J. Org. Chem. 2000, 65, 513-516
513
Restricted Motion of Guests Confined in Carceplexes and Capsules Robert G. Chapman and John C. Sherman* Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia, Canada V6T 1Z1 Received September 13, 1999
Guest orientation within carceplexes and capsules was determined qualitatively from NMR data, and the molecular mobility of guests was determined via coalescence of 1H NMR signals. Both are highly dependent on guest size and shape, as is interconversion of twistomers. Incarceration of 1,4-thioxane results in a large (1.8 kcal/mol) constraint on thioxane’s conformational mobility (chairto-chair interconversion). Similar conformational constraints (1.6 kcal/mol) were determined for 1,4-dioxane both when incarcerated in carceplex 1b and when encapsulated reversibly in capsule 3b. Encapsulation-induced conformational constraints of this magnitude are unprecedented, and are particularly striking for the noncovalently linked capsules. Introduction
Table 1. δ (ppm) Values of Guest Molecules in Carceplexes 1a‚Guest at Ambient Temperature in CDCl3
Chemistry in confined media is currently a highly active area of research.1 Confined media comprise the solid state as well as discrete species in solution such as carceplexes and capsules. The molecular (as opposed to conformational) mobility of guests permanently entrapped in carceplexes has been reported by Cram and others.2 Rebek has described the effect of reversible capsules on the conformational freedom of guests.3 We have recently elucidated the twisting of cavitands with respect to each other in carceplexes and related capsules.4 Here we report the conformational restrictions put on guests encapsulated in carceplexes and capsules. The effects are surprisingly large, and are most likely due to the rigidity of the cavitand subunits and the inflexibility of the intercavitand linkers. We begin with a discussion of guest orientation within a carceplex or capsule based on 1H NMR chemical shifts. We follow with the molecular mobility of encapsulated guests, and then present conformational restrictions of confined guests. Twisting of the cavitands is integral to each of these phenomena and is discussed in these sections. * To whom correspondence should be addressed. E-mail: sherman@ chem.ubc.ca. (1) (a) Rebek, J., Jr. Acc. Chem. Res. 1998, 32, 278-286. (b) Gamlin, J. N.; Jones, R.; Leibovitch, M.; Patrick, B.; Scheffer, J. R.; Trotter, J. Acc. Chem. Res. 1996, 29, 203-209. (2) (a) Kurdistani, S. K.; Robbins, T. A.; Cram, D. J. J. Chem. Soc., Chem. Commun. 1995, 1259. (b) Timmerman, P.; Verboom, W.; van Veggel, F. C. J. M.; van Duynhoven, J. P. M.; Reinhoudt, D. N. Angew. Chem., Int. Ed. Engl. 1994, 33, 2345-2348. (c) van Wageningen, A. M. A.; Timmerman, P.; van Duynhoven, J. P. M.; Verboom, W.; van Veggel, F. C. J. M.; Reinhoudt, D. N. Chem. Eur. 1997, 3, 639-654. (d) Fraser, J. R.; Borecka, B.; Trotter, J.; Sherman, J. C. J. Org. Chem. 1995, 60, 1207-1213. (e) Place, D.; Brown, J.; Deshayes, K. Tetrahedron Lett. 1998, 39, 5915-5918. See also: Jasat, A.; Sherman, J. C. Chem. Rev. 1999, 99, 931-967. (3) (a) O’Leary, B. M.; Grotzfeld, R. M.; Rebek, J., Jr. J. Am. Chem. Soc. 1997, 119, 11701-11702. (b) Hilmersson, G.; Rebek, J., Jr. Magn. Reson. Chem. 1998, 36, 663-669. (c) Rebek, J., Jr. Acc. Chem. Res. 1999, 32, 278-286. See also: Kirchhoff, P. D.; Dutasta, J.-P.; Collet, A.; McCammon, J. A. J. Am. Chem. Soc. 1999, 121, 381-390. (4) In a variety of bisbowl systems, the two cavitands are twisted with respect to one another. We have called the two enantiomeric forms twistomers: Chapman, R. G.; Sherman, J. C. J. Am. Chem. Soc. 1999, 121, 1962-1963.
b
a δ of free guest determined in CDCl at ambient temperature. 3 ∆δ ) δfree - δentrapped. c Carceplex 1b‚pyrazine.
Results Guest Orientation. Comparison of the crystal structures of carceplexes 1a‚DMA5 and 1b‚pyrazine2c with the 1 H NMR ∆δ (δ of free guest - δ of encapsulated guest) of the guest protons (Table 1) demonstrates that larger ∆δ values imply closer proximity of these moieties to the arenes lining the top and bottom of the hosts’ cavities.
10.1021/jo991433r CCC: $19.00 © 2000 American Chemical Society Published on Web 12/03/1999
514
J. Org. Chem., Vol. 65, No. 2, 2000
Chapman and Sherman
Table 2. Range in 1H NMR ∆δ (ppm) Values of Host Signals for Carceplexes 1a‚Guest in CDCl3 at Ambient Temperature guest
Hpa (ppm)
Hbb (ppm)
Houtc (ppm)
Hinc (ppm)
all aromatic 6.93-6.84 6.52-6.47 6.12-6.02 4.26-4.10 guests all nonaromatic 6.78-6.63 6.61-6.54 6.24-6.08 4.86-4.26 guestsd a
Hp, H para to interbowl acetal. b Hb, CH2 of interbowl acetal. Hin, Hout, see structure block. d Excludes the 1H NMR signals for carceplex 1a‚NMP, which was anomalous: Hp (6.74, 6.71), Hb (6.32), Hout (6.03), and Hin (4.68).
Table 3. guest pyrazine pyridine benzene
c
Data for nine representative guests are given in Table 1 (30 more are provided in the Supporting Information). Generally, ∆δ values over 4 ppm indicate a close proximity to the arenes, while ∆δ values of less than 2 ppm indicate positioning near the host’s equator. As has been observed by Cram in hemicarceplexes,6 host protons that line the cavity are sensitive to the encapsulated guest. Table 2 summarizes the range of δ for host protons in the presence of 7 aromatic guests and 33 nonaromatic guests in carceplex 1a‚guest. The sensitivity of host protons is indeed high for protons lining the cavity, and low for peripheral protons: Whereas Hin varies by 0.76 ppm, the pendent group protons and the methine protons of the host vary by
