Conformational analysis 29: Preparation and1H and13C NMR,FTIR, MS,and crystallographic conformational and configurational study of 3-Oxo-1,3-oxathiane and its monomethyl derivatives

3-Oxo-1,3-oxathiane (1) and its monomethyl derivatives were prepared by oxidation of the corresponding 1,3-oxathianes. The structural analysis was carried out by¹H and¹³C NMR, FTIR, and mass spectrometry. At 298 K compound1 was a 1 1 (at 173 K a 3 1) mixture of the SO(ax) and SO(eq) chair forms. The major oxidation products of methyl 1,3-oxathianes attained exclusively the SO(ax), Me(eq) chair forms except that of the 5-methyl derivative, which consisted of 7% of the SO(eq), Me(ax) chair conformation in CDCl₃ solution. The minor products of oxidation existed in anancomeric SO(eq), Me(eq) chair conformations. The oxidation of 2-methyl- 1,3-oxathiane, however, led to 3,3-dioxo derivative (6) in addition to thetrans [SO(eq)] monoxide. The crystal structures of6 andtrans-3-oxo-5-methyl-1,3-oxathiane were solved by X-ray diffractometry.     

Ranking the effect of [1A(ax), 1B(eq)] versus [1A(eq), 1B(ax)] cyclohexane ring substitution on the H chemical shifts of γ-methylene cyclohexane ring protons using 2,2-disubstituted adamantanes as models

When two different substituents are placed in the nonbridgehead position of adamantane, the two [1A(ax), 1B(eq)] and [1A(eq), 1B(ax)] cyclohexane chair conformers are modeled and features of their NMR spectra can be studied from a single spectrum at 298 K. The effect of [1A(ax), 1B(eq)] and [1A(eq), 1B(ax)] cyclohexane ring substitution on the ¹H resonance separation within the γ-CH₂s of cyclohexane ring is compared for various substituent pairs; this aim is approached by measuring the ¹H chemical shift separation within the 4′,9′-H and 8′,10′-H methylenes from the ¹H NMR spectrum of the model 2A,2B-disubstituted adamantane at 298 K.     

Conformational transitions of cyclic D,L-peptides

Conformational transitions of cyclic D,L-hexapeptides have been studied by first-principles calculations. Geometry optimizations for 20 types of homoresidue cyclic D,L-hexapeptide revealed that the cyclic peptides have two types of energetically stable backbone (extended (E) and bound (B) types); and for each type, the amino acid side chains have two orientations (equatorial and axial). Among the four types of isomer [E-type equatorial (E(eq)), B-type equatorial (B(eq)), E-type axial (E(ax)), and B-type axial (B(ax))], B(ax) is the energetically most preferred by most of the 20 encoded amino acid residues, whereas E(ax) is the least preferred. A search for transition states indicated that six types of conformational transition are possible between the isomers of the cyclic peptide, i.e., the backbone-backbone conversions (E(eq)-B(eq) and E(ax)-B(ax) transitions), the side chain-side chain conversions (E(eq)-E(ax) and B(eq)-B(ax) transitions), and the simultaneous conversions of the backbone and the side-chain orientation (E(eq)-B(ax) and E(ax)-B(eq) transitions). All the six transitions proceed with the breaking of the high molecular symmetry (S(6)) and go through the triangular (C(3)) intermediate structure with either equatorial or axial side-chain orientation.     

Déplacements chimiques induits en RMN par un réactif lanthanidique: I—Application á l'analyse conformationnelle de sulfites cycliques

The chemical shifts induced by Eu(fod)₃ in several series of 6-membered cyclic sulfites give the parameters K_c and Δ_SR of the complexation equilibrium for an assumed 1:1 stoicheiometry. The equilibrium constant K_c decreases with increasing bulk of the C-4 and C-6 substituents and polarity of the C-5 substituent, which corresponds to the increase of the i.r. stretching frequency vS?O. Thus axial S?O will be more tightly complexed than equatorial S?O. It can be predicted that when a conformational equilibrium exists without shift reagent, displacement towards an axial S?O form will occur with the reagent. Use of the Δ_SR pseudocontact equation confirms the following: (i) ax S?O chair forms are stabilized; (ii) eq S?O chairs with two eq C-4 and C-6 substituents show an equilibrium with a few percent of the ax S?O flexible conformation, particularly in the absence of an ax C-5 substituent; (iii) twist forms with a 2–5 axis, intermediate S?O and trans-4, 6-di-tert-Bu substituents give a boat form with O at the prow and ax S?O; (iv) the conformational equilibrium of trans-5-tert-butyl-2-oxo-1, 3, 2-dioxathiane (chair with ax tert-Bu and S?O ? 70%) is completely displaced towards that form; (v) cis-4,4,6-trimethyl-2-oxo-1,3,2-dioxathiane, which exists as an equilibrium in which the three types of S?O occur, is complexed essentially in the twist form with a 1–4 axis and ax S?O. Most of these results are supported by the coupling constants analysis for the ratio R₀/S₀ = 1.     

Conformations and 13C NMR shifts in tetralins

Force field (MM2) calculations, ¹³C NMR substituent-induced shifts (SIS) and epimeric shift differences (ESD) indicate a preference for equatorial substituents in the 2-position, but equal eq/ax populations in the 1-position of tetralines. Similar conclusions are reached from Yb(fod)₃-induced shifts, which are also used for signal assignments, e.g. in 1-tetralone. Configurational assignments are possible for 1,2- and 1,3-epimers (ESD up to 4 ppm) but, in line with the non-discriminating eq/ax conformations at C-I, not for 1,4-epimers (ESD<0.5 ppm). More than 50 compounds were measured, including functional derivatives which show regular SIS for substituents in the aromatic moiety only for m- and p-carbon atoms. OMe, but not OH or OAc substituents, induce o-carbon SIS varying from ?11 to ?19 ppm. Conversion of 1-hydroxytetralin to esters induces shielding variations at the aromatic carbon atoms which indicate the electrostatic origin of derivatization shifts.     

Iron pentacarbonyl: are the axial or the equatorial iron-carbon bonds longer in the gaseous molecule?

The structure of iron pentacarbonyl, Fe(CO)(5), was reinvestigated by gas-phase electron diffraction using an experimental rotational constant available from the literature as a constraint on the structural parameters. The study utilized a B3LYP/6-311+G(d) ab initio quadratic force field, scaled to fit observed infrared wavenumbers, from which were calculated corrections for the effects of vibrational averaging on distances and certain other quantities useful for the structural analysis. The results confirm that the equatorial Fe-C bonds are longer than the axial ones, an important difference with the structure in the crystal where the equatorial Fe-C bonds are the shorter. Some distance (r(g)/A) and vibrational amplitude (l(alpha)/A) parameter values with estimated 2sigma uncertainties based on assumption of D(3h) symmetry are [r(Fe-C)] = 1.829(2), r(Fe-C)(eq) - r(Fe-C)(ax) = 0.032(20), [r(C=O)] = 1.146(2), r(C=O)(eq) - r(C=O)(ax) = 0.006(27), r(Fe-C)(ax) = 1.810(16), r(Fe-C)(eq) = 1.842(11), r(C=O)(ax) = 1.142(23), r(C=O)(eq) = 1.149(16), l(Fe-C)(ax) = l(Fe-C)(eq) = 0.047(5), and l(C=O)(ax) = l(C=O)(eq) = 0.036(3).     

Studies in nuclear magnetic resonance—XII: Complete analysis of the proton spectra of tert-butylcyohexane-3,3,4,4,5,5-d6 and -3,3,5,5-d4

Accurate parameters for the two title compounds have been obtained by the aid of a spectral subtraction technique in conjunction with analysis by LAOCN3. It is observed that J_{1eq, 6eq} and J_{1ax, 2ax} are abnormally large and small, respectively, and the significance of these and other coupling constants are discussed in terms of the probable geometry of tert-butylcyclohexane. The tert-butyl group affects the chemical shifts of the 4-protons, indicating that tert-butylcyclohexyl derivatives are poor models for fixed conformers of monosubstituted cyclohexanes. The deuterium isotope effects on proton chemical shifts appear to be influenced by the same factors as proton-proton coupling constants.     

II. Etude de l'Influence de la Nature et de l'Orientation d'un Substituant (Cl,CO) sur les Déplacements Chimiques en Série Tertiobutyl-4 Cyclohexanonique par RMN Protonique à Haut Champ

From the 250 MHz ¹H n.m.r. spectra of seven α-chloro-4-tert-butlyclyclohexanones we were able to obtain the increments ΔδCI eq and ax for all the ring protons. Using values published by Jackman for the increments of the tert-butyl group we attempt to determine the increments of the carbonyl group.     

The involvement of metal-to-CO charge transfer and ligand-field excited states in the spectroscopy and photochemistry of mixed-ligand metal carbonyls. A theoretical and spectroscopic study of [W(CO)(4)(1,2-ethylenediamine)] and [W(CO)(4)(N,N'-bis-alkyl-1,4-diazabutadiene)

A new interpretation of the electronic spectroscopy, photochemistry, and photophysics of group 6 metal cis-tetracarbonyls [M(CO)(4)L(2)] is proposed, that is based on an interplay between M --> L and M --> CO MLCT excited states. TD-DFT and resonance Raman spectroscopy show that the lowest allowed electronic transition of [W(CO)(4)(en)] (en = 1,2-ethylenediamine) has a W(CO(eq))(2) --> CO(ax) charge-transfer character, whereby the electron density is transferred from the equatorial W(CO(eq))(2) moiety to pi orbitals of the axial CO ligands, with a net decrease of electron density on the W atom. The lowest, emissive excited state of [W(CO)(4)(en)] was identified as a spin-triplet W(CO(eq))(2) --> CO(ax) CT excited state both computationally and by picosecond time-resolved IR spectroscopy. This state undergoes 1.5 ps vibrational relaxation/solvation and decays to the ground state with a approximately 160 ps lifetime. The nu(CO) wavenumbers and IR intensity pattern calculated by DFT for the triplet W(CO(eq))(2) --> CO(ax) CT excited state match well the experimental time-resolved spectrum. For [W(CO)(4)(R-DAB)] (R-DAB = N,N'-bis-alkyl-1,4-diazabutadiene), the W(CO(eq))(2) --> CO(ax) CT transition follows in energy the W --> DAB MLCT transition, and the emissive W(CO(eq))(2) --> CO(ax) CT triplet state occurs just above the manifold of triplet W --> DAB MLCT states. No LF electronic transitions were calculated to occur in a relevant energetic range for either complex. Molecular orbitals of both complexes are highly delocalized. The 5d(W) character is distributed over many molecular orbitals, while neither of them contains a predominant metal-ligand sigma 5d(W) component, contrary to predictions of the traditional ligand-field approach. The important spectroscopic, photochemical, and photophysical roles of M(CO(eq))(2) --> CO(ax) CT excited states and the limited validity of ligand field arguments can be generalized to other mixed-ligand carbonyl complexes.     

Insight into the photoinduced ligand exchange reaction pathway of cis-[Rh2(μ-O2CCH3)2(CH3CN)6]2+ with a DNA model chelate

We previously showed that [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](2+) binds to dsDNA only upon irradiation with visible light and that photolysis results in a 34-fold enhancement of its cytotoxicity toward Hs-27 human skin fibroblasts, making it potentially useful for photodynamic therapy (PDT). With the goal of gaining further insight on the photoinduced binding of DNA to the complex, we investigated by NMR spectroscopy the mechanism by which 2,2'-bipyridine (bpy), a model for biologically relevant bidentate nitrogen donor ligands, binds to [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](2+) upon irradiation in D(2)O. The photochemical results are compared to the reactivity in the dark in D(2)O and CD(3)CN. The photolysis of [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](2+) with equimolar bpy solutions in D(2)O with visible light affords [Rh(2)(O(2)CCH(3))(2)(eq/eq-bpy)(CH(3)CN)(2)(D(2)O(ax))(2)](2+) (eq/eq) with the reaction reaching completion in ~8 h. Only vestiges of eq/eq are observed at the same time in the dark, however, and the reaction is ~20 times slower. Conversely, the dark reaction of [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](2+) with an equimolar amount of bpy in CD(3)CN affords [Rh(2)(O(2)CCH(3))(2)(η(1)-bpy(ax))(CH(3)CN)(5)](2+) (η(1)-bpy(ax)), which remains present even after 5 days of reaction. The photolysis results in D(2)O are consistent with the exchange of one equiv CH(3)CNeq for solvent, and the resulting species quickly reacting with bpy to generate eq/eq; the initial eq ligand dissociation is assisted by absorption of a photon, thus greatly enhancing the reaction rate. The photolytic reaction of [Rh(2)(O(2)CCH(3))(2)(CH(3)CN)(6)](2+):bpy in a 1:2 ratio in D(2)O affords the eq/eq and (eq/eq)(2) adducts. The observed differences in the reactivity in D(2)O vs CD(3)CN are explained by the relative ease of substitution of eq D(2)O vs CD(3)CN by the incoming bpy molecule. These results clearly highlight the importance of dissociation of an eq CH(3)CN molecule from the dirhodium core to attain high reactivity and underscore the importance of light for the reactivity of these compounds, which is essential for PDT agents.     

Functional analogue reaction systems of the DMSO reductase isoenzyme family: probable mechanism of S-oxide reduction in oxo transfer reactions mediated by bis(dithiolene)-tungsten(IV,VI) complexes

The recent development of structural and functional analogues of the DMSO reductase family of isoenzymes allows mechanistic examination of the minimal oxygen atom transfer paradigm M(IV) + QO M(VI) O + Q with the biological metals M = Mo and W. Systematic variation of the electronic environment at the WIV center of desoxo bis(dithiolene) complexes is enabled by introduction of para-substituted phenyl groups in the equatorial (eq) dithiolene ligand and the axial (ax) phenolate ligand. The compounds [W(CO)2(S2C2(C6H4-p-X)2)2] (54-60%) have been prepared by ligand transfer from [Ni(S2C2(C6H4-p-X)2)2] to [W(CO)3(MeCN)3]. A series of 25 complexes [W(IV)(OC6H4-p-X')(S2C2(C6H4-p-X)2)2]1- ([X4,X'], X = Br, F, H, Me, OMe; X' = CN, Br, H, Me, NH2; 41-53%) has been obtained by ligand substitution of five dicarbonyl complexes with five phenolate ligands. Linear free energy relationships between E1/2 and Hammett constant p for the electron-transfer series [Ni(S2C2(C6H4-p-X)2)2]0,1-,2- and [W(CO)2(S2C2(C6H4-p-X)2)2]0,1-,2- demonstrate a substituent influence on electron density distribution at the metal center. The reactions [WIV(OC6H4-p-X')(S2C2(C6H4-p-X)2)2]1- + (CH2)4SO [W(VI)O(OC6H4-p-X')(S2C2(C6H4-p-X)2)2]1- + (CH2)4S with constant substrate are second order with large negative activation entropies indicative of an associative transition state. Rate constants at 298 K adhere to the Hammett equations log(k([X4,X']/k[X4,H]) = rho(ax)sigma(p) and log(k[X4,X']/k([H4,X']) = 4rho(eq)sigma(p). Electron-withdrawing groups (EWG) and electron-donating groups (EDG) have opposite effects on the rate such that k(EWG) > k(EDG). The effects of X' on reactivity are found to be approximately 5 times greater than that of X (rho(ax) = 2.1, rho(eq) = 0.44) in the Hammett equation. Using these and other findings, a stepwise oxo transfer reaction pathway is proposed in which an early transition state, of primary W(IV)-O(substrate) bond-making character, is rate-limiting. This is followed by a six-coordinate substrate complex and a second transition state proposed to involve atom and electron transfer leading to the development of the W(VI)=O group. This work is the most detailed mechanistic investigation of oxo transfer mediated by a biological metal.     

Thermolysis of [1,2,4]triazolo[1,5-a]pyrimidine n-ylides

5,7-Dimethyl[1,2,4]triazolo[1,5-a]pyrimidinio-3-phenacylide ($\text{3}$) generated by the reaction of an iminium salt ($\text{2}$) with 1 eq. of triethylamine, underwent a new thermal ring cleavage of the triazole moiety to give the pyrimidine derivative. However reaction of $\text{2}$ with 2 eq. of triethylamine afforded the 2-iminooxazoline derivative. The iminooxazoline reacted with nucleophiles such as alcohols or amines to give imidazoles.     

Systematic preparation of Mo 2 4+ building blocks for supramolecular assemblies

The preparation of additional and useful building blocks for the construction of supramolecular entities with quadruply bonded Mo(2)(4+) units has been explored, and five new mixed-ligand complexes with three types of ligands and various basicities are reported. The ligands used were the DAniF (N,N'-di-p-anisylformamidinate) anion, the acetate anion, and neutral acetonitrile molecules. The formamidinate ligands are the least labile, and the acetonitrile molecules are the most labile. This difference as well as a relatively strong trans directing influence by the formamidinate anions in ligand substitution reactions allows designed synthesis of various mixed-ligand building blocks, including rare pairs of cis and trans isomers. The new compounds are cis-Mo(2)(DAniF)(2)(O(2)CCH(3))(2) (1), trans-Mo(2)(DAniF)(2)(O(2)CCH(3))(2) (2), trans-[Mo(2)(DAniF)(2)(O(2)CCH(3))(CH(3)CN(eq)())(2)]BF(4) (3), trans-[Mo(2)(DAniF)(2)(CH(3)CN(eq)())(4)](BF(4))(2) (4), and [Mo(2)(O(2)CH(3))(CH(3)CN(eq)())(6)(CH(3)CN(ax)())](BF(4))(3) (5), where eq and ax designate equatorial and axial ligands, respectively. A comparison with some previously synthesized complexes is given along with a discussion of the overall reactivity of all compounds.     

Manifestation of stereoelectronic effects on the calculated carbon-hydrogen bond lengths and one-bond 1J(C-H) NMR coupling constants. Relative acceptor ability of the carbonyl (C=O), thiocarbonyl (C=S), and methylidene (C=CH2) groups toward C-H donor bonds

Theoretical examination [B3LYP/6-31G(d,p), PP/IGLO-III//B3LYP/6-31G(d,p), and NBO methods] of six-membered cyclohexane 1 and carbonyl-, thiocarbonyl-, or methylidene-containing derivatives 2-27 afforded precise structural (in particular, C-H bond distances) and spectroscopic (specifically, one-bond (1)J(C)(-)(H) NMR coupling constants) data that show the consequences of stereoelectronic hyperconjugative effects in these systems. Major observations include the following. (1) sigma(C)(-)(H)(ax)() -->(C)(=)(Y) and pi(C)(=)(Y) --> sigma(C)(-)(H)(ax)() (Y = O, S, or CH(2)) hyperconjugation leads to a shortening (strengthening) of the equatorial C-H bonds adjacent to the pi group. This effect is reflected in smaller (1)J(C)(-)(H)(ax)() coupling constants relative to (1)J(C)(-)(H)(eq)(). (2) Comparison of the structural and spectroscopic consequences of sigma(C)(-)(H)(ax)() --> pi(C)(=)(Y) hyperconjugation in cyclohexanone 2, thiocyclohexanone 3, and methylenecyclohexane 4 suggests a relative order of acceptor orbital ability C=S > C=O > C=CH(2), which is in line with available pK(a) data. (3) Analysis of the structural and spectroscopic data gathered for heterocyclic derivatives 5-12 reveals some additivity of sigma(C)(-)(H)(ax)() --> pi(C)(=)(Y), pi(C)(=)(Y) --> sigma(C)(-)(H)(ax)(), n(X) --> sigma(C)(-)(H)(ax)(), n(beta)(O) --> sigma(C)(-)(H)(eq)(), and sigma(S)(-)(C) --> sigma(C)(-)(H)(eq)() stereoelectronic effects that is, nevertheless, attenuated by saturation effects. (4) Modulation of the C=Y acceptor character of the exocyclic pigroup by conjugation with alpha-heteroatoms O, N, and S in lactones, lactams, and methylidenic analogues 13-24 results in decreased sigma(C)(-)(H)(ax)() --> pi(C)(=)(Y) and pi(C)(=)(Y) --> sigma(C)(-)(H)(ax)() hyperconjugation. (5) Additivity of sigma(C)(-)(H)(ax)() --> pi(C)(=)(Y) and pi(C)(=)(Y) --> sigma(C)(-)(H)(ax)() hyperconjugative effects is also apparent in 1,3-dicarbonyl derivative 25 (C=Y equal to C=O), 1,3-dithiocarbonyl derivative 26 (C=Y equal to C=S), and 1,3-dimethylidenic analogue 27 (C=Y equal to C=CH(2)).     

Structure of decaazonium Tricyclo[28.2.2.213.16]tetratriacontane Decatetrafluoroborate Decahydrate

A new inclusion complex, decaazonium tricyclo[28.2.2.2^13.16]tetratriacontane (L) decatetrafluoroborate decahydrate [(H₁₀L)(BF₄)₁₀10H₂O] (I), has been prepared and characterized by X-ray crystallography. Crystal data: a = 8.156(2), b = 29.125(6), c = 12.981(3) , = 96.76(3)°, space group P2₁/c, Z = 2, the final R = 0.0662 for 5376 reflections with I> 2 (I) (MoK radiation). The azamacrocycle of the complex is a 10-charged cation. The components of the supramolecular system in crystal are stabilized by the hydrogen bonds between the macrocycle cations, the water molecules, and the tetrafluoroborate anions. The water molecules make a solvation shell of the macrocycle forming an octahydrate. The tetrafluoroborate anions alternate with the water molecules stitched to the macrocycle, forming polymer chains in the directions parallel to the z axis of the crystal, and serve as bridges between the macrocycle cations related by the c plane. The set of hydrogen bonds including weak ones unite the components of the complex into a three-dimensional framework. All tetrafluoroborate anions in the structure are disordered.     

Conformations of silicon-containing rings. 5. Conformational properties of 1-methyl-1-silacyclohexane: gas electron diffraction,low-temperature NMR,and quantum chemical calculations

The molecular structure of 1-methyl-1-silacyclohexane 3 has been determined by gas electron diffraction (GED). The conformational preference of the methyl group was studied experimentally in the gas phase (GED) and in solution (low-temperature (13)C NMR) and by quantum chemical calculations (HF, MP2, and B3LYP with 6-31G basis sets and mPW1PW91/6-311G(2df,p)). Both experimental methods result in a preference of the equatorial position of the methyl group, 68(7)% in the gas phase at 298 K and 74(1)% in solution at 110 K. The calculations predict 68-73% equatorial conformer at room temperature. From coalescence temperatures, Gibbs free energies of activation for ring inversion DeltaG++ (eq --> ax) = 5.81(18) and DeltaG++ (ax --> eq) = 5.56(18) kcal mol(-1) were derived. The calculated values for DeltaG++ (eq --> ax) are 5.92 (B3LYP) and 5.84 kcal mol(-1) (mPW1PW91).     

Synthesis and evaluation of a new water-soluble fluorescent red dye,xanthene bis-C-glycoside

Condensation of 2 eq. of C-β-D-glucosylphloroacetophenone with glyoxylic acid in an aqueous solution of Na₂CO₃, followed by air oxidation in MeOH in the presence of 11 eq. of pyridine to afford a 36% yield of a bright red dye, xanthene bis-C-glycoside. This dye is 10 times more fluorescent (Φ_{f [EtOH]}^{581 nm} = 3.9 × 10⁻²) and 7.5 times more water-soluble (57 mg/mL H₂O) than the natural red pigment, carthamin. Detailed NMR analysis of its methyl analogs was used to confirm the structure of the dye as methyl 4,5-diacetyl-1,3,8-trihydroxy-3-oxo-3H-2,7-di-C-β-D-glucopyranosylxanthene-9-carboxylate from among three possible ring-closure isomers. Xanthene is safe and shows high light-resistance; therefore, xanthene bis-C-glycoside could be used as a food colorant or an in vivo probe.     

One-pot synthesis of polycyclic heterocyclic compounds by condensation of 1-carbamoylmethyl-2,3,3-trimethyl-3H-indolium salts with pyridine-2, 3, and 4- and quinoline-4-carboxaldehydes

A one-pot synthesis of new polycyclic heterocyclic compounds was carried out via the condensation of 1-carbamoylmethyl-2,3,3-trimethyl-3H-indolium chloride with pyridine- and quinolinecarboxaldehydes. The heating of the aforementioned 3H-indolium salts with 1 eq. of pyridine-2, 3, and 4- or quinoline-4-carboxaldehyde in ethanol in the presence of piperidine as a catalyst provided 9a-[2-(pyridyl)ethenyl]- or 9a-[2-(quinolyl)ethenyl]-9,9a-dihydro-1H-imidazo[1,2-a]indol-2(3H)-one derivatives as the main products. However, reaction outcome was dramatically different for the analogous reactions in acetic acid. In this case, the heating of the chloride with 2 eq. of pyridine-2-carboxaldehyde afforded derivatives of 9a-[3-(pyridin-2-yl)indolizin-2-yl]-9,9a-dihydro-1H-imidazo[1,2-a]indol-2(3H)-one as the major product, while the use of 2 eq. of pyridine-3 and 4- or quinoline-4-carboxaldehyde led to the formation 2-heteroaryl-1-heteroarylmethyl-9H-pyrrolo[1,2-a]indole-3-carboxamides. Plausible pathways for the cyclization reactions are discussed. The structural assignments were based on ¹H, ¹³C and ¹⁵N NMR spectroscopy, HRMS and single-crystal X-ray diffraction data.     

The synthesis and conformational analysis of tetrahydro-1,2,4-oxadiazines

The synthesis and variable temperature ¹H and ¹³C NMR spectra of three tetrahydro-1,2,4-oxadiazines are reported. The N(4)-Me inversion barriers are 6.8–7.0 (ax→ts) and 7.4–7.9 kcal mol^?1 (eq→ts) with ΔG° 0.6–0.9 kcal mol^?1. The N(2)-Me inversion barriers are 10.4–11.4 (ax→ts) and 11.6–13.1 kcal mol^?1 (eq→ts) with ΔGδ 1.2–1.7 kcal mol^?1. The barrier to ring inversion is ca. 12.7 kcal mol^?1. “R value” analysis shows the ring to have a 56.5±2δ dihedral angle about the C(5)-(6) bond, indicative of the expected chair conformation.     

The effect of spiroadamantane substitution on the conformational preferences of N-Me pyrrolidine and N-Me piperidine: a description based on dynamic NMR spectroscopy and ab initio correlated calculations

Dynamic NMR spectroscopy and ab initio correlated calculations revealed that the attachment of a spiroadamantane entity at the C-2 position of N-methylpyrrolidine or N-methylpiperidine induces a severe steric crowding around nitrogen, which changes the conformational space of the heterocycle resulting in: (a) the complete destabilization of the N-Me(eq) conformer in spiranic structures; in contrast the N-Me(eq) conformer corresponds to the global minimum in N-methylpyrrolidine or N-methylpiperidine. The spiroadamantane structure raises the energy of the equatorial conformer because of the severe van der Waals repulsion between the N-Me(eq) group and adamantane C-H bonds. (b) The interconversion between the only populated enantiomeric N-Me(ax) conformers ax→[eq]→ax′; the interconversion eq→ax between N-Me(eq) and N-Me(ax) conformers, which are both populated, is observed in N-methylpyrrolidine or N-methylpiperidine. (c) The raising of ring and nitrogen inversion barriers ax→ts by ∼4-6 kcal mol⁻¹. The dynamic NMR study provides evidence that the most important process required for the enantiomerization between the axial N-Me conformers in spiropiperidine 4 and spiropyrrolidine 5 are different, i.e., a nitrogen inversion in 5 (9.10 kcal mol⁻¹) and a ring inversion in 4 (15.2 kcal mol⁻¹). While an enantiomerization interconverts N-Me axial conformers in spiropiperidine 5 and spiropyrrolidine 4, substitution of the pyrrolidine ring of 5 with a C-Me group effects a diastereomerization between two N-Me axial conformers and reduces effectively the nitrogen inversion barrier according to the protonation experiments and the calculations. In general, all the calculations levels used, i.e., the MM3, B3LYP/6-31+G^∗∗ and MP2/6-311++G^∗∗//B3LYP/6-31+G^∗∗, predict correctly the different stability of the local minima; however only MP2/6-311++G^∗∗//B3LYP/6-31+G^∗∗ was found to be reliable for the calculation of the nitrogen inversion barriers.