Transition State For Addition Research Articles

ChemInform Abstract: Anomalous Stereoselectivity in the Wittig Reaction: The Role of Steric Interactions.

AbstractDensity functional theory calculations combined with a distortion/interaction energy analysis show that the anomalous Z selectivity observed in Wittig reactions of ortho‐substituted benzaldehydes is not caused by phosphorus—heteroatom interactions in the addition transition state, as assumed in earlier work, but is predominantly conditioned by steric effects.

Theoretical study on the origin of enantioselectivity in the primary amine–Brønsted acid catalyzed epoxidation of cyclic enones

Computational studies to determine the origin of enantioselectivity in the (1R,2R)-1,2-diphenylethane-1,2-diamine (DEPN)–Brønsted acid catalyzed epoxidation of 2-cyclohexen-1-one have been performed using density functional theory. Transition states for conjugate addition and ring closure steps of the epoxidations catalyzed by three different catalyst systems were characterized. Our calculations show that the Csp2H⋯O H-bond interaction between the benzene ring of the catalyst and H2O is mainly responsible for the chiral discrimination observed. The Brønsted acid counterion plays a very important role in ensuring high enantioselectivity by improving the rigidity of the transition state structures to allow the efficient formation of the Csp2H⋯O H-bond. Moreover, we explain why these two diamine catalysts (1S,2S)-DACH and (1R,2R)-DPEN display consistent enantioselectivities in the catalytic epoxidation of 2-cyclohexen-1-one when combining with three different cocatalysts; achiral TFA, and chiral (R)- and (S)-TRIP.

Anomalous Stereoselectivity in the Wittig Reaction: The Role of Steric Interactions

Density functional theory calculations combined with a distortion/interaction energy analysis show that the anomalous Z selectivity observed in Wittig reactions of ortho-substituted benzaldehydes is not caused by phosphorus-heteroatom interactions in the addition transition state, as assumed in earlier work, but is predominantly steric in nature. The calculations reproduced correctly the stereoselectivity preferences for a wide range of reactant pairs as well as relative reactivities for different substituent types, providing deeper structural insight into the mechanism of Wittig olefination.

Rhodium(I) Silyl Complexes for C–F Bond Activation Reactions of Aromatic Compounds: Experimental and Computational Studies

The rhodium(I) silyl complexes [Rh{Si(OEt)3}(PEt3)3] (2a) and [Rh{Si(OMe)3}(PEt3)3] (2b) were synthesized by treatment of [Rh(CH3)(PEt3)3] (1) with the corresponding silanes HSi(OEt)3 and HSi(OMe)3 at low temperature. The intermediate oxidative addition products fac-[Rh(H)(CH3){Si(OR)3}(PEt3)3] (R = Et, 6a; R = Me, 6b) were observed by low-temperature NMR spectroscopy. A reaction of 2a with CO afforded trans-[Rh(CO){Si(OEt)3}(PEt3)2] (7) by the replacement of the phosphine ligand in the position trans to the silyl group. Treatment of 2a,b with pentafluoropyridine led to C–F activation reactions at the 2-position, yielding [Rh(2-C5F4N)(PEt3)3] (11). The silyl complexes [Rh{Si(OR)3}(PEt3)3] (2a,b) gave with 2,3,5,6-tetrafluoropyridine the C–F activation product [Rh(2-C5F3HN)(PEt3)3] (10), whereas complex 7 reacted by C–H activation to furnish trans-[Rh(CO)(4-C5F4N)(PEt3)2] (12). The C–F activation of pentafluoropyridine at 2b was studied with density functional theory calculations using a [Rh{Si(OMe)3}(PMe3)3] model complex (2′). The calculations indicate that a silyl-assisted C–F activation mechanism, analogous to related ligand-assisted processes at metal–phosphine and metal–boryl bonds, is more accessible than a C–F oxidative addition/Si–F reductive elimination pathway. The silyl-assisted process also proceeds with a kinetic preference for activation at the 2-position, as the transition state in this case derives extra stabilization through a Rh···N interaction. The C–F oxidative addition transition states show a significant degree of phosphine-assisted character and are not only higher in energy than the silyl-assisted process but also favor activation at the 4-position.

Mechanism and Stereoselectivity of Biologically Important Oxygenation Reactions of the 7-Dehydrocholesterol Radical

The mechanism of free radical oxygenation of 7-dehydrocholesterol (7-DHC), one of the biologically important sterols, is investigated by using density functional theory. The energetic origin of the product distribution and the stereoelectronic factors involved in various mechanistic pathways are delineated. The addition of triplet molecular oxygen to two types of conjugatively stabilized radicals, generated by the removal of the reactive allylic hydrogens from C9 or C14 positions, respectively denoted as H9 and H14 pathways, is studied. The distortion-interaction analysis of the C-O bond formation transition states suggests that the energetic preference toward the α prochiral face stems from reduced skeletal distortions of the cholesterol backbone as compared to that in the corresponding β prochiral face. This insight derived through a detailed quantitative analysis of the stereocontrolling transition states suggests that the commonly found interpretations solely based on steric interactions between the incoming oxygen and the protruding angular methyl groups (C10, C13 methyls) in the β face calls for adequate refinement. The relative energies of the transition states for molecular oxygen addition to C9, C5, and C14 (where spin densities are higher) and the ensuing products thereof are in agreement with the experimentally reported distribution of oxygenated 7-DHCs.

Oxidative addition transition states of Pd(0) complexes in polar solvent—a DFT study involving implicit and explicit solvation

Previous reports in the literature have suggested that concerted transition states for oxidative addition would not exist in solution. By contrast, this report describes the successful location of transition states for the oxidative addition of monoligated Pd(PtBu3), bisligated Pd(PtBu3)(MeCN), and anionic Pd(PtBu3)F− complexes to C–Cl and C–OTf of an aryl chloro triflate in polar solvent (MeCN). Optimizations were done with implicit solvation and a combined implicit/explicit solvation approach in which six acetonitrile molecules were additionally involved in the optimization. The geometries obtained from optimizations employing an implicit solvation model are structurally largely analogous to those found using a combination of implicit and explicit solvation.

ChemInform Abstract: Highly Selective Activation of Vinyl C—S Bonds over Aryl C—S Bonds in the Pd‐Catalyzed Coupling of (E)‐(β‐Trifluoromethyl)vinyldiphenylsulfonium Salts: Preparation of Trifluoromethylated Alkenes and Dienes.

We describe the Suzuki coupling reaction of (E)-(beta-trifluoromethyl)vinyldiphenylsulfonium salts with arylboronic acid. The highly efficient and selective reaction provides a useful and mild method for the synthesis of trifluoromethylated alkenes and dienes. Subsequent DFT studies showed that the oxidative addition transition state of the vinyl CS bond is much more favorable (11.7 kcal?mol1) than that of the aryl CS bond.

Mechanism and diastereoselectivity of arsenic ylide mediated cyclopropanation: a theoretical study

The mechanism and diastereoselectivity of cyclopropanation reactions of arsenic ylides with enones have been investigated using density functional theory (DFT) calculations. The reactions of two different arsenic ylides, semistabilized (Ph) and stabilized (COMe), with enone have been considered. Calculations reveal that the transoid mode of addition is more favoured than the cisoid mode of addition in both reactions. Steric interactions induced by ylidic substituents and the methyl group of enones, and weak C–H⋯O hydrogen bond interactions are mainly responsible for the inherent stability difference between the addition transition states. The initial addition is found to be the diastereoselectivity-determining step for both semistabilized and stabilized ylides. The slight preferences for the formation of cis-cyclopropanes over trans-cyclopropanes in both cases is explained on the basis of weak H-bonding interactions and steric interactions encumbered on the diastereomeric transition states.

How hydrogen‐bonded MnO4‐can influence oxidation of olefins in both gas phase and solution?

The reaction pathway (including the transition state) of ethylene addition to permanganate (MnO4‐) in the presence of ethylene glycol (EG) has been qualitatively and quantitatively studied by means of B3LYP/6‐311++G** theoretical analysis. Interestingly, by cluster formation of the EG with permanganate, oxidation reaction becomes thermodynamically and kinetically more favorable. The influences of electron‐withdrawing as well as electron‐donating substituents were also explored.Results of the quantum theory of atoms in molecules and natural bond orbital analyses revealed that [3 + 2] addition reaction of alkenes in the presence of EG as hydrogen bonding donor to MnO4‐becomes more exothermic. Natural resonance theory (NRT) is used to calculate natural bond order and bond polarity. The NRT result indicates that the polarity of Mn–O bond is affected by EG coordinated to MnO4‐. Moreover, the conceptual DFT descriptors such as chemical potential (μ), hardness (η) and electrophilicity index (ω) show that hydrogen bonding to permanganate can affect the addition of MnO4‐to double bond in a satisfactory way. We also carried out geometrical optimizations with the polarizable continuum model to account for the solvent effect, and the results were compared with those in the gas phase. Copyright © 2012 John Wiley & Sons, Ltd.

Highly Selective Activation of Vinyl C–S Bonds Over Aryl C–S Bonds in the Pd‐Catalyzed Coupling of (E)‐(β‐Trifluoromethyl)vinyldiphenylsulfonium Salts: Preparation of Trifluoromethylated Alkenes and Dienes

AbstractWe describe the Suzuki coupling reaction of (E)‐(β‐trifluoromethyl)vinyldiphenylsulfonium salts with arylboronic acid. The highly efficient and selective reaction provides a useful and mild method for the synthesis of trifluoromethylated alkenes and dienes. Subsequent DFT studies showed that the oxidative addition transition state of the vinyl C–S bond is much more favorable (11.7 kcal mol–1) than that of the aryl C–S bond.

Ruthenium hydride-catalyzed regioselective addition of benzaldehyde to dienes leading to β,γ-unsaturated ketones: a DFT study

Density functional theory (DFT) was used to investigate the ruthenium hydride-catalyzed regioselective addition reactions of benzaldehyde to isoprene leading to the branched β,γ-unsaturated ketone. All intermediates and the transition states were optimized completely at the B3LYP/6-31 G(d,p) level (LANL2DZ(f) for Ru, LANL2DZ(d) for P and Cl). Calculated results indicated that three catalysts RuHCl(CO)(PMe(3))(3) (1), RuH(2)(CO)(PMe(3))(3) (2), and RuHCl(PMe(3))(3) (3) exhibited different catalysis, and the first was the most excellent. The most favorable reaction pathway included the coordination of 1 to the less substituted olefin of isoprene, a hydrogen transfer reaction from ruthenium to the carbon atom C1, the complexation of benzaldehyde to ruthenium, the carbonyl addition, and the hydride elimination reaction. The carbonyl addition was the rate-determining step. The dominant product was the branched β,γ-unsaturated ketone. Furthermore, the presence of one toluene molecule lowered the activation free energy of the transition state of the carbonyl addition by hydrogen bonds between the protons of toluene and the chlorine, carbonyl oxygen of the ruthenium complex. On the whole, the solvent effect decreased the free energies of the species.

Iminoether Complexes of the Type, fac‐[Re(CO)3L{HNC(CH3)OCH3}]BF4 (L = Bipyridine or a Substituted Bipyridine): Synthesis and Properties

AbstractThe methyl acetimidate (an iminoether) complexes, fac‐[Re(CO)3L{HNC(CH3)OCH3}]BF4 [where L = 2,2′‐bipyridine (bipy), 4,4′‐Me2bipy, 5,5′‐Me2bipy, or 6,6′‐Me2bipy], were formed when fac‐[Re(CO)3(CH3CN)3]BF4 in acetonitrile/methanol was treated with 2,2′‐bipyridine (bipy) or the dimethyl‐2,2′‐bipyridines (4,4′‐Me2bipy, 5,5′‐Me2bipy, or 6,6′‐Me2bipy). Structural analysis of the four fac‐[Re(CO)3L{HNC(CH3)OCH3}]BF4 complexes revealed that all of the complexes crystallize with the iminoether ligand in the Z configuration and that distortions in L that involved the two pyridyl rings are minor except for 6,6′‐Me2bipy, which is highly distorted. This distortion of the 6,6′‐Me2bipy ligand is reflected in the NMR‐spectroscopic data. Upon complex formation, the methyl group signal in the 13C NMR spectrum shifted downfield significantly for 6,6′‐Me2bipy, but this did not occur in the 13C NMR spectrum of the 5,5′‐Me2bipy complex. The reaction times for forming the respective fac‐[Re(CO)3L{HNC(CH3)OCH3}]BF4 complexes for these two ligands were comparable, which indicated that the differences in the distortion of L and the methyl substituent position have little influence on the ease of iminoether formation. However, a higher steric bulk of the alcohol (methanol, ethanol, and2‐propanol) decreases the ease of fac‐[Re(CO)3(5,5′‐Me2bipy){HNC(CH3)OR}]BF4 formation. Isopropanol did not form the iminoether complex after two days of heating the reaction mixture at reflux. The low reactivity of the alcohols tested versus the amines that were tested previously suggests that selective bioconjugation to the fac‐{99mTc(CO)3}+ core through an amidine linkage is feasible for biomolecules that have both amine and hydroxy groups. Finally, a comparison of the C≡N bond lengths that were obtained for the fac‐[Re(CO)3(CH3CN)3]BF4/PF6 complexes with those values obtained for other rhenium acetonitrile complexes revealed that there is no significant difference between the C≡N bond lengths and that there is no correlation to the acetonitrile reactivity. It is possible that the fac‐{Re(CO)3}+ core stabilizes the transition state for amine or alcohol addition.

Applications of conformational design: rational resign of chiral ligands derived from a common chiral source for highly enantioselective preparations of ( R)- and ( S)-enantiomers of secondary alcohols

A pair of diastereomers 7 and 8 were easily synthesized in only two steps from a single common chiral source according to the concept of conformation design. The efficiency of these chiral ligands was evaluated by their application to the asymmetric addition of diethylzinc to aldehydes. This catalytic asymmetric process afforded the a most efficient access to the ( R)- and ( S)-enantiomers of a given secondary alcohol with similarly outstanding enantioselectivities and high yields. Our results also showed that the control of the desired conformer’s population by conformation design is a new and practical strategy for the rational and precise design of highly enantioselective chiral ligands for metal-catalyzed reactions. The mechanism and possible transition states for the catalytic asymmetric addition have been proposed on the basis of previous studies as well as the crystal structure of the chiral ligands 7 and 8.

Relative stabilities of transition states determine diastereocontrol in sulfur ylide additions onto chiral N‐sulfinyl imines

Additions of methylphenylsulfonium methylide onto chiral non-racemic N-sulfinyl imines (R'-SO-N=CH-R, R'=t-butyl, R=protected diol), followed by ring closure, yield terminal aziridines with high diastereoselectivity. Control reactions have established that both N- and C- iminyl substituents impact product preference, and when properly matched, one addition product is selected almost exclusively. Using solution-phase density functional computational methods, minima and transition state searches have been performed to reveal the structural origins of the diastereoselectivity. Our computational findings indicate that ring closure is fast and irreversible, and consequently, the relative energies of the transition states for the competing Re/Si addition steps determine the product diastereomeric ratios. Analysis of addition transition state structures reveals the causes of selectivity as arising from the N- and C- iminyl substituents, and we identify the S (R) configuration of the N-sulfinyl sulfur atom as the dominant director of Si (Re) addition. The control attributed to the sulfur configuration is tied to an important favorable internal interaction between the sulfinyl oxygen and the iminyl hydrogen. The protected diol acts as a secondary director, owing to steric/electrostatic interactions with the approaching ylide.

Alternative Mechanistic Explanation for Ligand-Dependent Selectivities in Copper-Catalyzed N- and O-Arylation Reactions

The ligand-dependent selectivities in Ullmann-type reactions of amino alcohols with iodobenzene by β-diketone- and 1,10-phenanthroline-ligated Cu(I) complexes were recently explained by the single-electron transfer and iodine atom transfer mechanisms (Jones, G. O., Liu, P., Houk, K. N., and Buchwald, S. L. J. Am. Chem. Soc. 2010, 132, 6205.). The present study shows that an alternative, oxidative addition/reductive elimination mechanism may also explain the selectivities. Calculations indicate that a Cu(I) complex with a negatively charged β-diketone ligand is electronically neutral, so that oxidative addition of ArI to a β-diketone-ligated Cu(I) prefers to occur (and occur readily) in the absence of the amino alcohol. Thus, coordination of the amino alcohol in its neutral form can only occur at the Cu(III) stage where N-coordination is favored over O-coordination. The coordination step is the rate-limiting step and the outcome is that N-arylation is favored with the β-diketone ligand. On the other hand, a Cu(I) complex with a neutral 1,10-phenanthroline ligand is positively charged, so that oxidative addition of ArI to a 1,10-phenanthroline-ligated Cu(I) has to get assistance from a deprotonated amino alcohol substrate. This causes oxidative addition to become the rate-limiting step in the 1,10-phenanthroline-mediated reaction. The immediate product of the oxidative addition step is found to undergo facile reductive elimination to provide the arylation product. Because O-coordination of a deprotonated amino alcohol is favored over N-coordination in the oxidative addition transition state, O-arylation is favored with the 1,10-phenanthroline ligand.

Singlet and triplet potential surfaces for the O2+C2H4 reaction

Electronic structure calculations at the CASSCF and UB3LYP levels of theory with the aug-cc-pVDZ basis set were used to characterize structures, vibrational frequencies, and energies for stationary points on the ground state triplet and singlet O(2)+C(2)H(4) potential energy surfaces (PESs). Spin-orbit couplings between the PESs were calculated using state averaged CASSCF wave functions. More accurate energies were obtained for the CASSCF structures with the MRMP2/aug-cc-pVDZ method. An important and necessary aspect of the calculations was the need to use different CASSCF active spaces for the different reaction paths on the investigated PESs. The CASSCF calculations focused on O(2)+C(2)H(4) addition to form the C(2)H(4)O(2) biradical on the triplet and singlet surfaces, and isomerization reaction paths ensuing from this biradical. The triplet and singlet C(2)H(4)O(2) biradicals are very similar in structure, primarily differing in their C-C-O-O dihedral angles. The MRMP2 values for the O(2)+C(2)H(4)→C(2)H(4)O(2) barrier to form the biradical are 33.8 and 6.1 kcal/mol, respectively, for the triplet and singlet surfaces. On the singlet surface, C(2)H(4)O(2) isomerizes to dioxetane and ethane-peroxide with MRMP2 barriers of 7.8 and 21.3 kcal/mol. A more exhaustive search of reaction paths was made for the singlet surface using the UB3LYP/aug-cc-pVDZ theory. The triplet and singlet surfaces cross between the structures for the O(2)+C(2)H(4) addition transition states and the biradical intermediates. Trapping in the triplet biradical intermediate, following (3)O(2)+C(2)H(4) addition, is expected to enhance triplet→singlet intersystem crossing.

Diastereoselective Synthesis of Tetrahydrofurans from Aryl 3-Chloropropylsulfoxides and Aldehydes

Carbanions of aryl 3-chloropropylsulfoxides react with nonenolizable aldehydes to give 2,3-disubstituted tetrahydrofurans. Deprotonation of the sulfoxides carried out in the presence of aldehydes results in the addition of the carbanions to the carbonyl group of the aldehydes, followed by 1,5-intramolecular substitution of the resulting aldol-type anion to produce the tetrahydrofuran ring. The 2-aryl and 3-arylsulfinyl substituents are always in trans relation, and the reaction proceeds with high diastereoselectivity also in respect to the chiral sulfur atom. The diastereoselectivity is attributed to the cyclic transition state of the aldol addition and increases when the aromatic ring of the sulfoxide contains electron-withdrawing substituents, whereas that of the aldehyde has electron-donating groups.

A computational study towards understanding the mechanism of phosphodiester cleavage by two mononuclear Zn(ii) complexes

In this study, the hydrolytic reaction mechanism of HPNP by two effective mononuclear Zn(II) catalysts was explored by using density functional calculations. With the assumption that the active catalyst is in Zn-aqua form, the water-assisted proton transfer mode was found to be energetically the most favorable one for both the catalysts among three possible reaction pathways. The rate-limiting step on this pathway is a concerted double-proton transfer, concomitant with the nucleophilic addition of the deprotonated hydroxyl group to form a five-coordinated phosphorus intermediate. A comparison of potential energy surfaces for both catalysts shows that the three amino groups in the second coordination sphere of one catalyst play an important role in stabilizing the proton transfer (or nucleophilic addition) transition state. The two coordination spheres are found to have almost the same contributions in catalyzing the phosphate ester cleavage reaction. Also, present calculations show that the water-assisted proton transfer mechanism with the catalyst L-Zn-OH(2) is more favorable in energy than the general base pathway with the active catalyst L-Zn-OH suggested previously.

Kinetic parameters and geometry of the transition state of acyl radical decarbonylation

Experimental data on acyl radical decomposition reactions (RC·O → R· + CO, where R = alkyl or aryl) are analyzed in terms of the intersecting parabolas method. Kinetic parameters characterizing these reactions are calculated. The transition state of methyl radical addition to CO at the C atoms is calculated using the DFT method. A semiempirical algorithm is constructed for calculating the transition state geometry for the decomposition of acyl radicals and for the reverse reactions of R· addition to CO. Kinetic parameters (activation energy and rate constant) and geometry (interatomic distances in the transition state) are calculated for 18 decomposition reactions of structurally different acyl radicals. A linear correlation between the interatomic distance r#(C…C) (or r#(C…O)) in the transition state the enthalpy of the reaction (δHe) is established for acyl decomposition reactions (at bre = const). A comparative analysis of the enthalpies, activation energies, and interatomic distances in the transition state is carried out for the decomposition and formation of acyl, carboxyl, and formyl radicals.

High Accuracy ab Initio Calculations on Reactions of OH with 1-Alkenes. The Case of Propene.

The energetics of terminal, central OH-additions as well as allylic H-abstractions by OH in its reaction with propene was studied as proxies for the 1-alkenes + OH reactions using several single and multireference ab initio techniques with basis set extrapolation where possible. Selection of the localized occupied orbitals forming the active space for multireference methods is discussed. Initial geometries of the reactants, prereaction complex (π-complex), and transition states were determined at the [5,5]-CASPT2/cc-pVTZ level of theory. Frequency analysis was also carried out at this level with the introduction of a scale factor. Analyzing the results, it will be concluded that multireference effects are negligible, and from the various single reference models we will opt for UCCSD(T)/cc-pVTZ for final geometry optimizations and vibrational frequency analysis. These results will be compared with those from approximate models yielding information on the reliability of the latter. Triples contributions are found to be very important, except for the π-complex, which has a UCCSD(T)/CBS relative enthalpy of -10.56 kJ/mol compared to infinitely separated propene + OH. The addition transition states are found to have relative enthalpies of -9.93 kJ/mol for the central and -9.84 kJ/mol for the terminal case. Allylic abstraction mechanisms, although lying significantly higher, still have only slightly positive barriers - a value of 3.21 kJ/mol for the direct and 1.67 kJ/mol for the consecutive case. Conventional transition state theory was used as a rough estimation for determining rate constants and turned out to agree well with experimental data.