Design and synthesis of the first triply twisted Möbius annulene

Journal name:
Nature Chemistry
Year published:
Published online


As long as 50 years ago theoretical calculations predicted that Möbius annulenes with only one π surface and one edge would exhibit peculiar electronic properties and violate the Hückel rules. Numerous synthetic attempts notwithstanding, the first singly twisted Möbius annulene was not prepared until 2003. Here we present a general, rational strategy to synthesize triply or even more highly twisted cyclic π systems. We apply this strategy to the preparation of a triply twisted [24]dehydroannulene, the structure of which was confirmed by X-ray analysis. Our strategy is based on the topological transformation of ‘twist’ into ‘writhe’. The advantage is twofold: the product exhibits a lower degree of strain and precursors can be designed that inherently include the writhe, which, after cyclization, ends up in the Möbius product. With our strategy, triply twisted systems are easier to prepare than their singly twisted counterparts.

At a glance


  1. Strategies to introduce multiple twists in a cycle.
    Figure 1: Strategies to introduce multiple twists in a cycle.

    a, Naive strategies may include the cyclotrimerization of three components each containing a single twist, or cyclization of a band with three twists. Both strategies are hampered because linear π systems cannot be twisted easily, and if constrained to do so would probably not cyclize easily. b, The transformation of twist (Tw) into writhe (Wr) in a closed band by winding around itself can release strain and suggests an alternative strategy. Tw is a measure of how often the upper edge of the band crosses the lower edge in 2D projections (local crossings, top), and Wr is a measure of the number of crossings of the ribbon axis with itself. The middle illustration shows three local self-crossings in the 2D projection of the view along the z axis (orthogonal to the paper plane). To calculate the writhe either the average of self-crossings in all projections from all vantage points has to be calculated or the double Gaussian integral has to be solved. Local crossings and self-crossings can be either positive or negative. To assign a sign to a crossing the band has to be given a direction and the crossings are analysed as shown in the bottom illustration (right handed, +; left handed, −). Tw and Wr can take any positive or negative real number, Lk is always an integer.

  2. Combining building blocks with writhe to produce a triply twisted system and identification of a target structure.
    Figure 2: Combining building blocks with writhe to produce a triply twisted system and identification of a target structure.

    ad, Different combinations of writhe units (ac) and formation of a Möbius ring with Lk = −3 (d). Structures with Lk = 3, Tw = 0 and Wr = 3 are difficult to draw. e,f, To derive clearly recognizable chemical structures that can be drawn in 2D, we use the homeomorphic Lk = 3, Tw = −3 and Wr = 6 projection (e). The bridging units that connect the loops are not twisted in the 3D structure (d). The twists arise from the topological transformation from d to e and projection into 2D. Target structure 1 is presented in this projection (f). However, for the discussion of the topology, and particularly of twist and writhe, or properties that rely on the 3D geometry (such as orbital overlap), please refer to the 3D structure as represented in d.

  3. Synthesis of the Möbius dehydroannulene.
    Figure 3: Synthesis of the Möbius dehydroannulene.

    a, Reagents: (i) (1) n-BuLi, THF, (2) DMF, yield of 3 = 63%; (ii) Bestmann–Ohira reagent, K2CO3, MeOH, yields of 5 = 74% and 4 = 23%; (iii) NBS, AgNO3, acetone, yield of 7 = 96%; (iv) (1) LiN(TMS)2, THF, (2) DMTS-Cl, yields of 8 = 65%, 5 = 25% and 6 = 10%; (v) TBAF, THF, yield of 8 = 98%; (vi) Pd2(dba)3, LiI, CuI, PMP, DMSO, yield of 9 = 32%; (vii) TBAF, THF, yield of 10 = 100%; (viii) Cu(OAc)2, pyridine, MeOH, yield of 1 = 11%. All references for the synthesis are given in the Supplementary Chapter 3. b, Owing to the axial chirality of the writhe units and the three possible ways to combine them, three diastereomers (enantiomeric pairs) are formed on the reaction of 7 with 8. In principle, the final ring closure of 10af can furnish two cyclic trimers with Möbius topology, besides oligomers and polymers. The Möbius structure 1c/d with Lk = 1 is not formed because ring closure is energetically unfavourable. The red stereo descriptors indicate those stereoisomers that have the correct stereochemistry to form the target (triply twisted) Möbius product (1a/b). The compounds that are not highlighted with red stereo descriptors form either oligomers or a Möbius product with Lk = 1. TMS, trimethylsilyl; dba, dibenzylideneacetone; DMTS, dimethyl-(1,1,2-trimethylpropyl)silyl; TBAF, tetra-n-butylammonium fluoride; NBS, N-bromosuccinimide; PMP, 1,2,2,6,6-pentamethylpiperidine; DMSO, dimethyl sulfoxide.

  4. Structure of the Möbius dehydroannulene 1a/b with Lk = 3 as determined by X-ray crystallography.
    Figure 4: Structure of the Möbius dehydroannulene 1a/b with Lk = 3 as determined by X-ray crystallography.

    a,b, Ball and stick model (a) and space-filling model (b). α, dihedral angle formed by two adjacent naphthyl units. Chloroform molecules are omitted for clarity. c, CD spectra of both enantiomers (1a/b, red and blue lines, respectively) of the Möbius dehydroannulene after separation on a chiral column.

  5. Topological procedure to determine the linking number Lk of the π system of 1.
    Figure 5: Topological procedure to determine the linking number Lk of the π system of 1.

    A band orthogonal to the π system is constructed and cut down the middle. The fact that a trefoil knot is obtained confirms the linking number, Lk = 3, of the original band (see also Supplementary Fig. 5).


10 compounds View all compounds
  1. 1,6,11-(2,2')-Tri-1,1'binaphthyla-cycopentadecaphane-2,4,7,9,12,14-hexayne
    Compound 1 1,6,11-(2,2')-Tri-1,1'binaphthyla-cycopentadecaphane-2,4,7,9,12,14-hexayne
  2. 2,2'-Dibromo-1,1'-binaphthalene
    Compound 2 2,2'-Dibromo-1,1'-binaphthalene
  3. (1,1'-Binaphthalene)-2,2'-dicarbaldehyde
    Compound 3 (1,1'-Binaphthalene)-2,2'-dicarbaldehyde
  4. 2'-Ethynyl-(1,1'-binaphthalene)-2-carbaldehyde
    Compound 4 2'-Ethynyl-(1,1'-binaphthalene)-2-carbaldehyde
  5. 2,2'-Diethynyl-1,1'-binaphthalene
    Compound 5 2,2'-Diethynyl-1,1'-binaphthalene
  6. 2,2'-Bis(((2,3-dimethylbutan-2-yl)dimethylsilyl)ethynyl)-1,1'-binaphthalene
    Compound 6 2,2'-Bis(((2,3-dimethylbutan-2-yl)dimethylsilyl)ethynyl)-1,1'-binaphthalene
  7. 2,2'-Bis(bromoethynyl)-1,1'-binaphthalene
    Compound 7 2,2'-Bis(bromoethynyl)-1,1'-binaphthalene
  8. ((2'-(Bromoethynyl)-(1,1'-binaphthalen)-2-yl)ethynyl)(2,3-dimethylbutan-2-yl)dimethylsilane
    Compound 8 ((2'-(Bromoethynyl)-(1,1'-binaphthalen)-2-yl)ethynyl)(2,3-dimethylbutan-2-yl)dimethylsilane
  9. 2,2'-Bis((2'-(((2,3-dimethylbutan-2-yl)dimethylsilyl)ethynyl)-(1,1'-binaphthalen)-2-yl)buta-1,3-diyn-1-yl)-1,1'-binaphthalene
    Compound 9 2,2'-Bis((2'-(((2,3-dimethylbutan-2-yl)dimethylsilyl)ethynyl)-(1,1'-binaphthalen)-2-yl)buta-1,3-diyn-1-yl)-1,1'-binaphthalene
  10. 2,2'-Bis((2'-ethynyl-(1,1'-binaphthalen)-2-yl)buta-1,3-diyn-1-yl)-1,1'-binaphthalene
    Compound 10 2,2'-Bis((2'-ethynyl-(1,1'-binaphthalen)-2-yl)buta-1,3-diyn-1-yl)-1,1'-binaphthalene


  1. Sobanski, A., Schmieder, R. & Vögtle, F. Topologische Stereochemie und Chiralität. Chemie in unserer Zeit 34, 160169 (2000).
  2. Walba, D. M. Topological stereochemistry. Tetrahedron 41, 31613212 (1985).
  3. Fenlon, E. E. Open problems in chemical topology. Eur. J. Org. Chem. 50235035 (2008).
  4. Heilbronner, E. Hückel molecular orbitals of Möbius-type conformations of annulenes. Tetrahedron Lett. 5, 19231928 (1964).
  5. Castro, C., Isborn, C. M., Karney, W. L., Mauksch, M. & Schleyer, P. v. R. Aromaticity with a twist: Möbius [4n]annulenes. Org. Lett. 4, 34313434 (2002).
  6. Castro, C., Karney, W. L., Valencia, M. A., Vu, C. M. H. & Pemberton, R. P. Möbius aromaticity in [12]annulenes: cistrans isomerization via twist-coupled bond shifting. J. Am. Chem. Soc. 127, 97049705 (2005).
  7. Mauksch, M. & Tsogoeva, S. B. Neutral Möbius aromatics: derivatives of the pyrrole congener aza[11]annulene as promising synthetic targets. Eur. J. Org. Chem. 34, 57555763 (2008).
  8. Zoellner, R. W. Krebs, J. F. & Browne, D. M. Violently twisted and strained organic molecules: a descriptor system for simple coronoid aromatics with a Möbius half-twist and semiempirical calculations on the Möbius analogs of coronene. J. Chem. Inf. Comput. Sci. 34, 252258 (1994).
  9. Havenith, R. W. A., Van Lenthe, J. H. & Jenneskens, L. W. Möbius aromaticity in small [n]trans-annulenes. Int. J. Quant. Chem. 85, 5260 (2001).
  10. Fowler, P. W. Hückel spectra of Möbius π systems. Phys. Chem. Chem. Phys. 4, 28782883 (2002).
  11. Mucke, E-K., Köhler, F. & Herges, R. The [13]annulene cation is a stable Möbius annulene cation. Org. Lett. 12, 17081711 (2010).
  12. Mucke, E-K., Schönborn, B., Köhler, F. & Herges, R. Stability and aromaticity of charged Möbius [4n]annulenes. J. Org. Chem. 76, 3541 (2011).
  13. Bucher, G. et al. Is the [9]annulene cation a Möbius annulene? Angew. Chem. Int. Ed. 48, 99719974 (2009).
  14. Braten, M. N, Castro, C., Herges, R., Köhler, F. & Karney, W. L. The [12]annulene global minimum. J. Org. Chem. 73, 15321535 (2008).
  15. Ajami, D., Oeckler, O., Simon, A. & Herges, R. Synthesis of a Möbius aromatic hydrocarbon. Nature 426, 819821 (2003).
  16. Ajami, D. et al. Synthesis and properties of the first Möbius annulenes. Chem. Eur. J. 12, 54345445 (2006).
  17. Lemal, D. M. Aromatics do the twist. Nature 426, 776777 (2003).
  18. Saito, S. & Osuka, A. Expanded porphyrins: intriguing structures, electronic properties, and reactivities. Angew. Chem. Int. Ed. 50, 43424373 (2011).
  19. Stepien, M., Sprutta, N. & Latos-Grażyński, L. Figure eights, Möbius bands, and more: conformation and aromaticity of porphyrinoids. Angew. Chem. Int. Ed. 50, 42884340 (2011).
  20. Sankar, J. et al. Unambiguous identification of Möbius aromaticity for meso-aryl-substituted [28]hexaphyrins( J. Am. Chem. Soc. 130, 1356813579 (2008).
  21. Herges, R. Aromatics with a twist. Nature 450, 3637 (2007).
  22. Crick, F. H. C. Linking numbers and nucleosomes. Proc. Natl Acad. Sci. USA 73, 26392643 (1976).
  23. Fuller, F. B. Decomposition of the linking number of a closed ribbon: a problem from molecular biology. Proc. Natl Acad. Sci. USA 75, 35573561 (1978).
  24. Klenin, K. & Langowski, J. Computation of writhe in modeling of supercoiled DNA. Biopolymers 54, 307317 (2000).
  25. Fuller, F. B. The writhing number of a space curve. Proc. Natl Acad. Sci. USA 68, 815819 (1971).
  26. Schaller, G. R. & Herges, R. Möbius molecules with twists and writhes. Chem. Commun. 12541260 (2013).
  27. Schaller, G. R. Design und Synthese Möbius-topologischer und Möbius-aromatischer Kohlenwasserstoffe PhD thesis, Univ. Kiel (2013).
  28. Călugăreanu, G. Sur les classes d'isotopie des noeuds tridimensionnels et leurs invariants. Czech. Math. J. 11, 588625 (1961).
  29. Lilley, O. M. J. DNA supercoiling. Biochem. Soc. Trans. 14, 489493 (1986).
  30. Hückel, E. Quantentheoretische Beiträge zum Benzolproblem. Z. Phys. 70, 204286 (1931).
  31. Hückel, E. Quantentheoretische Beiträge zum Problem der aromatischen und ungesättigten Verbindungen. Z. Phys. 76, 628648 (1932).
  32. Frost, A. A. & Musulin, B. J. A mnemonic device for molecular orbital energies. J. Chem. Phys. 21, 572573 (1953).
  33. Zimmerman, H. E. On molecular orbital correlation diagrams, the occurrence of Möbius systems in cyclization reactions, and factors controlling ground- and excited-state reactions. J. Am. Chem. Soc. 88, 15641565 (1966).
  34. Yoon, Z. S., Oskua, A. & Kim, D. Möbius aromaticity and antiaromaticity in expanded porphyrins. Nature Chem. 1, 113122 (2009).
  35. Higashino, T. et al. Möbius antiaromatic bisphosphorus complexes of [30]hexaphyrins. Angew. Chem. Int. Ed. 49, 49504954 (2010).
  36. Pacholska-Dudziak, E. et al. Palladium vacataporphyrin reveals conformational rearrangements involving Hückel and Möbius macrocyclic topologies. J. Am. Chem. Soc. 130, 61826195 (2008).
  37. Herges, R. Topology in chemistry: designing Möbius molecules. Chem. Rev. 106, 48204842 (2006).
  38. Rappaport, S. M. & Rzepa, H. S. Intrinsically chiral aromaticity. Rules incorporating linking number, twist, and writhe for higher-twist Möbius annulenes. J. Am. Chem. Soc. 130, 76137619 (2008).
  39. Rzepa, H. S. Möbius aromaticity and delocalization. Chem. Rev. 105, 36973715 (2005).
  40. Rzepa, H. S. A double-twist Möbius-aromatic conformation of [14]annulene. Org. Lett. 7, 46374639 (2005)
  41. Wannere, C. S. et al. The geometry and electronic topology of higher-order charged Möbius annulenes. J. Phys. Chem. A 113, 1161911629 (2009).
  42. Mislow, K., Bunnenberg, E., Records, R., Wellman, K. & Djerassi, C. Inherently dissymmetric chromophores and circular dichroism. II J. Am. Chem. Soc. 85, 13421349 (1963).
  43. Lim, J. M., Yoon, M-C., Kim, K. S., Shin, J-Y. & Kim, D. in Handbook for Porphyrin Science Vol. 1 (eds Kadish, K. M., Smith, K. M. & Guilard, R.) 507558 (World Scientific, 2010).
  44. Torrent-Sucarrat, M., Anglada, J. M. & Luis, J. M. Evaluation of the nonlinear optical properties for an expanded porphyrin Hückel–Möbius aromaticity switch. J. Chem. Phys. 137, 184306 (2012).
  45. Li, Z. & Ram-Mohan L. R. Quantum mechanics on a Möbius ring: energy levels, symmetry, optical transitions, and level splitting in a magnetic field. Phys. Rev. B 85, 195438 (2012).
  46. Zhong, R-L. et al. Spiral intramolecular charge transfer and large first hyperpolarizability in Möbius cyclacenes: new insight into the localized π electrons. Chem. Phys. Chem. 13, 23492353 (2012).
  47. Torrent-Sucarrat, M., Anglada, J. M. & Luis, J. M. Evaluation of the nonlinear optical properties for annulenes with Hückel and Möbius topologies. J. Chem. Theo. Comput. 7, 39353943 (2011).
  48. Chang, C-W. et al. Optical Möbius symmetry in metamaterials. Phys. Rev. Lett. 105, 235501 (2010).
  49. Ioffe, L. B. et al. Topologically protected quantum bits using Josephson junction arrays. Nature 415, 503506 (2002).

Download references

Author information


  1. Institute for Organic Chemistry, University of Kiel, Otto-Hahn Platz 4, 24098 Kiel, Germany

    • Gaston R. Schaller &
    • Rainer Herges
  2. Department of Chemistry, Nanoscience Center, University of Jyväskylä, PO Box 35, 40014 Jyväskylä, Finland

    • Filip Topić &
    • Kari Rissanen
  3. Nagoya University, 1E Miyahigashi-cho, Showa-ku, Nagoya 466-0804, Japan

    • Yoshio Okamoto
  4. College of Materials Science and Chemical Engineering, Harbin Engineering University, 145 Nantong Street, Harbin 150001, China

    • Jun Shen


G.R.S. worked out the topological construction strategy, developed the syntheses, carried out the experiments and characterized the compounds. R.H. developed the topological strategy and directed the study. F.T. prepared the single crystals, collected the data and solved and refined the structure together with K.R. K.R. supervised the X-ray diffraction part of the work. Y.O. and J.S. performed the separation and CD measurement of the enantiomers. G.R.S., R.H., F.T. and K.R. wrote the manuscript.

Competing financial interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to:

Author details

Supplementary information

PDF files

  1. Supplementary information (2,536 KB)

    Supplementary information

Image files

  1. Supplementary information (9,843 KB)

    Supplementary Movie

Crystallographic information files

  1. Supplementary information (628 KB)

    Crystallographic data for racemic compound 1

Additional data