The design and synthesis of highly functionalised calix[4]arenes are of great interest for research. The modification of the upper-rim of calix[4]arene allows the lower-rim to act as a potential molecular binding site. Our objective is to develop methodologies and synthetic routes that allow us to generate a range of tetra-substituted, upper-rim functionalised calix[4]arenes in an AABC and ABCD pattern. We started by the selective functionalisation of calix[4]arenes by iodination at the upper-rim in the presence of aldehyde moieties. The Cannizzaro method has been developed within the Bew group, utilising a simple pestle and mortar, which has proved to be an extremely efficient method of grinding both the base and the calix[4]arene with a few drops of solvent. Protection of the Cannizzaro compound made the next step easier as acid compounds tend to streak during purification via column chromatography. We were able to obtain AABC compounds via Sonogashira cross-coupling. For the ABCD compounds, the first step of the synthesis begins via a Suzuki-Miyuara coupling of the bis-1,3-aldehyde-bis-2,4-iodo calix[4]arene with a variety of boronic acids affording mono-aryl and di-aryl compounds, followed by the Cannizzaro and alkylation to the benzyl esters. This procedure is an amenable tool for the synthesis of ‘inherently chiral’ calix[4]arenes in an AABC and ABCD pattern
