Exo Conformation Research Articles

Synthesis and structures of binuclear half-sandwich cobalt (III) ortho-carboranedithiolato complexes with silyl-bridged bis(cyclopentadienyl) ligands

Five binuclear half-sandwich cobalt complexes, [(η 5-C 5H 4)Co(CO)I 2] 2SiMe 2 ( 3), [(η 5-C 5H 4)Co(S 2C 2B 10H 10)] 2SiMe 2 ( 4), [(η 5-C 5H 4)] 2Co 2(μ 2-S 2C 2B 10H 10)SiMe 2 ( 5), [(η 5-C 5H 3)CoI 2](μ-I)[(η 5-C 5H 3)Co(CO)I](SiMe 2) 2 ( 8), [(η 5-C 5H 3)Co(S 2C 2B 10H 10)] 2(SiMe 2) 2 ( 9), were successfully synthesized in moderate yield by the reactions of corresponding ligands, (C 5H 5) 2SiMe 2 ( 1) and (C 5H 4) 2(SiMe 2) 2 ( 6), respectively. The molecular structures of 3, 5, 6, 8 and 9 was determined by X-ray crystallographic analysis, which distinctly depict various molecular structures containing the Cp rings and the metal centers with halide or 1,2-dicarba- closo-dodecaborane-1,2-dithiolato ligands. For the (η 5-C 5H 4) 2SiMe 2 complexes, coordination of the fragments CpCo favors a exo conformation. With the rigid structure of the di-bridged ligand (C 5H 4) 2(SiMe 2) 2, only cis isomers of the corresponding (η 5-C 5H 3) 2(Si 2Me 2) 2 complexes are formed. All the complexes have been well characterized by elemental analysis, NMR and IR spectra.

Conformation of 3′CMP bound to RNase A using TrNOESY

The conditions for accurately determining distance constraints from TrNOESY data on a small ligand (3′CMP) bound to a small protein (RNase A, <14 kDa) are described. For small proteins, normal TrNOESY conditions of 10:1 ligand:protein or greater can lead to inaccurate structures for the ligand-bound conformation due to the contribution of the free ligand to the TrNOESY signals. By using two ligand:protein ratios (2:1 and 5:1), which give the same distance constraints, a conformation of 3′CMP bound to RNase A was determined (glycosidic torsion angle, χ = −166°; pseudorotational phase angle, 0° ⩽ P ⩽ 36°). Ligand–protein NOESY cross peaks were also observed and used to dock 3′CMP into the binding pocket of the apo-protein (7rsa). After energy minimization, the conformation of the 3′CMP:RNase A complex was similar to the X-ray structure (1rpf) except that a C3′-endo conformation for the ribose ring (rather than C2′-exo conformation) was found in the TrNOESY structure.

1-(1,1-Dioxo-3′-deoxy-2,3,5,6-tetrahydro-1,4-oxathiine-β-D-ribofuranosyl)uracil: a bicyclic nucleoside analogue

In the title compound, C11H14N2O7S, the furan­ose ring adopts a 3′-endo,4′-exo conformation 4T3. The orientation of the pyrimidine ring with respect to the sugar group is anti. The crystal packing is stabilized by inter­molecular N—H⋯O and O—H⋯O hydrogen bonds.

Factors affecting imine coordination in (iminoterpyridine)MX2(M = Fe, Co, Ni, Zn): synthesis, structures, DFT calculations and ethylene oligomerisation studies

The bulky arylimino-terpyridine ligands, 6-{(2,6-i-Pr2C6H3)NCR}-2,2′:6′,2″-C15H10N3 [R = H (L1), Me (L2)], have been prepared in high yield from the condensation reaction of the corresponding carbonyl compound with one equivalent of 2,6-diisopropylaniline. Interaction of an equimolar ratio of MX2 with aldimine-containing L1 in n-BuOH at 110 °C affords the mononuclear five-coordinate complexes, [(L1)MX2] (M = Fe, X = Cl 1a; M = Co, X = Cl 1b; M = Ni, X = Br 1c; M = Zn, X = Cl 1d), in which the metal centres occupy the terpyridine cavities in L1 with the imino group pendant and exo to the adjacent pyridine nitrogen atom. Similarly, a five-coordinate complex [(L2)ZnCl2] (2d) is accessible from the reaction of ketimine-containing L2 with ZnCl2 with the non-coordinated imine group in 2d, in this case, adopting a pseudo-exo configuration. In contrast, coordination of the imino-nitrogen atom (endo configuration) results on reaction of (DME)NiBr2 (DME = 1,2-dimethoxyethane) with L2 to furnish the six-coordinate complex trans-[(L2)NiBr2] (2c). With [(L2)MCl2] (M = Fe 2a; M = Co 2b) both solution and solid state IR spectroscopy suggest that the imine group prefers to adopt a bound conformation. Quantum mechanical calculations (DFT) have been performed on [(Lx)MX2] (Lx = L1, L2; M = Fe, Co, Ni, Zn; X = Cl, Br) and support the synthetic results with the exo conformations energetically preferred for 1a–1d and 2d, while a distinct energetic preference is observed for the endo conformation in 2c. For 2a and 2b, however, the closeness in energies for endo and exo configurations suggests dynamic behaviour is likely. The iron species 1a and 2a display low activities (on treatment with excess MAO) for ethylene oligomerisation at one bar ethylene pressure affording highly linear α-olefins (>98%); the cobalt (1b, 2b) and nickel (1c, 2c) species are inactive. Single crystal X-ray diffraction studies have been performed on 1a, 1b, 1d, 2c and 2d.

The “Azido Gauche Effect”Implications for the Conformation of Azidoprolines

The "azido gauche effect" was examined both experimentally and theoretically and was found to determine the conformation of, for example, (4R)- and (4S)-azidoproline (Azp) derivatives. For (4R)Azp derivatives, the azido gauche effect induces a preferred C(4)-exo conformation of the pyrrolidine ring, which leads to stabilization of the s-trans amide conformer of, e.g., Ac-(4R)Azp-OCH(3) (5R) via an n-->pi interaction between the nonbonding electrons of the oxygen of the acetyl group and the carbonyl group of the ester. For (4S)Azp derivatives, the azido gauche effect results in a C(4)-endo conformation of the pyrrolidine ring that does not allow for this stabilizing n-->pi interaction of the s-trans conformer. Consequently, a significantly higher s-trans:s-cis amide conformer ratio is observed for (4R)Azp compared to (4S)Azp derivatives (e.g., 6.1:1 versus 2.6:1 in D(2)O for Ac-(4R)Azp-OCH(3) (5R) compared to Ac-(4S)Azp-OCH(3) (5S)). These conformational preferences are reflected in the higher tendency of (4S)Azp-containing peptides to form cyclic peptides with all-cis amide bonds compared to (4R)Azp derivatives. Ab initio calculations demonstrate that the strength of the azido gauche effect is comparable to that of the well-known "fluorine gauche effect". For azidoethane derivatives N(3)-CH(2)CH(2)-X (X = N(3), NHCOH, NHAc, or N(CH(3))Ac), the ab initio calculations revealed energy differences of 5-13 kJ mol(-)(1) between the anti and gauche conformations in favor of the gauche conformer. Calculations were also performed for the (4R)Azp and (4S)Azp derivatives 5R and 5S, supporting the experimentally observed data.

C5‘-Adenosinyl Radical Cyclization. A Stereochemical Investigation

A variety of substituted 2'-deoxyadenosin-5'-yl radicals 3 were generated under different reaction conditions. Radicals 3 underwent intramolecular cyclization onto the C8-N7 double bond of the adenine moiety leading to aminyl radicals (5'S,8R)-4 and (5'R,8R)-4 and, eventually, to the corresponding cyclonucleosides 5 and 6. The effect of the solvent, the nature of the substituents, and the generation method of radicals 3 on the stereoselectivity of the C5'-radical cyclization have been considered. The observed increase of the (5'S)/(5'R) ratio by increasing the bulkiness of the R1 group is explained in terms of steric repulsion between R1 and the purine moiety which favors the C5'-endo conformation, whereas the effect of the water solvent in promoting the (5'R)-stereoselective cyclization is ascribed to intermolecular hydrogen bonding stabilizing the C5'-exo conformation.

Structure elucidation of dicarboxylate complex of Sn IV porphyrin with a ring current effect model

A new simple model of porphyrin ring current effect was proposed based on a line current approximation. It can reproduce the porphyrin-induced shifts for several Sn(IV)(tpp) and Sn(IV)(oep) dicarboxylate complexes quite satisfactorily. Perpendicular arrangement of the aromatic rings in the diaromatic-carboxylate complexes of Sn(IV)(tpp) and Sn(IV)(oep) was clarified with this porphyrin ring current effect model. There are two structures, exo and endo, in solution in dinaphthalene-1- and 2- carboxylate complexes of Sn(IV)(tpp) and Sn(IV)(oep). The exo conformer is in dynamic equilibrium with the endo form in solution. Thermodynamic data of these conformational equilibria are given.

Synthesis and Complexing Properties of N,N′-Bis(2-hydroxyethyl) Diaza Crown Ethers

The stability constants of complexes of 12-, 15-, and 18-membered diaza crown ethers, N,N′-dimethyl diaza crown ethers, and N,N′-bis(2-hydroxyethyl) diaza crown ethers with alkali and alkaline-earth metal ions in 95% aqueous methanol at 25°C were determined. The stability of the complexes of unsubstituted diaza crown ethers with alkali metal cations is low, probably because of stabilization of the exo,exo conformation of the ligands due to interaction of the nitrogen lone electron pairs with the solvent. The complexes with the double-charged cations are appreciably more stable. N,N′-Dimethyl diaza crown ethers form stable complexes with all the ions studied. As compared to the dimethyl derivatives, N,N′-bis(2-hydroxyethyl) diaza crown ethers form more stable complexes with the Na+, K+, Ca2+, Sr2+, and Ba2+ ions, which is due to participation of the side hydroxyethyl groups in the coordination.

Ricin A-Chain Activity on Stem−Loop and Unstructured DNA Substrates

Ricin toxin A-chain (RTA) depurinates a single adenylate on a GAGA stem-loop region of eukaryotic 28S RNA, making it a potent toxin. Steady state rate analysis is used to establish the kinetic parameters for depurination of short RNA, DNA, and RNA-DNA hybrids of GAGA linear segments and stem-loop regions as substrates for RTA. Both stem and tetraloop structures are essential for action on RNA. For DNA stem-loop substrates, stem stability plays a small role in enhancing catalytic turnover but can enhance binding by up to 3 orders of magnitude. DNA sequences of d[GAGA] without stem-loop structures are found to be slow substrates for RTA. In contrast, equivalent RNA sequences exhibit no activity with RTA. Introduction of a deoxyadenosine at the depurination site of short RNA oligonucleotides restores catalytic function. NMR analysis indicates that the short, nonsubstrate GAGA is converted to substrate in GdAGA by the presence of a more flexible ribosyl group at the deoxyadenosine site. Conversion between C2'-endo and C2'-exo conformations at the deoxyadenosine site moves the 3'- and 5'-phosphorus atoms by 1.1 A, and the former is proposed to place them in a catalytically favorable configuration. The ability to use short RNA-DNA hybrids as substrates for RTA permits exploration of related structures to function as substrates and inhibitors.

Studies on structure and conformational stability of free canonical 2′‐deoxyribonucleosides: Approximate SCC‐DFTB and LMP2 methods

AbstractThe molecular structure of free canonical 2′‐deoxyribonucleosides have been studied by applying the electron‐correlated local second‐order Møller–Plesset perturbation theory (LMP2) and self‐consistent‐charge density‐functional tight‐binding (SCC‐DFTB) methods. The variation of structural parameters for C2, C3 endo and exo conformations, and anti, syn orientation of the base unit with furanose ring have been discussed. The relative energies have been calculated for the anti and syn conformations of dT, dC, dG, and dA. Conformational analysis has been performed using the results of the LMP2 and SCC‐DFTB methods. Chemical hardness and chemical potential have been used to study the conformational stability of the conformers. The maximum hardness principle is obeyed for the furanose ring conformations and not for the nucleosides. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004

2′-Deoxy-2′,2′-difluorocytidine monohydrochloride (Gemcitabine hydrochloride)

Gemcitabine hydro­chloride (2′-deoxy-2′,2′-di­fluoro­cytidine hydro­chloride), C9H12N3F2O4+·Cl−, is a β-nucleoside that is of pharmaceutical interest as an antitumor agent. The N atom of the cytidine ring is protonated due to salt formation. The sugar residue adopts a C3′-endo and C4′-exo conformation. In the asymmetric unit, gemcitabine cations and chloride ions are linked by N—H⋯Cl hydrogen bonds. In the crystal structure, screw-related gemcitabine cations are linked by O—H⋯O hydrogen bonds to form molecular columns along the c axis and adjacent columns are interlinked by N—H⋯Cl and O—H⋯Cl hydrogen bonds.

Novel eta 3 -1-silaallyl tungsten complexes via Si-H bond activation of hydrovinylsilanes: structure and reactivity toward methanol.

Reactions of cis-Cp*(CO)2W(MeCN)Me (1) with HSiMe2(CH=CR2) (R = H, Me) afford the novel eta3-1-silaallyl complexes Cp*(CO)2W(eta3-Me2SiCHCR2) [R = H (2), Me (3)] accompanied by liberation of MeCN and CH4 via thermal Si-H bond activation. eta3-Coordination and exo conformation of the 1-silaallyl ligand in 3 are shown by X-ray crystal analysis, which reveals the partial double bond character of the Si-C bond (1.800(4) A) in the silaallyl moiety. Complexes 2 and 3 show extremely high reactivity toward MeOH to give the hydrido-(methoxysilyl)alkene complex trans-Cp*(CO)2WH(eta2-MeOMe2SiCH=CH2) (4) and the four-membered metallacycle Cp*(CO)2WCH(CHMe2)SiMe2OMe (6), respectively.

A novel extended covalent tripod for assembling triple-helical nine-co-ordinated lanthanide(iii) podates: the rational design of a single conformerElectronic supplementary information (ESI) available: tables of molecular peaks obtained by ESI-MS (Table S1), elemental analyses (Table S2), structural data for the lanthanide co-ordination sphere in [Eu(L13)](ClO4)3 (19, Table S3) and paramagnetic 1H NMR shifts (Table S4). Figures showing views of [Eu(L13)]3+ along

The connection of a methyl group to the apical carbon atom of a semi-rigid extended tripod provides the novel podand 1,1,1-tris-{2-[2-(6-diethylcarbamoyl-pyridin-2-yl)-1-ethyl-1H-benzoimidazol-5-ylmethoxy]-ethyl}-ethane (L13). Reaction with lanthanide(III) in acetonitrile produces stable and dynamically inert C3-symmetrical podates [Ln(L13)]3+ (Ln = La–Lu) in which LnIII is nine-co-ordinate in a pseudo-tricapped trigonal prismatic site. Electron-induced nuclear relaxation in the paramagnetic complex [Nd(L13)]3+ shows that the capping carbon atom adopts the exo conformation with the methyl group pointing outside the cavity of the podand. The crystal structure of [Eu(L13)](ClO4)3 confirms the exclusive formation of the exo conformer, which contrasts with the mixture of two endo conformers reported for the non-methylated analogue. Structural analysis combined with photophysical data in [Ln(L13)](ClO4)3 (Ln = La, Eu, Gd, Tb) point to negligible mechanical coupling mediated by the flexible four-atoms aliphatic chains between the apical carbon atom and the unsymmetrical tridentate binding units. However, the exo conformation of the tripod in [Eu(L13)]3+ removes some interactions between the high-frequency CH oscillators and the metal-centred excited electronic levels, thus leading to larger lifetime and improved quantum yield in solution.

A cryosolution infrared and DFT study of the complexes formed between vinylacetylene and hydrogen chloride

The formation of weak molecular complexes between vinylacetylene (1-buten-3-yne, CH 2CH–CCH) and HCl or DCl dissolved in liquid argon has been investigated using infrared spectroscopy. In all spectra, evidence was found for the formation of a 1:1 van der Waals complex. At higher concentrations of hydrogen chloride, weak absorption bands due to 1:2 species were also observed. Using spectra recorded at different temperatures between 102 and 125 K, the complexation enthalpies for the 1:1 and the 1:2 complex were determined to be −10.2(9) and −16.9(15) kJ mol −1. A density function theory study of the structures and the vibrational frequencies of the complexes is performed at the B3LYP/6-311++G(d,p) level. These calculations show that HCl can form a complex with either the triple or the double carbon–carbon bond, with the former giving stable endo and exo conformers. Comparison of the experimental frequencies with the calculated ones shows that all observed complex bands are due to the endo conformer of the triple bond complex, while those of the 1:2 complex are due to a chain-type complex in which the second HCl is attached to the first one. Using free energy perturbation Monte Carlo simulations to calculate the solvent influences, and statistical thermodynamics to account for zero-point vibrational and thermal contributions the complexation energies for the C 4H 4·HCl and C 4H 4·(HCl) 2 are estimated from the experimental complexation enthalpies to be −17.3(20) and −34.6(32) kJ mol −1. These numbers are compared with the theoretical values obtained at the B3LYP/6-311++G(d,p) level and with single-point energies calculated at the MP2/aug-cc-PVTZ level.

The hydrogen-bonded heterodimer between methylene cyclobutane and hydrogen chloride: Observation of an endo conformer

The formation of a hydrogen bond between methylene cyclobutane and hydrogen chloride has been investigated in the region 8–18 GHz using molecular-beam Fourier transform microwave spectroscopy. The rotational spectrum of an endo conformer in which methylene cyclobutane retains a puckered conformation and HCl is bonded in T-shape to the methylenic group has been observed. Searches for the exo form using Ar, Ne or He as carrier gases were unsuccessful. A Cs symmetry r0-like structure has been obtained for this conformer from the rotational data of three observed isotopomers (C5H8⋯H35Cl, C5H8⋯H37Cl, and C5H8⋯DCl). Ab initio calculations at MP2/6-311+G(d,p) level have been used to complement the analysis. These calculations predict the existence of both endo and exo conformers close in energy.

Collagen stability: insights from NMR spectroscopic and hybrid density functional computational investigations of the effect of electronegative substituents on prolyl ring conformations.

Collagen-like peptides of the type (Pro-Pro-Gly)(10) fold into stable triple helices. An electron-withdrawing substituent at the H(gamma)(3) ring position of the second proline residue stabilizes these triple helices. The aim of this study was to reveal the structural and energetic origins of this effect. The approach was to obtain experimental NMR data on model systems and to use these results to validate computational chemical analyses of these systems. The most striking effects of an electron-withdrawing substituent are on the ring pucker of the substituted proline (Pro(i)) and on the trans/cis ratio of the Xaa(i-1)-Pro(i) peptide bond. NMR experiments demonstrated that N-acetylproline methyl ester (AcProOMe) exists in both the C(gamma)-endo and C(gamma)-exo conformations (with the endo conformation slightly preferred), N-acetyl-4(R)-fluoroproline methyl ester (Ac-4R-FlpOMe) exists almost exclusively in the C(gamma)-exo conformation, and N-acetyl-4(S)-fluoroproline methyl ester (Ac-4S-FlpOMe) exists almost exclusively in the C(gamma)-endo conformation. In dioxane, the K(trans/cis) values for AcProOMe, Ac-4R-FlpOMe, and Ac-4S-FlpOMe are 3.0, 4.0, and 1.2, respectively. Density functional theory (DFT) calculations with the (hybrid) B3LYP method were in good agreement with the experimental data. Computational analysis with the natural bond orbital (NBO) paradigm shows that the pucker preference of the substituted prolyl ring is due to the gauche effect. The backbone torsional angles, phi and psi, were shown to correlate with ring pucker, which in turn correlates with the known phi and psi angles in collagen-like peptides. The difference in K(trans/cis) between AcProOMe and Ac-4R-FlpOMe is due to an n-->pi interaction associated with the Bürg-Dunitz trajectory. The decrease in K(trans/cis) for Ac-4S-FlpOMe can be explained by destabilization of the trans isomer because of unfavorable electronic and steric interactions. Analysis of the results herein along with the structures of collagen-like peptides has led to a theory that links collagen stability to the interplay between the pyrrolidine ring pucker, phi and psi torsional angles, and peptide bond trans/cis ratio of substituted proline residues.

Synthesis and Structural Investigation of Stable Zirconacyclopentanes Which Bear Additional Functional Groups

The reactions of zirconocene-alkyne complexes Cp‘2Zr(L)(η2-Me3SiC2SiMe3) {Cp‘2 = (η5-C5H5)2: L = THF, 1; L = pyridine, 2; Cp‘2 = rac-ebthi, 3, [ebthi = 1,2-ethylene-1,1‘-bis(η5-tetrahydroindenyl)]} with 2 equiv (or excess) of bicyclo[2.2.1]hepta-2,5-diene (NBD) in THF at 50 °C result in five-membered zirconacyclopentane complexes Cp2Zr(C14H16) (4) and rac-(ebthi)Zr(C14H16) (5) (C14H16 means two coupled NBDs) in good yields. NMR spectra of complexes 4 and 5 show the C2 symmetry of the molecules, indicating that the two NBD components in the complexes are in exo−trans−exo conformation. An X-ray crystallographic structure determination of 5 confirms that the two NBD fragments are exo−trans−exo linked to form a racemate. Both optical isomers are present in a 1:1 ratio in the crystals. Reactions of 1 and 2 with 1 equiv of NBD have also been investigated, and only zirconacyclopentane complex 4 was isolated from the reactions. The analogous zirconacyclopentane complexes Cp2Zr(C22H20) (6) and rac-(ebthi)Zr(C22H2...

Dynamic structures of horse liver alcohol dehydrogenase (HLADH): results of molecular dynamics simulations of HLADH-NAD(+)-PhCH(2)OH, HLADH-NAD(+)-PhCH(2)O(-), and HLADH-NADH-PhCHO.

Molecular dynamics simulations of the oxidation of benzyl alcohol by horse liver alcohol dehydrogenase (HLADH) have been carried out. The following three states have been studied: HLADH.PhCH(2)OH.NAD(+) (MD1), HLADH.PhCH(2)O(-).NAD(+) (MD2), and HLADH.PhCHO.NADH (MD3). MD1, MD2, and MD3 simulations were carried out on one of the subunits of the dimeric enzyme covered in a 32-A-radius sphere of TIP3P water centered on the active site. The proton produced on ionization of the alcohol when HLADH.PhCH(2)OH.NAD(+) --> HLADH.PhCH(2)O(-).NAD(+) is transferred from the active site to solvent water via a hydrogen bonding network consisting of serine48 hydroxyl, ribose 2'- and 3'-hydroxyl groups, and Hist51. Hydrogen bonding of the 3'OH of ribose to Ile269 carbonyl maintains this proton in position to be transferred to water. Molecular dynamic simulations have been employed to track water1287 from the TIP3 water pool to the active site, thus exhibiting the mode of entrance of water to the active site. With time the water1287 accumulates in two different positions in order to accept the proton from the ribose 3'-OH and from His51. There can be identified two structural substates for proton passage. In the first substate the imidazole Ne2 of His51 is adjacent to the nicotinamide ribose C2'-OH and hydrogen bonding distances for proton transfer through the hydrogen bonded relay series PhCH(2)OH...Ser48-OH...Ribose2'-OH...His51...OH(2) (path 1) average 2.0, 2.0, and 2.1 A and (for His51...OH(2)) minimal distances less or equal to 2.5 A. The structure for path 1 is present 20% of the time span. And in the second substate, there are two possible proton passages: path 1 as before and path 2. Path 2 involves the hydrogen-bonded relay series PhCH(2)OH...Ser48-OH...Ribose2'-OH...Ribose3'-OH...His51.OH(2) with the average bonding distances being 2.0, 2.0, 2.1, and 2.0 A and (for His51...OH(2)) minimal distances less or equal to 2.5 A (20% probability of the time span), respectively. During the molecular dynamics simulation the NAD(+) ribose conformations have stabilized at the C2'-endo-C3'-exo or the C2'-endo conformations. With the C2'-endo conformation the first and second substates are able to persist for different time spans, while with the C2'-endo-C3'-exo conformation the only possible pathway involves the first substate. For both first and second substates the fluctuation of the distances between the ribose-OH protons and N epsilon 2 of His51 imidazole ring is partially contributed by the "windshield wiper" motion of the His51 imidazole ring. Since the imidazole of His-51 contributes only about 10-fold to activity, as estimated from the decrease in activity upon substitution with a Gln, there must be an alternate route for the proton to pass to solvent without going through this histidine. A third pathway involves ribose C3'-OH and Ile-269. In MD2, near attack conformers (NACs) for hydride transfer from PhCH(2)O(-) to NAD(+) represent approximately 60% of E.S conformers. The molecular dynamic study of MD3 at mildly basic pH reveals that reactive ground state conformers (NACs) for hydride transfer from NADH to PhCHO amount to 12 mol % of conformers. In MD3, anisotropic bending of the dihydronicotinamide ring of NADH (average value of alpha(c) = 4.0 degrees and alpha(n) = 0.5 degrees, respectively) is observed.

Lithium Salts of Conformationally Constrained and Restricted Chiral Allylic α-Sulfonyl Carbanions − A Joint Study of their Structures, Dynamics, and Stereoselectivities

The structures of the lithium salts of the chiral bicyclic allylic α-sulfonyl carbanions 3−5, each possessing a norbornane skeleton and a tert-butyl group at the S atom, have been studied by 1H, 13C, 6Li, and 6Li,1H HOESY NMR spectroscopy, cryoscopy, and X-ray crystal structure analysis. Because of their relatively high endo-exo isomerization barriers, the Cα−S endo and exo diastereomers of 3−5 could be observed by NMR spectroscopy at −30 °C to −50 °C in [D8]THF. The endo diastereomer is the preferred equilibrium species under these conditions, as shown by 1H,1H HOESY experiments. Carbanion salt 3 has endo-exo isomerization barriers of ΔG#270 = 13.1±0.1 kcal/mol and 12.6±0.1 kcal/mol, while the 7-benzhydrylidene-substituted carbanion salt 5 has barriers of ΔG#288 = 13.5±0.1 kcal/mol and 13.3±0.1 kcal/mol. Cryoscopy and 6Li NMR spectroscopy of 5 in THF at −100 °C to −108 °C revealed the formation of dimers and monomers in a ratio of approximately 2:1. NMR spectroscopy of 3−5 at −90 °C to −105 °C allowed observation of the dimers and monomers of which the anions have endo conformations and also of which the anions adopt exo conformations. The NMR spectroscopic results for 3−5 are compatible with monomeric and dimeric CIPs, featuring planar allylic moieties and allylic stabilization by delocalization of the negative charge. 6Li,1H-HOESY examination of the mixture of the monomers and dimers of endo-5 and exo-5 in [D8]THF at room temperature gave only evidence for coordination of the Li atom to the O atom(s) in the CIPs. The NMR spectroscopic results for 3 were corroborated by X-ray crystal structure analysis of the monomer exo-3·PMDETA, which features (i) an essentially planar anionic C(2) atom, (ii) the exo conformation, (iii) the typical Cα−S conformation, also allowing for a stabilizing nC−σ*StBu interaction, and (iv) a single O−Li bond, but no C−Li bond. Upon treatment of the endo and exo sulfones 9, 10, and 12 with nBuLi at very low temperatures, the corresponding endo and exo carbanion salts endo-3−5 and exo-3−5, respectively, were selectively generated as mixtures of monomers and dimers, the reactions of which with electrophiles were studied. Deprotonation of the exo and endo sulfones with nBuLi proceeds stereoselectively, the exo sulfone preferentially giving the endo anion and vice versa. The diastereomeric endo and exo carbanion salts 3−5 each react with reactive electrophiles at the anionic C(2) atom syn to the sulfonyl O atoms, giving the corresponding substituted endo and exo sulfones, respectively, with significant degrees of asymmetric induction. Reactions of the endo and exo diastereomers of 3−5 with CF3COOD and MeOCH2I were faster than their endo-exo isomerization and approached kinetic quenching, while those with MeI and allyl iodide were slower, approaching the Curtin−Hammett limit and preferentially giving the exo sulfones. Deprotonation-deuteration experiments of the 7-oxa-sulfone endo-11 showed that the corresponding 7-oxa-substituted carbanion salts endo-6 and exo-6 not only can be generated at low temperatures but may also, despite their tendency to rearrange, be converted into the corresponding 7-oxa-sulfones on treatment with reactive electrophiles.

Remote substituent effects on the oxymercuration of 2-substituted norbornenes: an experimental and theoretical study.

The effect of a remote substituent on regioselectivity in the oxymercuration of 2-substituted norbornenes has been investigated experimentally and theoretically using density functional theory (DFT). Regioselectivities of 1:1 to 14:1 were observed with various 2-substituted norbornenes. Exo-2-substituted norbornenes always gave greater regioselectivities compared to the corresponding endo-2-substituted norbornenes. The effects of solvents on the regioselectivity have also been examined, and ethereal solvents were found to be the best choice giving the optimal yield and regioselectivity. The relative rate of oxymercuration was estimated by competition experiments. The least reactive substrate (X = OAc) gave the highest regioselectivity. According to DFT predictions, the increased difference between the reaction barriers that results in the greater regioselectivity is correlated directly with the larger polarity of the C=C double bond, which is attacked by the mercury and oxygen. A number of stable exo and endo conformers were predicted. All exo conformers show the same polarity of the double bond, while some endo conformers have a reversal of this polarity. All the conformers except those with the OAc substituent are very close in energy and thus should react. The existence of a mixture of endo conformers with the C=C double bond of opposite polarity clearly explains a decrease in regioselectivity for the endo species. The origin of the greatest regioselectivity for the OAc-2-norbornenes lies in the fact that the conformer with the largest polarity is notably lower in energy than others due to an internal C-H-O hydrogen bond.