pubs.acs.org/joc
dynamic motion,3 induce functional groups to adopt high-
Macrocycle Breathing in [2]Rotaxanes with
Tetralactam Macrocycles
energy conformations,4 and alter molecular reactivity.5-7 In
most cases the reactivity change is a decrease due to steric
protection; however, we recently reported an unusual exam-
ple of reaction acceleration. We discovered that the cyclor-
eversion reaction of a tetralactam macrocycle containing an
anthracene 9,10-endoperoxide group was increased substan-
tially when the macrocyle encapsulated a squaraine thread
component and thus existed as a [2]rotaxane.5 Furthermore,
large rate enhancements were obtained by making subtle
changes in the structure of the two bridging units in the
tetralactam macrocycle. For example, squaraine rotaxane
macrocycles with bridging 2,6-pyridine dicarboxamide units
were found to be 250 times more reactive than macrocycles
with bridging isophthalamide units.7a While the influence of
2,6-pyridine dicarboxamide units on structural dynamics is
well studied,8 enhanced reactivity is a new molecular attri-
bute that needs to be fully understood to ensure effective
exploitation. Published X-ray crystal structures indicate that
the 2,6-pyridine dicarboxamides contract the macrocycle
cavity so that it wraps more tightly around the encapsulated
squaraine thread.7a,9 The driving force for this cavity con-
traction is formation of hydrogen bonds between the pyridyl
nitrogen and the adjacent amide NH residues. This draws the
Ivan Murgu, Jeffrey M. Baumes, Jens Eberhard,
Jeremiah J. Gassensmith, Easwaran Arunkumar, and
Bradley D. Smith*
Department of Chemistry and Biochemistry, 236 Nieuwland
Science Hall, University of Notre Dame, Notre Dame,
Indiana 46556, United States
Received October 19, 2010
The structural dynamics of two pairs of [2]rotaxanes were
compared using variable-temperature NMR. Each rota-
xane had a surrounding tetralactam macrocycle with either
2,6-pyridine dicarboxamide or isophthalamide bridging
units. Differences were observed in two types of rota-
tional processes: spinning of the phenylene wall units in
the surrounding macrocycle of squaraine rotaxanes and
macrocycle pirouetting in xanthone rotaxanes. The ro-
taxanes with macrocycles containing 2,6-pyridine dicar-
boxamide bridges exhibited higher rotational barriers due
to a cavity contraction effect, which disfavored macro-
cycle breathing.
(3) (a) Clegg, W.; Gimenez-Saiz, C.; Leigh, D. A.; Murphy, A.; Slawin,
A. M. Z.; Teat, S. J. J. Am. Chem. Soc. 1999, 121, 4124–4129. (b) Yoon, I.;
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Miljanic, O. S.; Benitez, D.; Khan, S. I.; Stoddart, J. F. Chem. Commun. 2008,
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4561–4563. (c) Miljanic, O. S.; Dichtel, W. R.; Khan, S. I.; Mortezaei, S.;
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Heath, J. R.; Stoddart, J. F. J. Am. Chem. Soc. 2007, 129, 8236–8246. (d) Rijs,
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A. M.; Sandig, N; Blom, M. N.; Oomens, J.; Hannam, J. S.; Leigh, D. A.;
Zerbetto, F.; Buma, W. J. Angew. Chem., Int. Ed. 2010, 49, 3896–3900. (e)
Larsen, O. F. A.; Bodis, P.; Buma, W. J.; Hannam, J. S.; Leigh, D. A.;
Woutersen, S. Proc. Natl. Acad. Sci. U.S.A. 2005, 102, 13378–13382. (f) Zhu,
S. S.; Nieger, M.; Daniels, J.; Felder, T.; Kossev, I.; Schmidt, T.; Sokolowski,
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M.; Millet, O. Prog. Nucl. Magn. Reson. Spectrosc. 2001, 38, 267–324. (h)
Coutrot, F.; Busseron, E. Chem.;Eur. J. 2009, 15, 5186–5190. (i) Busseron,
E.; Romuald, C.; Coutrot, F. Chem.;Eur. J. 2010, 16, 10062–10073. (j)
Romuald, C.; Busseron, E.; Coutrot, F. J. Org. Chem. 2010, 75, 6516–6531.
(k) Loeb, S. J.; Tiburcio, J.; Vella, S. J. Chem. Commun. 2006, 1598–1600.
(4) (a) Leigh, D. A.; Lusby, P. J.; Slawin, A. M. Z.; Walker, D. B. Angew.
Chem., Int. Ed. 2005, 44, 4557–4564. (b) Brancato, G.; Coutrot, F.; Leigh,
D. A.; Murphy, A.; Wong, J. K. Y.; Zerbetto, F. Proc. Natl. Acad. Sci. U.S.A.
2002, 99, 4967–4971.
Essentially all modern methods for preparing rotaxanes
involve templated synthetic reactions, and in most cases the
assembled product retains the noncovalent interactions
that were the basis of the template effect.1,2 The internally
directed interactions, enforced by the mechanical bond,
keep the interlocked components in close contact, restrict
(5) Baumes, J. M.; Gassensmith, J. J.; Giblin, J.; Lee, J. -J.; White, A. G.;
Culligan, W. J.; Leevy, W. M.; Kuno, M.; Smith, B. D. Nature Chem. 2010, 2,
1025–1030.
(6) For recent examples of steric protection, see: (a) Fernandes, A.;
Viterisi, A.; Coutrot, F.; Potok, S.; Leigh, D. A.; Aucagne, V.; Papot, S.
Angew. Chem., Int. Ed. 2009, 48, 6443–6447. (b) D’Souza, D. M.; Leigh,
D. A.; Mottier, L.; Mullen, K. M.; Paolucci, F.; Teat, S. J.; Zhang, S. J. Am.
Chem. Soc. 2010, 132, 9465–9470. (c) Gassensmith, J. J.; Matthys, S.; Lee,
J. -J.; Wojcik, A.; Kamat, P. V.; Smith, B. D. Chem.;Eur. J. 2010, 16, 2916–
2921.
€
(1) For recent reviews of rotaxanes, see: (a) Hanni, K. D.; Leigh, D. A.
(7) (a) Baumes, J. M.; Murgu, I.; Oliver, A.; Smith, B. D. Org. Lett. 2010,
12, 4980–4983. (b) Gassensmith, J. J.; Baumes, J. M.; Eberhard, J.; Smith,
B. D. Chem. Commun. 2009, 2517–2519.
(8) See, for example: (a) Johnston, A. G.; Leigh, D. A.; Nezhat, L.; Smart,
J. P.; Deegan, M. D. Angew. Chem., Int. Ed. Engl. 1995, 34, 1212–1216. (b)
Chem. Soc. Rev. 2010, 39, 1240–1251. (b) Ma, X.; Tian, H. Chem. Soc. Rev.
2010, 39, 70–80. (c) Harada, A.; Hashidzume, A.; Yamaguchi, H.; Takashima,
Y. Chem. Rev. 2009, 109, 5974–6023. (d) Balzani, V.; Credi, A.; Venturi, M.
Chem. Soc. Rev. 2009, 38, 1542–1550. (e) Stoddart, J. F. Chem. Soc. Rev. 2009,
38, 1802–1820. (f) Mullen, K. M.; Beer, P. D. Chem. Soc. Rev. 2009, 38, 1701–
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€
Schalley, C. A. J. Phys. Org. Chem. 2004, 17, 967–972. (c) Affeld, A.; Hubner,
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references therein.
(2) For examples of rotaxane syntheses that eliminate the internally
€
directed template interactions, see: (a) Aucagne, V.; Hanni, K. D.; Leigh,
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J. Org. Chem. 2009, 74, 6462–6468. (b) Gassensmith, J. J.; Arunkumar, E.;
Barr, L.; Baumes, J. M.; DiVittorio, K. M.; Johnson, J. R.; Noll, B. C.;
Smith, B. D. J. Am. Chem. Soc. 2007, 129, 15054–15059. (c) Arunkumar, E.;
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D. A.; Lusby, P. J.; Walker, D. B. J. Am. Chem. Soc. 2006, 128, 2186–2187.
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M. D. Chem. Commun. 2010, 46, 2382–2384. (d) Saito, S.; Takahashi, E.;
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688 J. Org. Chem. 2011, 76, 688–691
Published on Web 12/17/2010
DOI: 10.1021/jo1020739
r
2010 American Chemical Society