Seven-membered Transition State Research Articles

Protodemetalation of (Bipyridyl)Ni(II)-Aryl Complexes Shows Evidence for Five-, Six-, and Seven-Membered Cyclic Pathways.

Protonation of C-M bonds and its microscopic reverse, metalation of C-H bonds, are fundamental steps in a variety of metal-catalyzed processes. As such, studies on protonation of C-M bonds can shed light on C-H activation. We present here studies on the rate of protodemetalation (PDM) of a suite of arylnickel(II) complexes with various acids that provide evidence for a concerted, cyclic transition state for the PDM of C-Ni bonds and demonstrate that five-, six-, and seven-membered transition states are particularly favorable. Our data show that while the rate of protodemetalation of arylnickel(II) complexes scales with acidity for many acids, several are faster than predicted by pKa. For example, while acetic acid and acetohydroxamic acid are much less acidic than HCl, they both protodemetalate arylnickel(II) complexes significantly faster than HCl. Our data also show how in the case of acetohydroxamic acid, a seven-membered cyclic transition state (CH3C(O)NHOH) can be more favorable than a six-membered transition state (CH3C(O)NHOH). Similarly, five-membered transition states, such as for pyrazole, are highly favorable as well. Comparison of transition state polarization (from density functional theory) compares these new nickel transition states to better-studied precious-metal systems and demonstrates how the base can change the polarization of the transition state giving rise to opposing electronic preferences. Collectively, these studies suggest several new avenues for study in C-H activation as well as approaches to accelerate or slow protodemetalation in nickel catalysis.

Expansion of Phosphane Treasure Box for Staudinger Peptide Ligation.

A smooth traceless ligation strategy using an air-stable phosphane probe (2-(diphenylphosphanyl)phenyl)methanol as a C-terminus activator has been demonstrated at simple and sterically hindered amino acid junctions (Gly, Ala, Trp, Glu). This Staudinger peptide ligation proceeds via formation of a seven-membered transition state to afford di-, tetra-, and pentapeptides in 78-95% yields. The experimental results of ligation at Gly junction and regioselective ligation at Glu junction were theoretically studied by computational calculations. These findings established the versatile behavior of our synthesized phosphane probe for Staudinger peptide ligation toward synthesizing peptides and proteins of choice.

Mechanisms of reactions of sulfur hydride hydroxide: tautomerism, condensations, and C-sulfenylation and O-sulfenylation of 2,4-pentanedione.

The conformations, equilibrium structures, hydrogen bonds, and non-covalent interactions involved in the mechanisms of tautomerization, condensations, and C-sulfenylation and O-sulfenylation of 2,4-pentanedione by sulfur hydride hydroxide (hydrogen thioperoxide, oxadisulfane, H-SOH) have been studied using BD(T), CCSD(T), and QCISD(T) with the cc-pVTZ basis set and using B3LYP, B3PW91, CAM-B3LYP, PBE1PBE, PBEh1PBE, LC-ωPBE, M06-2X, and ωB97XD with the 6-311+G(d,p) basis set. All levels of theory predict the sulfenyl (H-SOH) tautomer of hydrogen thioperoxide to be lower in energy than the sulfinyl (H2S═O) tautomer. Four reasonable mechanisms were considered for the tautomerization of the sulfenyl tautomer of hydrogen thioperoxide to the sulfinyl tautomer: a cyclic three-membered water-free transition state (TS, CCSD(T) activation energy barrier E(⧧) = 65.1 kcal/mol), a cyclic five-membered transition state with one water molecule (TSH2O, E(⧧) = 31.1 kcal/mol), a cyclic seven-membered transition state with two water molecules (TS2H2O, E(⧧) = 14.5 kcal/mol), and a cyclic nine-membered transition state with three water molecules (TS3H2O, E(⧧) = 5.6 kcal/mol). The mechanisms involve hydrogen-bonded reactant complexes and hydrogen-bonded product complexes. The CCSD(T)-predicted energy barriers for the condensation of hydrogen thioperoxide to form thiosulfinic acid through transition states with zero, one, and two waters are E(⧧) = 42.0, 18.3, and 0 kcal/mol, respectively. Mixed condensation reactions are predicted to afford organosulfur products and compounds containing sulfur-selenium bonds. Hydrogen thioperoxide is predicted to add to 2,4-pentanedione to form C-sulfenylated (sulfide, thioether) and O-sulfenylated (sulfenate ester) products. Similar mechanistic trends and reaction pathways are observed in the tautomerism, condensations, and C-sulfenylation and O-sulfenylation reactions of hydrogen thioperoxide. The water molecules set up proton relay networks (bridges) that reduce ring strain, generate favorable conformations for reactivity, lower energy barriers, and increase the numbers of stabilizing hydrogen bonds and nonbonding interactions.

Mechanism of the catalytic gas-phase aldehyde production from trinuclear W 3S 4 complexes bearing W-OEt groups

Collision induced dissociation experiments of the alkoxo [W 3S 4(dmpe) 2(O)(OCH 2CH 3)] + tungsten (IV) cation reveal that aldehyde elimination is the dominant reaction pathway. Complementary deuterium labelling experiments give support to a hydrogen transfer mechanism, where the hydrogen atom exclusively originates from the α-position of the alkoxo ligand. On the basis of DFT calculations, two competitive mechanisms are proposed: one of them involving a proton transfer from the α-position of the alkoxo ligand to an oxygen atom of the vicinal W O group; the other corresponding to a hydride transfer mechanism from the α-position of the alkoxo ligand to the geminate tungsten center. The calculated energy profiles show that the former is thermodynamically favoured and the second is kinetically favoured, with small energy differences between the two reaction paths; in consequence, both mechanisms compete under our experimental conditions. The proton transfer mechanism occurs through a seven-membered transition state structure while hydride transfer takes place through a four-center structure defined by the metal and the oxygen, carbon and hydrogen atoms of the ethoxo group.

Premixed ignition behavior of C 9 fatty acid esters: A motored engine study

An experimental study on the premixed ignition behavior of C 9 fatty acid esters has been conducted in a motored CFR engine. For each test fuel, the engine compression ratio was gradually increased from the lowest point (4.43) to the point where significant high temperature heat release (HTHR) was observed. The engine exhaust was sampled and analyzed through GC-FID/TCD and GC-MS. Combustion analysis showed that the four C 9 fatty acid esters tested in this study exhibited evidently different ignition behavior. The magnitude of low temperature heat release (LTHR) follows the order, ethyl nonanoate > methyl nonanoate ≫ methyl 2-nonenoate > methyl 3-nonenoate. The lower oxidation reactivity for the unsaturated fatty acid esters in the low temperature regime can be explained by the reduced amount of six- or seven-membered transition state rings formed during the oxidation of the unsaturated esters due to the presence of a double bond in the aliphatic chain of the esters. The inhibition effect of the double bond on the low temperature oxidation reactivity of fatty acid esters becomes more pronounced as the double bond moves toward the central position of the aliphatic chain. GC-MS analysis of exhaust condensate collected under the engine conditions where only LTHR occurred showed that the alkyl chain of the saturated fatty acid esters participated in typical paraffin-like low temperature oxidation sequences. In contrast, for unsaturated fatty acid esters, the autoignition can undergo olefin ignition pathways. For all test compounds, the ester functional group remains largely intact during the early stage of oxidation.

Intramolecular 1,8‐Hydrogen‐Atom Transfer Reactions in (1→4)‐O‐Disaccharide Systems: Conformational and Stereochemical Requirements

The stereochemical and conformational factors controlling the intramolecular hydrogen-atom transfer (HAT) reaction between the two pyranose units in a (1-->4)-O-disaccharide when promoted by a primary 6-O-yl radical are studied. Models with alpha-D-Glcp-(1-->4)-beta-D-Glcp, alpha-L-Rhamp-(1-->4)-alpha-D-Galp or alpha-D-Manp-(1-->4)-beta-L-Gulp skeletons led exclusively to the abstraction of the hydrogen from H--C-5' and the formation, through a nine-membered transition state, of a 1,3,5-trioxocane ring system in a stable boat-chair conformation. Notwithstanding, derivatives of alpha-L-Rhamp-(1-->4)-alpha-D-Glcp or alpha-D-Manp-(1-->4)-alpha-D-Galp exclusively abstract the hydrogen from H--C-1' through a seven-membered transition state and, therefore, lead to an interglycosidic spiro ortho ester.

The Inner-Sphere Process in the Enantioselective Tsuji Allylation Reaction with (S)-t-Bu-phosphinooxazoline Ligands

We propose an inner-sphere mechanism explaining the unique performance of the Tsuji asymmetrical allylation reaction using hard prochiral enolate nucleophiles and non-prochiral allyl groups. Using first principles quantum mechanics (B3LYP density functional theory), we find that the pathway for this reaction involves nucleophilic attack followed by interconversion from a five-coordinate Pd complex to a four-coordinate complex. This intermediate is trapped in a potential well and escapes via reductive elimination that proceeds through a seven-membered transition state to generate the product and a Pd0 complex. This seven-membered transition state contrasts dramatically from the usual three-centered C−C reductive elimination paradigm generally associated with C−C coupling reactions. This inner-sphere asymmetric allylation pathway involving hard enolates is energetically more favorable than outer-sphere nucleophilic attack, a process understood to occur in asymmetric allylic alkylations with soft enolates.

Intramolecular 1,8- versus 1,6-Hydrogen Atom Transfer between Pyranose Units in a (1→4)-Disaccharide Model Promoted by Alkoxyl Radicals. Conformational and Stereochemical Requirements

[reaction: see text] The stereochemical and conformational factors controlling the intramolecular hydrogen atom transfer (HAT) reaction between the two pyranose units in a (1-->4)-disaccharide when promoted by a primary 6-O-yl radical are studied. Models with alpha-d-Glcp-(1-->4)-beta-d-Glcp or alpha-l-Rhamp-(1-->4)-alpha-d-Galp skeletons lead exclusively to the abstraction of H-C-5' and the formation, through a nine-membered transition state, of a 1,3,5-trioxocane ring system in a stable boat-chair conformation. Notwithstanding, derivatives of alpha-l-Rhamp-(1-->4)-alpha-d-Glcp abstract exclusively H-C-1' through a seven-membered transition state and therefore lead to an interglycosidic spiro ortho ester.

Kinetic Study on the Esterification of Hexanoic Acid with N,N-Dialkylamino Alcohols: Evidence for an Activation by Hydrogen Bonding

The pseudo-first order rate constant for the esterification of hexanoic acid (1) and five different N,N-dialkylamino alcohols (2) was determined in comparison to 1-hexanol (k = 0.67 · 10−5 s−1). The values range from 0.60 · 10−5 s−1 to 9.3 · 10−5 s−1. The data suggest a differing reactivity for structurally related compounds, which is directly correlated to the ability of the corresponding amino alcohol to activate the carboxylic acid by hydrogen bonding. A seven-membered transition state C≠ is postulated for reactions of 2-amino alcohols. The fastest reaction was observed for trans-2-(N,N-dimethylamino) cyclohexanol (2e), in which the amino and the hydroxyl groups are in an almost perfect synperiplanar 1,2-position. Attempts to further enhance the rate of the esterification by the addition of potential catalysts failed. Only Cu(OTf)2 (2.5 mol-%) allowed for a moderate rate increase from 7.5 · 10−5 s−1 (uncatalyzed) to 14.8 · 10−5 s−1 (catalyzed) in the esterification of hexanoic acid (1) with 2-(N,N-dimethylamino)ethanol (2a).

Intramolecular nucleophilic capture of radical cations by tethered hydroxy functions

Abstract A range of systems bearing hydroxy functions tethered to the molecular framework gives rise to a family of interesting radical cations, 5 + – 11 + , upon electron transfer to photo-excited cyanoaromatics. Geraniol ( 5 ), nerol ( 6 ), citronellol ( 7 ), chrysanthemol ( 8 ), homochrysanthemol ( 9 ), trans -1- o -hydroxyphenyl-2-phenylcyclopropane ( 10 ), and endo -5-hydroxymethylnorbornene ( 11 ), generate a series of mono-, bi-, or tricyclic ethers via a series of four- to seven-membered transition states. Two of the radical cations, 5 + and 6 + , undergo tandem cyclizations where 1,5- and/or 1,6-C–C cyclizations precede nucleophilic capture.

An MO study of regioselective amine addition to ortho-quinones relevant to melanogenesis

Energy profiles for alternative intramolecular cyclisations of 4-(aminoalkyl)- ortho-quinones have been calculated using the AM1 method and ab initio energies of the transition states are determined. In all the cases cyclisation at position 5 occurs via a significantly lower energy transition state than cyclisation at position 3. This is consistent with experimental observations. Optimal trajectories for attack have been determined from a study of the reactions of methylamine with 4-methyl- ortho-quinone. For cyclisation of aminoalkyl derivatives deviation from the optimal direction is less for reaction at position 5 but constraint on angle of attack only partially accounts for the regioselectivity. Intrinsic differences in the electronic energies of the alternative transition states are the main contributor to regioselectivity. The relative energies of transition states can be modified by variation of the substituent at position 4. The calculations suggest that seven-membered ring formation may occur via a boat transition state and steric hindrance in the seven-membered transition states may account for the experimentally observed influence of N-substituents on the mode of reaction.

Intramolecular γ‐Hydroxylations of Nonactivated CH Bonds with Copper Complexes and Molecular Oxygen

Copper(I) complexes incorporating the isomeric bidentate ligands IMPY (iminomethyl-2-pyridines) or AMPY (aminomethylene-2-pyridines) are quite unusual in their ability to bind and activate molecular oxygen. Using these complexes, hydroxylations of nonactivated CH, CH2, or CH3 groups in the gamma-position in relation to the imino-nitrogen atom, and with a specific orientation of one H atom with respect to the binuclear Cu-O species, can be achieved in synthetically useful yields. Through mechanistic studies employing conformationally well-defined molecules (for example, cyclic isoprenoids), coupled with solid-state X-ray structure analyses and force-field calculations, we postulate a seven-membered transition state for this reaction in which six atoms lie approximately in a plane. This plane is defined by the positions of the lone pairs on the nitrogen atoms, as well as the copper and the oxygen atoms. For a successful hydroxylation, one hydrogen atom should be located close to this plane. Prediction of the stereochemical course of these reactions is possible based on a simple geometrical criterion. The convenient introduction of IMPY and AMPY groups as auxiliaries into oxo and primary amino compounds and the simple hydrolysis after the hydroxylation procedure has allowed the synthesis of 3-hydroxy-1-oxo and 3-hydroxy-1-amino compounds. If desired, the 3-hydroxy-1-IMPY and -1-AMPY compounds can be reduced with NaBH4 to obtain 3-hydroxy-1-aminomethylpyridines. For a successful hydroxylation procedure, the method employed for the synthesis of the CuI complexes is very important. Starting either from CuI salts or from CuII salts with a subsequent reduction with benzoin/triethylamine may turn out to be the better way, depending on the ligand and the molecular structure.

Degradation of three oxygenated alkoxy radicals of atmospheric interest: HOCH2O˙, CH3OCH2O˙, CH3OCH2OCH2O˙. RRKM theoretical study of the β-C–H bond scission and the 1,6-isomerisation kinetics

A detailed theoretical study on the pressure and temperature dependence of the rate constants k1, k2, k3 for the thermal β-C–H dissociation of the three radicals: HOCH2O˙, CH3OCH2O˙, CH3OCH2OCH2O˙ is presented. This investigation is extended to the rate constant k4 for the 1,6-H-shift isomerisation of CH3OCH2OCH2O˙. High-level ab initio computations (CCSD(T)//MP2) have been performed and combined with RRKM theory to obtain rate constants. The β-C–H scission pathway is predicted to occur with an activation energy of 10–13 kcal mol−1. Estimation of the competition between the β-C–H and β-C–O decompositions, the isomerisation process, and the reaction with oxygen has been done. At 760 Torr and 298 K, k1, k2, k3, k4 are 4.4 × 104 s−1, 5.2 × 104 s−1, 4.2 × 103 s−1 and 5.6 × 103 s−1 respectively. An interesting result is that the isomerisation through a seven-membered transition state may compete with the H-atom elimination from the CH3OCH2OCH2O˙ radical.

Reactions of mono- and bimolecular hydrogen transfer in alkyl radicals: analysis using the parabolic model and density functional calculations

Experimental data on monomolecular hydrogen transfer in the reactions of the type RC·H(CH2)nCH2R1 → RCH2(CH2)nC·HR1 (n = 2—4, R and R1 are alkyl substituents) were analyzed using the parabolic model (PM). The parameters characterizing this class of reactions were calculated. Isomerization of alkyl radicals via cyclic transition states (TS) is characterized by the following energy barriers to thermoneutral reaction Ee0: 53.5, 65.4, and 63.2 kJ mol–1 for the six-, five-, and seven-membered TS, respectively. The Ee0 energy and the strain energy change in parallel in the series of cycloparaffins CnH2n. Density functional calculations of intramolecular hydrogen transfer in the n-butyl and n-pentyl radicals and of the bimolecular hydrogen abstraction from the ethane molecule by the ethyl radical were performed. The activation energies of the intra- and intermolecular hydrogen transfer were compared. The parameters of the PM were compared with the interatomic distances in the reaction center of the TS calculated by the density functional method.

Methyl Migration and Transannular 1,5‐Hydride Shift on Oxidative Cleavage of CPd Bonds with CuCl2

The high regio- and stereoselectivity of the reaction 1 → 2 points to a mechanism involving a transannular 1,5 hydrogen migration; the CH activation probably takes place via a cyclic, seven-membered transition state. This was the result of a detailed mechanistic study of the PdCu catalyzed functionalization of CH groups, a reaction that may eventually be extended to steroids.

Genese von C 7H 8+− aus n-pentylbenzol-radikalkationen zwischen 10 −10 und 10 −5 s: Eine fik-studie zu kompetitiven wasserstoff-umlagerungen [1

Field ionization measurements (FIK) of several deuterium-labelled n-pentylbenzene derivatives demonstrate that the hydrogen transfer from the side chain in the formation of C 7H 8 +− occurs via five-, six- and seven-membered transition states. At the shortest measurable life times ( t < 10 −10 s) this elimination is not preceded by a hydrogen exchange process between the side chain and the ortho positions (degenerated isomerizations), whereas at 10 −5 s extensive, but not complete, exchange processes are of special importance.

Massenspektrometrische Untersuchungen zur Genese von [M—Me] [M-Et] [C7H7]+ und [C7H8]+ aus n-Butyl- und n-Pentylbenzol: Zeitabhängige Nachbargruppeneffekte, Isomerisierungen und kompetitive Wasserstoff-Umlagerungen / Mass Spectrometric Investigations on the Formation of [M-Me] [M-Et] [C7H7]+ und [C7H8]+ from w-Butyl and w-Pentyl Benzenes: Time Dependent Neighbouring Group Participation, Isomerization and Competitive Hydrogen Rearrangements

Abstract The details of the elimination of CH3· and C2H5· from the molecular ions of n-butyl and n-pentyl benzenes as well as the formation of C7H7+ and C7H7+ -have been established using a combination of different mass spectrometric techniques. Among these techniques are field ionization kinetics (FIK), collisional activation (CA), unimolecular decomposi-tion of metastable ions (MI), kinetic energy release determinations (Tkin)&gt; appearance potential measurements (AP) as well as high resolution mass spectrometry. The appli-cation of these methods and the investigation of nine 13 carbon and eleven deuterium labelled n-butyl and n-pentyl benzenes clearly demonstrate that 1) the loss of methyl and ethyl from terminal positions of the alkyl chains are accompanied by an interaction with the phenyl ring and 2) the regioselectivity of these processes is time dependent. Contrary to previous conclusions it is shown that hydrogen transfer in the formation of C7H8+ -occurs via five-, six-and seven-membered transition states. The time dependence of the hydrogen exchange reaction preceding the alkene eliminations is discussed in detail.

Electron impact studies. Part CIV. Cyclisation reactions of negative ions. The o-O2NC6H4(CHCH)nCOR system

Negative-ion mass spectra of compounds of the general type o-O2NC6H4(CHCH)nCOR (n= 1–3) show rearrangement peaks produced by novel cyclisation reactions occurring between the adjacent substituents. When n= 1. reactions proceed mainly through six- and seven-membered transition states, whereas for n= 2, six-centred states still predominate, but reactions also occur via five-membered transition states. Major fragment ions correspond to charged 1,2-dicarbonyl (n= 1), 2-ene-1,4-dicarbonyl (n= 2), and 2,4-diene-1,6-dicarbonyl (n= 3) systems. Rearrangement ions are not observed when the nitro-group is replaced by a carboxy-group.

A laboratory model for the atisane leads to aconane conversion.

Atisine (1) has been converted into the epimeric toluene-p-sulphonates (28) and (29). On acetolysis either (28) or (29) affords the same 14(8 → 15)abeo-17-oxa-8-ene (19). In contrast, whereas gas phase pyrolysis of the ester (28) gives the olefin (19), the isomer (29) gives a 9(8 → 15)abeo-17-oxa-8(14)ene (20); each conversion takes place stereospecifically via a seven-membered transition state. The structure of the olefin (20) has been confirmed by an X-ray crystal structure analysis of the derived ethylene acetal hydriodide (48). An n.m.r. analysis of hindered rotation in two amides [(19) and (21)] is presented.

δ-versusγ-Hydrogen abstraction in the photocyclization of β-alkoxy-ketones

Photocyclization of β-alkoxy-ketones can give tetrahydrofuranols and cyclobutanols viaδ- or γ-hydrogen abstraction, respectively: the occurrence of δ-hydrogen abstraction via a seven-membered transition state is attributable to the enhanced stability of the resulting α-oxalkyl radical.