Equatorial Methyl Research Articles

Palladium mediated C–H activation in the field of terpenoids: synthesis of rostratone

We present results, which indicate that Pd-mediated C–H bond activation can be used under mild conditions for the remote functionalization of C-4 methyl groups of molecules with different terpenoid-like skeletons containing six- or seven-membered A rings. This procedure has allowed us to complete a novel strategy for the synthesis of γ-dioxygenated terpenoids in three stages: (i) selective epoxidation of commercial polyenes, (ii) titanium(III)-catalyzed cyclization of epoxypolyprenes, and (iii) Pd-mediated remote functionalization of equatorial methyl groups. This strategy has proved to be useful for the synthesis of the natural labdane rostratone (1).

Photoinduced functionalization of diterpenes: photochemical behaviour of grandiflorolic acid in methanol and acetonitrile

Irradiation of grandiflorolic acid ( 11) at λ=254 nm in acetonitrile gave the two epimers 13 and 14 through a photodecarboxylation reaction of the carboxylic group on C-4. Irradiation of compound 11 in methanol at λ=254 nm provided the transformation of the C-20 angular methyl into a carbomethoxymethyl group. In this case, unlike compounds 13 and 14, only one of the two possible isomers ( 15) was obtained (equatorial methyl at C-4). A mechanistic approach of this reaction in discussed, and the role of mutual stereochemistry between C-20 methyl and C-19 carboxylic group in determining the course of the reaction is pointed out.

The shape and information content of high-field solid-state proton NMR spectra of methyl groups

The possible variation of the lineshape of the high-field 1 H spectrum of methyl groups is explored by simulation and experiment. The spectrum of an isolated methyl group depends, apart from the orientation of the applied field B 0 relative to the C 3-axis of the group, on its rotational tunnel frequency ν t and on its stochastic reorientation rate k. For quantitative analyses, the directional mobility of the C 3-axis must also be taken into account. A distinct but frequently occurring case arises when the methyl groups come as pairs of magnetically equivalent close neighbours. For the experiments, single crystals of four compounds I – IV were grown that were isotopically substituted such that they contained protons only in the methyl positions. The crystal symmetry of all compounds I – IV allowed us to record spectra with all methyl groups being orientationally and otherwise equivalent. I , acetonitrile in deuterated hydroquinone, represents the case of a well-isolated methyl group with a “high” tunnel frequency ν t . Its spectrum is (almost) independent of the temperature T. In II , monomethyl malonic acid, ν t is comparable in size with the strength of the intramolecular dipolar H – H interaction. All seven theoretically expected lines in the 1 H spectrum are clearly resolved in the spectra of II . ν t can be inferred with an uncertainty of only ±300 Hz . ν t ( T) is found to possess a (flat) maximum near 40 K . Compound III , l -alanine, allows the study of the case of a methyl group with an extremely low, although nonzero tunnel frequency ( ν t≈3 kHz) while IV , dimethylglyoxime, represents the case of a close pair of equivalent methyl groups. Its spectrum reflects intriguing structural implications.

Mercury methylation rates in coastal sediments versus microbial diversity and specific activity

To investigate the role of microbial communities on the rate of mercury methylation, and in opposition, the impact of mercury on the diversity and activity of sedimentary bacteria, two different experiments were achieved. First, laboratory incubations were performed on estuarine sediments collected in the Adour estuary (Southwest France) under various conditions (oxic, anoxic, sterilized). Second, to confirm the batch experiments, in situ cores experiments were performed to investigate potential methylation of mercury in the Thau Lagoon (South France). The microbial diversity and mercury-linked activities were also analyzed using DNA fingerprinting technique (T-RLFP) and mer genes analysis. The two sets of results exhibit equivalent net methylation yields for surface sediments indicating similar methylation potentials for sediments from the Adour estuary (1% for 12 hours incubation) and the Thau Lagoon (0.9% for 1 day incubation). Methylation rates in sediment slurries decrease with the incubation time pointing out the needed of kinetic laboratory studies to complete in situ experiments. Furthermore, mercury methylation was strictly observed in anoxic slurries and correlates to anaerobic bacteria activity.

An Electron Spin Resonance Investigation of the Radiolysis of Hexamethylbenzene and Hexamethyl(Dewar)Benzene

Exposure of hexamethyl(Dewar)benzene (HMD) to γ-rays in a solid CFC13 matrix at 77K generated the corresponding radical cation (HMD+•) as shown by the observation of hyperfine coupling (A = 9·5 G) to the protons of four equivalent methyl groups: thus the 2B2 state (I) of the ion is established. On annealing to 140 K, ring-opening occurred to give the hexamethylbenzene cation (HMB+•). When CF2ClCFCl2 was used as the matrix material, a completely different spectrum was produced, consisting of seven lines with a common spacing of 14 G. Results obtained using different batches of the freon, and from careful annealing and concentration studies, establish that the low-field line is not part of the remaining six-line spectrum which can be assigned to the allylic radical (III), formed by deprotonation of the parent cation. γ-Irradiation of HMD in 2- methyltetrahydro-furan (MeTHF) followed by annealing gave the ψs* Jahn-Teller distorted form of the (ring-opened) HMB-• radical anion [A(6H) = 9 G] and so the parent anion is unstable, as is the cation. This was confirmed by an identical spectrum being obtained after the irradiation of an authentic sample of HMB in MeTHF. γ-Irradiation of pure HMD gave rise to a spectrum that can be analysed in terms of (III) and the endo H-atom adduct of HMD (IV). Hexamethylbenzene (HMB) on γ-irradiation in solid CFC13 gave the parent radical cation (HMB+•) At 130 K, this has a 6·7 G splitting and correct binomial intensities for 18 equivalent protons; on cooling to 77 K, the cation distorts so that a ψA type SOMO is adopted with four strongly coupled (A = 11·5G) and two weakly coupled (A = −2·8G) methyl groups. γ-Irradiation of pure HMB gave only broad features which we ascribe to a mixture of pentamethylbenzyl (VIII) and hexamethylcyclohexadienyl (IX) radicals, in which proton hyperfine structure is unresolved due to a range of restricted conformations being adopted by various methyl groups because of steric hindrance between them.

Fe+-Mediated Interconversion of n- and i-C3H7OH Preceding Their Gas-Phase Dehydrations: Experimental and Computational Evidence for Memory Effects and Inherent Asymmetry of Constitutionally Equivalent Methyl Groups.

Fe⁺-Mediated Interconversion of <i>n</i>- and <i>i</i>-C₃H₇OH Preceding Their Gas-Phase Dehydrations: Experimental and Computational Evidence for Memory Effects and Inherent Asymmetry of Constitutionally Equivalent Methyl Groups.

Fe+-Mediated Interconversion of n- and i-C3H7OH Preceding Their Gas-Phase Dehydrations: Experimental and Computational Evidence for Memory Effects and Inherent Asymmetry of Constitutionally Equivalent Methyl Groups,

The n-propyl/isopropyl isomerization operative in Fe+-mediated dehydrations of n-propyl and isopropyl alcohols has been rigorously analyzed by tandem mass spectrometry and density functional calculations. Metastable ion studies of complexes of atomic Fe+ with a set of selectively deuterated propyl alcohols address structural details of the reversibility of β-hydrogen transfer steps. The labeling distributions in the ionic products reveal that the transiently focused, constitutionally equivalent methyl groups remain distinguishable in the course of n-C3H7 → i-C3H7 isomerizations. This asymmetry causes a memory effect operative in the Fe+-mediated dehydration of n-propyl alcohol. While density functional calculations provide detailed insight into the nature of the reaction intermediates and, inter alia, suggest that the experimentally deduced asymmetry can be attributed to agostic interactions of the iron center with a β-hydrogen atom of the emerging methyl group, a comprehensively consistent, quantitative ...

Conformational Analysis of oligo-1,3-Dioxan-4-yls

Whereas simple 4,4′-bi(1,3-dioxanyl)s 16 and 19 displayed little conformational preference at the inter-ring bond, their derivatives 4 and 13, with equatorial methyl groups in the 5- and 5′-positions, each showed a strong conformational preference to populate a conformation with a gauche arrangement of the oxygen atoms. These results form the basis of a modular approach to oligo-1,3-dioxanyls 5, 6, and 29, in each of which a strong conformational preference prevails at all of the inter-ring bonds. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Torsional effects on reactivity in glycosyl transfer

The net effect of the four substituents on a hexapyranoside is to reduce reactivity at the anomeric centre by a factor of >107 compared with the parent tetrahydropyranyl acetal. The magnitude of the steric contribution to this factor is assessed by measuring the effect of four equatorial methyl groups on the rate of hydrolysis of 4-nitrophenyl tetrahydropyranyl acetal. Though the electronic effects of methyl substituents will be to increase the rate of hydrolysis, the net effect of the four equatorial methyl groups is a 4-fold decrease, evidence for an opposing steric effect estimated at two orders of magnitude. Torsional effects in a glycopyranoside thus contribute a factor of up to 50 towards the total of 107.

Solvation Structure of Bromide Ion in Anion-Exchange Resins

The local structures of Br- in ion-exchange resins are studied with XAFS at the Br−K edge. Br--form anion-exchange resins having different ion-exchange groups, i.e., tertiary ammonium (R-3) and quaternary ammonium ion (R-4), are examined after being soaked in water, methanol (MeOH), and some polar aprotic solvents. The resins soaked in aprotic solvents give almost the same spectral features as dry resins, indicating that Br- is tightly bound by the ion-exchange sites. Br- is entrapped inside the tripod composed of three equivalent methyl groups of the ion-exchange group in the R-4 resin, while it strongly interacts with the ammonium hydrogen of the ion-exchange group of the R-3 resin. In the latter case, the scattering from methyl and methylene carbon atoms in the ion-exchange group also contributes to XAFS spectra. In contrast, characteristic features are confirmed when the resins are soaked in water and MeOH. Detailed analyses of XAFS spectra imply that two species, i.e., solvated Br- and that bound on ...

Triangulo-Hg3(µ-dppm)3](O3SCF3)4: first complete NMR analysis of a homoleptic [M3(µ-dppm)3] type system and study of the conformation dynamics in solution by use of its dpam/mdppm derivatives

The 31P and 199Hg spectra of the new subvalent [triangulo-Hg3]4+ based clusters [Hg3(μ-mdppm)3](O3SCF3)4 (1a; mdppm = Ph2PCH(Me)PPh2), which is formed stereoselectively with a syn–anti–anti orientation of the methyl groups, and [Hg3(μ-dppa)3](O3SCF3)4 (4; dppa = Ph2PNHPPh2) are successfully simulated with the program WIN-DAISY. By use of the parameters derived from 1a and 4 the spectra of the parent system [Hg3(μ-dppm)3](O3SCF3)4, which show a very complex pattern, are for the first time completely analysed. The simplification of the spectral pattern in 1a or 4 compared to [Hg3(μ-dppm)3](O3SCF3)4, respectively, is a result of either symmetry reduction (1a) or quasi selective variation of one Hg–P coupling constant (4). For δ(31P), δ(199Hg), J(HgHg) and the different classes of P–P and Hg–P couplings specific values are found, some of which are powerful tools for the identification of [triangulo-Hg3]4+ compounds. The 1H NMR parameters of 1a, anti- and syn-[Hg3(μ-dpam)(μ-mdppm)2](O3SCF3)4 (2a, 2b; dpam = Ph2AsCH2AsPh2), [Hg3(μ-dpam)2(μ-mdppm)](O3SCF3)4 (3) and [Hg3(μ-dpam)3](O3SCF3)4 lead to a rational interpretation of conformation dynamics in these systems: The three five-membered rings formed by the edges of the [triangulo-Hg3]4+ cluster and the three bridging ligands adopt C-envelope conformations in a way that two of the flaps are oriented above and one below the Hg3 plane, and vice versa. The mdppm ligands feature a rigid conformation with an equatorial methyl group and an axial hydrogen atom at the flap carbon atom. The methylene carbon atom of the dpam ligands is able to flip between two positions above and below the Hg3 plane, if the relative orientations of the three flaps mentioned above are retained. The overall found rigid conformation of the bridging mdppm ligand allows a qualitative estimation of relative thermodynamic preferences of isomers resulting from syn or anti orientation of mdppm methyl groups.

Inherent Asymmetry of Constitutionally Equivalent Methyl Groups in the H/D Equilibration of n- and i-C3 H7 Fe(OH)+ Complexes.

Transiently formed, constitutionally identical methyl groups remain inequivalent in the course of an n-propyl⇄isopropyl isomerization operative in Fe+ -mediated dehydration of propanols. The reversibility of the β-hydrogen transfer steps is addressed by examination of the H/D equilibration in metastable complexes of Fe+ with a set of selectively deuterated propanols by using tandem mass spectrometry.

Acid-induced transannular cyclization of 2-methyl- and 10-methyl-5-cyclodecenone

2-Methyl- and 10-methyl-5-cyclodecenone were made by anionic oxy-Cope rearrangement of the corresponding 1,2-divinylcyclohexanols, and their transannular cyclizations were induced using trifluoroacetic acid. In each case, a single diastereomer of a trans fused bicyclo[4.4.0]decan-1-ol with an equatorial methyl group was isolated. The methyl substituent at C2 or C10 of the 5-cyclodecenone did not alter the regio- and stereochemistry previously observed for the parent ring system, ( E)-5-cyclodecenone. The relative stereochemistry of the products was determined spectroscopically from J-value analysis and NOE.

Synthesis and Characterization of HC{C(Me)N(C6H3-2,6-i-Pr2)}2MX2 (M = Al, X = Cl, I; M = Ga, In, X = Me, Cl, I): Sterically Encumbered β-Diketiminate Group 13 Metal Derivatives

A series of group 13 metal complexes featuring the beta-diketiminate ligand [[(C(6)H(3)-2,6-i-Pr(2))NC(Me)](2)CH](-) (i.e., [Dipp(2)nacnac](-), Dipp = C(6)H(3)-2,6-i-Pr(2)) have been prepared and spectroscopically and structurally characterized. The chloride derivatives Dipp(2)nacnacMCl(2) (M = Al (3), Ga (5), In (8)) were isolated in good yield by the reaction of 1 equiv of Dipp(2)nacnacLi.Et(2)O (2) and the respective metal halides. The iodide derivatives Dipp(2)nacnacMI(2) (M = Al (4), Ga (6), In (9)), which are useful for reduction to afford M(I) species, were made by a variety of routes. Thus, 4 was obtained by treatment of the previously reported Dipp(2)nacnacAlMe(2) with I(2), whereas the gallium analogue 6 was obtained as a product of the reaction of "GaI" with Dipp(2)nacnacLi.Et(2)O, and 9 was obtained by direct reaction of InI(3) and the lithium salt. The methyl derivatives Dipp(2)nacnacMMe(2) (M = Ga (7), In (10)), which are analogous to the previously reported Dipp(2)nacnacAlMe(2), were synthesized by the reaction of GaMe(3) with Dipp(2)nacnacH (1) or by reaction of the indium chloride derivative 8 with 2 equiv of MeMgBr in diethyl ether. The compounds 3-10 exist as colorless, air- and moisture-sensitive crystalline solids. Their X-ray crystal structures feature nearly planar C(3)N(2) arrays in the Dipp(2)nacnac ligand backbone with short C-C and C-N distances that are consistent with a delocalized structure. However, there are large dihedral angles between the C(3)N(2) plane and the N(2)M metal coordination plane which have been attributed mainly to steric effects. The relatively short M-N distances are consistent with the coordination numbers of the metals and the normal/dative character of the nitrogen ligands. The compounds were also characterized by (1)H and (13)C NMR spectroscopy. (1)H NMR data for 7 revealed equivalent methyl groups whereas the spectrum of 10 displayed two In-Me signals which indicated that ring wagging was slow on the (1)H NMR time scale.

Isotope effects in partially deuterated tetramethylsilane cations studied by EPR spectroscopy

Well-resolved isotropic EPR spectra were observed for Si(CH3)4+ (TMS+), Si(CH3)3CD3+ (TMS-d3+) and Si(CH3)2(CD3)2+ (TMS-d6+), generated by ionizing radiation in SnCl4 matrices at 77 K. The TMS+ radical has been reported to have a C2v structure possessing two apical methyl groups with long Si–C bonds and two equatorial methyl groups with short Si–C bonds. The observed couplings of 0.95 and 0.47 mT for TMS+ were assigned to 1H nuclei in the apical and equatorial methyl groups, respectively. The small separation of spectral lines, 0.47 mT, for TMS-d3+ and TMS-d6+ is the same as that observed for TMS+. Thus, the C2v structure is retained for these partially deuterated tetramethylsilane cations. The simple well-resolved isotropic spectra unambiguously revealed that TMS-d3+ had the CD3 group in an equatorial position and that TMS-d6+ possessed the CD3 group in each of the apical and equatorial positions. Furthermore, multiplet spectra for TMS-d3+ were observed below 20 K and were attributed to A- and E-lines, which are characteristic of quantum mechanical tunneling rotation of the methyl protons.

Potentiometric and spectroscopic studies on the dimethyltin(IV) complexes of 2-hydroxyhippuric acid

Equilibrium and spectroscopic (1H, 13C NMR and 119Sn Mössbauer) studies in aqueous solution are reported for dimethyltin(IV) complexes of 2-hydroxyhippuric acid (Sal-Gly). Below pH 4, oxygen-coordinated complexes MLH and ML are formed. In the pH range 5–8.5, the species MLH−1 predominates at any metal-to-ligand ratio. The ligand exchange of this species is slow on the NMR time scale, which allows its structural characterization by NMR spectroscopy: the coordination polyhedron around the tin atom is distorted trigonal bipyramidal, with tridentate {O−,N−,COO−} coordination of Sal-Gly, involving two equatorial methyl groups. The NMR results reveal that the main cause of the distortion of the polyhedron is the large CH3–Sn–CH3 angle of 136±4°. The presented results supplement the data available on the dimethyltin(IV)-promoted amide deprotonation of peptides, and provide further arguments for the fundamental role of the carboxylate as an anchoring group in this process.

Preparation and Activation of Complexes of the Type [((mesityl)NCH2CH2)2NX]ZrMe2 (X = H, Me) with [Ph3C][B(C6F5)4] or [PhNMe2H][B(C6F5)4

The zirconium dimethyl complexes [N2NX]ZrMe2 (N2NX = [(MesNCH2CH2)2NX]; Mes = mesityl; X = H (1a), Me (1b)), have “mer” structures in the solid state in which the amido nitrogens occupy “axial” positions in a trigonal bipyramid. The reaction of 1b with 1 equiv of [Ph3C][B(C6F5)4] followed by addition of diethyl ether yielded the ether adduct {[N2NMe]ZrMe(Et2O)}+ (with [B(C6F5)4]- as the anion), an X-ray study of which revealed it to be a fac trigonal-bipyramidal species in which the diethyl ether is coordinated in an apical position. The reaction of 1b with 1 equiv of [PhNMe2H][B(C6F5)4] led to {[N2NMe]ZrMe(NMe2Ph)}[B(C6F5)4], solution NMR studies of which suggest a structure analogous to that of {[N2NMe]ZrMe(Et2O)}+. Heating solutions of {[N2NMe]ZrMe(NMe2Ph)}[B(C6F5)4] led to C−H activation in one mesityl o-methyl group and formation of methane. The reaction of 1b with 0.5 equiv of [Ph3C][B(C6F5)4] yielded [{[N2NMe]ZrMe}2(μ-Me)][B(C6F5)4] (5b), an X-ray diffraction study of which revealed an almost linear (167.4°) methyl bridge linking two distorted TBP moieties through the apical positions (average Zr−C(bridge) = 2.48 Å, average Zr−C(terminal) = 2.24 Å). The equatorial methyl groups in 5b exchange readily between Zr centers, while the bridging methyl group and the equatorial methyl groups exchange relatively slowly on the NMR time scale, but still rapidly on the chemical time scale. Exchange of free [N2NMe]ZrMe2 with the [N2NMe]ZrMe2 fragment in 5b is also facile on the chemical time scale. The reaction of 1b with 1.0 equiv or more of [Ph3C][B(C6F5)4] led to formation of a cationic species (6b), two forms of which could be observed at low temperature. Activation of 1a with [Ph3C][B(C6F5)4] yielded only one cationic form of 6a at low temperatures. Exchange of methyl groups between 6a and 6b is slow on the chemical time scale. All evidence is consistent with the observation of different ion pairs of 6b at low temperatures.

The Rotational Spectrum of Tricarbonyl(trans,trans-2,4-hexadiene) Iron

The microwave spectrum of tricarbonyl(trans,trans-2,4-hexadiene) iron has been recorded in the range from 3 to 22 GHz using a Balle–Flygare type Fourier transform microwave spectrometer. The b- and c-type spectrum for the 56Fe and the 54Fe isotopomer could be assigned. The internal rotation of the two equivalent methyl groups results in a fine structure of the rotational transitions which is analogous to that of 2,2-dimethyloxirane [H. Hartwig and H. Dreizler, Z. Naturforsch., A: Phys. Sci. 47, 1063–1066 (1992)] and cis-2,3-dimethyloxirane [H. Hartwig and H. Dreizler, Z. Naturforsch., A: Phys. Sci. 47, 1051–1057 (1992)]. Analyzing this fine structure yields the internal rotation barrier in addition to the rotational constants and the quartic centrifugal distortion constants.

Pseudoreceptor model for ryanodine derivatives at calcium release channels.

This paper describes the generation of a pseudoreceptor model for ryanodine receptor (RyR) modulating ryanoids in rabbit skeletal muscle. For this purpose, the molecular modelling software PrGen was applied to correlate experimentally determined and calculated free energies of binding for a set of 15 ryanodine derivatives. The final model indicates a narrow cleft with hydrogen bond donor and acceptor capacities (represented by an Asn) as most crucial for binding the pyrrole carboxylate substituent at C3 of ryanodine. In addition, hydrophobic residues flank the aromatic pyrrole ring (Tyr, Phe, and Ile). Two of those residues (Tyr and Ile) interact with the 2-isopropyl moiety, which seems to contribute to binding. Opposite to the pyrrole locus, a second hydrophobic region (represented by a Leu) restricts ryanodine derivatives in their longitudinal axis and leads to the discrimination of equatorial and axial positioned methyl groups and of polar substituents at C9. Finally, a charged glutamate residue generates strong hydrogen bonding and electrostatic interactions with the hydroxyl groups at C10 and C15. For this binding-site model--composed of six amino acid residues--a correlation for the training set ligands of R = 0.99 (Q2 = 0.975) and a root mean square (rms) deviation of 0.568 kcal/mol for the prediction of the binding energies of four test set ligands was obtained. Based on this pseudoreceptor model the putative topology of the real binding site of ryanoids will be discussed.

A study of the internal dynamics of trimethylamine by means of the non-rigid group theory

The non-rigid molecule group theory (NRG) in which the dynamical symmetry operations are defined as physical operations is applied to determine the character table for the triple equivalent methyl rotation and pyramidal inversion in trimethylamine. The restricted NRG of this molecule is seen to be a group of order 648, formed as a product of two subgroups: the G324 subgroup corresponding to planar trimethylamine and the pyramidal inversion. For this purpose the structure of the r-NRG of planar trimethylamine is first deduced, i.e., the number of classes, irreducible representations, as well as their dimensions. Finally, guidelines are given to deduce systematically the symmetry eigenvectors developed on the basis of quadruple products of trigronometric functions. The r-NRG molecule group theory is seen to be used advantageously to study the internal dynamics of such small organic molecules.