Preparation and use of sterically hindered organobis(2,4,6-triisopropylphenyl)hydroborates and their polystyrene derivatives for the diastereoselective reduction of ketones

(Note: The full text of this document is currently only available in the PDF Version )

Keith Smith, Gamal A. El-Hiti, Duanjie Hou and Gareth A. DeBoos


Abstract

Preparations of benzyl and phenylbis(2,4,6-triisopropylphenyl)hydroborates [organoditripylhydroborates] are outlined. The lithium and potassium benzylditripylhydroborates reduce substituted cyclohexanones with diastereoselectivities comparable to those obtained with the most selective reagents known (e.g. 99% cis-4-methylcyclohexanol from 4-methylcyclohexanone). Lithium phenylditripylhydroborate also reduces ketones with significant selectivity. For example, 4-methylcyclohexanone is reduced to cis-4-methylcyclohexanol in 88% isomeric purity. Unlike with most other highly selective reagents the reactions take place at room temperature and have the additional advantage that the boron reagent can be recovered quantitatively. Coupling of Merrifield’s resin with ditripylfluoroborane in the presence of lithium naphthalenide affords (ditripylborylmethyl)polystyrene. Similarly, coupling of bromopolystyrene with ditripylfluoroborane in the presence of n-BuLi affords (ditripylboryl)polystyrene. Reactions of these polymeric organoboranes with t-BuLi give the corresponding polymer-supported lithium hydroborates. Lithium ditripylhydroboratylmethylpolystyrene reduces cyclic ketones in identical fashion to its non-polymeric counterpart, giving the corresponding thermodynamically less stable alcohols in 99% or better isomeric purity. Similarly, lithium ditripylhydroboratylpolystyrene behaves like its non-polymeric counterpart and reduces 4-methylcyclohexanone to cis-4-methylcyclohexanol in 89% isomeric purity. Recovery and reuse of the organoboranes are even easier for the polymeric reagents.


References

  1. (a) K. Smith, in Organometallics in Synthesis, ed. A. Manual and M. Schlosser, John Wiley & Sons, Chichester, 1994, pp. 461–508 Search PubMed; (b) A. Pelter, K. Smith and H. C. Brown, Borane Reagents, Academic Press, London, 1988 Search PubMed; (c) R. S. Atkinson, Stereoselective Synthesis, John Wiley & Sons, Chichester, 1995 Search PubMed.
  2. E. C. Ashby and J. R. Boone, J. Org. Chem., 1976, 41, 2890 CrossRef CAS.
  3. D. C. Wigfield and D. J. Phelps, J. Org. Chem., 1976, 41, 2396 CrossRef CAS.
  4. D. C. Wigfield, Tetrahedron, 1979, 35, 449 CrossRef CAS.
  5. H. C. Brown and V. Varma, J. Am. Chem. Soc., 1974, 39, 1631 CAS.
  6. H. C. Brown and W. C. Dickason, J. Am. Chem. Soc., 1970, 92, 709 CrossRef CAS.
  7. H. C. Brown and S. Krishnamurthy, J. Am. Chem. Soc., 1972, 94, 7159 CrossRef; H. C. Brown, J. Am. Chem. Soc., 1973, 95, 4100 CrossRef.
  8. H. C. Brown and S. Krishnamurthy, J. Am. Chem. Soc., 1976, 98, 3383 CrossRef CAS.
  9. K. Smith, A. Pelter and A. Norbury, Tetrahedron Lett., 1991, 32, 6243 CrossRef CAS.
  10. A. Pelter, K. Smith, D. Buss and A. Norbury, Tetrahedron Lett., 1991, 32, 6239 CrossRef CAS.
  11. K. Smith and D. Hou, J. Chem. Soc., Perkin Trans. 1, 1995, 185 RSC.
  12. C. A. Brown, J. Org. Chem., 1974, 39, 3913 CrossRef CAS; H. C. Brown, B. Nazer and J. A. Silkorski, Organometallics, 1983, 2, 634 CrossRef CAS; H. C. Brown, J. S. Cha and B. Nazer, Inorg. Chem., 1984, 23, 2929 CrossRef CAS; J. A. Soderquist and I. Rivera, Tetrahedron Lett., 1988, 29, 3195 CrossRef CAS.
  13. J. Seyden-Penne, in Reductions by the Alumino- and Borohydrides in Organic Synthesis, ed. D. P. Curran, Wiley-VCH, New York, 1997 Search PubMed.
  14. H. C. Brown, G. W. Kramer, J. L. Hubbard and S. Krishnamurthy, J. Organomet. Chem., 1980, 188, 1 CrossRef CAS.
  15. Solid Supports and Catalysts in Organic Synthesis, ed. K. Smith, Ellis Horwood, Chichester, 1992 Search PubMed; J. M. J. Fréchet, Tetrahedron, 1981, 37, 663 Search PubMed; A. Akelah and D. C. Sherrington, Chem. Rev., 1981, 81, 557 CrossRef CAS.
  16. S. Itsuno, G. D. Darling, H. D. H. Stover and J. M. J. Fréchet, J. Org. Chem., 1987, 52, 4644 CrossRef CAS.
  17. M. J. Farral and J. M. J. Fréchet, J. Org. Chem., 1976, 41, 3877 CrossRef CAS.
  18. M. Bernard and W. T. Ford, J. Org. Chem., 1983, 48, 326 CrossRef CAS.
  19. These are conditions developed in our laboratory for other purposes by M. Tzimas; lithiation with concentrated n-butyllithium is more complete than with a dilute solution.
  20. S. C. Watson and J. F. Eastham, J. Organomet. Chem., 1967, 9, 165 CrossRef CAS.
  21. Vogel's Textbook of Practical Organic Chemistry, 5th edn., Longman, Harlow, 1989 Search PubMed.
  22. D. D. Perrin and W. L. F. Armarego, Purification of Laboratory Chemicals, Pergamon, 3rd edn., Butterworth Heinemann, Oxford, 1988 Search PubMed.
Click here to see how this site uses Cookies. View our privacy policy here.