Synthesis and conformational studies of calixarene‐analogous trihydroxy[3.3.3]metacyclophanes and their O ‐alkylated derivatives

Tri‐ tert ‐butyltrihydroxy[3.3.3]metacyclophane 13 was prepared in 6 steps from p‐tert ‐butylanisole in 25% overall yield by using the TosMIC method, followed by Wolff‐Kishner reduction and demethylation with boron tribromide. AlCl 3 /MeNO 2 ‐catalyzed trans‐ tert ‐butylation of 13 in benzene gave the desired metacyclophane 14 in 85% yield, along with tert ‐butylbenzene ( 15 ). Weak intramolecular hydrogen bonding was observed in the triols 13 and 14 .–6,15,24‐Tri‐ tert ‐butyl‐9,18,27‐trihydroxy[3.3.3]MCP 13 was tri‐ O ‐alkylated with alkyl halides (RX: R = Et, Pr, and Bu) in the presence of Cs 2 CO 3 to yield partial‐cone confomer 12b‐d in quantitative yield. Ring inversion by oxygen‐through‐the‐annulus rotation is allowed for triethoxy derivative 12b (coalescence temperature ca. 90°C) but inhibited for the tripropoxy‐ 12c and the tributoxy derivative 12d . The reaction of the triol 13 with ethyl bromoacetate in the presence of Cs 2 CO 3 yielded cone and partial‐cone 12e , respectively. In contrast, a significant amount of cone conformer 12f resulted when NaH was used as base. Only when the template metal can hold the ester or amide group(s) and the oxide group(s) on the same side of the [3.3.3]MCP is the conformation immobilized to the cone.–Titration of cone amide cone ‐ 12f with KSCN monitored by 1 H NMR clearly demonstrates that a 1:1 complex is formed which is stable on the NMR time scale, and the original C 3 symmetry is retained after the complete metal cation complexation.–The stability of multimembered carbon skeletons permits the interconversion of functional groups without special regard to ring‐opening side reactions as was observed for homotrioxacalix[3]arenes with ethereal linkages. For example, the introduction of nitro groups was accomplished on the upper rim by direct threefold ipso ‐nitration of tert ‐butyltrimethoxy derivative 12a .