6.13:
SN1 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.
SN2 reactions are stereospecific since the nucleophile directly attacks the substrate from the backside, which invariably results in an inverted product.
In contrast, SN1 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.
6.13:
SN1 Reaction: Stereochemistry
This lesson provides an in-depth discussion of the stereochemical outcomes in an SN1 reaction.
In the first step of an SN1 reaction, the bond between the electrophilic carbon and the leaving group ionizes to generate the carbocation intermediate. The second step of the mechanism is the nucleophilic attack.
In the formed carbocation, the positively charged carbon is sp2 hybridized with a trigonal planar geometry. As all the three substituents lie on the same plane, a plane of symmetry for the carbocation is formed, making it achiral. Thus, a nucleophile can approach this symmetrical carbocation from either side with equal likelihood and rate.
The frontside attack leads to the retention of configuration, while a backside attack yields to an inversion of configuration in the product. However, in an achiral substrate, with either mode of attack, no difference in the product’s configuration is observed; in a chiral substrate, an optically inactive racemic mixture is expected.
Nevertheless, an enantiomeric excess with a predominantly inverted product is often observed because complete racemization cannot be achieved due to the ionization step. Upon ionization, the ions remain loosely associated, forming an intimate ion pair. During this period, the anion shields the carbocation from the frontside attack until they diffuse apart. Thus, the nucleophile is more prone to attack the unhindered backside resulting in products with an inversion of configuration. Once fully dissociated, both sides of the carbocation are available for substitution, and a racemic mixture of products is obtained. Thus, overall a net excess of inverted product is observed in an SN1 reaction.