ConspectusMacrocyclic chemistry has relied on the dominance of some key cavitands, including cyclodextrins, calixarenes, cyclophanes, and cucurbiturils, to advance the field of host-guest science. Very few of the many other cavitands introduced by chemists during these past few decades have been developed to near the extent of these four key players. A relatively new family of macrocycles that are becoming increasingly dominant in the field of macrocyclic chemistry are the pillar[n]arenes composed of n hydroquinone rings connected in their 2- and 5-positions by methylene bridges. This substitution pattern creates a cylindrical or pillar-like structure that has identical upper and lower rims. The preparation of pillar[n]arenes is facile, with pillar- through pillararene being readily accessible and the larger macrocycles (n = 8-14) being accessible in diminishing yields. The rigid pillar[n]arene cavities are highly π-electron-rich on account of the n activated aromatic faces pointing toward their centers, allowing the cavities to interact strongly with a range of π-electron-deficient guests including pyridiniums, alkylammoniums, and imidazoliums. The substitution pattern of pillar[n]arenes bestows chirality onto the macrocycle in the form of n chiral planes. The absolute configuration of the chiral planes in pillar[n]arenes can be either fixed or rapidly undergoing inversion.The future of pillar[n]arenes is going to be dependent on their ability to fulfill specific applications. Chemical modification of the parent pillar[n]arenes lets us create functionalized hosts with anticipated chemical or physical properties. The featured potential applications of pillar[n]arenes to date are far reaching and include novel hosts with relevance to nanotechnology, materials science, and medicine. Pillar[n]arenes have an overwhelming advantage over other hosts since the number of ways available to incorporate handles into their structures are diverse and easy to implement. In this Account, we describe the routes to chemically modified pillar[n]arenes by discussing the chemistry of their functionalization: monofunctionalization, difunctionalization, rim differentiation, perfunctionalization, and phenylene substitution. We assess the synthetic complications of employing these functionalization procedures and survey the potential applications and novel properties that arise with these functionalized pillar[n]arenes. We also highlight the challenges and the synthetic approaches that have yet to be fully explored for the selective chemical modification of these hosts. Finally, we examine a related class of macrocycles and consider their future applications. We trust that this Account will stimulate the development of new methods for functionalizing these novel hosts to realize pillar[n]arene-containing compounds capable of finding applications.
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