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PubMed2006

Cobalt-catalyzed reductive coupling of saturated alkyl halides with activated alkenes.

[reaction: see text] An efficient cobalt-catalyzed reductive coupling reaction of alkyl halides with electron-withdrawing alkenes (CH(2)=CR(1)EWG, EWG = electron-withdrawing group) in the presence of water and zinc powder in acetonitrile to give the corresponding Michael-type addition product (RCH(2)CR(1)EWG) was described. The methodology is versatile such that unactivated primary, secondary, and tertiary alkyl bromides and iodides and various conjugated alkenes including acrylates, acrylonitrile, methyl vinyl ketone, and vinyl sulfone all successfully participate in this coupling reaction. For the alkyl halides used in the reaction, the iodides generally gave better yields compared to those of the corresponding bromides. It is a unique method employing CoI(2)dppe, zinc, and alkyl halides, affording conjugate addition products in high yields. Mechanistically, the reaction appears to follow an oxidative addition driven route rather than the previously reported radical route.

Journal Article↗
PubMed2006

Synthesis of (Z)-alkene and (E)-fluoroalkene-containing diketopiperazine mimetics utilizing organocopper-mediated reduction-alkylation and diastereoselectivity examination using DFT calculations.

We have carefully examined the organocopper-mediated reduction-alkylation of gamma-acetoxy or gamma,gamma-difluoro-alpha,beta-unsaturated-delta-lactams for the synthesis of (Z)-alkene- or (E)-fluoroalkene-containing diketopiperazine mimetics. Reduction of acetates 2, 12, 14, and difluorolactam 18 with higher-order cuprate reagents (Me3CuLi2 x LiI x 3 LiBr), followed by trapping the resulting metal dienolate with an electrophile in a one-pot procedure gave alpha-alkylated-beta,gamma-unsaturated-delta-lactams in good yields. Because of side-chain steric repulsion, we found that alkylation using relatively large electrophiles such as BnBr gave mostly 3,6-trans isomers by kinetic trapping of metal enolates. On the other hand, MeI-mediated alkylations predominantly provided the unexpected 3,6-cis isomers despite the presence of a bulky benzyl side chain. Based on density functional theory calculations, we concluded that formation of the 3,6-cis isomers was due to the occurrence of oxa-pi-allyllithium complexes 29 and 31.

Alkenes↗
PubMed2006

Mn-mediated coupling of alkyl iodides and chiral N-acylhydrazones: optimization, scope, and evidence for a radical mechanism.

Stereoselective radical additions have excellent potential as mild, nonbasic carbon-carbon bond constructions for direct asymmetric amine synthesis. Efficient intermolecular radical addition to C=N bonds with acyclic stereocontrol has previously been limited mainly to secondary and tertiary radicals, a serious limitation from the perspective of synthetic applications. Here, we provide full details of the use of photolysis with manganese carbonyl to mediate stereoselective intermolecular radical addition to N-acylhydrazones. Photolysis (300 nm) of alkyl halides and hydrazones in the presence of Mn2(CO)10 and InCl(3) as a Lewis acid led to reductive radical addition; diastereomer ratios ranged from 93:7 to 98:2 at ca. 35 degrees C. The reaction tolerates additional functionality in either reactant, enabling subsequent transformations as shown in an efficient asymmetric synthesis of coniine. A series of hydrazones bearing different substituents on the oxazolidinone auxiliary were compared; consistently high diastereocontrol revealed that the identity of the substituent had little practical effect on the diastereoselectivity. Further mechanistic control experiments confirmed the intermediacy of radicals and showed that independently prepared alkyl- or acylmanganese pentacarbonyl compounds do not undergo efficient addition to the N-acylhydrazones under thermal or photolytic (300 nm) conditions. These Mn-mediated conditions avoid toxic tin reagents and enable stereoselective intermolecular radical additions to C=N bonds with the broadest range of alkyl halides yet reported, including previously ineffective primary alkyl halides.

Free Radicals↗
PubMed2006

Enantioselective enzymatic reductions of sterically bulky aryl alkyl ketones catalyzed by a NADPH-dependent carbonyl reductase.

The enantioselective reductions of aryl alkyl ketones, ArC(O)R, with a diverse number of alkyl groups have been achieved with an isolated carbonyl reductase from Sporobolomyces salmonicolor. Of special interest is the observation that ketones with sterically bulky alkyl groups could be reduced to the corresponding alcohols in excellent optical purity. An unusual alkyl chain-induced enantiopreference reversal was observed but was shown to be consistent with the enzyme-substrate docking calculations.

Alcohol Oxidoreductases↗
PubMed1997

Mechanism of the Solution-Phase Reaction of Alkyl Sulfides with Atomic Hydrogen. Reduction via a 9-S-3 Radical Intermediate.

The low selectivity of benzyl alkyl sulfide fragmentation subsequent to its reaction with atomic hydrogen is indicative of a reaction that proceeds via an early transition state. The competitive reduction of a series of substituted-benzyl alkyl sulfides was insensitive to the substituent on the aromatic ring (rho = -0.13, r = 0.99). The relative rates of fragmentation of a series of the substituted-benzyl alkyl sulfides gave a V-shaped Hammett plot. Both electron-donating and electron-withdrawing groups destabilized the transition state (rho = +0.99, r = 0.999; rho = -0.82, r = 0.992). Since the relative rates of disappearance of the alkyl benzyl sulfides are not substituent dependent, but the relative rates of fragmentation are, a 9-S-3 intermediate is preferred as the structure leading to products.

Journal Article↗
PubMed2000

Pairwise gibbs energies of interaction involving N-alkyl-2-pyrrolidinones and related compounds in aqueous solution obtained from kinetic medium effects

Kinetic solvent effects of N-alkyl-2-pyrrolidinones and structurally related compounds on the water-catalyzed hydrolysis reactions of p-methoxyphenyl dichloroacetate (MPDA), 1-benzoyl-3-phenyl-1,2, 4-triazole (BPhT), and 1-benzoyl-1,2,4-triazole (BT) in highly dilute aqueous solutions at pH 4 and 298.15 K have been determined by UV/vis spectroscopy. Using a thermodynamic description of solute-solute interactions in aqueous solutions, the kinetic results have been analyzed in terms of pairwise Gibbs energy interaction parameters: G(c) values. These are negative, indicating that hydrophobic interactions in the initial state dominate the medium effects. The interaction parameters increase in the order MPDA BT>BPhT. However, when differences in reactivity and transition state effects are taken into account, it appears that BPhT is more successful in establishing hydrophobic interactions with the cosolutes than are MPDA and BT. Using the SWAG-approach for additivity of group interactions, additivity is observed for the first three consecutive CH(2) groups in the cosolute in all three hydrolysis reactions. Larger alkyl substituents cause larger retardations than anticipated on basis of this additivity. The results are explained by intramolecular destructive overlap of the polar hydration shell of the amide functionality and the apolar (hydrophobic) hydration shell of the alkyl group, which extends to the third CH(2) group in the N-alkyl group of the cosolute molecule. The inner apolar groups, therefore, have a reduced apparent hydrophobicity. More remote CH(2) groups develop independent hydrophobic hydration shells. The effect of the position of a CH(2) group in the cosolute molecule is also considered. Kinetic solvent effects with structurally related esters show that amide-amide, ester-ester, and amide-ester group interactions affect the transition state in different ways. Finally, the effects of PVP polymers on the three hydrolysis reactions have been examined. The data presented enhance the understanding of pairwise hydrophobic interactions in aqueous solutions. In addition the results provide insights into the interactions between hydrophobic and hydrophilic hydration shells as well as into the energetics of amide hydration and interactions involving amides in aqueous solution, both playing important roles in protein stabilization.

Journal Article↗
PubMed2000

Synthesis of fischer-type (Alkoxy)carbene complexes using diphenylsulfonium salts with functionalized alkyl groups

A new and general method for preparing Fischer-type alkoxycarbene complexes 1 is reported. This method involves the alkylation of acylate complexes 7 with alkyldiphenylsulfonium salts 10 with a variety of functionalized alkyl groups. The alkylation of tetramethylammonium pentacarbonyl(1-oxyalkylidene)chromate(0) 7a-c, tetramethylammonium pentacarbonyl(1-oxymethylidene)molybdate(0) 7d, and pentacarbonyl(1-oxymethylidene)tungstate(0) 7e with alkyldiphenylsulfonium salts 10 proceeded smoothly under mild conditions to give the corresponding alkoxycarbene complexes 12-39 in good to high yields. Competitive alkylation of 7a with methyl-11 and isopropyldiphenylsulfonium tetrafluoroborate 40 shows a higher reactivity of the isopropyl group, suggesting the participation of an S-O sulfurane intermediate 41.

Journal Article↗
PubMed2005

Voltammetric studies of through-space and through-bond electrostatic interactions in alkyl linked ferrocene and benzoaza-15-crown-5 receptor molecules in acetonitrile.

Six new ferrocene alkyl-benzoaza-15-crown-5 molecules with different alkyl spacer lengths were synthesized and investigated by voltammetry in acetonitrile. Their mean potentials (E(o)') were more negative than that of ferrocene. The changes were greater for the bis-substituted ligands than for the monosubstituted ones. Increasing the alkyl spacer length shifted E(o)' negatively from -CH2- to -(CH2)2- but positively from -(CH2)2- to -(CH2)4-. This unusual variation is attributed to the combined electron donating and withdrawing influences and also the steric effect from the substituents on the ferrocene moiety. Analyses of the potentials of the molecules and their fully protonated forms suggested intramolecular electrostatic signaling through not only the space but also the alkyl chain which is usually considered to be an insulator for through-bond communication. Diffusion coefficients with insignificant differences between the receptors and their fully protonated forms were derived from cyclic voltammograms, suggesting insignificant further conformational variation upon protonation.

Journal Article↗
PubMed2005

Theoretical studies of alkyl radicals in the NaY and HY zeolites.

Interplay of quantum mechanical calculations and experimental data on hyperfine coupling constants of ethyl radical in zeolites at several temperatures was engaged to study the geometries and binding energies and to predict the temperature dependence of hyperfine splitting of a series of alkyl radicals in zeolites for the first time. The main focus is on the hyperfine interaction of alkyl radicals in the NaY and HY zeolites. The hyperfine splitting for neutral free radicals and free radical cations is predicted for different zeolite environments. This information can be used to establish the nature of the muoniated alkyl radicals in the NaY and HY zeolites via muSR experiments. The muon hyperfine coupling constants of the ethane radical cation in these zeolites are very large with relatively little dependence on temperature. It was found that the intramolecular dynamics of alkyl free radicals are only weakly affected by their strong binding to zeolites. In contrast, the substrate binding has a significant effect on their intermolecular dynamics.

Journal Article↗
PubMed2005

Extrathermodynamic study of surface diffusion in reversed-phase liquid chromatography with silica gels bonded with alkyl ligands of different chain lengths.

Surface diffusion on adsorbents made of silica gels bonded to C1, C4, C8, and C18 alkyl ligands was studied in reversed-phase liquid chromatography (RPLC) from the viewpoints of two extrathermodynamic relationships: enthalpy-entropy compensation (EEC) and linear free-energy relationship (LFER). First, the values of the surface diffusion coefficient (D(s)), normalized by the density of the alkyl ligands, were analyzed with the modified Arrhenius equation, following the four approaches proposed in earlier research. This showed that an actual EEC resulting from substantial physicochemical effects occurs for surface diffusion and suggested a mechanistic similarity of molecular migration by surface diffusion, irrespective of the alkyl chain length. Second, a new model based on EEC was derived to explain the LFER between the logarithms of D(s) measured under different RPLC conditions. This showed that the changes of free energy, enthalpy, and entropy of surface diffusion are linearly correlated with the carbon number in the alkyl ligands of the bonded phases and that the contribution of the C18 ligand to the changes of the thermodynamic parameters corresponds to that of the C10 ligand. The new LFER model correlates the slope and intercept of the LFER to the compensation temperatures derived from the EEC analyses and to several parameters characterizing the molecular contributions to the changes in enthalpy and entropy. Finally, the new model was used to estimate D(s) under various RPLC conditions. The values of D(s) that were estimated from only two original experimental D(s) data were in agreement with corresponding experimental D(s) values, with relative errors of approximately 20%, irrespective of some RPLC conditions.

Journal Article↗
PubMed2005

Adsorption and thermal reactions of alkanethiols on pt(111): Dependence on the length of the alkyl chain.

The adsorption and thermal decomposition of alkanethiols (R-SH, where R = CH3, C2H5, and C4H9) on Pt(111) were studied with temperature-programmed desorption (TPD) and X-ray photoelectron spectroscopy (XPS) with synchrotron radiation. Dissociation of sulfhydryl hydrogen (RS-H) of alkanethiol results in the formation of alkanethiolate; the extent of dissociation at an adsorption temperature of 110 K depends on the length of the alkyl chain. At small exposure, all chemisorbed CH3SH, C2H5SH, and C4H9SH decompose to desorb hydrogen below 370 K and yield carbon and sulfur on the surface. Desorption of products containing carbon is observed only at large exposure. In thermal decomposition, alkanethiolate is proposed to undergo a stepwise dehydrogenation: R'-CH2S --> R'-CHS --> R'-CS, R' = H, CH3, and C3H7. Further decomposition of the R'-CS intermediate results in desorption of H2 at 400-500 K and leaves carbon and sulfur on the surface. On the basis of TPD and XPS data, we conclude that the density of adsorption of alkanethiol decreases with increasing length of the alkyl chain. C4H9SH is proposed to adsorb mainly with a configuration in which its alkyl group interacts with the surface; this interaction diminishes the density of adsorption of alkanethiols but facilitates dehydrogenation of the alkyl group.

Journal Article↗
PubMed2006

Quantum mechanics calculations of the thermodynamically controlled coverage and structure of alkyl monolayers on Si(111) surfaces.

The heat of formation, Delta E, for silicon (111) surfaces terminated with increasing densities of the alkyl groups CH3- (methyl), C2H5- (ethyl), (CH3)2CH- (isopropyl), (CH3)3C- (tert-butyl), CH3(CH2)5- (hexyl), CH3(CH2)7- (octyl), and C6H5- (phenyl) was calculated using quantum mechanics (QM) methods, with unalkylated sites being H-terminated. The free energy, Delta G, for the formation of both Si-C and Si-H bonds from Si-Cl model compounds was also calculated using QM, with four separate Si-H formation mechanisms proposed, to give overall Delta G(S) values for the formation of alkylated Si(111) surfaces through a two step chlorination/alkylation method. The data are in good agreement with measurements of the packing densities for alkylated surfaces formed through this technique, for Si-H free energies of formation, Delta G(H), corresponding to a reaction mechanism including the elimination of two H atoms and the formation of a C=C double bond in either unreacted alkyl Grignard groups or tetrahydrofuran solvent.

Journal Article↗
PubMed2006

High-resolution soft X-ray photoelectron spectroscopic studies and scanning auger microscopy studies of the air oxidation of alkylated silicon(111) surfaces.

High-resolution soft X-ray photoelectron spectroscopy was used to investigate the oxidation of alkylated silicon(111) surfaces under ambient conditions. Silicon(111) surfaces were functionalized through a two-step route involving radical chlorination of the H-terminated surface followed by alkylation with alkylmagnesium halide reagents. After 24 h in air, surface species representing Si(+), Si(2+), Si(3+), and Si(4+) were detected on the Cl-terminated surface, with the highest oxidation state (Si(4+)) oxide signal appearing at +3.79 eV higher in energy than the bulk Si 2p(3/2) peak. The growth of silicon oxide was accompanied by a reduction in the surface-bound Cl signal. After 48 h of exposure to air, the Cl-terminated Si(111) surface exhibited 3.63 equivalent monoleyers (ML) of silicon oxides. In contrast, after exposure to air for 48 h, CH(3)-, C(2)H(5)-, or C(6)H(5)CH(2)-terminated Si surfaces displayed <0.4 ML of surface oxide, and in most cases only displayed approximately 0.20 ML of oxide. This oxide was principally composed of Si(+) and Si(3+) species with peaks centered at +0.8 and +3.2 eV above the bulk Si 2p(3/2) peak, respectively. The silicon 2p SXPS peaks that have previously been assigned to surface Si-C bonds did not change significantly, either in binding energy or in relative intensity, during such air exposure. Use of a high miscut-angle surface (7 degrees vs < or =0.5 degrees off of the (111) surface orientation) yielded no increase in the rate of oxidation nor change in binding energy of the resultant oxide that formed on the alkylated Si surfaces. Scanning Auger microscopy indicated that the alkylated surfaces formed oxide in isolated, inhomogeneous patches on the surface.

Journal Article↗
PubMed2006

Radiation damage to alkyl chain monolayers on semiconductor substrates investigated by electron spectroscopy.

Monolayers of alkyl chains, attached through direct Si-C bonds to Si(111), via phosphonates to GaAs(100) surfaces, or deposited as alkyl-silane monolayers on SiO2, are investigated by ultraviolet and inverse photoemission spectroscopy and X-ray absorption spectroscopy. Exposure to ultraviolet radiation from a He discharge lamp, or to a beam of energetic electrons, leads to significant damage, presumably associated with radiation- or electron-induced H-abstraction leading to carbon-carbon double-bond formation in the alkyl monolayer. The damage results in an overall distortion of the valence spectrum, in the appearance of (occupied) states above the highest occupied molecular orbital of the alkyl molecule, and in a characteristic (unoccupied state) pi resonance at the edge of the carbon absorption peak. These distortions present a serious challenge for the interpretation of the electronic structure of the monolayer system. We show that extrapolation to zero damage at short exposure times eliminates extrinsic features and allows a meaningful extraction of the density of state of the pristine monolayer from spectroscopy measurements.

Journal Article↗
PubMed2006

Raman spectral conformational order indicators in perdeuterated alkyl chain systems.

Conformational order indicators for perdeuterated alkyl chain systems are identified in the Raman spectra of nonadecane-d40, polyethylene-d4, and stearic acid-d35. Six spectral indicators are identified: I[nu(a)(CD2)2196]/I[nu(a)(CD2)2172], I[nu(C-C)G]/I[nu(C-C)T], I[nu(s)(CD3)]/I[nu(a)(CD2)2172], I[nu(s)(CD2)]/I[nu(a)(CD2)2172], and the full width at half-maximum (fwhm) and frequency of the nu(s)(CD2) mode. Among these indicators, the ratio of I[nu(a)(CD2)2196]/I[nu(a)(CD2)2172] is considered a primary indicator of conformational order, since it responds to alkyl chain conformational changes in a manner similar to the I[nu(a)(CH2)]/I[nu(s)(CH2)] primary indicator for hydrogenated systems. Other indicators are correlated to this primary indicator to derive a better understanding of the effect of structural attributes on conformational order in perdeuterated alkyl chain systems. These Raman spectral order indicators are applicable to any perdeuterated alkyl-containing system including lipids, biological membranes, alkylsilane-based chromatographic stationary phases, and self-assembled monolayers.

Journal Article↗
PubMed2004

Loosely packed self-assembled monolayers on gold generated from 2-alkyl-2-methylpropane-1,3-dithiols.

A series of 2-alkyl-2-methylpropane-1,3-dithiol derivatives with increasing alkyl chain lengths (i.e., CH3(CH2)mC(CH3)[CH2SH]2, where m = 7, 9, 11, 13, 15) were synthesized and used to generate self-assembled monolayers (SAMs) on gold. The resulting monolayers were analyzed by ellipsometry, contact angle goniometry, polarization modulation infrared reflection-absorption spectroscopy, and X-ray photoelectron spectroscopy. These data were compared with those obtained on SAMs on gold derived from normal alkanethiols (CH3(CH2)(m+2)SH) and 2-monoalkylpropane-1,3-dithiols (CH3(CH2)(m)CH[CH2SH]2) having the same number of carbon atoms in the primary chain. The results demonstrate that the 2-alkyl-2-methylpropane-1,3-dithiols generate conformationally disordered monolayer films in which the density of alkyl chains is less than those generated from normal alkanethiols and the 2-monoalkylpropane-1,3-dithiols.

Journal Article↗
PubMed2005

Conformational pseudopolymorphism and orientational disorder in two-dimensional alkyl carbamate crystals.

The structures of self-assembled physisorbed monolayers of alkyl carbamates were examined with atomic detail by scanning tunneling microscopy at the liquid-solid interface. Through systematic variation of molecular structure, the factors determining the two-dimensional crystal packing and dynamics of alkyl carbamate monolayers were isolated. Two different conformational pseudopolymorphs on the surface were observed and their order of stability was varied by changing the length of the alkyl groups. The relative size of the two alkyl groups in a molecule affected the frequency of orientational flipping within a column, which in turn, exerts an influence on the relative orientation of the two-dimensional crystalline domains. These phenomena were explained on the basis of the preferred hydrogen-bonding geometry of the carbamate functional group and the different degree of van der Waals interaction for each form.

Alkanes↗
PubMed2005

Simple and complex lattices of N-alkyl fatty acid amides on a highly oriented pyrolytic graphite surface.

STM investigations of three N-alkyl fatty acid amide molecules have been carried out to get information of their molecular arrangement on a highly oriented pyrolytic graphite surface. With variable positions of amide along the alkyl chain, complex lattices with different lattice constants were observed. Besides the lattices with a repeat unit matching one or two molecular lengths, a lattice with a repeat unit corresponding to three molecular lengths was found. In addition, the portion of different lattices depends on the length of the shorter alkyl chain. DFT-D calculations point to interactions of antiparallel oriented dipoles due to the amide group, which are distance dependent and thus larger for shorter N-alkyl chains.

Journal Article↗