The first regioselective double electrophilic substitution of the C2-symmetric pseudo-meta-disubstituted [2.2]paracyclophanes

We report here the first examples of the regioselective double electrophilic substitution of chiral C2-symmetric pseudo-meta-disubstituted [2.2]paracyclophanes. Thus, the double acylation of 4,15-dihydroxy[2.2]paracyclophane occurs ortho-regioselectively, whereas the double acylation of its respective dimethyl ether is completely para-regioselective. Double bromination of 4,15-dicarbomethoxy[2.2]paracyclophane regioselectively generates the pseudo-gem-substitution pattern. The approaches elaborated allow the synthesis of all three possible types of chiral bis-bifunctional compounds, which have two independent, although chemically and stereochemically equal, functional fragments with pseudo-meta mutual orientation of both pairs of identical substituents.

Ortho-, para-, and pseudo-gem-regioselective double electrophilic substitution of pseudo-meta-disubstituted [2.2]paracyclophanes gave rise to three possible types of chiral C2-symmetric bis-bifunctional derivatives.