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41946-AC4
Non-Cone Conformations in 'Classic' Tetrahydroxycalix[4]Arenes
The preferred conformation of the calix macrocycle may be affected by the presence of substituents attached to the methylene bridges. However, a general synthetic method for the introduction of substituents at all the methylene groups of the calix scaffold has remained an elusive goal in calixarene chemistry. We found that calix[4]arenes monosubstituted at all bridges by bromine atoms are useful intermediates for the preparation of the systems. The tetrabromo derivatives of calix[4]arene and p-tert-butylcalix[4]arene were prepared by reaction of the corresponding tetramethoxy derivatives with NBS under irradiation using a minor modification of the reported literature procedures. The tetrabromocalixarenes readily undergo solvolysis in the presence of ionizing solvents (such as trifluoroethanol and hexafluoroisopropanol) and react with nucleophiles to yield tetrafunctionalized calixarenes derivates. In most cases examined the reactions proceeded in diastereoselective fashion and yielded a main product characterized by solution NMR spectroscopy and X-ray crystallography as the rccc (all-cis) stereoisomer that adopts a pinched cone conformation. However, reaction in TFE or hexafluoroisopropanol in the presence of sodium azide yielded the tetraazido derivative, but in contrast to the reaction with alcohols, a mixture of three stereoisomers was obtained. Remarkably, even C-C bonds can be formed by this method. The reaction was patterned based on the recent report by Mayr and coworkers that Friedel-Crafts alkylations can be conducted in alcoholic solutions in the absence of a Lewis acid catalyst. Solvolysis of a tetrabromocalix[4]arene derivative in TFE in the presence of 2-methylfuran and propylene oxide (a scanvenger of HBr) yielded the tetrafuranyl derivative. X-ray analysis of a single crystal of the compound grown from chloroform/MeOH indicated that the all-cis isomer was obtained. The molecule adopts a pinched cone conformation with all the furanyl substituents located at equatorial positions of the macrocycle. The furanyl groups could be further modified by Diels-Alder reaction with benzyne.
