Extended transition state approach

The observed high anti selectivity may reflect the acyclic extended transition-state mechanism postulated in the fluoride-catalyzed reactions (Figure 9.1) [27]. Judging from the product configuration, chiral ammonium cation should effectively cover the si- face of the nitronate and the selective approach of aldehyde from the re-face should result. 

The posibility of extending MD to slower diffusion processes has been discussed (98). But applying such algorithms has a tradeoff on the overall quality of the computational approach. To perform calculations at time scales beyond those accessible to MD is possible nowadays only by using the transition state approach (TSA) proposed in (97,115,132). This method will be presented briefly below. 

The mechanistic reinterpretation of the data that had been considered to support an 8 1 mechanism developed from a generalized interpretation of how minimal-energy reaction pathways are determined. Jencks (1985) has demonstrated the importance of mechanisms involving borderline transition states, where the borderline divides concerted and stepwise mechanisms. These occur where necessary intermediates may be too unstable to exist. In terms of the three-dimensional energy diagram, these mechanisms involve reaction paths that approach the corner occupied by the intermediate but do not reach to the corner. Herschlag and Jencks (1986) analyse the kinetic evidence that has been presented in support of a metaphosphate intermediate in a variety of reactions in solution. They conclude that none establishes the existence of metaphosphate ion as an intermediate but that all are expectedly consistent with an unsymmetrically extended transition state in a concerted mechanism (2). 

The interacting fragment orbital analysis can be put on more quantitative terms by performing explicit energy decomposition analysis of FIF or DFT wave functions. The extended transition state (ETS) approach decomposes the energy change into four... 

Cieplak stated that the lone pair back-donation of C5 substituent also stabilizes the transition state during the syn approach since it improves hyperconjugation of the C5-H bond (extended hyperconjugation). He pointed out that for the cyclopen-tadienes having C5 substituents such as hydroxy, methoxy, amino, and chloro moiety, the hyperconjugative stabilization and the back-donation work in the same direction (Scheme 27). 

Smooth COSMO solvation model. We have recently extended our smooth COSMO solvation model with analytical gradients [71] to work with semiempirical QM and QM/MM methods within the CHARMM and MNDO programs [72, 73], The method is a considerably more stable implementation of the conventional COSMO method for geometry optimizations, transition state searches and potential energy surfaces [72], The method was applied to study dissociative phosphoryl transfer reactions [40], and native and thio-substituted transphosphorylation reactions [73] and compared with density-functional and hybrid QM/MM calculation results. The smooth COSMO method can be formulated as a linear-scaling Green s function approach [72] and was applied to ascertain the contribution of phosphate-phosphate repulsions in linear and bent-form DNA models based on the crystallographic structure of a full turn of DNA in a nucleosome core particle [74],... 

Reactions in solution proceed in a similar manner, by elementary steps, to those in the gas phase. Many of the concepts, such as reaction coordinates and energy barriers, are the same. The two theories for elementary reactions have also been extended to liquid-phase reactions. The TST naturally extends to the liquid phase, since the transition state is treated as a thermodynamic entity. Features not present in gas-phase reactions, such as solvent effects and activity coefficients of ionic species in polar media, are treated as for stable species. Molecules in a liquid are in an almost constant state of collision so that the collision-based rate theories require modification to be used quantitatively. The energy distributions in the jostling motion in a liquid are similar to those in gas-phase collisions, but any reaction trajectory is modified by interaction with neighboring molecules. Furthermore, the frequency with which reaction partners approach each other is governed by diffusion rather than by random collisions, and, once together, multiple encounters between a reactant pair occur in this molecular traffic jam. This can modify the rate constants for individual reaction steps significantly. Thus, several aspects of reaction in a condensed phase differ from those in the gas phase ... 

It seems that the repulsive steric interactions play a more dominant role in regioselectivity of aryne reactions than is sometimes realized. In fact, it has been argued that in nucleophilic addition to arynes, the transition state is reached early, while the incipient bond is still very much extended. Consequently, steric effects were considered not to be of great importance.80 81 It should, however, be noted that the dehydro bond orbitals are so oriented that the optimal approach trajectory for the nucleophile lies in the... 

Let us consider first the in vacuo cases. Dynamical aspects of the reaction in vacuo may be recovered by resorting to calculations of semiclassical trajectories. A cluster of independent representative points, with accurately selected classical initial conditions, are allowed to perform trajectories according to classical mechanics. The reaction path, which is a static semiclassical concept (the best path for a representative point with infinitely slow motion), is replaced by descriptions of the density of trajectories. A widely employed approach to obtain dynamical information (reaction rate coefficients) is based on modern versions of the Transition State Theory (TST) whose original formulation dates back to 1935. Much work has been done to extend and refine the original TST. 

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