Birch Reduction - Regioselectivity

Regioselectivity

The reduction of anisole is one of the simplest examples and is shown in Eqn. 1. Still another example is that of benzoic acid illustrated in Eqn. 2.

Where the radical-anion is protonated initially determines the structure of the product. With an electron donor such as methoxy (MeO), alkyl protonation has been thought by some investigators as being ortho (i.e. adjacent or 1,2) to the substituent. Other investigators have thought the protonation is meta (1,3) to the substituent. Arthur Birch favored meta protonation. With electron withdrawing substituents protonation has been thought to come at the site (ipso) of the substituent or para (1,4). Again, there has been varied opinion. A. J. Birch’s empirical rules say that for the donor substituents the final product has the maximum number of substituents on the final double bonds. For electron withdrawing groups the double bonds of the product have avoided the substituents. The placement preference of groups in the mechanism and in the final product is termed regioselectivity.