Walden-inversion transition state

Validating DFT Methods for Transition States the Walden Inversion... 

Unlike the dankd Sal and 8 2 mechanism of nucleophilic substitution, these processes both involve Walden inversion at the reaction cite. It appears, moreover, that both are bimoleoular as well, although some conflict exists in the literature on this particular puint.ioz , ic4b. uoi, uis. uii. W73 Where they do differ, however, is in relative proportions of bond forming and bond breaking in the transition states involved. The latter may be depicted as shown in Eq. (B04) for the general case, where X - is a nucleophilic anion but could equally well be replaced by some neutral species X. 

The isonitrile originally bound in the complex is expelled on the other side and a Walden inversion occurs at the asymmetric Mo atom28 29 Complex 13b, with the opposite configuration to 13a at the Mo atom, may react again with free isonitrile via a similar S 2 transition state. A series of such inversion steps ultimately leads to the epimerization which results in the observed decrease in optical rotation on addition of free a-phenyl ethyl isonitrile to solution of 13a or 13b 28 29 ... 

So effective was the collinear three-center transition state in clarifying the Walden inversion problem, that concerted backside attacks were proposed or considered for the Beckman rearrangement, isomerization of alkenes, etc. (Olson, 1933 Marvel, 1943), as well as substitution in alkenes (Gold, 1951 Ross et al., 1952). Since an appropriate arrangement of hybrid orbitals is available, some of the transition states did not... 

The results of our simulation are summarized in Figure 4-19. The detailed discussion was presented in the original article.33 Here we will only discuss some major points. The reaction mechanism involves Walden inversion of chloromethane, with the planar CH3 group in the symmetrical transition state geometry. The IRP involves linear movement of the carbon and two chlorine atoms, accompanied by bending the C-H bonds toward tetrahedrical orientation. 

Alhambra C, Wu L, Zhang ZY, Gao JL (1998) Walden-inversion-enforced transition-state stabilization in a protein tyrosine phosphatase, J Am Chem Soc, 120 3858—3866... 

The kinetic evidence is a necessary but not a sufficient condition we will meet other mechanisms that are also consistent with these data. Much more convincing evidence is obtained from the fact that the mechanism predicts inversion of configuration when substitution occurs at a chiral carbon and this has been observed many times. This inversion of configuration (see p. 158) that proceeds through transition state 1 is called the Walden inversion and was observed long before the Sn2 mechanism was formulated by Hughes and Ingold. ... 

When substitution occurs by an Sn2 mechanism, the nucleophile directly attacks the substrate, with the angle of approach being 180" to the C-L bond. This is called "backside attack," and the reaction proceeds with inversion of stereochemistry, the so-called "Walden inversion." The C-L bond is being broken concurrently with the formation of the C-Nu bond, so both the substrate, R-L, and the nucleophile are involved in the transition state of the rate-determining step. Reactions in which two reactants are involved in the transition state of the rate-determining step are termed bimolecular, and the rate of such processes depends on the concentration of the substrate and the nucleophile, as shown in Equation 14.5, where k2 is the second-order rate constant. 

Brook addressed this important mechanistic issue early, developing evidence for retention of configuration at silicon in the rearrangement. Based on the precedented assumption of inversion at asymmetric silicon in chloride displacement with either an organolithium or an alcohol, Brook and coworkers showed a stereochemical Walden cycle that implicated retention at silicon in the rearrangement step. Mechanistically, retention at silicon corresponds to a frontside-type displacement, consistent with the mechanism shown above. The displacement might implicate 10 as a pentacoordinate silicon intermediate rather than a transition state. 

The reactions Sn2 are accompanied by the inversion of configuration of the tetrahedral carbon atom—Walden inversion, discovered as early as 1895 [13]. This result constituted the basis for the firmly established view regarding the concerted reaction mechanism whose important features are the rear-side approach of the nucleophile Y to the breaking bond C—X and the emergence of a trigonal-bipyramidal transition state structure II in Eq. (5.2) ... 

The central barrier in the double-minimum potential energy profile, a Walden-inversion transition state, may lie above or below the initial energy of the reactants. The rate coefficients for 5 2 reactions show a slight negative temperature dependence. 

The abstraction process proceeds by homolysis and is kinetically of the first-order (SNl-like). It involves two steps formation of new radicals, via the homolytic cleavage of the nonpolar, perfectly covalent bond in H2, in absence of any electrophile or nucleophile to initiate the heterolytic pattern, and the subsequent recombination of a new radical with another radical species. The hydride exchange is an example of the kinetically second-order, the first-order in both the incoming (nucleophile) and leaving (nucleofuge) hydride groups. It proceeds via the familiar Walden-inversion Transition State (TS) in a single, concerted reaction. 

A natural consequence of an antarafacial interaction on the Z component is inversion at the migrating centre, modes (c) and (d). For a carbon atom this is synonymous with a Walden inversion, and therefore such migration must, at the transition state, involve the use of a p-type orbital by the carbon atom concerned. The inversion at the migrating carbon atom can usually only be detected from the stereochemical nature of the product if the migrating centre is chiral. Since divalent or trivalent atoms usually can not support chirahty, it is impossible to detect antarafacial interactions in oxygen or nitrogen atom migrations. 

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