Medium-sized cyclophanes. Part 61.ipso-Acylation of tert-butyl[n.2]metacyclophanes: through-space electronic interactions between two benzene rings

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.