Borromean Rings: a One-Pot Synthesis Christoph A

Angewandte Chemie

Topochemistry Borromean Rings: A One-Pot Synthesis Christoph A. Schalley*

Keywords: self-assembly · structure elucidation · template synthesis · topochemistry

The aesthetics of beautiful molecules topological properties, although their have only so far[5] been realized at the has been, and still is, a strong motivation functions as molecular machines[2] have molecular level through the DNA nano- for many chemists. Complex interwoven become more and more of the focus of assembly methodology developed by structures[1] such as catenanes, rotax- interest. Seeman and co-workers.[6] Consequent- anes, and knots are even nowadays The ability of chemistry to realize ly, the first chemical synthesis of Borro- appealing because of their interesting the mathematical zoo of knots (Fig- mean rings by Stoddart, Atwood, and ure 1),[3] at the molecular level still their co-workers[7] is certainly a high- suffers from narrow limitations, and it light in supramolecular chemistry. is thus well-justified to consider the Borromean rings consist of three synthesis of trefoil knots as a major rings which are entangled in a way achievement.[4] Borromean rings possess which prevents separation of the rings an even more complex topology than just by changing their shape (Figure 2). the trefoil knot, thus making them a Opening one of the rings, however, challenging target for chemical synthe- makes the whole assembly fall apart. It sis. This is reflected in the fact that they is this property which has made the

Figure 1. A small selection from the mathematical zoo of knots.

[*] Priv.-Doz. Dr. C. A. Schalley KekulØ-Institut für Organische Chemie und Biochemie Universität Bonn Gerhard-Domagk-Strasse 1 53121 Bonn (Germany) Fax : (+49)228-735-662 Figure 2. Top: Catenane (left) and trefoil knot (right). Center: Three views of Borromean rings. E-mail: [email protected] Bottom: Chemical realization of Borromean rings through self-organization.

Angew. Chem. Int. Ed. 2004, 43, 4399 –4401 DOI: 10.1002/anie.200460583 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 4399 Highlights

Borromean rings important in historical The fact that the Borromean rings to reach its thermodynamic minimum. terms as a symbol for strength in unity. fall apart if one of them is missing or cut The retrosynthetic strategy and the Borromean rings can be found was utilized as evidence for the topology building blocks used in this synthesis throughout the history of mankind— of the DNA-based Borromean rings: are shown in Figure 2. The condensation from the vikings to christian iconogra- enzymatic cleavage of one of the rings of the dialdehydes and diamines shown phy to far-East family emblems.[8] Their destroys the whole structure and results to form imines serves as the reversible name originated from the inclusion of in the formation of three independent bond-formation step in the macrocycli- the rings in the fifteenth century crest of parts. What is an advantage for charac- zations.[13] The resulting macrocycle the Borromeo family from Milan. Fig- terization is a problem for the synthesis bears two pairs of opposing endo-tri- ure 3 shows the rings on the entrance to of Borromean rings in the laboratory. dentate and exo-bidentate metal-coor- the church San Sigismondo in Cremona Although precursors for catenanes and dination sites and has the overall oval in the dukedom of Milan. rotaxanes can be found relatively easily shape required for the threading pro- because they need to organize only two cess. subunits into a suitable crossed arrange- Under template-free conditions, a ment, a total of six such crossing points complicated mixture of macrocyclic and need to be generated in the correct linear oligomers would be expected to geometry for the synthesis of Borro- form from these building blocks. There- mean rings. fore, the presence of transition-metal The latter can only be successful ions is required to form kinetically labile with a sophisticated template synthe- complexes with the coordination sites sis.[9] One possible synthetic strategy built into the macrocycles. Six zinc(ii) relies on the application of two different ions are perfectly suited for this pur- template effects and leads to a stepwise pose; they template the formation of synthesis (Figure 4).[10] In the first step Borromean rings by binding to one of the second ring is moved into and bound the exocyclic bipyridine units of one of by the first ring.[11] The second step the three macrocycles and to one of the involves the third ring being subse- tridentate endocyclic coordination sites quently threaded into the complex by a of the next one, thus bridging one ring second template effect in which all the with the others and providing a way of geometric requirements necessary for threading the macrocycles into each the generation of Borromean rings are other. After one macrocycle is encapsu- fulfilled. Such a strategy has the merit of lated within another, nonsaturated co- structural variability: if two different ordination sites remain at the zinc ions, templates are used successively, the and these control the threading of the three rings can be different from each open-chain precursor of the third mac- other. rocycle. A final macrocyclization termi- The other synthetic extreme, that is, nates the synthesis, with the product an elegant one-pot synthesis utilizing formed in a yield of about 90%. self-assembly processes,[12] has now been The characterization was achieved Figure 3. The entrance door to San Sigismon- used by Stoddart, Atwood, and co- by NMR spectroscopy, ESI mass spec- do in Cremona, carved from walnut wood by [7] [14] Paolo and Giuseppe Sacca between 1536 and workers. Self-assembly requires rever- trometry, and crystal-structure analy- 1542. Reproduced with kind permission of sible, multiple error-checking and error- sis. In the solid state the Borromean [8] II Dr. Peter Cromwell. correction steps that enable the system rings have an S6 symmetry. The Zn ions

Figure 4. Stepwise synthesis of Borromean rings: Precursors and intermediates.

4400 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim www.angewandte.org Angew. Chem. Int. Ed. 2004, 43, 4399 –4401 Angewandte Chemie are 12.7 apart and have an almost O. A. Matthews, S. Menzer, F. M. Ray- for a report on this publication, see J. S. octahedral coordination environment mo, N. Spenzer, J. F. Stoddart, D. J. Siegel, Science, 2004, 304, 1256. consisting of five nitrogen atoms and Williams, Liebigs Ann. 1997, 2485; [8] P. R. Cromwell, E. Beltrami, M. Ram- d) G. Rapenne, C. Dietrich-Buchecker, one oxygen atom from one of the triflate pichini, Mathematical Intelligencer 1998, J.-P. Sauvage, J. Am. Chem. Soc. 1999, 20, 53. counterions. In addition to all their 121, 994; e) S. C. J. Meskers, H. P. J. M. [9] a) T. J. Hubin, A. G. Kolchinski, A. L. special topological features, the Borro- Dekkers, G. Rapenne, J.-P. Sauvage, Vance, D. H. Busch, Adv. Supramol. mean rings have a particular property Chem. Eur. J. 2000, 6, 2129; f) O. 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