SYNTHESIS AND CONFORMATIONAL STUDIES OF REGIO-ISOMERS AND CONFORMATIONAL ISOMERS DERIVED BY O-ALKYLATION OF TETRAHYDROXY[3.1.3.1]METACYCLOPHANE

The Synthesis and structure of O-alkylated tetrahydroxy[3.1.3.1]metacy clophanes are described, tyl-9,16,25,32-tetrahydroxy[3.1.3.1]metacyclo phane 3 was tetra-O-alkylated with alkyl bromides (RBr: R = Pt, Pr and Bu) in the presence of Cs2CO3 to yield-one pure stereoisomer in each case (ie. the 1,4-alternate conformer) 5b-d as a major product; other possible isomers were not observed, Ring inversion by oxygen-through-t he-annulus rotation is allowed;for tetraethoxy and tetrapropoxy deriva tives 5b,c (for 5c; coalescence temperature ca. 90 degrees C) but inhi bited for the tetrabutoxy derivative 5d. In contrast, alkyl halides ha ving larger alkyl groups than ethyl afforded poor yields of the corres ponding tetra-O-alkylated compounds 5 although a significant amount of 1,3-di-O-substitution products 4 resulted when NaH was used as a base , On the other hand, the tetraol 3 was tetra-O-alkylated with benzyl b romide in the presence of NaH to yield exclusively the cone conformer cone-5f in quantitative yield, Only when the cation-a interactions bet ween the alkali-metal cations and the pi-electrons of the benzyl group (s) are able to hold the latter and the oxide group(s) on the same sid e of the [3.1.3.1]MCP is the conformation immobilized to the cone, The template effect of the sodium cation plays an important role in this benzylation, The H-1 NMR spectral behaviour of these macrocyclic metac yclophanes is also discussed.