A Close Look to the Oxaphosphetane Formation along the Wittig Reaction: A [2+2] Cycloaddition?

The Wittig reaction between triphenylphosphine methylide and benzaldehyde has been studied both from conceptual and computational approaches. The supernucleophilic character of ylide accounts for the feasibility of the initial nucleophilic attack. The nature of bonding driving the formation of the first oxaphosphetane (OPA) intermediate in such a domino reaction is examined within a topological-based bonding evolution theory perspective. The sequence of the electronic flow associated to the changes in electron density supports a rationalization via two main electronic stages characterizing the single kinetic step: first, the C-C bond formation, which takes place via donation of electron density of the ylide carbon to the carbonyl carbon of benzaldehyde at a C-C distance of 2.02 Å, is formally associated to the transition state region; then, the P-O bond formation via the donation of electron density of the nonbonding region of the carbonyl oxygen to phosphorus at a P-O distance of 2.06 Å is located at the end of the reaction path. The detailed picture of bonding patterns suggests that the OPA formation in the Wittig mechanism can be better understood in terms of a two-stage one-step mechanism beyond molecular orbital considerations behind the traditionally accepted [2+2] cycloaddition proposal.

Unraveling the kinetics and molecular mechanism of gas phase pyrolysis of cubane to [8]annulene.

The kinetic and electron density flows are studied theoretically for the gas phase pyrolysis of cubane via its cage opening to reach bicyclooctatriene and then thermal rearrangement of bicyclooctatriene to produce [8]annulene which is the experimentally observed major product. The observed kinetic data at the MN15-L/maug-cc-pVTZ level of theory were in good agreement with the experimental results as compared to the CBS-QB3 method. The cage opening and the thermal rearrangement steps at the experimentally employed temperature of 520 K were exergonic and exothermic. The atmospheric rate constants calculated by means of the RRKM theory show that the cage opening is the rate-determining step. The temperature dependence of the rate constant for the cage opening step at the MN15-L level can be expressed as log(k/s-1)1bar MN15-L = (15.63) - (48.99 kcal mol-1)/RT ln 10. The molecular mechanism of the reactions has been investigated by means of the bonding evolution theory (BET) at the B3LYP/6-311G (d,p) level of theory. The cage opening course is described topologically by cleaving of C1-C2, C4-C8, and C5-C6 single bonds and electron saturation of the C1-C4, C2-C6, and C5-C8 bonds, while the rearrangement of bicyclooctatriene is described by C3-C7 bond rupture, depopulation of C1-C4 and C5-C8 double bonds, and electron saturation of C1-C5, C3-C4, and C7-C8 bonds. Electron density rearrangement along the two successive steps are asynchronous and the sequence of catastrophes can be represented as: η-1-13-C†C†FFFC†C†FFFC†C†-2-6-[C]2C†[F]2[C†]2C†-0.

A computational and conceptual DFT study on the mechanism of hydrogen activation by novel frustrated Lewis pairs.

A computational and conceptual density functional theory (DFT) study on the mechanism of molecular hydrogen activation by a set of three frustrated Lewis pairs (FLPs) was performed at the ωB97X-D/6-311G(d,p) level of theory. A reduced model and other two prototypes derived from experimental data, based on the donor nitrogen and acceptor boron atoms, were used. Analysis based on the energy results, geometries and the global electron density transfer at the TSs made it possible to obtain some interesting conclusions: (i) despite the well-known very low reactivity of molecular hydrogen, the catalytic effectiveness of the three FLPs produces reactions with almost unappreciable activation energies; (ii) the reactions, being exothermic, follow a one-step mechanism via polarised TSs; (iii) there are neither substituent effects on the kinetics nor on the thermodynamics of these reactions; (iv) the activation of molecular hydrogen seems to be attained when the N-B distance in the FLP derivatives is around 2.74 Å; and (v) the proposed FLP model is consistent with the behaviour of the experimental prototypes. Finally, the ability of the three FLPs as efficient catalysts was evaluated studying the hydrogenation of acetylene to yield ethylene.

Complementarity of reaction force and electron localization function analyses of asynchronicity in bond formation in Diels-Alder reactions.

We have computationally compared three Diels-Alder cycloadditions involving cyclopentadiene and substituted ethylenes; one of the reactions is synchronous, while the others are slightly or highly asynchronous. Synchronicity and weak asynchronicity are characterized by the reaction force constant κ(ξ) having just a single minimum in the transition region along the intrinsic reaction coordinate ξ, while for high asynchronicity κ(ξ) has a negative maximum with minima on both sides. The electron localization function (ELF) shows that the features of κ(ξ) can be directly related to the formation of the new C-C bonds between the diene and the dienophile. There is thus a striking complementarity between κ(ξ) and ELF; κ(ξ) identifies the key points along ξ and ELF describes what is happening at those points.

Theoretical study on the molecular mechanism of the [5 + 2] vs. [4 + 2] cyclization mediated by Lewis acid in the quinone system.

The thermal and Lewis acid (LA) catalyzed cyclizations of quinone 1 involved in the synthesis of Colombiasin A and Elipsaterosin B have been theoretically studied using DFT methods at the B3LYP/6-311G(d,p) computational level. B3LYP calculations suggest that the formal endo [4 + 2] cycloadduct allowing the synthesis of Colombiasin A is preferentially formed under thermal conditions, while in the presence of the BF3 LA catalyst the formal [5 + 2] cycloadduct is seen, allowing the synthesis of Elipsaterosin B. The BF3 LA catalyst not only accelerates the nucleophilic attack on the C2 carbon of the quinone framework through a more polar C-C bond formation, but also provokes a different electron density rearrangement along the nucleophilic attack favoring the subsequent C-C bond formation at the C4 carbon with the formation of the formal [5 + 2] cycloadduct. ELF bonding analysis along these cyclizations indicates that the C-C single bond formation takes place in the range of 1.91-2.1 Å by C-to-C coupling of two pseudoradical centers. Along the formation of the first C2-C9 single bond, these pseudoradical centers appear at one of the most electrophilic and at one of the most nucleophilic centers of quinone 1, C2 and C9 carbons, respectively. Analysis of the Parr functions suggests that although the most favorable electrophilic/nucleophilic interaction is that involving the C2 carbon of quinone and the C12 carbon of the butadiene framework, the intramolecular nature of the cyclization prevents the corresponding reactive channel.

On the catalytic effect of water in the intramolecular Diels­Alder reaction of quinone systems: a theoretical study.

The mechanism of the intramolecular Diels–Alder (IMDA) reaction of benzoquinone 1, in the absence and in the presence of three water molecules, 1w, has been studied by means of density functional theory (DFT) methods, using the M05-2X and B3LYP functionals for exploration of the potential energy surface (PES). The energy and geometrical results obtained are complemented with a population analysis using the NBO method, and an analysis based on the global, local and group electrophilicity and nucleophilicity indices. Both implicit and explicit solvation emphasize the increase of the polarity of the reaction and the reduction of activation free energies associated with the transition states (TSs) of this IMDA process. These results are reinforced by the analysis of the reactivity indices derived from the conceptual DFT, which show that the increase of the electrophilicity of the quinone framework by the hydrogen-bond formation correctly explains the high polar character of this intramolecular process. Large polarization at the TSs promoted by hydrogen-bonds and implicit solvation by water together with a high electrophilicity-nucleophilicity difference consistently explains the catalytic effects of water molecules.

Quantitative characterization of group electrophilicity and nucleophilicity for intramolecular Diels-Alder reactions.

In a previous work (L. R. Domingo, M. J. Aurell, P. Perez and R. Contreras, Tetrahedron 2002, 58, 4417) we proposed that the difference in global electrophilicity index be taken as a measure of the polarity at the transition state in intermolecular Diels-Alder reactions. We herein extend this model to deal with intramolecular Diels-Alder (IMDA) processes. The transferability of the empirical reactivity rules established for the intermolecular DA reactions to the IMDA reactions is discussed. The analysis based on group electrophilicity and nucleophilicity in general fails because having two different reactivity patterns within the same molecule hampers a clean classification of electrophilicity and nucleophilicity of the interacting fragments. We introduce dual philicity indexes E1 and E2 that solve this problem by separating a series of 30 IMDA reactions into two families, namely the diene to dienophile electron flow (DDpF) and the dienophile to diene electron flow (DpDF) processes. The new indexes correctly describe the charge transfer at the transition state and the reaction mechanism expected for the title reactions.