Transition states synchronous/asynchronous

Nitrones are a rather polarized 1,3-dipoles so that the transition structure of their cydoaddition reactions to alkenes activated by an electron-withdrawing substituent would involve some asynchronous nature with respect to the newly forming bonds, especially so in the Lewis acid-catalyzed reactions. Therefore, the transition structures for the catalyzed nitrone cydoaddition reactions were estimated on the basis of ab-initio calculations using the 3-21G basis set. A model reaction indudes the interaction between CH2=NH(0) and acrolein in the presence or absence of BH3 as an acid catalyst (Scheme 7.30). Both the catalyzed and uncatalyzed reactions have only one transition state in each case, indicating that the reactions are both concerted. However, the synchronous nature between the newly forming 01-C5 and C3-C4 bonds in the transition structure TS-J of the catalyzed reaction is rather different from that in the uncatalyzed reaction TS-K. For example, the bond lengths and bond orders in the uncatalyzed reaction are 1.93 A and 0.37 for the 01-C5 bond and 2.47 A and 0.19 for the C3-C4 bond, while those in... 

The mechanism of the carbo-Diels-Alder reaction has been a subject of controversy with respect to synchronicity or asynchronicity. With acrolein as the dieno-phile complexed to a Lewis acid, one would not expect a synchronous reaction. The C1-C6 and C4—C5 bond lengths in the NC-transition-state structure for the BF3-catalyzed reaction of acrolein with butadiene are calculated to be 2.96 A and 1.932 A, respectively [6]. The asynchronicity of the BF3-catalyzed carbo-Diels-Alder reaction is also apparent from the pyramidalization of the reacting centers C4 and C5 of NC (the short C-C bond) is pyramidalized by 11°, while Cl and C6 (the long C-C bond) are nearly planar. The lowest energy transition-state structure (NC) has the most pronounced asynchronicity, while the highest energy transition-state structure (XT) is more synchronous. 

Equation 1.7). A concerted synchronous transition state [15] (the formation of new bonds occurs simultaneously) and a concerted asynchronous transition state [16] (the formation of one reaction depends on the nature of the reagents and the experimental conditions [17]. 

Beno, B. R., Houk, K. N., Singleton, D. A., 1996, Synchronous or Asynchronous An Experimental Transition State from a Direct Comparison of Experimental and Theoretical Kinetic Isotope Effects for a Diels-Alder Reaction , J. Am. Chem. Soc., 118, 9984. 

TWo of the monoclonal antibodies produced, 7D4 and 22C8, proved to be completely stereoselective, separately catalysing the endo and the exo Diels-Alder reactions, with a fccat of 3.44 X 10-3 and 3.17 X 10 3 min-1 respectively at 25°C. That the turnover numbers are low was attributed in part to limitations in transition state representation modelling studies had shown that the transition states for both the exo and endo processes were asynchronous whereas both TSAs [61] and [62] were based on synchronous transition states (Gouverneur et al., 1993). 

Hartree-Fock calculations, 48-50 rate factors, 58-65 synchronous/asynchronous transition states, 50-8... 

In order to test this hypothesis, calculations were carried out by various techniques for various models of asynchronous (biradicaloid) and synchronous transition states. The results of these calculations are shown in Figs. 2 and 3s. For the Diels-Alder reaction, the procedure consisted of optimizing the butadiene-ethylene coordinates by MINDO/3 for certain fixed values of r i i and t 2 (Pig- 2). The resulting geometries were than used as input for calculations by the other techniques. For fulminic acid-ethylene, the Poppinger transition state was chosen as the mid-point, and rcc and rco were varied, while the fulminic acid and acetylene fragments were held fixed. Operationally, this variation was carried out by a variation in a (Fig. 3). 

All of the ab initio calcnlations that include electron correlation to some extent clearly favor the concerted pathway for Reaction 4.1. All of these computations also identified a transition state with Q symmetry, indicating perfectly synchronons bond formation. One method for distinguishing a synchronous from an asynchronous transition state is by secondary kinetic isotope effects (KIEs). Isotopic snbstitution alters the frequencies for all vibrations in which that isotope is involved. This leads to a different vibrational partition function for each isotopicaUy labeled species. Bigeleisen and Mayer determined the ratio of partition functions for isotopicaUy labeled species. Incorporating this into the Eyring transition state theory results in the ratio of rates for the isotopicaUy labeled species (Eq. (d. ))." Computation of the vibrational frequencies is thus... 

More interesting would be Diels-Alder cycloadditions between reactants that could potentially conserve Q symmetry, and thereby pass through a synchronous transition state, bnt rather prefer an asynchronous route. Somewhat remarkably, there are examples of such cases. The transition state (13) for the cyclization of... 

Two mechanistic variations can be envisioned to be operative in some Wittig reactions. In some cases (Z-stereoselective reactions) a very asynchronous reaction with a 2-center "anti" pseudo betaine transition state is involved. The other mechanism involves a more synchronous concerted reaction with a 4-center "syn" transition state. These two mechanisms may compete, e.g., in the reactions of semistabilized ylides with aldehydes where mixtures of Z- and E-alkenes are obtained. Further details of these studies will be provided in future publications, as well as additional data about solvent effects. 

Stepwise PT and ET reactions occur along the edges of Fig. 17.1, while PCET includes the entire space within the square. The stepwise and PCET mechanisms (including HAT) are clearly distinct. The PCET mechanism is defined by a single transition state in which the proton and electron both transfer in one step, with no intermediate states populated along the reaction coordinate PCET is thus concerted but the electron and proton events can be asynchronous as opposed to their synchronous transfer for a HAT reaction. In a stepwise mechanism, an intermediate is formed and there are two distinct rate constants for the forward reaction and two separate transition states. Stepwise ET/PT or PT/ET can, in principle, be broken down and treated experimentally and theoretically as separate ET and PT events. Like any series of reactions, the rate-limiting rule applies. 

Clearly 6 valence orbitals and 6 electrons are required to represent the MC-SCF or VB wavefunction in the region of the synchronous or asynchronous transition state. 

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