Kinetic resolution of constitutional isomers controlled by selective protection inside a supramolecular nanocapsule

Abstract

The concept of self-assembling container molecules as yocto-litre reaction flasks is gaining prominence. However, the idea of using such containers as a means of protection is not well developed. Here, we illustrate this idea in the context of kinetic resolutions. Specifically, we report on the use of a water-soluble, deep-cavity cavitand to bring about kinetic resolutions within pairs of esters that otherwise cannot be resolved because they react at very similar rates. Resolution occurs because the presence of the cavitand leads to a competitive binding equilibrium in which the stronger binder primarily resides inside the host and the weaker binding ester primarily resides in the bulk hydrolytic medium. For the two families of ester examined, the observed kinetic resolutions were highest within the optimally fitting smaller esters.

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Figure 1: Molecular structures of the host and guests used in this study.
Figure 2: Binding of esters inside a deep-cavity cavitand.
Figure 3: Kinetics for the hydrolysis of ester 6 in the presence or absence of the cavitand.
Figure 4: Hydrolysis of similarly sized esters encapsulated within host 12.

References

  1. 1

    Vriezema, D. M. et al. Self-assembled nanoreactors. Chem. Rev. 105, 1445–1489 (2005).

  2. 2

    Leung, D. H., Bergman, R. G. & Raymond, K. N. Highly selective supramolecular catalyzed allylic alcohol isomerization. J. Am. Chem. Soc. 129, 2746–2747 (2007).

  3. 3

    Kaanumalle, L. S., Gibb, C. L. D., Gibb, B. C. & Ramamurthy, V. Controlling photochemistry with distinct hydrophobic nano-environments. J. Am. Chem. Soc. 126, 14366–14367 (2004).

  4. 4

    Kaanumalle, L. S., Gibb, C. L. D., Gibb, B. C. & Ramamurthy, V. A hydrophobic nano-capsule controls the photophysics of aromatic molecules by suppressing their favored solution pathways. J. Am. Chem. Soc. 127, 3674–3675 (2005).

  5. 5

    Kaanumalle, L. S., Gibb, C. L. D., Gibb, B. C. & Ramamurthy, V. Photo-Fries reaction in water made selective with a capsule. Org. Biomol. Chem. 5, 236–238 (2007).

  6. 6

    Natarajan, A. et al. Controlling photoreactions with restricted spaces and weak intermolecular forces: remarkable product selectivity during oxidation of olefins by singlet oxygen. J. Am. Chem. Soc. 129, 4132–4133 (2007).

  7. 7

    Gibb, C. L. D., Sundaresan, A. K., Ramamurthy, V. & Gibb, B. C. Templation of the excited-state chemistry of α-(n-alkyl) dibenzyl ketones: how guest packing with a nanoscale supramolecular capsule influences photochemistry. J. Am. Chem. Soc. 130, 4069–4080 (2008).

  8. 8

    Sundaresan, A. K., Gibb, C. L.D., Gibb, B. C. & Ramamurthy, V. Chiral photochemistry in a confined space: torquoselective photoelectrocyclization of pyridones within an achiral hydrophobic capsule. Tetrahedron 65, 7277–7288 (2009).

  9. 9

    Sundaresan, A. K., Kaanumalle, L. S., Gibb, C. L. D., Gibb, B. G. & Ramamurthy, V. Chiral photochemistry within a confined space: diastereoselective photorearrangements of a tropolone and a cyclohexadienone included in a synthetic cavitand. Dalton Trans. 4003–4011 (2009).

  10. 10

    Pluth, M. D., Bergman, R. G. & Raymond, K. N. Acid catalysis in basic solution: a supramolecular host promotes orthoformate hydrolysis. Science 316, 85–88 (2007).

  11. 11

    Pluth, M. D., Bergman, R. G. & Raymond, K. N. Catalytic deprotection of acetals in basic solution with a self-assembled supramolecular ‘nanozyme’. Angew. Chem. Int. Ed. 46, 8587–8589 (2007).

  12. 12

    Pluth, M. D., Bergman, R. G. & Raymond, K. N. Supramolecular cataysis of orthoformate hydrolysis in basic solution: an enzyme like mechanism. J. Am. Chem. Soc. 130, 11423–11429 (2008).

  13. 13

    Furusawa, T., Kawano, M. & Fujita, M. The confined cavity of a coordination cage suppresses the photocleavage of α-diketones to give cyclization products through kinetically unfavorable pathways. Angew. Chem. Int. Ed. 46, 5717–5719 (2007).

  14. 14

    Murase, T., Sato, S. & Fujita, M. Nanometer-sized shell molecules that confine endohedral polymerizing units. Angew. Chem. Int. Ed. 46, 1083–1085 (2007).

  15. 15

    Nishioka, Y., Yamaguchi, T., Kawano, M. & Fujita, M. Asymmetric (2+2) olefin cross photoaddition in a self-assembled host with remote chiral auxiliaries. J. Am. Chem. Soc. 130, 8160–8161 (2008).

  16. 16

    Yamaguchi, T. & Fujita, M. Highly selective photomediated 1,4-radical addition to o-quinones controlled by a self-assembled cage. Angew. Chem. Int. Ed. 47, 2067–2069 (2008).

  17. 17

    Chen, J., Körner, S., Craig, S. L., Rudkevich, D. M. & Rebek, J. Jr. Amplification by compartmentalization. Nature 415, 385–386 (2002).

  18. 18

    Hayashida, O., Sebo, L. & Rebek, J. Jr. Molecular discrimination of N-protected amino acid esters by a self-assembled cylindrical capsule: spectroscopic and computational studies. J. Org. Chem. 67, 8291–8298 (2002).

  19. 19

    Purse, B. W., Gissot, A. & Rebek, J. Jr. A deep-cavitand provides a structured environment for the Menschutkin reaction. J. Am. Chem. Soc. 127, 11222–11223 (2005).

  20. 20

    Iwasawa, T., Wash, P., Gibson, C. & Rebek, J. Jr. Reaction of an introverted carboxylic acid with carbodiimide. Tetrahedron 63, 6506–6511 (2007).

  21. 21

    Shenoy, S. R., Crisostomo, F. R. P., Iwasawa, T. & Rebek, J. Jr. Organocatalysis in a synthetic receptor with and inwardly directed carboxylic acid. J. Am. Chem. Soc. 130, 5658–5659 (2008).

  22. 22

    Crisostomo, F. R. P., Lkedo, A., Shenoy, S. R., Iwasawa, T. & Rebek, J. Jr. Recognition and organocatalysis with a synthetic cavitand receptor. J. Am. Chem. Soc. 131, 7402–7410 (2009).

  23. 23

    Warmuth, R. & Yoon, J. Recent highlights in hemicarcerand chemistry. Acc. Chem. Res. 34, 95–105 (2001).

  24. 24

    Yebeutchou, R. M. & Dalcanale, E. Highly selective monomethylation of primary amines through host–guest product sequestration. J. Am. Chem. Soc. 131, 2452–2453 (2009).

  25. 25

    Vedejs, E. & Jure, M. Efficiency in nonenzymatic kinetic resolution. Angew. Chem. Int. Ed. 44, 3974–4001 (2005).

  26. 26

    Williams, J. M. J., Parker, R. J. & Neri, C. Enzyme Catalysis in Organic Synthesis (eds Drauz, K. & Waldmann H.) (Wiley-VCH, 2002).

  27. 27

    Pellissier, H. Recent developments in dynamic kinetic resolution. Tetrahedron 64, 1563–1601 (2008).

  28. 28

    Martín-Matute, B. & Bäckvall, J. Dynamic kinetic resolution catalyzed by enzymes and metals. Curr. Opin. Chem. Biol. 226–232 (2007).

  29. 29

    Gibb, B. C. in Organic Nano-Structures (eds Atwood, J. L.& Steed, J. W.) (John Wiley & Sons, 2007).

  30. 30

    Liu, S. & Gibb, B. C. High-definition self-assemblies driven by the hydrophobic effect: synthesis and properties of a supramolecular nanocapsule. Chem. Commun. 3709–3716 (2008).

  31. 31

    Ewell, J., Gibb, B. C. & Rick, S. W. Water inside a hydrophobic cavitand molecule. J. Phys. Chem. B 112, 10272–10279 (2008).

  32. 32

    Gibb, C. L. D. & Gibb, B. C. Templated assembly of water-soluble nano-capsules: inter-phase sequestration, storage and separation of hydrocarbon gases. J. Am. Chem. Soc. 128, 16498–16499 (2006).

  33. 33

    Gibb, C. L. D. & Gibb, B. C. Well defined, organic nano-environments in water: the hydrophobic effect drives a capsular assembly. J. Am. Chem. Soc. 126, 11408–11409 (2004).

  34. 34

    Gibb, C. L. D. & Gibb, B. C. Guests of differing polarities provide insight into structural requirements for templates of water-soluble nano-capsules. Tetrahedron 65, 7240–7248 (2009).

  35. 35

    Gibb, C. L. D. & Gibb, B. Straight-chain alkanes template the assembly of water-soluble nano-capsules. Chem. Commun. 1635–1637 (2007).

  36. 36

    Trembleau, L. & Rebek, J. Jr. Helical conformation of alkanes in a hydrophobic cavitand. Science 301, 1219–1220 (2003).

  37. 37

    Seeman, J. I. Effects of conformational change on reactivity in organic chemistry. evaluations, applications and extensions of Curtin–Hammett/Winstein–Holness kinetics. Chem. Rev. 83, 83–134 (1983).

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Acknowledgements

B.C.G. acknowledges financial support from the National Science Foundation (NSF; CHE-0718461), the National Institutes of Health (NIH; GM074031) and the Post-Katrina Support Fund Initiative (PKSFI, LEQSF(2007-12)-ENH-PKSFI-PRS-04). S.W.R. acknowledges financial support from the NSF (CHE-0611679). The authors also thank G. Raman and A. Sankaranarayanan for calculating the dipole, log P and solubility values of esters 2 to 6.

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B.C.G. and S.L. conceived and designed the experiments. S.L. synthesized esters 26 and performed the experiments involving these guests. H.G. and A.T.H contributed equally to the syntheses and experiments involving esters 711. B.C.G. wrote the paper.

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Correspondence to Bruce C. Gibb.

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The authors declare no competing financial interests.

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Liu, S., Gan, H., Hermann, A. et al. Kinetic resolution of constitutional isomers controlled by selective protection inside a supramolecular nanocapsule. Nature Chem 2, 847–852 (2010). https://doi.org/10.1038/nchem.751

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