Markovnikov's Rule - Anti-Markovnikov Reactions

Anti-Markovnikov Reactions

Mechanisms that avoid the carbocation intermediate may react through other mechanisms that are regioselective, against what Markovnikov's rule predicts, such as free radical addition. Such reactions are said to be anti-Markovnikov, since the halogen adds to the less substituted carbon, exactly the opposite of Markovnikov reaction. Again, like the positive charge, the radical is most stable when in the more substituted position.

Anti-Markovnikov behaviour extends to other chemical reactions than just additions to alkenes. One anti-Markovnikov manifestation is observed in hydration of phenylacetylene that, gold-catalyzed, gives regular acetophenone but with a special ruthenium catalyst the other regioisomer 2-phenylacetaldehyde:

Anti-Markovnikov behaviour can also manifest itself in certain rearrangement reactions. In a titanium(IV) chloride-catalyzed formal nucleophilic substitution at enantiopure 1 in the scheme below, two racemic products are formed - 2a and 2b:

This product distribution can be rationalized by assuming that loss of the hydroxy group in 1 gives the tertiary carbocation A, which rearranges to the seemingly less attractive secondary carbocation B. Chlorine can approach this center from two faces leading to the observed mixture of isomers.

Another famous example of anti-Markovnikov addition is hydroboration.