ORGANIC
LETTERS
2
007
Vol. 9, No. 5
45-748
Electrophilic Substitution of Deep Cavity
Cavitands: Selective Exo
7
Functionalization of Molecular Concavity
Kannupal Srinivasan and Bruce C. Gibb*
Department of Chemistry, UniVersity of New Orleans, New Orleans, Louisiana 70148
Received November 29, 2006
ABSTRACT
The functionalization of deep-cavity cavitands via electrophilic substitution was investigated. In the parent structures, substitution occurs
both at the exo position of the bowl-shaped hosts and on the convex face. Little or no endo substitution was observed. In contrast, derivatives
in which methyl groups blocked the reaction sites on the convex face reacted selectively at the exo positions.
Molecular concavity, and its corresponding supramolecular
phenomenon, molecular encapsulation, lies at the heart of
many chemical processes. The masters of chemical transforma-
tionsenzymessrely on substrate encapsulation for their
remarkable selectivities and rate accelerations. Although
synthetic systems are some way from attaining the much
sought after acceleration and oft sought after selectivity of
enzymes, progress is being made, in terms of both catalyst
developers increasingly building cavities around their cata-
lytic centers of choice and host-guest chemists introducing
catalytic centers into their cavities of choice. In regards to
We have previously reported on the synthesis of deep-
cavity cavitands such as 1 (Figure 1). These hosts are readily
available (three steps from commercially available materials)
6
(2) (a) Darbost, U.; Rager, M.-N.; Petit, S.; Jabin, I.; Reinaud, O. J. Am.
Chem. Soc. 2005, 127, 8517. (b) S e´ n e` que, O.; Rager, M.-N.; Giorgi, M.;
Prang e´ , T.; Tomas, A.; Reinaud, O. J. Am. Chem. Soc. 2005, 127, 14833.
c) Rondelez, Y.; Rager, M. N.; Duprat, A.; Reinaud, O. J. Am. Chem.
Soc. 2002, 124, 1334. (d) Rondelez, Y.; Bertho, G.; Reinaud, O. Angew.
Chem., Int. Ed. 2002, 41, 1044. (e) S e´ n e` que, O.; Rager, M.-N.; Giorgi, M.;
Reinaud, O. J. Am. Chem. Soc. 2001, 123, 8442. (f) S e´ n e` que, O.; Rager,
M.-N.; Giorgi, M.; Reinaud, O. J. Am. Chem. Soc. 2000, 122, 6183. (g)
Blanchard, S.; Le Clainche, L.; Rager, M.-N.; Tuchagues, J.-P.; Dupart, A.
F.; Le Mest, Y.; Reinaud, O. Angew. Chem., Int. Ed. 1998, 37, 2732. (h)
Zeng, X.; Hucher, N.; Reinaud, O.; Jabin, I. J. Org. Chem. 2004, 69, 6886.
(
1
the latter, the pioneering work of Breslow demonstrated the
(
4
i) Darbost, U.; Giorgi, M.; Reinaud, O.; Jabin, I. J. Org. Chem. 2004, 69,
879. (j) Jabin, I.; Reinaud, O. J. Org. Chem. 2003, 68, 3416.
importance of having the binding cavity of a host and its
catalytic machinery as proximate as possible. Building on
this earlier work, considerable progress has recently been
(
3) Laughrey, Z. R.; Gibb, B. C. J. Org. Chem. 2006, 71, 1289.
(4) (a) Hooley, R. J.; Van Anda, H. J.; Rebek, J., Jr. J. Am. Chem. Soc.
2006, 128, 3894. (b) Hooley, R. J.; Biros, S. M.; Rebek, J., Jr. Angew.
Chem., Int. Ed. 2006, 45, 3517.
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3-5
made using calixarenes and resorcinarenes in the devel-
opment of single-portal hosts possessing concave functional-
ity. Indeed, included in this list of endeavors are a range of
resorcinarene-based hosts which possess not just exception-
(5) (a) Hooley, R. J.; Biros, S. M.; Rebek, J., Jr. Chem. Commun. 2006,
509. (b) Purse, B. W.; Rebek, J., Jr. Proc. Natl. Acad. Sci. U.S.A. 2005,
1
2
1
02, 10777. (c) Purse, B. W.; Gissot, A.; Rebek, J., Jr. J. Am. Chem. Soc.
005, 127, 11222. (d) Richeter, S.; Rebek, J., Jr. J. Am. Chem. Soc. 2004,
26, 16280. (e) Gissot, A.; Rebek, J., Jr. J. Am. Chem. Soc. 2004, 126,
ally integrated binding sites and functionality but also reactive
7424. (f) Purse, B. W.; Ballester, P.; Rebek, J., Jr. J. Am. Chem. Soc. 2003,
125, 14682. (g) Gibson, C.; Rebek, J., Jr. Org. Lett. 2002, 4, 1887. (h)
Renslo, A. R.; Rebek, J., Jr. Angew. Chem., Int. Ed. 2000, 39, 3281. (i)
Starnes, S. D.; Rudkevich, D. M.; Rebek, J., Jr. J. Am. Chem. Soc. 2001,
123, 4659. (j) Wash, P. L.; Renslo, A. R.; Rebek, J., Jr. Angew. Chem., Int.
Ed. 2001, 40, 1221.
or catalytic properties.5
(1) (a) Breslow, R.; Dong, S. D. Chem. ReV. 1998, 98, 1997. (b) Breslow,
R. Acc. Chem. Res. 1995, 28, 146.
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0.1021/ol062897w CCC: $37.00
© 2007 American Chemical Society
Published on Web 02/06/2007