Reversible Bergman cyclization by atomic manipulation

Journal name:
Nature Chemistry
Year published:
Published online


The Bergman cyclization is one of the most fascinating rearrangements in chemistry, with important implications in organic synthesis and pharmacology. Here we demonstrate a reversible Bergman cyclization for the first time. We induced the on-surface transformation of an individual aromatic diradical into a highly strained ten-membered diyne using atomic manipulation and verified the products by non-contact atomic force microscopy with atomic resolution. The diyne and diradical were stabilized by using an ultrathin NaCl film as the substrate, and the diyne could be transformed back into the diradical. Importantly, the diradical and the diyne exhibit different reactivity, electronic, magnetic and optical properties associated with the changes in the bond topology, and spin multiplicity. With this reversible, triggered Bergman cyclization we demonstrated switching on demand between the two reactive intermediates by means of selective C–C bond formation or cleavage, which opens up the field of radical chemistry for on-surface reactions by atomic manipulation.

At a glance


  1. Bergman cyclizations.
    Figure 1: Bergman cyclizations.

    a, The seminal experiment1 regarding the thermal isomerization of deuterated enediynes 1 and 3 through the formation of the diradical [2,3-D2]-1,4-didehydrobenzene (2). b, Bergman cyclization of the cyclic diyne 3,4-benzocyclodeca-3,7,9-triene-1,5-diyne (4) to generate the 9,10-didehydroanthracene diradical 5.

  2. Structures and AFM imaging of the starting material, reaction intermediates and product.
    Figure 2: Structures and AFM imaging of the starting material, reaction intermediates and product.

    ad, Chemical structures of the reaction products formed by successive STM-induced debromination of DBA (6) (a) and subsequent retro-Bergman cyclization: DBA, 9-dehydro-10-bromoanthracene (radical 7) (b), 9,10-didehydroanthracene (diradical 5) (c) and 3,4-benzocyclodeca-3,7,9-triene-1,5-diyne (diyne 4) (d). eh, Corresponding constant-height AFM images of the molecules in ad, respectively, on NaCl(2ML)/Cu(111) using a CO tip. Δf corresponds to the frequency shift of the oscillating cantilever.

  3. Diyne identification.
    Figure 3: Diyne identification.

    a, Constant-current STM image (I = 2 pA, V = 1.65 V) of diyne 4. bd, Constant-height AFM images of diyne 4 on NaCl(2ML)/Cu(111) at different heights z. e, Calculated LUMO orbital of diyne 4 with the molecular structure overlaid as a guide to the eye. fh, Calculated Δf maps of diyne 4 interacting with a CO tip at tip–molecule distances that correspond to the estimated experimental distances in bd.

  4. Reversible Bergman cyclization.
    Figure 4: Reversible Bergman cyclization.

    ac, Laplace-filtered AFM images of diyne 4R (a), diradical 5 (b) and diyne 4L (c) on NaCl(2ML)/Cu(111). The molecule is adsorbed at a step edge of an NaCl(3ML)/Cu(111) island, seen in the lower part of the images. d, Current trace during a voltage pulse of V = 1.64 V at the position indicated by the white circle in b. The different current levels correspond to the molecular structures of the same colour shown in the inset. e, Calculated energies of the Bergman cyclization using the distance between the carbons indicated by red circles (dC–C) as the reaction coordinate.


7 compounds View all compounds
  1. [1,6-D2]-(Z)-hexa-3-en-1,5-diyne
    Compound 1 [1,6-D2]-(Z)-hexa-3-en-1,5-diyne
  2. [2,3-D2]-1,4-didehydrobenzene
    Compound 2 [2,3-D2]-1,4-didehydrobenzene
  3. [3,4-D2]-(Z)-hexa-3-en-1,5-diyne
    Compound 3 [3,4-D2]-(Z)-hexa-3-en-1,5-diyne
  4. 3,4-benzocyclodeca-3,7,9-triene-1,5-diyne
    Compound 4 3,4-benzocyclodeca-3,7,9-triene-1,5-diyne
  5. 9,10-didehydroanthracene
    Compound 5 9,10-didehydroanthracene
  6. 9,10-dibromoanthracene
    Compound 6 9,10-dibromoanthracene
  7. 9-bromo-10-dehydroanthracene
    Compound 7 9-bromo-10-dehydroanthracene


  1. Jones, R. R. & Bergman, R. G. p-Benzyne. Generation as an intermediate in a thermal isomerization reaction and trapping evidence for the 1,4-benzenediyl structure. J. Am. Chem. Soc. 94, 660661 (1972).
  2. Wenk, H. H., Winkler, M. & Sander, W. One century of aryne chemistry. Angew. Chem. Int. Ed. 42, 502528 (2003).
  3. Nicolaou, K. C., Dai, W.-M., Tsay, S.-C., Estevez, V. A. & Wrasidlo, W. Designed enediynes: a new class of DNA-cleaving molecules with potent and selective anticancer activity. Science 256, 11721178 (1992).
  4. Nicolaou, K., Smith, A. & Yue, E. Chemistry and biology of natural and designed enediynes. Proc. Natl Acad. Sci. USA 90, 58815888 (1993).
  5. Sinha, S. C. et al. Prodrugs of dynemicin analogs for selective chemotherapy mediated by an aldolase catalytic Ab. Proc. Natl Acad. Sci. USA 101, 30953099 (2004).
  6. Darby, N. et al. Concerning the 1,5-didehydro-[10]-annulene system. J. Chem. Soc. D 23, 15161517 (1971).
  7. Chapman, O., Chang, C. & Kolc, J. 9,10-Dehydroanthracene. A derivative of 1,4-dehydrobenzene. J. Am. Chem. Soc. 98, 57035705 (1976).
  8. Schottelius, M. J. & Chen, P. 9,10-Dehydroanthracene: p-benzyne-type biradicals abstract hydrogen unusually slowly. J. Am. Chem. Soc. 118, 48964903 (1996).
  9. Wenk, H. H. & Sander, W. Photochemistry of 9,10-dicarbonyl-9,10-dihydroanthracene—a source of 9,10-dehydroanthracene? Eur. J. Org. Chem. 1999, 5760 (1999).
  10. Kötting, C., Sander, W., Kammermeier, S. & Herges, R. Matrix isolation of 3,4-benzocyclodeca-3,7,9-triene-1,5-diyne. Eur. J. Org. Chem. 1998, 799803 (1998).
  11. Perepichka, D. F. & Rosei, F. Extending polymer conjugation into the second dimension. Science 323, 216217 (2009).
  12. Palma, C.-A. & Samorì, P. Blueprinting macromolecular electronics. Nature Chem. 3, 431436 (2011).
  13. Hla, S.-W., Bartels, L., Meyer, G. & Rieder, K.-H. Inducing all steps of a chemical reaction with the scanning tunneling microscope tip: towards single molecule engineering. Phys. Rev. Lett. 85, 27772780 (2000).
  14. Grill, L. et al. Nano-architectures by covalent assembly of molecular building blocks. Nature Nanotech. 2, 687691 (2007).
  15. Cai, J. et al. Atomically precise bottom-up fabrication of graphene nanoribbons. Nature 466, 470473 (2010).
  16. Lafferentz, L. et al. Controlling on-surface polymerization by hierarchical and substrate-directed growth. Nature Chem. 4, 215220 (2012).
  17. Sun, Q. et al. On-surface formation of one-dimensional polyphenylene through Bergman cyclization. J. Am. Chem. Soc. 135, 84488451 (2013).
  18. de Oteyza, D. G. et al. Direct imaging of covalent bond structure in single-molecule chemical reactions. Science 340, 14341437 (2013).
  19. Stipe, B. et al. Single-molecule dissociation by tunneling electrons. Phys. Rev. Lett. 78, 44104413 (1997).
  20. Lee, H. J. & Ho, W. Single-bond formation and characterization with a scanning tunneling microscope. Science 286, 17191722 (1999).
  21. Zhao, A. et al. Controlling the Kondo effect of an adsorbed magnetic ion through its chemical bonding. Science 309, 15421544 (2005).
  22. Repp, J., Meyer, G., Paavilainen, S., Olsson, F. E. & Persson, M. Imaging bond formation between a gold atom and pentacene on an insulating surface. Science 312, 11961199 (2006).
  23. Liljeroth, P., Repp, J. & Meyer, G. Current-induced hydrogen tautomerization and conductance switching of naphthalocyanine molecules. Science 317, 12031206 (2007).
  24. Albrecht, F., Neu, M., Quest, C., Swart, I. & Repp, J. Formation and characterization of a molecule–metal–molecule bridge in real space. J. Am. Chem. Soc. 135, 92009203 (2013).
  25. Kumagai, T. et al. Controlling intramolecular hydrogen transfer in a porphycene molecule with single atoms or molecules located nearby. Nature Chem. 6, 4146 (2014).
  26. Gross, L., Mohn, F., Moll, N., Liljeroth, P. & Meyer, G. The chemical structure of a molecule resolved by atomic force microscopy. Science 325, 11101114 (2009).
  27. Mohn, F. et al. Reversible bond formation in a gold-atom–organic-molecule complex as a molecular switch. Phys. Rev. Lett. 105, 266102 (2010).
  28. Pavliček, N. et al. On-surface generation and imaging of arynes by atomic force microscopy. Nature Chem. 7, 623628 (2015).
  29. Riss, A. et al. Local electronic and chemical structure of oligo-acetylene derivatives formed through radical cyclizations at a surface. Nano Lett. 14, 22512255 (2014).
  30. Pavliček, N. et al. Atomic force microscopy reveals bistable configurations of dibenzo[a,h]thianthrene and their interconversion pathway. Phys. Rev. Lett. 108, 086101 (2012).
  31. Schuler, B. et al. Adsorption geometry determination of single molecules by atomic force microscopy. Phys. Rev. Lett. 111, 106103 (2013).
  32. Mohn, F., Schuler, B., Gross, L. & Meyer, G. Different tips for high-resolution AFM and STM imaging of single molecules. Appl. Phys. Lett. 102, 073109 (2013).
  33. Repp, G., Meyer, G., Stojkovic, S. M., Gourdon, A. & Joachim, C. Molecules on insulating films: scanning-tunneling microscopy imaging of individual molecular orbitals. Phys. Rev. Lett. 94, 026803 (2005).
  34. Gross, L. et al. Bond-order discrimination by atomic force microscopy. Science 337, 13261329 (2012).
  35. Moll, N. et al. Image distortions of partly fluorinated hydrocarbons in atomic force microscopy with carbon monoxide terminated tips. Nano Lett. 14, 61276131 (2014).
  36. Swart, I., Sonnleitner, T., Niedenführ, J. & Repp, J. Controlled lateral manipulation of molecules on insulating films by STM. Nano Lett. 12, 10701074 (2012).
  37. Gross, L. et al. Organic structure determination using atomic resolution scanning probe microscopy. Nature Chem. 2, 821825 (2010).
  38. Giessibl, F. J. High-speed force sensor for force microscopy and profilometry utilizing a quartz tuning fork. Appl. Phys. Lett. 73, 39563958 (1998).
  39. Albrecht, T. R., Grütter, P., Horne, D. & Rugar, D. Frequency modulation detection using high-Q cantilevers for enhanced force microscope sensitivity. J. Appl. Phys. 69, 668673 (1991).
  40. Boneschanscher, M. P., Hämäläinen, S. K., Liljeroth, P. & Swart, I. Sample corrugation affects the apparent bond lengths in atomic force microscopy. ACS Nano 8, 30063014 (2014).
  41. Hapala, P. et al. The mechanism of high-resolution STM/AFM imaging with functionalized tips. Phys. Rev. B 90, 085421 (2014).
  42. Hohenberg, P. & Kohn, W. Inhomogeneous electron gas. Phys. Rev. 136, B864B871 (1964).
  43. Blum, V. et al. Ab initio molecular simulations with numeric atom-centered orbitals. Comp. Phys. Comm. 180, 21752196 (2009).
  44. Perdew, J. P., Burke, K. & Ernzerhof, M. Generalized gradient approximation made simple. Phys. Rev. Lett. 77, 38653868 (1996).
  45. Tkatchenko, A. & Scheffler, M. Accurate molecular van der Waals interactions from ground-state electron density and free-atom reference data. Phys. Rev. Lett. 102, 073005 (2009).
  46. Ruiz, V. G., Liu, W., Zojer, E., Scheffler, M. & Tkatchenko, A. Density-functional theory with screened van-der-Waals interactions for the modeling of hybrid inorganic–organic systems. Phys. Rev. Lett. 108, 146103 (2012).
  47. Zhang, G.-X., Tkatchenko, A., Paier, J., Appel, H. & Scheffler, M. Van der Waals interactions in ionic and semiconductor solids. Phys. Rev. Lett. 107, 245501 (2011).

Download references

Author information

  1. Present address: ABB Corporate Research, 5405 Baden-Dättwil, Switzerland

    • Fabian Mohn


  1. IBM Research – Zurich, 8803 Rüschlikon, Switzerland

    • Bruno Schuler,
    • Shadi Fatayer,
    • Fabian Mohn,
    • Nikolaj Moll,
    • Niko Pavliček,
    • Gerhard Meyer &
    • Leo Gross
  2. CIQUS, Universidade de Santiago de Compostela, 15782 Santiago de Compostela, Spain

    • Diego Peña


B.S., S.F., F.M., N.P., G.M. and L.G. performed the STM/AFM experiments. N.M. performed the DFT calculations. D.P. identified the reaction. All the authors analysed the data and contributed to the manuscript.

Competing financial interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to:

Author details

Supplementary information

PDF files

  1. Supplementary information (600 KB)

    Supplementary information

Additional data