Hypervalent Iodine-Mediated Selective Monofunctionalization of Calix[4]arenes

The selective introduction of a single functionality on the upper rim of calix[4]arene is challenging due to the identical reactivity of its four aryl units. In this study, we introduce a novel strategy for monofunctional modification of calix[4]arenes using a hypervalent iodine-mediated C-H functionalization. This process yields a calix[4]arene-iodonium salt, which can be easily isolated due to its distinct solubility compared to the native calixarene. This versatile intermediate efficiently undergoes C-O, C-N, and C-S couplings with a variety of nucleophiles, including amines, phenols, thiols, and sulfinate salts under mild conditions. This strategy enables streamlined structural diversification of calix[4]arenes, opening new avenues for the design of supramolecular macrocycles with tailored functions.