9628
J. Am. Chem. Soc. 2000, 122, 9628-9630
New Molecular Vessels: Synthesis and Chiroselective Recognition
Shoichi Saito, Colin Nuckolls, and Julius Rebek, Jr.*
Contribution from The Skaggs Institute for Chemical Biology and Department of Chemistry, The Scripps
Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037
ReceiVed June 21, 2000
Abstract: A new structural motif for synthetic receptors is reported. This new motif allows for the incorporation
of a variety of nonracemic groups into the structure’s upper rim. These stereocenters effectively transfer their
asymmetry to the flexible walls of the vessel and result in handed spaces with increased stability in protic
media. Their synthesis and chiroselective recognition for their guest molecules are described.
Synthetic receptors such as 1 are maintained in their receptive
states by a seam of hydrogen bonds.1 These molecular hosts
show high barriers to the exchange of guests in solution,2 form
complexes with ions in the gas phase,3 and yield molecule-
within-molecule crystals in the solid state.4 We report here a
new structural motif, 2, that allows for the incorporation of a
variety of nonracemic groups into the structure’s upper rim.
These stereocenters effectively transfer their asymmetry to the
flexible walls of the vessel and result in handed spaces with
increased stability in protic media.
The synthesis of these molecules 2a-g 5 involves the
straightforward condensation of each of the protected dichloro-
imides with Ho¨gberg’s resorcinarene6 followed by liberation
of the alcohol function (Scheme 1). The solution-phase con-
formation of the structures can be monitored by NMR: when
in the vase-like C4 conformation (shown in Figure 1), the
methine protons appear at ca. 5.6 ppm; when the walls inter-
conVert between the two pseudo-C2V, “kite” conformations7 (not
shown) these same signals appear upfield of 4 ppm.8 Using this
criterion, structures 2a-f exist in the vase shape in CDCl3sa
solvent that does not effectively compete for hydrogen bondss
and the kite-like conformation in competitive media such as
DMF.9
repulsive interactions between the oxygens of neighboring
carbonyls and to bring the hydroxyls into proximity for hydrogen
bonds. The hydrogen bond donors in Figure 1a bifurcate
between the carbonyls of its own and neighboring phthalimide.
Alternatively, the hydroxyls of each phthalimide cooperate as
donor and acceptor as in Figure 1b to form a cyclic seam of
hydrogen bonds. We cannot distinguish between the two motifs,
Two different arrangements of intramolecular hydrogen bonds
(Figure 1) are predicted through molecular modeling.10 In both
models, the walls collapse inward presumably to minimize the
(1) Rudkevich, D. M.; Rebek, J., Jr. Eur. J. Org. Chem. 1999, 1991-
2005 and references therein.
(2) Kinetically stable host-guest complexes of a resorcinarene containing
a hydrogen-bonding seam were first shown by Aoyama and co-workers:
(a) Kikuchi, Y.; Kato, Y.; Tanaka, Y.; Toi, H.; Aoyama, Y. J. Am. Chem.
Soc. 1991, 113, 1349-54. (b) Kobayashi, K.; Asakawa, Y.; Kikuchi, Y.;
Toi, H.; Aoyama, Y. J. Am. Chem. Soc. 1993, 115, 2648-54. More closely
related molecules also show high barriers to guest exchange: (c) Rudkevich,
D. M.; Hilmersson, G.; Rebek, J., Jr. J. Am. Chem. Soc. 1998, 120, 12216-
25. (d) Ma, S.; Rudkevich, D. M.; Rebek, J., Jr. Angew. Chem., Int. Ed.
Engl. 1999, 38, 2600-2602 and the work cited in ref 1 therein.
(3) For cavitands without a seam of hydrogen bonds, see: (a) Vincenti,
M.; Dalcanale, E.; Soncini, P.; Guglielmetti, G. J. Am. Chem. Soc. 1990,
112, 445-7. (b) Vincenti, M.; Minero, C.; Pelizzetti, E.; Secchi, A.;
Dalcanale, E. Pure Appl. Chem. 1995, 67, 1075-84. (c) Dickert, F. L.;
Baumler, U. P. A.; Stathopulos, H. Anal. Chem. 1997, 69, 1000-5.
(4) For cavitands containing a seam of hydrogen bonds that crystallize
as “molecule-within-vase” complexes, see: Shivanyuk, A.; Rissanen, K.;
Konner, S. K., Rudkevich, D. M.; Rebek, J., Jr. HelV. Chim. Acta In press.
(5) The synthetic method generally follows the procedure developed by
Cram and co-workers: Moran, J. R.; Karbach, S.; Cram, D. J. J. Am. Chem.
Soc. 1982, 104, 5826-8. Protocols and characterization for the syntheses
of 2a-g can be found in the Supporting Information.
(7) A description of the dynamic folding process for similar molecules
(derivatives of 1) can be found in: Tucci, F.; Rudkevich, D.; Rebek, J., Jr.
Chem., Eur. J. 2000, 122, 4573-82.
(8) The methine protons of flexible-walled cavitands resonate at 5.67
ppm in the C4V (vase) conformation and at 3.92 ppm in the dynamic, C2V
(kite) conformation: (a) Moran, J. R.; Ericson, J. L.; Dalcanale, E.; Bryant,
J. A.; Knobler, C. B.; Cram, D. J. J. Am. Chem. Soc. 1991, 113, 5707-14.
(b) Cram, D. J.; Choi, H.-J.; Bryant, J. A.; Knobler, C. B. J. Am. Chem.
Soc. 1992, 114, 7748-65. The methine protons for cavitands whose walls
are covalently held upright but slightly open resonate at 4.96 ppm: Cram,
D. J.; Karbach, S.; Kim, H.-E.; Knobler, C. B.; Maverick, E. F.; Ericson,
J. L.; Helgeson, R. C. J. Am. Chem. Soc. 1988, 110, 2229-37.
(9) The methine chemical shift for 2a-f is 5.6 ( 0.1 ppm in CDCl3 and
4.0 ( 0.1 ppm in DMF-d7. In CDCl3 appropriately sized guest molecules
could be added and their resonances appeared upfield of 0 ppm but did not
appear in DMF-d7.
(10) Molecular modeling of assemblies was carried out using Macro-
Model 6.5 and the Amber* force field: Mohamadi, F.; Richards, N. G. J.;
Guide, W. C.; Liskamp, R.; Lipton, M.; Caufield, C.; Chang, G.;
Hendrickson, T.; Still, W. C. J. Comput. Chem. 1990, 11, 440-67.
(6) Ho¨gberg, A. G. S. J. Am. Chem. Soc. 1980, 102, 6046-8.
10.1021/ja002220i CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/23/2000