Relationship between Stereochemistry and Mechanism of Substitution

Studies of the stereochemistry are a powerful tool for investigation of nucleophilic substitution reactions. Direct displacement reactions by the Sjv2(lim) mechanism are expected to result in complete inversion of configuration. The stereochemical outcome of the ionization mechanism is less predictable, because it depends on whether reaction occurs via an ion pair intermediate or through a completely dissociated ion. Borderline mechanisms may also show variable stereochemistry, depending upon the lifetime of the intermediates and the extent of ion pair recombination. 

25°C C2H5OH, DTBP, 40° C HCO2H, DTBP, 0°C CF3CH2OH, 

Entry 2 exhibits high, but not complete, inversion for acetolysis, which is attributed to competing racemization of the reactant by ionization and internal return. Entry 3 shows that reaction of a secondary 2-octyl system with the moderately good nucleophile acetate ion occurs with complete inversion. The results cited in Entry 4 serve to illustrate the importance of solvation of ion pair intermediates in reactions of secondary tosylates. The data show that partial racemization occurs in aqueous dioxane but that an added nucleophile (azide ion) results in complete inversion in the products resulting from reaction with both azide ion and water. The alcohol of retained configuration is attributed to an intermediate oxonium ion resulting from reaction of the ion pair 

This selection of stereochemical results points out the relative rarity of the idealized Sjvl(lim) stereochemistry of complete racemization. On the other hand, the predicted inversion of the S 2 mechanism is consistently observed, and inversion also characterizes the ion pair mechanisms with nucleophile participation. Occasionally net retention is observed. The most likely cause of retention is a double-displacement mechanism, such as proposed for Entry 4, or selective front-side solvation, as in Entry 7c. 

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