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.

Automated summary

Desymmetrization of persubstituted calix[4]arenes can yield distally disubstituted derivatives that are difficult to obtain by other methods. This study demonstrates the usefulness of this method and provides a possible explanation for the unexpected selectivity, using a combination of synthetic and theoretical approaches.