Template-directed synthesis of kinetically and thermodynamically stable molecular necklace using ring closing metathesis

Abstract

We report the template-directed synthesis of a well-defined, kinetically stable [5]molecular necklace with dialkylammonium ion (R₂NH₂⁺) as recognition site and DB24C8 as macrocycle. A thread containing four dialkylammonium ions with olefin at both ends was first synthesized and then subjected to threading with an excess amount of DB24C8 to form pseudo[5]rotaxane, which in situ undergoes ring closing metathesis at the termini with second generation Grubbs catalyst to yield the desired [5]molecular necklace. The successful synthesis of [5]molecular necklace is mainly attributed to the self-assembly and dynamic covalent chemistry which allows the formation of thermodynamically most stable product. The self-assembly of the DB24C8 ring onto the recognition site known as templating effect was driven by noncovalent stabilizing interactions like [N⁺–H⋯O], [C–H⋯O] hydrogen bonds as well as [π⋯π] interactions which is facilitated in non-polar solvents. The reversible nature of olefin metathesis reaction makes it suitable for dynamic covalent chemistry since proof-reading and error-checking operates until it generates thermodynamically the most stable interlocked molecule. Riding on the success of [5]molecular necklace, we went a step further and attempted to synthesize [7]molecular necklace using the same protocol. This led to the synthesis of another thread with olefin at both ends but having six dibenzylammonium ions along the thread. However, the extremely poor solubility of this thread containing six secondary ammonium ions limits the self-assembly process even after we replaced the typical PF₆⁻ counter anion with a more lipophilic BPh₄⁻ anion. Although the poor solubility of the thread remains the bottleneck for making higher order molecular necklaces yet this approach of “threading-followed-by-ring-closing-metathesis” for the first time produces kinetically and thermodynamically stable, well-defined, homogeneous molecular necklace which was well characterized by one-dimensional, two-dimensional, variable temperature proton NMR spectroscopy and ESI mass spectroscopy.