Symmetry as a guiding tool for development of strategies in the synthesis of calix[4]arenes and related macrocycles

Symmetry commonly associated with beauty is a distinct feature present in many objects natural or artificial. Sometimes the symmetry embedded in molecular structures is either obvious or more subtle nevertheless it affects the molecular properties to a significant extent. The synthetic strategies explored in this thesis rely principally on the targeting certain symmetry elements present in the three dimensional structure of calix[4]arenes.; A new convergent "Triple Annulation" approach has been realized in this regard for the preparation of several calixarenes and other related macrocycles. The studies described herein are exploratory so as to examine the scope of this strategy and fall into three broad categories.; Calix[4]arenes with ABAB and ABAC substitution pattern exhibiting C2 and CS symmetry were synthesized via the reaction of bis-carbene complexes and diynes. This method is unique compared to existing methods for calix[4]arene formation in that it involves the formation of two of the four benzene rings of the calixarene and the macrocyclic ring of the calixarene in the same step. The syntheses of calix[4]arenes with specific substitution patterns in the inner and outer rims was also accomplished by this strategy and the conformations of these macrocycles was examined in depth.; One of the most important attractive features of the Triple Benzannulation approach is that the two adjacent arene rings of the calix skeleton are non-identical and this unique feature has been exploited in developing an efficient synthesis of chiral methylene substituted calix[4]arenes with either C2 or C1 symmetry. These calix[4]arenes were an unknown class of supramolecules prior to this study and hold significant potential for development as chiral building blocks for variety of applications. Moreover, the syntheses of several regio and stereoisomers of methylene functionalized calix[4]arenes has also been demonstrated during the course of this work.; Homocalix[4]arenes have been less examined due to the lack of conformational rigidity in these macrocycles and the limited methods for their preparation. The macrocyclization of bis-carbene complex and diyne allows for the construction of larger macrocycles as illustrated in the synthesis of a bis-homocalix[4]arene.