Bimolecular Reaction via the Successive Introduction of Two Substrates into the Crystals of Networked Molecular Cages

Two substrates, 4-hydroxydiphenylamine (3) and ethyl isocyanate (4), were successively introduced into the crystals of networked M6L4 cages 1. Because of the encapsulation effect, most of the initially introduced substrate 3 remained within the crystals during immersion in a solution of 4. X-ray analysis revealed that before the reaction, the nucleophilic NH group of 3 is effectively protected by tight packing within the cage units while the OH group is exposed to the incoming second substrate. Successive introduction of 4 into the crystal results in the chemoselective acylation of 3 at the less nucleophilic OH group. The observed chemoselectivity is consistent with that exhibited by discrete M6L4 cage 2 in solution.