Methyl Exchange Research Articles

Frontispiece: The Dimethylbismuth Cation: Entry Into Dative Bi−Bi Bonding and Unconventional Methyl Exchange

Organometallic Chemistry In their Communication on page 24388, Crispin Lichtenberg et al. report the synthesis of the dimethylbismuth cation as a simple, fundamentally important organometallic compound.

The Dimethylbismuth Cation: Entry Into Dative Bi-Bi Bonding and Unconventional Methyl Exchange.

The isolation of simple, fundamentally important, and highly reactive organometallic compounds remains among the most challenging tasks in synthetic chemistry. The detailed characterization of such compounds is key to the discovery of novel bonding scenarios and reactivity. The dimethylbismuth cation, [BiMe2(SbF6)] (1), has been isolated and characterized. Its reaction with BiMe3 gives access to an unprecedented dative bond, a Bi→Bi donor–acceptor interaction. The exchange of methyl groups (arguably the simplest hydrocarbon moiety) between different metal atoms is among the most principal types of reactions in organometallic chemistry. The reaction of 1 with BiMe3 enables an SE2(back)‐type methyl exchange, which is, for the first time, investigated in detail for isolable, (pseudo‐)homoleptic main‐group compounds.

Das Dimethylbismut‐Kation: Zugang zu dativen Bi‐Bi‐Bindungen und unkonventionellem Methylaustausch

AbstractDie Isolierung einfacher, hochreaktiver metallorganischer Verbindungen von grundlegendem Interesse gehört nach wie vor zu den schwierigsten Aufgaben in der Synthesechemie. Die detaillierte Charakterisierung solcher Verbindungen ist der Schlüssel zum Verständnis neuer Bindungsszenarien und Reaktivitäten. Das Dimethylbismut‐Kation, [BiMe2(SbF6)] (1), wurde isoliert und charakterisiert. Seine Reaktion mit BiMe3 ermöglicht den Zugang zu einer bislang unbekannten dativen Bindung, der Bi→Bi‐Donor/Akzeptor‐Wechselwirkung. Der Austausch von Methylgruppen (der wohl einfachsten Kohlenwasserstoffeinheit) zwischen verschiedenen Metallatomen gehört zu den wichtigsten Reaktionstypen in der metallorganischen Chemie. Die Reaktion von 1 mit BiMe3 ermöglicht einen Methylaustausch über eine Rückseiten‐SE2‐Reaktion, welche zum ersten Mal im Detail für isolierbare, (pseudo‐)homoleptische Hauptgruppenverbindungen untersucht wird.

Detection of chemical exchange in methyl groups of macromolecules.

The zero- and double-quantum methyl TROSY Hahn-echo and the methyl 1H-1H dipole-dipole cross-correlation nuclear magnetic resonance experiments enable estimation of multiple quantum chemical exchange broadening in methyl groups in proteins. The two relaxation rate constants are established to be linearly dependent using molecular dynamics simulations and empirical analysis of experimental data. This relationship allows chemical exchange broadening to be recognized as an increase in the Hahn-echo relaxation rate constant. The approach is illustrated by analyzing relaxation data collected at three temperatures for E. coli ribonuclease HI and by analyzing relaxation data collected for different cofactor and substrate complexes of E. coli AlkB.

Catalyst Nuclearity Effects on Stereo- and Regioinduction in Pyridylamidohafnium-Catalyzed Propylene and 1-Octene Polymerizations

In comparison to monometallic controls, bimetallic olefin polymerization catalysts often exhibit superior performance in terms of higher polyolefin Mw, higher comonomer incorporation, and higher polar comonomer tolerance. However, using cooperating catalyst centers to modulate stereoselectivity in α-olefin polymerizations is relatively unexplored. In this contribution, the monometallic Hf(IV) complex, L1-HfMe2 (catalyst A, L1 = 2,6-diisopropyl-N-{(2-isopropylphenyl)[6-(naphthalen-1-yl)pyridin-2-yl]methyl}aniline), and homo-bimetallic Hf(IV) complexes, L2-Hf2Me5 (catalyst B) and L2-Hf2Me4 (catalyst C) (L2 = N,N′-{[naphthalene-1,4-diylbis(pyridine-6,2-diyl)]bis[(2-isopropylphenyl)methylene)]bis(2,6-diisopropylaniline}), are activated with Ph3C+B(C6F5)4– and investigated in propylene and 1-octene homopolymerizations. In propylene polymerizations, the conformationally flexible catalyst B-derived bimetallic dicationic catalyst produces higher Mw polypropylene (up to 7.8×), higher total stereo- and regiodefect densities (up to 3.5×), and lower Tm (by as much as ∼14 °C) versus the monometallic catalyst A-derived control. In 1-octene polymerizations, the conformationally flexible catalyst B-derived bimetallic dicationic catalyst induces greatly reduced isotacticity (23% reduction in [mmmm]) versus the catalyst A-derived monometallic control ([mmmm] > 99%). Interestingly, conformationally flexible catalyst B-derived cationic bimetallic Hf catalysts are also known to undergo rapid intramolecular/intermetal methyl exchange and to exhibit strong Hf···Hf cooperative enchainment effects in ethylene homo- and copolymerizations. Steric effects and intramolecular intermetal chain transfer likely both contribute to the increased isotactic polyolefin stereo- and regiodefect content.

Exploring the structural landscape by chloro–methyl exchange

Exploring the structural landscape by chloro–methyl exchange

Protein Dynamics in the Solid State from (2)H NMR Line Shape Analysis. II. MOMD Applied to C-D and C-CD3 Probes.

Deuterium line shape analysis from mobile C–D and C–CD3 groups has emerged as a particularly useful tool for studying dynamics in the solid state. The theoretical models devised so far consist typically of sets of independent dynamic modes. Each such mode is simple and usually case-specific. In this scenario, model improvement entails adding yet another mode (thereby changing the overall model), comparison of different cases is difficult, and ambiguity is unavoidable. We recently developed the microscopic order macroscopic disorder (MOMD) approach as a single-mode alternative. In MOMD, the local spatial restrictions are expressed by an anisotropic potential, the local motion by a diffusion tensor, and the local molecular geometry by relative (magnetic and model-related) tensor orientations, all of adjustable symmetry. This approach provides a consistent method of analysis, thus resolving the issues above. In this study, we apply MOMD to PS-adsorbed LKα14 peptide and dimethylammonium tetraphenylborate (C–CD3 and N–CD3 dynamics, respectively), as well as HhaI methyltransferase target DNA and phase III of benzene-6-hexanoate (C–D dynamics). The success with fitting these four disparate cases, as well as the two cases in the previous report, demonstrates the generality of this MOMD-based approach. In this study, C–D and C–CD3 are both found to execute axial diffusion (rates R⊥ and R∥) in the presence of a rhombic potential given by the L = 2 spherical harmonics (coefficients c02 and c22). R⊥ (R∥) is in the 102–103 (104–105) s–1 range, and c02 and c22 are on the order of 2–3 kBT. Specific parameter values are determined for each mobile site. The diffusion and quadrupolar tensors are tilted at either 120° (consistent with trans–gauche isomerization) or nearly 110.5° (consistent with methyl exchange). Future prospects include extension of the MOMD formalism to include MAS, and application to 15N and 13C nuclei.

Reactions and products revealed by NMR spectra of deuterated dimethylsulfoxide with iodomethane in neutral and basic media

Reactions occurring within each one of two mixtures, a mixture of deuterated dimethylsulfoxide, DMSO-d6, with CH3I (system I) and another mixture of DMSO-d6 with CH3I, NaOH and water (system II), were monitored by 1D and 2D nuclear magnetic resonance (1H, 13C, heteronuclear multiple quantum correlation, heteronuclear multiple bond correlation and diffusion-ordered NMR spectroscopy). The analysis of the spectra as a function of reaction time revealed the formation of methoxy-bis(trideuteromethyl)sulfonium iodide, 3; the precipitation of hexadeuterated trimethyloxosulfonium, 2a; a methyl exchange between DMSO-d6 and 2a to produce trideuterated dimethylsulfoxide, DMSO-d3, 4, and nona-deuterated trimethyloxosulfonium iodide, 2b; and the production of small quantities of methanol, 5, trideuterated dimethylsulfide, 6, and dimethyl ether, 7, in both systems. Only system II precipitated deuterated [Na4(DMSO-dx)15][(I3)3I], 1a, a green solid with metallic shine that corresponds to an isotopomer of 1, which is produced by the self-assembly of DMSO and CH3I in the presence of NaOH and water.

Organometallic Nucleophiles and Pd: What Makes ZnMe2 Different? Is Au Like Zn?

The cis/trans isomerization of [PdMeAr(PR3)2] complexes (Ar = C6F5, C6F3Cl2) can take place spontaneously (via dissociation and topomerization, studied experimentally) or be catalyzed by ZnMe2. The latter mechanism, studied by DFT methods, involves methyl exchange between Pd and Zn. The study of this catalyzed isomerization shows that, in contrast with the typical acidic behavior of Zn in ZnMeCl, Zn in ZnMe2 (or, more exactly, the ZnMe bond) behaves as a strong basic center, able to attack the relatively high in energy acceptor orbital at Pd in fairly electron rich Pd complexes such as [PdArMeL2] or [PdMe2L2]. This makes the two reagents very different in Negishi couplings. The catalyzed isomerization occurs via transmetalation; thus, both processes are connected. A comparison of the Pd/Zn intermediates and transition states with those found previously for Pd/Au transmetalations reveals very similar structures with intermetallic distances in the order of or noticeably shorter than the sum of the vdW radii...

Bis-hydrocarbyl Platinum(II) Ambiphilic Ligand Complexes: Alkyl–Aryl Exchange between Platinum and Boron

Reaction of TXPB (2,7-di-tert-butyl-5-diphenylboryl-4-diphenylphosphino-9,9-dimethylthioxanthene) with [PtMe2(COD)] (COD = 1,5-cyclooctadiene) yielded [PtMePh(TXPB′)] (1; TXPB′ = 2,7-di-tert-butyl-5-methylphenylboryl-4-diphenylphosphino-9,9-dimethylthioxanthene), presumably via undetected [PtMe2(TXPB)]. The ambiphilic ligand in 1 is κ2PS-coordinated, and the trigonal plane of the borane is oriented approximately parallel to the square plane at platinum. In solution, 1 is in equilibrium with zwitterionic [PtMe(TXPB-Me)] (1′), in which the Pt-phenyl group in 1 has been abstracted by the borane; the ratio of 1 to 1′ is approximately 90:10 at room temperature and 50:50 at 183 K. The presence of 1′ in solution suggests that the pathway for phenyl–methyl exchange between platinum and boron involves a zwitterionic platinum(II) intermediate, rather than a platinum(IV) boryl complex resulting from B–C bond oxidative addition. Heating compound 1 provided an approximate 14:86 mixture of 1 and [PtPh2(TXPB″)] (2; TXPB...

Heterobi‐ and ‐trimetallic Ion Pairs of Zirconocene‐Based Isoselective Olefin Polymerization Catalysts with AlMe3

AbstractThe reactivity towards AlMe3 of discrete cationic ansa‐zirconocenes 2 a,b that are ubiquitously used in isoselective propylene polymerization and based on [{Ph(H)C(3,6‐tBu2‐Flu)(3‐tBu‐5‐Et‐Cp)}ZrMe2)] {Cp‐Flu} and rac‐[{Me2Si‐(2‐Me‐4‐Ph‐Ind)2}ZrMe2] {SBI} was scrutinized. The first example of a structurally characterized Group 4 metallocene AlMe3 adduct (3 b) is reported. In the presence of excess AlMe3, the {SBI}‐based AlMe3 adduct 3 b undergoes a slow decomposition via CH activation in a bridging methyl unit to yield a new species (4 b) with a trimetallic {Zr(μ‐CH2)(μ‐Me)AlMe(μ‐Me)AlMe2} core. EXSY NMR data for the process 2 b⇄3 b→4 b suggest very rapid and reversible binding of an additional AlMe3 molecule onto AlMe3 adduct 3 b. The resulting heterotrimetallic species intermediates exchange of methyl groups between different metal centers and slowly undergoes the CH activation reaction towards 4 b.

Heterobi- and -trimetallic Ion Pairs of Zirconocene-Based Isoselective Olefin Polymerization Catalysts with AlMe₃.

The reactivity towards AlMe3 of discrete cationic ansa-zirconocenes 2 a,b that are ubiquitously used in isoselective propylene polymerization and based on [{Ph(H)C(3,6-tBu2-Flu)(3-tBu-5-Et-Cp)}ZrMe2)] {Cp-Flu} and rac-[{Me2Si-(2-Me-4-Ph-Ind)2}ZrMe2] {SBI} was scrutinized. The first example of a structurally characterized Group 4 metallocene AlMe3 adduct (3 b) is reported. In the presence of excess AlMe3, the {SBI}-based AlMe3 adduct 3 b undergoes a slow decomposition via C-H activation in a bridging methyl unit to yield a new species (4 b) with a trimetallic {Zr(μ-CH2)(μ-Me)AlMe(μ-Me)AlMe2} core. EXSY NMR data for the process 2 b⇄3 b→4 b suggest very rapid and reversible binding of an additional AlMe3 molecule onto AlMe3 adduct 3 b. The resulting heterotrimetallic species intermediates exchange of methyl groups between different metal centers and slowly undergoes the C-H activation reaction towards 4 b.

Phosphinimine-substituted boranes and borenium ions.

The phosphinimines R3PNSiMe3 (R = t-Bu: 1a, R = Cy: 1b, R = Et: 1c, R = Ph: 1d) are reacted with a series of chloro and fluoroboranes (9Cl-9-BBN, (C6F5)2BCl, PhBCl2 and Mes2BF) to access a family of phosphinimine-substituted boranes (2a-d, 3b-d, 4c,d and 6a,b) via Me3SiX elimination (X = Cl, F). The steric and electronic factors governing the formation of monomeric or dimeric products (7c,d) are presented. In addition, in some cases a Lewis acid mediated exchange of Si-bonded methyl groups for a chloro-substituent was observed (5a,b). Based on the phosphinimine-substituted boranes, a series of borenium ion salts (8b-d, 9c, 10b-d) was prepared upon reaction with MeOTf. All compounds were fully characterized and a number of molecular structures were determined by X-ray diffraction.

Light-Driven Methyl Exchange Reactions in Square-Planar Palladium(II) and Platinum(II) Complexes

Square-planar palladium(II) and platinum(II) methyl complexes with terpyridine and 6,6″-diamino terpyridine ligands undergo methyl exchange reactions upon exposure to light. The half-life of the methyl exchange reactions correlates with the relative Pd–C and Pt–C bond strengths. No exchange between methyl and phenyl groups is observed, probably due to the stronger Pt–C bond in the platinum phenyl complex. A mechanism is proposed whereby a dinuclear intermediate is generated upon irradiation that has a weakened M–C bond in the excited state, resulting in the observed methyl exchange reactions.

Exchange of Methyl‐ and Azobenzene‐Terminated Alkanethiols on Polycrystalline Gold Studied by Tip‐Enhanced Raman Mapping

Mixed thiol self-assembled monolayers (SAMs) presenting methyl and azobenzene head groups were prepared by chemical substitution from the original single-component n-decanethiol or [4-(phenylazo)phenoxy]hexane-1-thiol SAMs on polycrystalline gold substrates. Static contact-angle measurements were carried out to confirm a change in the hydrophobicity of the functionalized surfaces following the exchange reaction. The mixed SAMs presented contact-angle values between those of the more hydrophobic n-decanethiol and the more hydrophilic [4-(phenylazo)phenoxy]hexane-1-thiol single-component SAMs. By means of tip-enhanced Raman spectroscopy (TERS) mapping experiments, it was possible to highlight that molecular replacement takes place easily and first at grain boundaries: for two different mixed SAM compositions, TERS point-by-point maps with <50 nm step sizes showed different spectral signatures in correspondence to the grain boundaries. An example of the substitution extending beyond grain boundaries and affecting flat areas of the gold surface is also shown.

Lanthanoid Tetramethylaluminates and Their Paramagnetic NMR Parameters

AbstractTris(tetramethylaluminate)s of the lanthanoids cerium (1), holmium (2), and erbium (3) were synthesized by treating lanthanoid amide complexes of the type [Ln(NMe2)3(LiCl)3] with an excess amount of AlMe3. These compounds were characterized by single‐crystal X‐ray diffraction, elemental analysis, and NMR spectroscopy. Paramagnetic NMR spectroscopic studies were undertaken to investigate the influence of the compounds on the solvent chemical shifts. NMR parameters for the 1H, 13C, and 27Al nuclei of all the reported lanthanoid tris(tetramethylaluminate)s were measured. The reactions of tris(tetramethylaluminate)s of samarium and holmium with an excess amount of tetrahydrofuran led to [LnMe2(thf)5][AlMe4] {Ln = Ho (4), Sm (5)}. NMR spectroscopic investigations of the paramagnetic holmium and samarium methyl compounds (i.e., 4, 5) as well as the known diamagnetic analogue [YMe2(thf)5][AlMe4] revealed methyl group exchange processes in solution.

Protein conformational exchange measured by 1H R1ρ relaxation dispersion of methyl groups

Activated dynamics plays a central role in protein function, where transitions between distinct conformations often underlie the switching between active and inactive states. The characteristic time scales of these transitions typically fall in the microsecond to millisecond range, which is amenable to investigations by NMR relaxation dispersion experiments. Processes at the faster end of this range are more challenging to study, because higher RF field strengths are required to achieve refocusing of the exchanging magnetization. Here we describe a rotating-frame relaxation dispersion experiment for (1)H spins in methyl (13)CHD2 groups, which improves the characterization of fast exchange processes. The influence of (1)H-(1)H rotating-frame nuclear Overhauser effects (ROE) is shown to be negligible, based on a comparison of R 1ρ relaxation data acquired with tilt angles of 90° and 35°, in which the ROE is maximal and minimal, respectively, and on samples containing different (1)H densities surrounding the monitored methyl groups. The method was applied to ubiquitin and the apo form of calmodulin. We find that ubiquitin does not exhibit any (1)H relaxation dispersion of its methyl groups at 10 or 25°C. By contrast, calmodulin shows significant conformational exchange of the methionine methyl groups in its C-terminal domain, as previously demonstrated by (1)H and (13)C CPMG experiments. The present R 1ρ experiment extends the relaxation dispersion profile towards higher refocusing frequencies, which improves the definition of the exchange correlation time, compared to previous results.

Stereoengineering of Poly(1,3-methylenecyclohexane) via Two-State Living Coordination Polymerization of 1,6-Heptadiene

External control over the rate of dynamic methyl group exchange between configurationally stable active species and configurationally unstable dormant species with respect to chain-growth propagation within a highly stereoselective and regiospecific living coordination polymerization of 1,6-heptadiene has been used to generate a spectrum of different physical forms of poly(1,3-methylenecyclohexane) (PMCH) in which the stereochemical microstructure has been systematically varied between two limiting forms. The application of this strategy to manipulate the bulk properties of PMCH and the solid-state microphase behavior of well-defined PMCH-b-poly(1-hexene) block copolymers is further demonstrated.

ChemInform Abstract: Direct Exchange of a Ketone Methyl or Aryl Group to Another Aryl Group Through C—C Bond Activation Assisted by Rhodium Chelation.

AbstractThe method is applied to a broad spectrum of quinolines and quinoxaline (VI) to offer a novel approach for ketone synthesis.

On the polarity of partially fluorinated methyl groups

A series of indole and 5-methoxyindole derivatives, substituted at C3 with n-propyl or 4-methylcyclohexyl scaffolds bearing varying degrees of fluorination of the terminal methyl group, have been prepared and studied. These compounds exhibit characteristic polarity patterns, measured either by logP or chromatographic capacity factors, which are consistent with the partially known lipophilicity pattern for the corresponding n-propylbenzene series. Based on a simple CF bond vector analysis, the polarity increase upon exchange of a terminal methyl by a trifluoromethyl group in an aliphatic substituent should be comparable to that arising from a single H/F exchange at the terminal methyl group, while the volume increase in the former case is three times larger than that in the latter. This may explain the observation that replacement of a methyl by a fluoromethyl group results in a more pronounced lowering of molecular lipophilicity than its replacement by a trifluoromethyl group. The same analysis predicts a difluoromethyl group to exhibit a lipophilicity reduction similar to that of a fluoromethyl group.