6.10:
SN2 Reaction: Stereochemistry
Recall that an SN2 reaction follows a concerted mechanism, where the nucleophilic attack and the departure of the leaving group occur simultaneously.
High electron density around the leaving group blocks the frontside of the substrate, which forces the nucleophile to initiate a backside attack.
As the HOMO of the nucleophile effectively overlaps with the LUMO of the electrophile, a new bond begins to form, and simultaneously, the bond between the electrophile and the leaving group weakens.
Concurrently, the angle between the substituents and the leaving group reduces from 109.5° to 90°, and the geometry of the carbon atom changes from tetrahedral — in the substrate — to trigonal bipyramidal, in the pentacoordinate transition state.
However, to retain the tetravalency of carbon, the leaving group departs the transition state, and the geometry of carbon becomes tetrahedral once again.
In the product, the substituents on carbon have turned inside out, resulting in an inverted tetrahedron — similar to an umbrella that flips in strong wind. Also, the nucleophile is placed directly opposite to the original position of the leaving group.
In an achiral substrate, due to the plane of symmetry, the configuration of the inverted product is identical to that of the reactant, and therefore, no evident inversion is observed.
On the contrary, a chiral substrate like (R)-2-bromobutane— with an asymmetric alpha-carbon — undergoes an apparent inversion in configuration, also known as Walden inversion, to give (S)-2-butanol with a reversed carbon stereocenter.
Likewise, (S)-2-chloropentane undergoes an SN2 reaction to form (R)-2-pentanol.
In a cyclic molecule, a trans substrate gives a cis product, while a cis substrate generates a trans product.
Thus, SN2 reactions are stereospecific as the product's stereochemical outcome depends on the configuration of the substrate.
6.10:
SN2 Reaction: Stereochemistry
In an SN2 reaction, the nucleophilic attack on the substrate and departure of the leaving group occurs simultaneously through a transition state. As the nucleophile approaches the substrate from the back-side, the configuration of the substrate carbon changes from tetrahedral to trigonal bipyramidal and then back to tetrahedral, leading to an inversion in the configuration of the product.
If the substrate is an achiral molecule at the α-carbon, the inversion of configuration is not observed.
However, if the substrate is a chiral molecule, inversion of configuration is more prominent. When the α-carbon undergoing substitution is chiral, the stereochemistry of the product is reversed. Molecules with R configuration result in products with S stereochemistry and vice-versa. Similarly, an inversion of configuration of the product is observed in case of a cyclic substrate. Substrates in cis form becomes products with a trans form. Thus, SN2 reactions are said to be stereospecific reactions.