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 ste ps from p-tert-butylanisole in 25% overall yield by using the TosMIC m ethod, followed by Wolff-Kishner reduction and demethylation with boro n tribromide. AlCl3/MeNO(2)-catalyzed trans-tert-butylation of 13 in b enzene gave the desired metacyclophane 14 in 85% yield, along with ter t-butylbenzene (15). Weak intramolecular hydrogen bonding was observed in the triols 13 and 14. - 6,15,24-Tritert-butyl-9,18,27-trihydroxy[3 .3.3]MCP 13 was tri-O-alkylated with alkyl halides (RX: R = Et, Pr, an d Bu) in the presence of Cs2CO3 to yield partial-cone confomer 12b-d i n quantitative yield. Ring inversion by oxygen-through-the-annulus rot ation is allowed for triethoxy derivative 12b (coalescence temperature ca. 90 degrees C) but inhibited for the tripropoxy-12c and the tribut oxy derivative 12d. The reaction of the triol 13 with ethyl bromoaceta te in the presence of Cs2CO3 yielded cone and partial-cone 12e, respec tively. In contrast, a significant amount of cone conformer 12f result ed when NaH was used as base. Only when the template metal can hold th e ester or amide group(s) and the oxide group(s) on the same side of t he [3.3.3]MCP is the conformation immobilized to the cone. - Titration of cone amide cone-12f with KSCN monitored by H-1 NMR clearly demonst rates that a 1:1 complex is formed which is stable on the NMR time sca le, and the original C-3 symmetry is retained after the complete metal cation complexation. - The stability of multimembered carbon skeleton s permits the interconversion of functional groups without special reg ard to ring-opening side reactions as was observed for homotrioxacalix [3]arenes with ethereal Linkages. For example, the introduction of nit ro groups was accomplished on the upper rim by direct three-fold ipso- nitration of tert-butyltrimethoxy derivative 12a.