Medium-sized cyclophanes.

Abstract

The selective introduction of one or two acetyl groups by direct replacement of tert-butyl groups via the ipso aromatic acetylation of meta-bridged aromatic compounds having two arene rings is described. Acetylation of syn- and anti-di-tert-butyl[n.2]metacyclophanes 3 (n=2,3,4) with acetyl chloride in the presence of TiCl4 gave the ipso-acetylation product at the tert-butyl group. However, only one tert-butyl group is ipso-acetylated under mild reaction conditions in the presence of TiCl4 because of deactivation of the second aromatic ring by the introduced acetyl group. Higher yields of monoacetylated product are obtained from the anti-conformer than the syn-conformer. Therefore, the intra-annular interaction might be much more favorable to stabilize the initial σ-complex intermediate than face-to-face overlap in the case of ipso-acetylation. On the other hand, acetylation of 3 with acetyl chloride in the presence of AlCl3–MeNO2 afforded the two-fold ipso-acetylation product 6 in quantitative yield. Thus, the extent of ipso-acetylation at the tert-butyl groups of 3 was strongly affected by the activity of the acylation catalyst. The presently developed procedure was further applied to the direct removal of a tert-butyl group by electrophilic substitution of tert-butyl-8-methoxy[2.2]MCPs 11, which are prone to give transannular reaction products under electrophilic reaction conditions.