Chemical Science
Page 4 of 6
DOI: 10.1039/C4SC03528C
The four cubes shown in Fig. 2e correspond to the four experiments
presented in Fig. 2aꢀd. Each bottom corner represents one of the four
possible orthoester products, while the top corners represent
unbound alcohols in solution in such a way that the compounds on
opposing corners of the cube are engaged in an agonistic
relationship28ꢀ30 (i.e., if one of the two compounds is stabilized or
destabilized, the other one is amplified or deamplified as a direct
result). In experiment (d) for example, the key to understanding the
somewhat counterintuitive reaction outcome is to realize that
unbound alcohol D is most effective at stabilizing the Na+ template
through chelate binding. Hence, the agonist pair of 3xD and 1E3
could be the ideal candidate for stabilizing the naked sodium ion,
however, the amplification of this pair of compounds is precluded by
the high ground state energy of agonist 1E3. The second best
solution for stabilizing Na+ would be the agonist pair of alcohols
2xD/1xE and orthoester 1E2D, which is indeed found as major
product, despite orthoester 1E2D being evidently more strained than
compound 1ED2 (see Fig. 2c and Scheme 2b for comparison).
Crucially, this type of analysis provides an accessible rational
explanation for the system’s behaviour in all four experiments
shown in Fig. 2, including the counterꢀintuitive reaction outcome
upon metal addition (Fig. 2d).31
1
(
a
) P. T. Corbett, J. Leclaire, L. Vial, K. R. West, J.ꢀL. Wietor, J. K.
M. Sanders and S. Otto, Chem. Rev., 2006, 106, 3652; ( ) Y. Jin, C.
Yu, R. J. Denman and W. Zhang, Chem. Soc. Rev., 2013, 42, 6634.
) S. Otto, R. L. E. Furlan and J. K. M. Sanders, Science, 2002, 297
590; ( ) A. Herrmann, Chem. Soc. Rev., 2014, 43, 1899.
) O. Ramström and J.ꢀM. Lehn, Nat. Rev. Drug Discov., 2002,
26; (
and M. Barboiu, Chem. Commun., 2014, 50, 8043; (
b
2
3
(a
,
,
b
(a
1
b
) M. Y. M. Abdelrahim, M. Tanc, J.ꢀY. Winum, C. T. Supuran
) M. Mondal, N.
c
Radeva, H. Köster, A. Park, C. Potamitis, M. Zervou, G. Klebe and
A. K. H. Hirsch, Angew. Chem., Int. Ed., 2014, 53, 3259.
4
(
a
) K. S. Chichak, S. J. Cantrill, A. R. Pease, S.ꢀH. Chiu, G. W. V.
Cave, J. L. Atwood and J. F. Stoddart, Science, 2004, 304, 1308; (
J.ꢀF. Ayme, J. E. Beves, D. A. Leigh, R. T. McBurney, K. Rissanen
and D. Schultz, Nat. Chem., 2012, , 15; ( ) N. Ponnuswamy, F. B.
b
)
4
c
L. Cougnon, J. M. Clough, G. D. Pantoꢂ and J. K. M. Sanders,
Science, 2012, 338, 783.
5
6
7
(
a
) S.ꢀY. Ding and W. Wang, Chem. Soc. Rev., 2013, 42, 548; (
Sforazzini, E. Orentas, A. Bolag, N. Sakai and S. Matile, J. Am.
Chem. Soc., 2013, 135, 12082; ( ) Y. Jin, Q. Wang, P. Taynton and
W. Zhang, Acc. Chem. Res., 2014, 47, 1575.
) J.ꢀM. Lehn, Prog. Polym. Sci., 2005, 30, 814; (
Cormos and N. Giuseppone, Chem. Soc. Rev., 2012, 41, 1031; (
b) G.
c
(a
b
) E. Moulin, G.
) Z.
Conclusions
c
We have demonstrated that the exchange of O,O,Oꢀorthoesters with
simple alcohols proceeds cleanly under relatively mild conditions.
Our experiments show that the reaction is suitable for the generation
of DCLs and that the equilibrium distribution can be shifted towards
different products by removal of methanol, by using a sterically
crowded orthoester starting material or by addition of a metal
template. Within the diverse toolbox of DCC, the dynamic orthoester
motif stands out due to its tripodal geometry, which enables the rapid
selfꢀassembly of molecules with threefold symmetry from up to four
components in only one step. Thanks to their three ‘docking sites’
for alcohols, orthoesters provide access to dynamic systems of high
complexity in one single step. The high potential of orthoester
exchange for applications in the field of systems chemistry was
demonstrated in this work by the observation of an unexpected
template effect and its rationalization by agonistic relationships in a
3D dynamic network. Our findings are relevant to all current
applications of DCC, in which the use of aqueous (coꢀ)solvent is not
required during the exchange process. Further studies on the
exploitation of template effects en route to more complex orthoester
architectures are underway in our laboratory.
Wei, J. H. Yang, J. Zhou, F. Xu, M. Zrinyi, P. H. Dussault, Y. Osada
and Y. M. Chen, Chem. Soc. Rev., 2014, 43, 8114.
(
a
) M. Kindermann, I. Stahl, M. Reimold, W. M. Pankau and G. von
Kiedrowski, Angew. Chem., Int. Ed., 2005, 44, 6750; ( ) R. F.
Ludlow and S. Otto, Chem. Soc. Rev., 2008, 37, 101; ( ) J. M. A.
Carnall, C. A. Waudby, A. M. Belenguer, M. C. A. Stuart, J. J.ꢀP.
Peyralans and S. Otto, Science, 2010, 327, 1502; ( ) Q. Ji, R. C.
Lirag and O. S. Miljanic, Chem. Soc. Rev., 2014, 43, 1873; ( ) A.
b
c
d
e
Jiménez, R. A. Bilbeisi, T. K. Ronson, S. Zarra, C. Woodhead and J.
R. Nitschke, Angew. Chem., Int. Ed., 2014, 53, 4556.
8
9
(
a
) J.ꢀM. Lehn, Chem. Eur. J., 1999,
Soc. Rev., 2007, 36, 151.
S. Billiet, K. De Bruycker, F. Driessen, H. Goossens, V. Van
5, 2455; (b) J.ꢀM. Lehn, Chem.
Speybroeck, J. M. Winne and F. E. Du Prez, Nat. Chem., 2014, 6,
815.
10 H. Otsuka, Polym. J., 2013, 45, 879.
11 Y. Yi, H. Xu, L. Wang, W. Cao and X. Zhang, Chem. Eur. J., 2013,
19, 9506.
Acknowledgements
12 (
Campaña, D. A. Leigh and U. Lewandowska, J. Am. Chem. Soc.
2013, 135, 8639; ( ) Y. Zhong, Y. Xu and E. V. Anslyn, Eur. J. Org.
a) G. Joshi and E. V. Anslyn, Org. Lett., 2012, 14, 4714; (b) A. G.
,
This work was supported by the Fonds der Chemischen Industrie
(Liebig fellowship for M.v.D.; FCI doctoral fellowship for R.ꢀC.B.)
and the Deutsche Forschungsgemeinschaft (EmmyꢀNoether grant
DE1830/2ꢀ1). We thank Andreas Zech and Michael Bothe for
experimental work carried out as part of undergraduate projects.
c
Chem., 2013, 2013, 5017.
13 H. Ying, Y. Zhang and J. Cheng, Nat. Commun., 2014, 5.
14 Y. Ruff, V. Garavini and N. Giuseppone, J. Am. Chem. Soc., 2014,
136, 6333.
Notes and references
15 A. SanchezꢀSanchez, D. A. Fulton and J. A. Pomposo, Chem.
Commun., 2014, 50, 1871.
a
FriedrichꢀAlexanderꢀUniversity ErlangenꢀNürnberg (FAU), Department
16 (
53, 6781; (
Pittelkow, Chem. Commun., 2014, 50, 3716.
17 ( ) R. Larsson, Z. Pei and O. Ramström, Angew. Chem., Int. Ed.
2004, 43, 3716; ( ) M. G. Woll and S. H. Gellman, J. Am. Chem.
Soc., 2004, 126, 11172; ( ) J. Leclaire, L. Vial, S. Otto and J. K. M.
Sanders, Chem. Commun., 2005, 1959; ( ) Y. Ura, J. M. Beierle, L. J.
a
) S. Ji, W. Cao, Y. Yu and H. Xu, Angew. Chem., Int. Ed., 2014,
of Chemistry and Pharmacy, Henkestrasse 42, 91054 Erlangen, Germany.
Eꢀmail: max.vondelius@fau.de
b
) B. Rasmussen, A. Sorensen, H. Gotfredsen and M.
† Electronic Supplementary Information (ESI) available: Experimental
procedures and spectroscopic data. See DOI: 10.1039/c000000x/
a
,
b
c
d
This journal is © The Royal Society of Chemistry 2013
Chem. Sci., 2014, 00, 1-3 | 4