Catalytic “Active-Metal” Template Synthesis of [2]Rotaxanes, [3]Rotaxanes, and Molecular Shuttles, and Some Observations on the Mechanism of the Cu(I)-Catalyzed Azide−Alkyne 1,3-Cycloaddition

A synthetic approach to rotaxane architectures is described in which metal atoms catalyze covalent
bond formation while simultaneously acting as the template for the assembly of the mechanically interlocked
structure. This “active-metal” template strategy is exemplified using the Huisgen−Meldal−Fokin Cu(I)-catalyzed 1,3-cycloaddition of azides with terminal alkynes (the CuAAC “click” reaction). Coordination of
Cu(I) to an endotopic pyridine-containing macrocycle allows the alkyne and azide to bind to metal atoms
in such a way that the metal-mediated bond-forming reaction takes place through the cavity of the
macrocycleor macrocyclesforming a rotaxane. A variety of mono- and bidentate macrocyclic ligands
are demonstrated to form [2]rotaxanes in this way, and by adding pyridine, the metal can turn over during
the reaction, giving a catalytic active-metal template assembly process. Both the stoichiometric and catalytic
versions of the reaction were also used to synthesize more complex two-station molecular shuttles. The
dynamics of the translocation of the macrocycle by ligand exchange in these two-station shuttles could be
controlled by coordination to different metal ions (rapid shuttling is observed with Cu(I), slow shuttling with
Pd(II)). Under active-metal template reaction conditions that feature a high macrocycle:copper ratio, [3]rotaxanes (two macrocycles on a thread containing a single triazole ring) are also produced during the
reaction. The latter observation shows that under these conditions the mechanism of the Cu(I)-catalyzed
terminal alkyne−azide cycloaddition involves a reactive intermediate that features at least two metal ions.