Balancing on a Knife's Edge: Studies on the Synthesis of Pillar[6]arene Derivatives

Pillar[6]arenes are established as crucial building blocks in supramolecular chemistry, however they can be difficult to synthesize, particularly in the absence of large solubilizing substituents. In this work we explore variability in literature syntheses of pillar[6]arene derivatives, and suggest that the outcome is dependent on whether oligomeric intermediates stay in solution long enough for thermodynamically favourable macrocyclization to occur. We demonstrate that in a previously capricious BF3OEt2-mediated procedure, 5 mol% of a Brnsted acid can slow down the reaction to favour macrocycle formation.