6.13 : S_N1 Reaction: Stereochemistry

In nucleophilic substitution reactions, the stereochemical outcome of the product, that is,­ inversion or retention of configuration, can be studied if substitution occurs in a chiral substrate.

S_N2 reactions are stereospecific since the nucleophile directly attacks the substrate from the backside, which invariably results in an inverted product.

In contrast, S_N1 reactions are not stereospecific. This is because the substrate first ionizes to generate an sp² hybridized carbocation intermediate with the three substituents lying in the same plane.

The nucleophile then approaches the carbocation from either side with equal likelihood. While an attack from the frontside leads to the retention of configuration in the product, a backside attack results in an inversion of configuration.

When an achiral substrate is used, irrespective of the mode of nucleophilic attack, the product’s configuration stays the same.

When the substrate is chiral, complete racemization is expected, leading to a racemate of the product’s enantiomers. However, more commonly, only partial racemization occurs, generating an enantiomeric excess of the inverted product.

A plausible explanation for this lies in the ionization step of the substrate, wherein the carbocation and the leaving group remain loosely associated, forming an intimate ion pair for about ten nanoseconds before they diffuse away. 

During this association, the leaving group partially shields the carbocation from the frontside attack. Thus, the nucleophile attacks the carbon center from the unhindered backside, resulting in an inverted product.

After the ion pair fully dissociates, the carbocation undergoes substitutions at both ends with an equal probability to yield a racemic product. Since both inversion and racemization occur during the substitution process, a net excess of the inverted product is obtained.