o-Quinone methide as alkylating agent of nitrogen, oxygen, and sulfur nucleophiles. The role of H-bonding and solvent effects on the reactivity through a DFT computational study

The reactivity of the alkylating agent o-quinone methide (o-QM) toward NH(3), H(2)O, and H(2)S, prototypes of nitrogen-, oxygen-, and sulfur-centered nucleophiles, has been studied by quantum chemical methods in the frame of DF theory (B3LYP) in reactions modeling its reactivity in water with biological nucleophiles. The computational analysis explores the reaction of NH(3), H(2)O, and H(2)S with o-QM, both free and H-bonded to a discrete water molecule, with the aim to rationalize the specific and general effect of the solvent on o-QM reactivity. Optimizations of stationary points were done at the B3LYP level using several basis sets [6-31G(d), 6-311+G(d,p), adding d and f functions to the S atom, 6-311+G(d,p),S(2df), and AUG-cc-pVTZ]. The activation energies calculated for the addition reactions were found to be reduced by the assistance of a water molecule, which makes easier the proton-transfer process in these alkylation reactions by at least 12.9, 10.5, and 6.0 kcal mol(-1) [at the B3LYP/AUG-cc-pVTZ//B3LYP/6-311+G(d,p) level], for ammonia, water, and hydrogen sulfide, respectively. A proper comparison of an uncatalyzed with a water-catalyzed reaction mechanism has been made on the basis of activation Gibbs free energies. In gas-phase alkylation of ammonia and water by o-QM, reactions assisted by an additional water molecule H-bonded to o-QM (water-catalyzed mechanism) are favored over their uncatalyzed counterparts by 5.6 and 4.0 kcal mol(-1) [at the B3LYP/6-311+G(d,p) level], respectively. In contrast, the hydrogen sulfide alkylation reaction in the gas phase shows a slight preference for a direct alkylation without water assistance, even though the free energy difference (DeltaDeltaG(#)) between the two reaction mechanisms is very small (by 1.0 kcal mol(-1) at the B3LYP/6-311+G(d,p),S(2df) level of theory). The bulk solvent effect, evaluated by the C-PCM model, significantly modifies the relative importance of the uncatalyzed and water-assisted alkylation mechanism by o-QM in comparison to the case in the gas phase. Unexpectedly, the uncatalyzed mechanism becomes highly favored over the catalyzed one in the alkylation reaction of ammonia (by 7.0 kcal mol(-1)) and hydrogen sulfide (by 4.0 kcal mol(-1)). In contrast, activation induced by water complexation still plays an important role in the o-QM hydration reaction in water as solvent.     

Theoretical study of the decomposition reactions in substituted nitrobenzenes

The influence of substituent nature and position on the unimolecular decomposition of nitroaromatic compounds was investigated using the density functional theory at a PBE0/6-31+G(d,p) level. As the starting point, the two main reaction paths for the decomposition of nitrobenzene were analyzed: the direct carbon nitrogen dissociation (C6H5 + NO2) and a two step mechanism leading to the formation of phenoxyl and nitro radicals (C6H5O + NO). The dissociation energy of the former reaction was calculated to be 7.5 kcal/mol lower than the activation energy of the second reaction. Then the Gibbs free energies were computed for 15 nitrobenzene derivatives characterized by different substituents (nitro, methyl, amino, carboxylic acid, and hydroxyl) in the ortho, meta, and para positions. In meta position, no significant changes appeared in the reaction energy profiles whereas ortho and para substitutions led to significant deviations in energies on the decomposition mechanisms due to the resonance effect of the nitro group without changing the competition between these mechanisms. In the case of para and meta substitutions, the carbon-nitro bond dissociation energy has been directly related to the Hammett constant as an indicator of the electron donor-acceptor effect of substituents.     

Atmospheric chemistry of linear perfluorinated aldehydes: dissociation kinetics of CnF2n+1CO radicals

Linear perfluorinated aldehydes (PFALs, CnF2n+1CHO) are important intermediate species in the atmospheric oxidation pathway of many polyfluorinated compounds. PFALs can be further oxidized in the gas phase to give perfluorinated carboxylic acids (PFCAs, CnF2n+1C(O)OH, n = 6, 12) which have been detected in animal tissues and at low parts per billion levels in human blood sera. In this paper, we report ab initio quantum chemistry calculations of the decarbonylation kinetics of CnF2n+1CO radicals. Our results show that CnF2n+1CO radicals have a strong tendency to decompose to give CnF2n+1 and CO under atmospheric conditions: the Arrhenius activation energies for decarbonylation of CF3CO, C2F5CO, and C3F7CO obtained using PMP4/6-311++G(2d,p) are 8.8, 6.6, and 5.8 kcal/mol, respectively, each of which is about 5 kcal/mol lower than the barrier for the corresponding nonfluorinated radicals. The lowering of the barrier for decarbonylation of CnF2n+1CO relative to that of CnH2n+1CO is well explained by electron withdrawal by F atoms that serve to weaken the critical C-CO bond. These results have important implications for the atmospheric fate of PFALs and the atmospheric pathways to PFCAs. The main effect of decarbonylation of CnF2n+1CO is to decrease the molar yield of CnF2n+1C(O)OH; if 100% of the CnF2n+1CO decompose, the yield of CnF2n+1C(O)OH must be zero. There is considerable scope for additional experimental and theoretical studies.     

Calculation of solvation free energies of charged solutes using mixed cluster/continuum models

We derive a consistent approach for predicting the solvation free energies of charged solutes in the presence of implicit and explicit solvents. We find that some published methodologies make systematic errors in the computed free energies because of the incorrect accounting of the standard state corrections for water molecules or water clusters present in the thermodynamic cycle. This problem can be avoided by using the same standard state for each species involved in the reaction under consideration. We analyze two different thermodynamic cycles for calculating the solvation free energies of ionic solutes: (1) the cluster cycle with an n water cluster as a reagent and (2) the monomer cycle with n distinct water molecules as reagents. The use of the cluster cycle gives solvation free energies that are in excellent agreement with the experimental values obtained from studies of ion-water clusters. The mean absolute errors are 0.8 kcal/mol for H(+) and 2.0 kcal/mol for Cu(2+). Conversely, calculations using the monomer cycle lead to mean absolute errors that are >10 kcal/mol for H(+) and >30 kcal/mol for Cu(2+). The presence of hydrogen-bonded clusters of similar size on the left- and right-hand sides of the reaction cycle results in the cancellation of the systematic errors in the calculated free energies. Using the cluster cycle with 1 solvation shell leads to errors of 5 kcal/mol for H(+) (6 waters) and 27 kcal/mol for Cu(2+) (6 waters), whereas using 2 solvation shells leads to accuracies of 2 kcal/mol for Cu(2+) (18 waters) and 1 kcal/mol for H(+) (10 waters).     

Aspirin. An ab initio quantum-mechanical study of conformational preferences and of neighboring group interactions.

The potential energy surface of acetylsalicylic acid, aspirin, has been explored at the RHF/6-31G* and B3LYP/6-31G* levels, and single-point calculations were performed at levels up to B3LYP/6-311G**//B3LYP/6-31G*. All conformational isomers have been located, the thermochemical functions have been computed, and relative energies and free enthalpies were determined. The conformational space of aspirin is spanned by three internal coordinates, and these are the carboxylic acid C-O conformation (s-trans preferred by about 7 kcal/mol), the C-COOH conformation (Z preferred unless there are H-bonding opportunities), and the ester C-O conformation (s-trans preferred by about 4 kcal/mol). There are nine aspirin isomers since one of the conformers realizes hydrogen-bonding structure isomerism as well. Neighboring group interactions are discussed with reference to the intrinsic properties of benzoic acid and phenyl acetate. The intrinsic conformational preference energies for benzoic acid and phenyl acetate are not additive. The acid s-trans preference energies differ by as much as 9 kcal/mol depending on the Ph-COOH and ester conformations. Similarly, the E-preference energies about the Ph-COOH bond vary by as much as 6 kcal/mol depending on the ester conformation. The structural discussion suggests an overall ortho repulsion between the functional groups in all aspirin isomers including the intramolecularly hydrogen-bonded isomers. The isodesmic reaction between the most stable conformers of benzoic acid and phenyl acetate to form aspirin and benzene is found to be endothermic by 2.7 kcal/mol and provides compelling evidence for and a quantitative measure of ortho repulsion. The ortho repulsion of 2.7 kcal/mol is a lower limit, and the ortho repulsion can increase to as much as 6 kcal/mol in some aspirin isomers.     

Carboranes and baskets from reaction of B4H10 with allene

The reaction of the boron hydride B4H10 with allene was studied at the CCSD(T)/6-311+G(d)//MP2/6-31G(d) level. The mechanism is surprisingly complex with 44 transition states and several branching points located. The four carboranes and one basket that have been observed experimentally are all connected by pathways that have very similar free energies of activation. In addition, two new structures, a basket (2,4-(CH2CH2CH2)B4H8, 5a) and a "classical" structure (1,4-(Me2C)bisdiborane, 7), which might be obtained from the B4H10 + C3H4 reaction under the right conditions (hot/cold, quenched, etc.) have been identified. The first branch point in the reaction is the competition between H2 elimination from B4H10 (DeltaG(298 K) = 32.2 kcal/mol) and the hydroboration of allene by B4H10 (DeltaG(298 K) = 31.3 kcal/mol). The next branch point in the hydroboration mechanism controls the formation of 2,4-(MeCHCH2)B4H8 (1) (DeltaG(298 K) = 31.5 kcal/mol) and arachno-1,2/arachno-1,3-Me2-1-CB4H7 (8 and 8a) (DeltaG(298 K) = 34.3 kcal/mol). Another branch point in the H2-elimination mechanism controls the formation of 1-Me-2,5-micro-CH2-1-CB4H7 (29) (DeltaG(298 K) = 0.1 kcal/mol) and 2,5-micro-CHMe-1-CB4H7 (25/26) (DeltaG(298 K) = 7.3 kcal/mol). Formation of 2-Me-2,3-C2B4H7, a carborane observed in the reaction of methylacetylene with B4H10, is calculated to be blocked by a high barrier for H2 elimination. All free energies are relative to B4H10 + allene. An interesting reaction step discovered is the "reverse hydroboration step" in which a hydrogen atom is transferred from carbon back to boron, which allows a CH hydrogen to shuttle between the terminal and central carbon of allene.     

Accuracy of free energies of hydration for organic molecules from 6-31g*-derived partial charges

Absolute free energies of hydration have been computed for 13 diverse organic molecules using partial charges derived from ab initio 6-31G* wave functions. Both Mulliken charges and charges fit to the electrostatic potential surface (EPS) were considered in conjunction with OPLS Lennard–Jones parameters for the organic molecules and the TIP4P model of water. Monte Carlo simulations with statistical perturbation theory yielded relative free energies of hydration. These were converted to absolute quantities through perturbations to reference molecules for which absolute free energies of hydration had been obtained previously in TIP4P water. The average errors in the computed absolute free energies of hydration are 1.1 kcal/mol for the 6-31G* EPS charges and 4.0 kcal/mol for the Mulliken charges. For the EPS charges, the largest individual errors are under 2 kcal/mol except for acetamide, in which case the error is 3.7 kcal/mol. The hydrogen bonding between the organic solutes and water has also been characterized. © John Wiley & Sons, Inc.     

Theoretical study of 1,6-anhydrosugar formation from phenyl D-glucosides under basic condition: reasons for higher reactivity of β-anomer

Degradation of anomeric phenyl d-glucosides to levoglucosan under basic condition is theoretically studied. MP4(SDQ)//DFT(B3LYP)-computational results indicate that the degradation of phenyl α-glucoside (R(α)) occurs via the S(N)icB mechanism. In this mechanism, the oxyanion at the C6, which is formed through deprotonation of the OH group, directly attacks the anomeric carbon. On the other hand, the degradation of phenyl β-glucoside (R(β)) occurs via the S(N)icB(2) mechanism. In this mechanism, the oxyanion at the C2 attacks the anomeric carbon in a nucleophilic manner to afford 1,2-anhydride intermediate and then the oxyanion at the C6 attacks the anomeric carbon to afford levoglucosan. The activation barrier is much lower in the reaction of R(β) (ΔG(0++) = 25.6 kcal/mol and E(a) = 26.5 kcal/mol) than in the reaction of R(α) (ΔG(0++) = 38.1 kcal/mol and E(a) = 37.2 kcal/mol), which is consistent with the experimental observation that β-glucoside is generally much more reactive than the corresponding α-glucoside. The lower activation barrier of the reaction of R(β) arises from the stereoelectronic effect, which is induced by the charge transfer from the ring oxygen to the anomeric carbon, and the staggered conformation around the C1-C2 bond. When the stereoelectronic effect is absent, the degradation needs larger activation energy; for instance, the degradation of phenyl 5a-carba-β-d-glucoside (R(Cβ)) occurs with large ΔG(0++) and E(a) values like those of α-glucosides, because the methylene group of R(Cβ) does not contribute to the stereoelectronic effect. Also, the conformation around the C1-C2 bond is staggered in the transition state of the R(β) reaction but eclipsed in that of the R(α) reaction, which also leads to the larger reactivity of R(β).     

Kinetics of the Reaction of Abstracting Hydrogen from Ethylene by Hydrogen Atom

Hydrogen abstraction reaction, H C2H4 --H2 C2H2 was studied by using A initio SCF method. Ge-ometries were fully optimized at SCF level and energies were computed at STO-3G basis set for reactants and transition state. Vibrational analysis was performed thereupon. Finally, the rate constant calculations were carried out at different temperatures for all range of reaction temperature according to Eyring's sbwlute reaction rate theory. The calculated activation energy is 12. 68 kcal/mol, lower than observed value (H. S kcal/mol) by 1. 82 kcal/mol only. The agreement of the calculated rate constants with the experiments is satisfactory.     

Binding of anticancer drug Ru(η 6 -C6H5(CH2)2OH)Cl2(DAPTA) to DNA purine bases and amino acid residues: a theoretical study

The hydrolyzed Ru(η ⁶ -C₆H₅(CH₂)₂OH)Cl₂(DAPTA) (DAPTA = 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane) binding to guanine(G), adenine (A), cytosine(C), cysteine (Cys), and histidine (His) residues were explored using the B3LYP hybrid functional and IEF-PCM solvation models. The computed activation barriers for the reactions of diaqua complex were lower than those of chloroaqua complex except for binding to cytosine. For the chloroaqua complex, the activation free energy was lowest when binding to cytosine (10.5 kcal/mol). Whereas, the substitution reaction of diaqua complex binding to cysteine showed the lowest activation free energy with 10.1 kcal/mol, closely followed by histidine (15.8 kcal/mol), adenine (20.1 kcal/mol), cytosine (20.7 kcal/mol), and guanine (24.4 kcal/mol) by turns. It could be deduced that the completely hydrolyzed Ru(η ⁶ -C₆H₅(CH₂)₂OH)Cl₂(DAPTA) compounds might preferentially bind to amino acids residues in vivo. In addition, to simulate the protein and DNA environment in vivo, a detailed investigation of the activation free energies for the substitution reactions in dependence of the dielectric constant ε (4, 24, and 78.39) was systematically performed as well. The calculated results demonstrated that the environmental effect had a little impact on these substitution reactions.     

Reactivity of isobutane on zeolites: a first principles study

In this work, ab initio and density functional theory methods are used to study isobutane protolytic cracking, primary hydrogen exchange, tertiary hydrogen exchange, and dehydrogenation reactions catalyzed by zeolites. The reactants, products, and transition-state structures are optimized at the B3LYP/6-31G* level, and the final energies are calculated using the CBS-QB3 composite energy method. The computed activation barriers are 52.3 kcal/mol for cracking, 29.4 kcal/mol for primary hydrogen exchange, 29.9 kcal/mol for tertiary hydrogen exchange, and 59.4 kcal/mol for dehydrogenation. The zeolite acidity effects on the reaction barriers are also investigated by changing the cluster terminal Si-H bond lengths. The analytical expressions between activation barriers and zeolite deprotonation energies for each reaction are proposed so that accurate activation barriers can be obtained when using different zeolites as catalysts.     

Mechanisms of the Knoevenagel hetero Diels-Alder sequence in multicomponent reactions to dihydropyrans: experimental and theoretical investigations into the role of water

The role of water in a multicomponent domino reaction (MCR) involving styrene, 2,4-pentanedione, and formaldehyde was studied. Whereas anhydrous conditions produced no reaction, the MCR successfully proceeded in the presence of water, affording the targeted dihydropyran derivatives with good yield. The mechanism of this MCR (Knoevenagel hetero Diels-Alder sequence) was studied with and without explicit water molecules using the SMD continuum solvation model in combination with the B3LYP density functional and the 6-311++G** basis set to compute the water and acetone (aprotic organic solvent) solution Gibbs free energies. In the Knoevenagel step, we found that water acted as a proton relay to favor the formation of more flexible six-membered ring transition state structures both in concerted (direct H(2)O elimination) and stepwise (keto-enol tautomerization and dehydration) pathways. The inclusion of a water molecule in our model resulted in a significant decrease (-8.5 kcal mol(-1)ΔG(water)(?)) of the direct water elimination activation barrier. Owing to the presence of water, all chemical steps involved in the MCR mechanism had activation free energies barriers lower than 39 kcal mol(-1) at 25 °C in aqueous solvent (<21 kcal mol(-1) ZPE corrected electronic energies barriers). Consequently, the MCR proceeded without the assistance of any catalyst.     

Quantum dynamics of vibrationally activated OH-CO reactant complexes

The MP2 complete basis set (CBS) limit for the binding energy of the two low-lying water octamer isomers of D2d and S4 symmetry is estimated at -72.7+/-0.4 kcal/mol using the family of augmented correlation-consistent orbital basis sets of double through quintuple zeta quality. The largest MP2 calculation with the augmented quintuple zeta (aug-cc-pV5Z) basis set produced binding energies of -73.70 (D2d) and -73.67 kcal/mol (S4). The effects of higher correlation, computed at the CCSD(T) level of theory, are estimated at <0.1 kcal/mol. The newly established MP2/CBS limit for the water octamer is reproduced quite accurately by the newly developed all atom polarizable, flexible interaction potential (TTM2-F). The TTM2-F binding energies of -73.21 (D2d) and -73.24 kcal/mol (S4) for the two isomers are just 0.5 kcal/mol (or 0.7%) larger than the MP2/CBS limit.     

The catalytic mechanism of mouse renin studied with QM/MM calculations

Hypertension is a chronic condition that affects nearly 25% of adults worldwide. As the Renin-Angiotensin-Aldosterone System is implicated in the control of blood pressure and body fluid homeostasis, its combined blockage is an attractive therapeutic strategy currently in use for the treatment of several cardiovascular conditions. We have performed QM/MM calculations to study the mouse renin catalytic mechanism in atomistic detail, using the N-terminal His6-Asn14 segment of angiotensinogen as substrate. The enzymatic reaction (hydrolysis of the peptidic bond between residues in the 10th and 11th positions) occurs through a general acid/base mechanism and, surprisingly, it is characterized by three mechanistic steps: it begins with the creation of a first very stable tetrahedral gem-diol intermediate, followed by protonation of the peptidic bond nitrogen, giving rise to a second intermediate. In a final step the peptidic bond is completely cleaved and both gem-diol hydroxyl protons are transferred to the catalytic dyad (Asp32 and Asp215). The final reaction products are two separate peptides with carboxylic acid and amine extremities. The activation energy for the formation of the gem-diol intermediate was calculated as 23.68 kcal mol(-1), whereas for the other steps the values were 15.51 kcal mol(-1) and 14.40 kcal mol(-1), respectively. The rate limiting states were the reactants and the first transition state. The associated barrier (23.68 kcal mol(-1)) is close to the experimental values for the angiotensinogen substrate (19.6 kcal mol(-1)). We have also tested the influence of the density functional on the activation and reaction energies. All eight density functionals tested (B3LYP, B3LYP-D3, X3LYP, M06, B1B95, BMK, mPWB1K and B2PLYP) gave very similar results.     

Theoretical investigations on the stereoselectivity of the proline catalyzed Mannich reaction in DMSO

The stereocontrol steps of the (S)-proline catalyzed Mannich reaction of cyclohexanone, formaldehyde, and aniline were theoretically investigated. The geometries of reactants, products, and transition states were optimized using density functional theory using the B3LYP functional with the 6-31++G(d,p) basis set. The energies of these compounds were then more accurately determined at the MP2 level, and the effect of DMSO as the solvent was included using a polarizable continuum model (PCM). The reaction was modeled from the previously proposed mechanism that cyclohexanone reacts with (S)-proline to generate an enamine, while formaldehyde reacts with aniline to produce an imine, and that the conformation around the C-N bond of the enamine 1 is crucial for the further enantioselective step. The formation of two conformations of the enamine via a proton transfer process was examined, revealing activation barriers for syn- and anti-enamine proton transfer of 10.2 and 17.9 kcal/mol, respectively. The transformation of syn- to anti-enamine through C-N bond rotation, however, was predicted to require only 4.2 kcal/mol, while the (S)- and (R)-intermediates could be obtained from subsequent reactions between enamine and imine with energy barriers of 8.5 and 12.4 kcal/mol, respectively. The difference between these barriers, but not the C-N rotation energy, becomes larger at the MP2 level and when DMSO as a solvent is included. This predicted enantioselective reaction, through the kinetic and thermodynamic favoring of the (S)-pathway, is in agreement with experimental results, which have reported the (S)-configuration as the major product.     

Synthesis, structure, and reactivity of O-donor Ir(III) complexes: C-H activation studies with benzene

Various new thermally air- and water-stable alkyl and aryl analogues of (acac-O,O)2Ir(R)(L), R-Ir-L (acac-O,O = kappa2-O,O-acetylacetonate, -Ir- is the trans-(acac-O,O)2Ir(III) motif, R = CH3, C2H5, Ph, PhCH2CH2, L = Py) have been synthesized using the dinuclear complex [Ir(mu-acac-O,O,C3)-(acac-O,O)(acac-C3)]2, [acac-C-Ir]2, or acac-C-Ir-H2O. The dinuclear Ir (III) complexes, [Ir(mu-acac-O,O,C3)-(acac-O,O)(R)]2 (R = alkyl), show fluxional behavior with a five-coordinate, 16 electron complex by a dissociative pathway. The pyridine adducts, R-Ir-Py, undergo degenerate Py exchange via a dissociative mechanism with activation parameters for Ph-Ir-Py (deltaH++ = 22.8 +/- 0.5 kcal/mol; deltaS++ = 8.4 +/- 1.6 eu; deltaG++298 K) = 20.3 +/- 1.0 kcal/mol) and CH3-Ir-Py (deltaH++ = 19.9 +/- 1.4 kcal/mol; deltaS++ = 4.4 +/- 5.5 eu; deltaG++298 K) = 18.6 +/- 0.5 kcal/mol). The trans complex, Ph-Ir-Py, undergoes quantitatively trans-cis isomerization to generate cis-Ph-Ir-Py on heating. All the R-Ir-Py complexes undergo quantitative, intermolecular CH activation reactions with benzene to generate Ph-Ir-Py and RH. The activation parameters (deltaS++ =11.5 +/- 3.0 eu; deltaH++ = 41.1 +/- 1.1 kcal/mol; deltaG++298 K = 37.7 +/- 1.0 kcal/mol) for CH activation were obtained using CH3-Ir-Py as starting material at a constant ratio of [Py]/[C6D6] = 0.045. Overall the CH activation reaction with R-Ir-Py has been shown to proceed via four key steps: (A) pre-equilibrium loss of pyridine that generates a trans-five-coordinate, square pyramidal intermediate; (B) unimolecular, isomerization of the trans-five-coordinate to generate a cis-five-coordinate intermediate, cis-R-Ir- square; (C) rate-determining coordination of this species to benzene to generate a discrete benzene complex, cis-R-Ir-PhH; and (D) rapid C-H cleavage. Kinetic isotope effects on the CH activation with mixtures of C6H6/C6D6 (KIE = 1) and with 1,3,5-C6H3D3 (KIE approximately 3.2 at 110 degrees C) are consistent with this reaction mechanism.     

Effect of geminal substitution at silicon on 1-sila- and 1,3-disilacyclobutanes' strain energies, their 2+2 cycloreversion enthalpies, and Si=C pi-bond energies in silenes.

To evaluate the effect of geminal substitution at silicon on 1-sila- and 1,3-disilacyclobutanes' strain energies, their 2+2 cycloreversion enthalpies, and Si=C pi-bond energies in silenes, an ab initio MO study of silenes, R2Si=CH2 (1), 1-silacyclobutanes, cyclo-R2Si(CH2)3 (2), and 1,3-disilacyclobutanes, cyclo-(R2SiCH2)2 (3), was performed using the level of theory denoted MP4/TZ(d)//MP2/6-31G(d) (TZ means the 6-311G(d) basis set for elements of the second period and hydrogen, and the McLean-Chandler (12s,9p)/[6s,5p](d) basis set for the third period elements). In the series R = H, CH3, SiH3, CH3O, NH2, Cl, F, the growth of the reaction enthalpies and strain energies is proportional to the substituents' electronegativities. 2+2 cycloreversion of 2 is endothermic by 40.6-63.1 kcal/mol, whereas that of 3 is endothermic by 72.7-114.2 kcal/mol. On going from a silicon to a fluorine substituent at the sp2-hybridized silicon atom, the pi-bond energy in 1 weakens by 11.3 kcal/mol, and the Si=C bond length shortens by 0.053 A. The effect of substituents' electronegativities at the double-bonded silicon atom in silenes is formulated as follows: the higher electronegativity, the shorter and the weaker the Si=C pi-bond. The latter is rationalized in terms of more strained geometry resulting from the energetic cost for planarizing the R2SiC moiety. The enthalpies of the ring-opening reaction are 68.0-80.1 kcal/mol (a cleavage of the Si-C bond in 3), 65.0-76.4 kcal/mol (a cleavage of the Si-C bond in 2), and 58.0-64.9 kcal/mol (a cleavage of the C-C bond in 2). The pronounced difference in the enthalpies of 2+2 cycloreversion of 1-sila- and 1,3-disilacyclobutanes is mainly due to the difference in the enthalpies of diradicals' decomposition. The decomposition of diradicals resulting from a cleavage of C-C and Si-C bonds in 2 is exothermic by 24.3-3.3 kcal/mol (apart from the difluoro derivative which is endothermic by 5.1 kcal/mol) and 27.0-13.3 kcal/mol, respectively. The decomposition of a 1,4-diradical resulting from ring opening of 3, apart from the disilyl derivative, is the endothermic process for which the enthalpy varies from 10.6 to 40.4 kcal/mol.     

Oxidative addition of the fluoromethane C-F bond to Pd. An ab initio benchmark and DFT validation study

We have computed a state-of-the-art benchmark potential energy surface (PES) for two reaction pathways (oxidative insertion, OxIn, and S(N)2) for oxidative addition of the fluoromethane C-F bond to the palladium atom and have used this to evaluate the performance of 26 popular density functionals, covering LDA, GGA, meta-GGA, and hybrid density functionals, for describing these reactions. The ab initio benchmark is obtained by exploring the PES using a hierarchical series of ab initio methods (HF, MP2, CCSD, CCSD(T)) in combination with a hierarchical series of seven Gaussian-type basis sets, up to g polarization. Relativistic effects are taken into account through a full four-component all-electron approach. Our best estimate of kinetic and thermodynamic parameters is -5.3 (-6.1) kcal/mol for the formation of the reactant complex, 27.8 (25.4) kcal/mol for the activation energy for oxidative insertion (OxIn) relative to the separate reactants, 37.5 (31.8) kcal/mol for the activation energy for the alternative S(N)2 pathway, and -6.4 (-7.8) kcal/mol for the reaction energy (zero-point vibrational energy-corrected values in parentheses). Our work highlights the importance of sufficient higher angular momentum polarization functions for correctly describing metal-d-electron correlation. Best overall agreement with our ab initio benchmark is obtained by functionals from all three categories, GGA, meta-GGA, and hybrid DFT, with mean absolute errors of 1.4-2.7 kcal/mol and errors in activation energies ranging from 0.3 to 2.8 kcal/mol. The B3LYP functional compares very well with a slight underestimation of the overall barrier for OxIn by -0.9 kcal/mol. For comparison, the well-known BLYP functional underestimates the overall barrier by -10.1 kcal/mol. The relative performance of these two functionals is inverted with respect to previous findings for the insertion of Pd into the C-H and C-C bonds. However, all major functionals yield correct trends and qualitative features of the PES, in particular, a clear preference for the OxIn over the alternative S(N)2 pathway.     

Jailbreaking benzene dimers

We suggest four new benzene dimers, (C(6)H(6))(2), all featuring one or more cyclohexadiene rings trans-fused to 4- or 6-membered rings. These hypothetical dimers are 50-99 kcal/mol less stable than two benzenes, but have computed activation energies to fragmentation ≥27 kcal/mol. A thorough search of potential escape routes was undertaken, through cyclobutane ring cleavage to 12-annulenes, sigmatropic 1,5-H-shifts, electrocyclic ring-openings of the 6-membered rings, and Diels-Alder dimerizations. Some channels for reaction emerge, but there is a reasonable chance that some of these new benzene dimers can be made.     

Enantioselective lithiation of O-alkyl and O-alk-2-enyl Carbamates in the presence of (-)-sparteine and (-)-alpha-isosparteine. A theoretical study

Quantum chemical DFT calculations at the B3LYP/6-31G(d) level have been used to study the enantioselective lithiation/deprotonation of O-alkyl and O-alk-2-enyl carbamates in the presence of (-)-sparteine and (-)-alpha-isosparteine. Complete geometry optimization of the precomplexes consisting of the carbamate, the chiral ligand, and the base (iPrLi), for the transition states of the proton-transfer reaction, and for the resulting lithio carbamates have been performed in order to quantify activation barriers and reaction energies. For the lithiodeprotonation of ethyl carbamate 12 in the presence of (-)-sparteine (5) the preferred abstraction of the pro-S proton (by 2.75 kcal/mol) gives the (S)-lithio derivate (S)-14, which is in good agreement with experimental observations. (-)-alpha-Isosparteine (6) is predicted to be significantly less selective favoring the abstraction of the pro-R proton by 1.2 kcal/mol. The O-alkenyl carbamate 17 as an example of an allylic carbamate is more easily lithiated than 12. As for 12 (-)-sparteine (5) favors the abstraction of the pro-S proton, although with smaller preference (0.7 kcal/mol). Structural parameters are discussed to rationalize the theoretical results.