Conformational Restriction of the Calix[6]arene Macrocycle by the Ritter Reaction

Herein we report on the development of a novel and efficient approach to the restriction of the conformational mobility of calix[6]arenes. The method involves the addition of tertiary alcohols to calix[6]arenes with one, three and six cyanomethoxy groups attached to the lower rim under modified Ritter reaction conditions. Alkylation of monocyanomethoxy‐ p‐tert ‐butylcalix[6]arene ( 1 ) and 37,39,41‐trimethoxy‐38,40,42‐tricyanomethoxy‐ p‐tert ‐butylcalix[6]arene ( 2 ) with 3‐R‐1‐adamantanols (R = H, CH 2 COOH) in trifluoroacetic acid afforded the corresponding mono‐ and triamides with cone‐like conformations. The partial alkylation of hexanitrile derivatives showed unexpected regioselectivity. Addition of 1‐adamantanol or tert ‐butyl alcohol to hexacyanomethoxy‐ p ‐X‐calix[6]arenes 3a – c (X = tert ‐butyl, 1‐adamantyl, 3‐methoxycarbonylmethyl‐1‐adamantyl) gave 37,40‐dinitrile‐38,39,41,42‐tetraamides as the major products. These tetraamides are conformationally restricted in solution over a wide range of temperatures and adopt a flattened 1,2,3‐alternate conformation, as shown by 2D and variable‐temperature NMR experiments. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)