T. Yamato et al., SYNTHESIS AND CONFORMATIONAL STUDIES OF CALIXARENE-ANALOGOUS TRIHYDROXY[3.3.3]METACYCLOPHANES AND THEIR O-ALKYLATED DERIVATIVES, Liebigs Annalen, (7), 1995, pp. 1259-1267
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.