Stereochemistry bimolecular nucleophilic

Walden inversion was the term given to the change in stereochemistry observed in bimolecular nucleophilic substitutions. For example, reaction of (2S)-2-triflyloxyesters with sodium azide gives (2R )-2-a/,idocstcrs. 

There is good evidence for the existence of the 4-oxo intermediate and this means that the reversal of configuration does not arise from a bimolecular nucleophilic substitution (or Sn2 reaction), but from a unimolecular (Snl) reaction forming a carbonium ion. Hence the stereochemistry must reflect... 

Consider the two Felkin transition states 10 and 11. Obviously, if perpendicular attack is assumed, the intermolecular steric and torsional interactions between the nucleophile and the substrate are identical, all distances (Nu-0, Nu-R, Nu-S, Nu-M) being the same in 10 and 11. The discrimination can come only from intramolecular interactions in the substrate, which is rather surprising for a bimolecular reaction. In their original paper Felkin and his coworkers postulated that the interactions of substituents M and S are stronger with R than with 0. It is not clear why this should be so, as the predominance of R over O must hold even for R = H. Nevertheless, this hypothesis allows the correct prediction of the stereochemistry, agrees well with the observation that selectivity increases with the bulkiness of R, and for these reasons, has not been questioned. 

The most synthetically useful nucleophilic substitution reaction is the bimolecular Sn2 reaction, shown in the section 2.7.A. A unimolecular substitution (ionization followed by substitution) is less useful in synthesis in a general sense, but is often the best specific reaction to effect a particular functional group exchange. In Chapter 12 we will see many examples where cationic reactions are very useful. Unimolecular substitution also occurs as a side reaction in aqueous media and can influence both the yield, stereochemistry, and regiochemistry of the final product. 

The importance of nonbonded interactions in chemical systems is illustrated by the stereochemistry of the abnormal bimolecular substitution reaction (Sf 2 ). It has been suggested that the nucleophile attacks the same side from which the leaving group departs However, the mechanism of the reaction is still unclear ... 

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. 

Nucleophilic bimolecular ring-opening of ethylene oxide by the hydride anion has been investigated theoretically. Molecular orbital calculations of the interaction energy (a combination of coulomb, exchange, delocalization, and polarization interaction terms) were carried out. The kinetics and stereochemistry of base-catalysed polymerization of epoxides have been studied using optically active epoxide monomers. 

In Summary The reaction of chloromethane with hydroxide to give methanol and chloride, as well as the related transformations of a variety of nucleophiles with haloalkanes, are examples of the bimolecular process known as the 8 2 reaction. Two single-step mechanisms— frontside attack and backside attack—may be envisioned for the reaction. Both are concerted processes, consistent with the second-order kinetics obtained experimentally. Can we distinguish between the two To answer this question, we return to a topic that we have considered in detail stereochemistry. 

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