Paracyclophanes: Extending the Bridges. Reactions

Abstract

[m.n]Paracyclophanes with bridges of equal and unequal length (m,n ≤ 4) undergo electrophilic aromatic substitution (Friedel–Crafts acylation, bromination) under very mild conditions as long as the bridge contains less than four atoms. Whenever there is a choice, the aromatic ring is attacked at the position closest to the shorter alkano bridge, which indicates that the transannular benzene moiety acts as a neighboring group. By brominating the acetyl derivatives obtained, and the acids and esters derived therefrom, a second substituent is introduced into the pseudo-geminal position, that is, directly opposite the directing group. However, this effect is observed only for those [m.n]phanes in which the length of the neighboring bridge does not exceed three atoms. For the butano-bridged derivatives, the regioselectivity is lost completely. Very similar results were observed for [m.n]paracyclophanes carrying two ester substituents on one benzene ring, the limiting case being the [4.3]paracyclophane derivative. We propose that the stereocontrolling effect of a substituent can only occur when the intra-annular distance is below 4 Å. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)