6.17 : E2 Reaction: Stereochemistry and Regiochemistry

Elimination reactions of alkyl halides can give one or more alkenes based on specific regiochemical and stereochemical requirements.

While regiochemistry governs the location of the double bond in the product, stereochemical requirements often influence the geometry.

Consider the E2 elimination of 2-bromo-2-methyl-butane, which has two different beta hydrogens. In the presence of a strong base like sodium ethoxide, it gives two regioisomeric alkenes.

The major product is the more substituted alkene called the Zaitsev product, whereas the less substituted alkene is the Hofmann product, and each product is formed through a different pathway

Each reaction has a transition state showing a partial double bond character. Since the more substituted carbon-carbon double bond has a higher stability, the transition state leading to the Zaitsev product requires less energy and proceeds faster.

Thus, the Zaitsev product is more stable and readily formed.

However, the regiochemical outcome of an E2 elimination reaction can be controlled using a sterically hindered base, like potassium tert-butoxide, to give the less substituted alkene in higher yields.

Stereochemical requirements strongly influence the outcome of E2 reactions. Here, the filled carbon-hydrogen σ bonding orbital and the empty carbon-halogen σ* antibonding orbital, lie in the same plane and overlap to give a π bond.

Both conformations —  one where the hydrogen and halide are anti-coplanar and staggered, and the other where they are syn-coplanar and eclipsed — fulfill the coplanarity requirement to form an alkene.

E2 eliminations preferentially occur via a lower energy anti-coplanar transition state, where the base and the leaving group are farther apart and the two orbitals are fully parallel, allowing for best overlap.

The stereochemistry of E2 reactions depends on the number of β hydrogens. Alkyl halides with two β hydrogens undergo stereoselective elimination, forming the more stable E-alkene as the major product.

However, an alkyl halide with only one beta hydrogen gives a single stereospecific isomer. Depending upon the stereochemistry of the substrate, either E-alkene  or Z-alkene is formed as the product, irrespective of their relative stabilities.