Medium-sized cyclophanes. Part 62:1 Formylation of anti-[n.2]metacyclophanes — Through-space electronic interactions between two benzene rings

Abstract

Formylation of anti-[n.2]metacyclophanes (1) (n = 2, 3, 4) with dichloromethyl methyl ether in the presence of TiCl4 occurred selectively at para-position to the internal methyl substituents of anti-[n.2]metacyclophanes. Similar reaction of anti-5,13-di-tert-butyl-8,16-dimethyl[2.2]metacyclophane (6a) with dichloromethyl methyl ether in the presence of TiCl4 led to ipso-formylation at the tert-butyl group to give anti-5-tert-butyl-13-formyl-8,16-dimethyl[2.2]-meta cyclophane (7a) as well as the corresponding 2,7-di-tert-butyl-trans-10b,10c-dimethyl-10b,10c-dihydropyrene (10), anti-5-tert-butyl-8,16-dimethyl-13-(3-methyl-1-butene-2-yl)[2.2]metacyclophane (8), and anti-5,13-di-tert-butyl-exo-1-hydroxy-8,16-dimethyl[2.2]metacyclophane (9) depending on the reaction conditions. The higher yield of ipso-formylated product is obtained in the presence of AlCl3 MeNO2 in 80% yield along with anti-5-tert-butyl-8,16-dimethyl-13-(3-methyl-1-butene-2-yl)[2.2]metacyclophane (13). Thus, the yield of ipso-formylation at the tert-butyl group of 6a was strongly affected by the activity of the formylation catalyst. Interestingly, in the formylation of anti-6,14-di-tert-butyl-9,17-dimethyl[3.2]metacyclophane (6b) under the same reaction conditions, syn-6,14-di-tert-butyl-7-formyl-9,17-dimethyl[3.2]metacyclophane (14b) was obtained in 40% yield arising from the anti-syn-ring inversion of the formylation intermediate along with ipso-formylation product 7b in 42% yield. In the formylation of anti-[4.2] meta cyclophane (6c) only the mono-ipso-formylated product 7c was obtained in 92% yield. The formation of a two-fold ipso-formation product, i.e., anti-5,13-diformyl-8,16-dimethyl[2.2]metacyclophane (3a), was not observed under the reaction conditions used. The mechanism of the ipso-formation as well as the formation of the present novel reaction products 8 and 9 is also discussed. Key words: cyclophanes, strained molecules, electrophilic aromatic substitution, ipso-formylation, σ-complex intermediates, through-space electronic interactions.