Oxymercuration Reaction - Regioselectivity and Stereochemistry

Regioselectivity and Stereochemistry

Oxymercuration is very regioselective and is a textbook Markovnikov reaction; ruling out extreme cases, the water nucleophile will always preferentially attack the more substituted carbon, depositing the resultant hydroxy group there. This phenomenon is explained by examining the three resonance structures of the mercurinium ion formed at the end of the step one.

By inspection of these structures, it is seen that the positive charge of the mercury atom will sometimes reside on the more substituted carbon (approximately 4% of the time). This forms a temporary tertiary carbocation, which is a very reactive electrophile. The nucleophile will attack the mercurinium ion at this time. Therefore, the nucleophile attacks the more substituted carbon because it retains more positive character than the lesser substituted carbon.

Stereochemically, oxymercuration is an anti addition. As illustrated by the second step, the nucleophile cannot attack the carbon from the same face as the mercury ion because of steric hindrance. There is simply insufficient room on that face of the molecule to accommodate both a mercury ion and the attacking nucleophile. Therefore, when free rotation is impossible, the hydroxy and acetoxymercuri groups will always be trans to each other.

Shown below is an example of regioselectivity and stereospecificity of the oxymercuration reaction with substituted cyclohexenes. A bulky group like t-butyl locks the ring in a chair conformation and prevents ring flips. With 4-t-butylcyclohexene, oxymercuration yields two products - where addition across the double bond is always anti - with slight preference towards acetoxymercury group trans to the t-butyl group, resulting in slightly more cis product. With 1-methyl-4-t-butylcyclohexene, oxymercuration yields only one product - still anti addition across the double bond - where water only attacks the more substituted carbon. The reason for anti addition across the double bond is to maximize orbital overlap of the lone pair of water and the empty orbital of the mercurinium ion on the opposite side of the acetoxymercury group. Regioselectivity is observed to favor water attacking the more substituted carbon, but water does not add syn across the double bond which implies that the transition state favors water attacking from the opposite side of the acetomercury group.