Covalent Template-Guided Synthesis of endo-Functionalized Oligophenylene Cages.

Abstract

Herein, we demonstrate the efficient covalent template-guided synthesis of lantern-shaped endo-functionalized oligophenylene cages 1. The synthetic route proceeds by virtue of cooperative bond formations via Suzuki-Miyaura cross-coupling and the use of covalent templates through intermolecular 6-fold coupling among three molecules. Using templates 4a and 4b, template-containing cages 6a and 6b were constructed in 68 and 36% yield, respectively, and the subsequent quantitative removal of the templates led to the corresponding OH- and NH2-functionalized cages 1a and 1b. In the absence of templates, intermolecular 4-fold coupling among three molecules afforded cages 1a and 1b in only 7 and 1% yield, respectively. The proposed mechanism for the efficient intermolecular 6-fold coupling was corroborated by electrospray ionization mass spectrometry (ESI-MS) monitoring experiments. Moreover, OH- and NH2-functionalized cages were found to encapsulate l-TrpOMe (G1) and diphenyl phosphate (G2), respectively, within their cavities through interactions between polar functional groups.