). A Boltzmann distribution of these conformations at 25 °C is estimated to be respectively (%) 80.3, 18.3, and 1.4. Copyright © 2002 John Wiley & Sons, Ltd.

The 1,4-cis-diethynylated α-D-mannopyranose analogue 11 has been prepared from 1,6 : 2,3-dianhydro-β-D-allopyranose (6) by alkynylating epoxide and acetal opening (Scheme 2). Eglinton coupling of 11 gave the cyclodimer 18 (Scheme 3). Crystal-structure analysis of the corresponding bis(methanesulfonate) 19 revealed substantially bent butadiyne moieties; one mannopyranosyl ring adopts the 4C1 and the other one a slightly distorted OS2 conformation (Fig. 1). Hydrogenation of 18, followed by deprotection, gave the stable butane-1,4-diyl-bridged cyclodimer 21 (Scheme 3). Crystal-structure analysis shows the 4C1 conformation of the mannopyranosyl units (Fig. 2). The two butane fragments are characterised by a combination of gauche and antiperiplanar arrangements.

Four different dehydrogenases are known that catalyse the reversible dehydrogenation of N5,N10-methylenetetrahydromethanopterin (methylene-H4MPT) or N5,N10-methylenetetrahydrofolate (methylene-H4F) to the respective N5,N10-methenyl compounds. Sequence comparison indicates that the four enzymes are phylogenetically unrelated. They all catalyse the Re-face-stereospecific removal of the pro-R hydrogen atom of the coenzyme's methylene group. The Re-face stereospecificity is in contrast to the finding that in solution the pro-S hydrogen atom of methylene-H4MPT and of methylene-H4F is more reactive to heterolytic cleavage. For a better understanding we determined the conformations of methylene-H4MPT in solution and when enzyme-bound by using NMR spectroscopy and semiempirical quantum mechanical calculations. For the conformation free in solution we find an envelope conformation for the imidazolidine ring, with the flap at N10. The methylene pro-S C-H bond is anticlinal and the methylene pro-R C-H bond is synclinal to the lone electron pair of N10. Semiempirical quantum mechanical calculations of heats of formation of methylene-H4MPT and methylene-H4F indicate that changing this conformation into an activated one in which the pro-S C-H bond is antiperiplanar, resulting in the preformation of the leaving hydride, would require a deltadeltaH(f) of +53 kJ mol-1 for methylene-H4MPT and of +51 kJ mol-1 for methylene-H4F. This is almost twice the energy required to force the imidazolidine ring in the enzyme-bound conformation of methylene-H4MPT (+29 kJ mol-1) or of methylene-H4F (+35 kJ mol-1) into an activated conformation in which the pro-R hydrogen atom is antiperiplanar to the lone electron pair of N10. The much lower energy for pro-R hydrogen activation thus probably predetermines the Re-face stereospecificity of the four dehydrogenases. Results are also presented explaining why the chemical reduction of methenyl-H4MPT+ and methenyl-H4F+ with NaBD4 proceeds Si-face-specific, in contrast to the enzyme-catalysed reaction.

The crystal structure of the title compound has been determined from X- ray diffraction studies. The compound was crystallized from ethanol in the monoclinic system with the space group P2 1 . The unit cell parameters are a = 9.650(2) A, b = 6.505(2) A, c = 14.251(2) A and p = 93.70(2)°. The number of molecules in the unit cell Z = 2 and the volume of the cell is V = 892.7(4) A 3 . The structure was determined by direct methods and refined to a final R(F) factor of 0.062. The glycosyl torsion angle about C(1')- N(9) shows anti conformation. The furanose ring adopts C(3') - endo puckering geometry.

The Raman spectra (3400–10 cm−1) of liquid and solid and the infrared spectra (3400–50 cm−1) of gaseous, xenon solution and solid 4-chlorobut-1-yne, CH2ClCH2CCH, were recorded. These data indicate that the molecule exists in the anti (the C—Cl bond is trans to the CC bond) and the gauche conformations in the vapor and liquid and that both conformers persist in the solid with an indication that the gauche conformer may be more stable in this physical state. From a variable-temperature infrared study of the xenon solution, the anti conformation has been determined to be more stable than the gauche form by 147 ± 10 cm−1 (1.76 ± 0.12 kJ mol−1). From these data it is estimated that 50% of the sample is in the gauche form at ambient temperature. The optimized geometries, conformation stabilities, harmonic force fields, Raman activities, depolarization ratios and infrared intensities were obtained from MP2/6–31G(d) ab initio calculations with full electron correlation. These quantities were compared with the corresponding experimental quantities when appropriate. Equilibrium geometries and energies for both conformers were obtained from ab initio MP2/6–311 + G(d, p) and MP2/6–311 + G(2d, 2p) calculations. Vibrational assignments for the 24 normal modes for both the anti and gauche conformers are proposed. These experimental and theoretical results are compared with the corresponding quantities for some similar molecules. Copyright © 2001 John Wiley & Sons, Ltd.

To obtain further evidence for the importance of the ground state conformational and orbital properties in π-facial diastereoselection of 1,3-diheteran-5-ones (heteroatom = O, S, Se), 2-phenyl-1,3-diselenan-5-one (3a) has been synthesized, and its π-facial diastereoselection upon hydride reduction has been examined. The experimental data of π-facial stereoselection of 3a has been successfully rationalized by the exterior frontier orbital extension model (the EFOE model). Intrinsic reaction coordinate (IRC) and natural bond orbital (NBO) analyses of transition states of LiAlH4 reduction of this ketone have strongly indicated that the transition state effects (the torsional strain of the carbonyl moieties and the antiperiplanar effects involving the incipient bond proposed by the conventional theoretical models for π-facial diastereoselection; the Felkin-Anh model and the Cieplak model) are not responsible for facial selection. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:358–368, 2001

The interpretation of 1H-NMR chemical shifts, coupling constants, and coefficients of temperature dependence (δ(OH), J(H,OH), and Δδ(OH)/ΔT values) evidences that, in (D6)DMSO solution, the signal of an OH group involved as donor in an intramolecular H-bond to a hydroxy or alkoxy group is shifted upfield, whereas the signal of an OH group acting as acceptor of an intramolecular H-bond and as donor in an intermolecular H-bond to (D6)DMSO is shifted downfield. The relative strength of the intramolecular H-bond depends on co-operativity and on the acidity of OH groups. The acidity of OH groups is enhanced when they are in an antiparallel orientation to a C−O bond. A comparison of the 1H-NMR spectra of alcohols in CDCl3 and (D6)DMSO allows discrimination between weak and strong intramolecular H-bonds. Consideration of IR spectra (CHCl3 or CH2Cl2) shows that the rule according to which the downfield shift of δ(OH) for H-bonded alcohols in CDCl3 parallels the strength of the H-bond is valid only for alcohols forming strong intramolecular H-bonds. The combined analysis of J(H,OH) and δ(OH) values is illustrated by the interpretation of the spectra of the epoxyalcohols 14 and 15 (Fig. 3). H-Bonding of hexopyranoses, hexulopyranoses, alkyl hexopyranosides, alkyl 4,6-O-benzylidenehexopyranosides, levoglucosans, and inositols in (D6)DMSO was investigated. Fully solvated non-anomeric equatorial OH groups lacking a vicinal axial OR group (R=H or alkyl, or (alkoxy)alkyl) show characteristic J(H,OH) values of 4.5 – 5.5 Hz and fully solvated non-anomeric axial OH groups lacking an axial OR group in β-position are characterized by J(H,OH) values of 4.2 – 4.4 Hz (Figs. 4 – 6). Non-anomeric equatorial OH groups vicinal to an axial OR group are involved in a partial intramolecular H-bond (J(H,OH)=5.4 – 7.4 Hz), whereas non-anomeric equatorial OH groups vicinal to two axial OR form partial bifurcated H-bonds (J(H,OH)=5.8 – 9.5 Hz). Non-anomeric axial OH groups form partial intramolecular H-bonds to a cis-1.3-diaxial alkoxy group (as in 29 and 41: J(H,OH)=4.8 – 5.0 Hz). The persistence of such a H-bond is enhanced when there is an additional H-bond acceptor, such as the ring O-atom (43 – 47: J(H,OH)=5.6 – 7.6 Hz; 32 and 33: 10.5 – 11.3 Hz). The (partial) intramolecular H-bonds lead to an upfield shift (relative to the signal of a fully solvated OH in a similar surrounding) for the signal of the H-donor. The shift may also be related to the signal of the fully solvated, equatorial HO−C(2), HO−C(3), and HO−C(4) of β-D-glucopyranose (16: 4.81 ppm) by using the following increments: −0.3 ppm for an axial OH group, 0.2 – 0.25 ppm for replacing a vicinal OH by an OR group, ca. 0.1 ppm for replacing another OH by an OR group, 0.2 ppm for an antiperiplanar C−O bond, −0.3 ppm if a vicinal OH group is (partially) H-bonded to another OR group, and −0.4 to −0.6 for both OH groups of a vicinal diol moiety involved in (partial) divergent H-bonds. Flip-flop H-bonds are observed between the diaxial HO−C(2) and HO−C(4) of the inositol 40 (J(H,OH)=6.4 Hz, δ(OH)=5.45 ppm) and levoglucosan (42; J(H,OH)=6.7 – 7.1 Hz, δ(OH)=4.76 – 4.83 ppm; bifurcated H-bond); the former is completely persistent and the latter to ca. 40%. A persistent, unidirectional H-bond C(1)−OH⋅⋅⋅O−C(10) is present in ginkgolide B and C, as evidenced by strongly different δ(OH) and Δδ(OH)/ΔT values for HO−C(1) and HO−C(10) (Fig. 9). In the absence of this H-bond, HO−C(1) of 52 resonates 1.1 – 1.2 ppm downfield, while HO−C(10) of ginkgolide A and of 48 – 50 resonates 0.5 – 0.9 ppm upfield.

compound 1 was not found to form a gel even at concentrations as high as 0.2m. As discussed in the text, we rationalize this in terms of 1, but not these other compounds, being present in a syn conformation. The observation that the less sterically hindered compound, (2’,3’,5’-tri-O-isobutyrylribofuranosidyl)-2-aminopurin-6one, which lacks an aryl substituent and which should be present mostly in anti conformation, forms a gel at concentrations as low as 0.02m is considered consistent with this theory.

Seven different optimized conformers of α-fluoroglycine (H2NCHFCOOH) were obtained from ab initio calculations. Some of these conformers are exceptionally stable compared to similar conformers of glycine. Conformers in which the lone pair of electrons on the nitrogen atom are antiperiplanar to the CF bond are more stable than conformers that do not have such an arrangement. The stability difference between conformers with such an arrangement and conformers that have the lone pair of electrons synperiplanar to the CF bond is about 27 kJ/mol (calculated at the MP2/6-31+G* level). Conformers that have the lone pair of electrons antiperiplanar to the CF bond possess a longer CF bond, a shorter CN bond, and sp2-like amino bond angles. For some conformers an unusual hydrogen bond involving the acidic carboxylic acid hydrogen and the electronegative fluorine atom is observed. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 426–431, 2000