Stereochemistry of the SN2 Reaction

Stereochemistry of the S_N2 Reaction

– As we have seen, the reaction S_N2 requires attack by a nucleophile on the back side of an electrophilic carbon atom (see Figure)

– A carbon atom can have only four filled bonding orbitals (an octet), so the leaving group must leave as the nucleophile bonds to the carbon atom.

– The nucleophile’s electrons insert into the back lobe of carbon’s sp³ hybrid orbital in its antibonding combination with the orbital of the leaving group (because the bonding MO is already filled).

– These electrons in the antibonding MO help to weaken C-Br the bond as bromide leaves.

– The transition state shows partial bonding to both the nucleophile and the leaving group.

– Back-side attack literally turns the tetrahedron of the carbon atom inside out, like an umbrella caught by the wind (the previous Figure).

– In the product, the nucleophile assumes a stereochemical position opposite the position the leaving group originally occupied.

– We call this result an inversion of configuration at the carbon atom.

MECHANISM: Inversion of Configuration in the SN2 Reaction

Back-side attack inverts the configuration of the carbon atom

– In the case of an asymmetric carbon atom, back-side attack gives the opposite configuration of the carbon atom.

– The S_N2 displacement is the most common example of a Walden inversion, a step (in a reaction sequence) where an asymmetric carbon atom undergoes inversion of configuration.

– In the 1890s, Paul Walden, of the University of T bingen (Germany), was one of the first to study reactions giving inversion of configuration.

– In some cases, inversion of configuration is readily apparent.

– For example, when cis-1-bromo-3 methylcyclopentane undergoes S_N2 displacement by hydroxide ion, inversion of configuration gives trans-3-methylcyclopentanol.

– The S_N2 displacement is a good example of a stereospecific reaction: one in which different stereoisomers react to give different stereoisomers of the product.

– To study the mechanism of a nucleophilic substitution, we often look at the product to see if the reaction is stereospecific, with inversion of configuration.

– If it is, the mechanism is a good possibility, especially if the reaction kinetics are second order.

– In many cases (no asymmetric carbon or ring, for example), it is impossible to determine whether inversion has occurred.

– In these cases, we use kinetics and other evidence to help determine the reaction mechanism.