Trefoil knot template synthesis

As seen above, the randomness of the Mobius strip approach and numerous difficult steps in Schill s directed approach were highly limiting factors in a trefoil knot synthesis. Both these major obstacles might be circumvented by the use of an unambiguous templated synthesis procedure. 

Figure 14. Template synthesis of a trefoil knot (two metal centers involved).

Figure 24. The template-directed synthesis of the trefoil knot 69-6PF6 and of its isomeric trivial knot 70-6PF6-...

Ashton, P. R., Matthews, 0. A., Menzer, S., et ai, Molecular meccano, 27 - A template-directed synthesis of a molecular trefoil knot. Liebigs Annalen-Recueil 1997, 2485-2494. 

Template synthesis of a free trefoil knot and an unknotted product. 

Fig. 29. Template synthesis of the trefoil knot. The molecular thread is a metal-ligand that contains two chelating sites and the black dot represents a transition-metal ion in a pseudo-tetrahedral environment...

We have seen how elegantly transition metals can template the formation of knots, but what about Nature s favourite templating interaction, the hydrogen bond A remarkably efficient molecular trefoil knot synthesis based on this interaction was reported by Vogtle and co-workers, who made a knotane in 20% yield [39]. This amazing route (Fig. 11) was uncovered serendipitously during the synthesis of catenanes. The crystal structure of the compound was the definitive proof for the structure, because neither NMR nor mass spectrometry could tell it apart conclusively from the macrocycles that are also formed. 

A remarkably efficient molecular trefoil knot synthesis based on organic templates was reported by VOgtle and coworkers, who serendipitously made and astutely identified the knotane. In the course of the synthesis of [ ]catenanes, reaction of the simple precursors 9 and 10 in the presence of triethylamine under high dilution conditions (10 mM in dichloromethane) produced three colorless products macrocycle 11 (15% yield, 1 1 ratio of reagents... 

A strategy of using polynuclear double helices as precursors to more complex interlocked and knotted systems should allow the carrying out of template synthesis of trefoil, pentafoil, heptafoil... knots containing a set of two, four, six. .. metals, respectively. 

SCH EME 17.4 Hydrogen templated synthesis of trefoil knot obtained by [3 + 3] macrocycli-zation.2 Right Crystal structure (adapted from CCDC 139484) of trefoil knot with intrastrand H-bonding interactions. H atoms, cyclohexyl, and methyl groups are omitted for clarity. 

Recently, we reported the synthesis of a metal-templated trefoil knot using dynamic covalent chemistry of imine bonds. Inspired by the work of Stoddart on the synthesis of Borromean rings and with the aid of DFT calculations, we anticipated that the combination of a 5,5 -dimethyl-2,2 -bipyridine functionalized with para-aminomethyl-phenyl ether (Scheme 17.6) would provide adequate geometry for the bidentate coordination to a Zinc(II) cation. 

---