Regioselective Lithiation of Tetrabromocalix[4]arenes: A Simple Way for the Desymmetrization of the Macrocyclic Skeleton.

Desymmetrization of persubstituted calix[4]arenes represents an interesting way to yield distally disubstituted derivatives. The reaction of tetrabrominated calixarenes in three different conformations ( cone , partial cone , and 1,3-alternate ) with an excess of n -BuLi surprisingly leads with high selectivity to distally dilithiated derivatives that, by reaction with electrophiles, give substitution patterns which are difficult to obtain by other ways. Using a combination of synthetic and theoretical approaches (DFT), we tried to demonstrate the usefulness of this method and provide a possible explanation for this unexpected selectivity.