Enantioselective intramolecular cyclizations of prochiral cyclohexanones using chiral lithium amide bases

Abstract

The first examples of intramolecular cyclizations of prochiral cyclohexanones with chiral lithium amide bases have been effected in good yields and enantiomeric ratios.

References

1. (a) For reviews, see: K. Koga, J. Synth. Org. Chem. Jpn., 1990, 48, 463; (b) P. J. Cox and N. S. Simpkins, Tetrahedron: Asymmetry, 1991, 2, 1; (c) K. Koga, Pure Appl. Chem., 1994, 66, 1487; (d) K. Koga and M. Shindo, J. Synth. Org. Chem. Jpn., 1995, 53, 1021; (e) N. S. Simpkins, Pure Appl. Chem., 1996, 68, 691; (f) P. O'Brien, J. Chem. Soc., Perkin Trans. 1, 1998, 1439.
2. The large majority of the work on enantioselective deprotonation of prochiral ketones using chiral lithium amide bases involves trapping the resulting enolates as silyl enol ethers: K. Aoki and K. Koga, Tetrahedron Lett., 1997, 38, 2505; R. Shirai, D. Sato, K. Aoki, M. Tanaka, H. Kawasaki and K. Koga, Tetrahedron, 1997, 53, 5963; H. Chatani, M. Nakajima, H. Kawasaki and K. Koga, Heterocycles, 1997, 46, 53; K. Aoki, K. Tomioka, H. Noguchi and K. Koga, Tetrahedron, 1997, 53, 13 641.
3. In addition, chiral lithium amide bases have beeen successfully used for the enantioselective rearrangement of epoxides (ref. 4), aromatic and benzylic functionalization of aryl chromium complexes (ref. 5), as well as the asymmetric [2,3]-Wittig rearrangement (ref. 6).
4. M. Asami, J. Synth. Org. Chem. Jpn., 1996, 54, 188; D. M. Hodgson, A. R. Gibbs and G. P. Lee, Tetrahedron, 1996, 52, 14 361.
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6. S. E. Gibson, P. Ham and G. R. Jefferson, Chem. Commun., 1998, 123.
7. Iodo ketone 1 was synthesized from 4-(3-chloropropyl) cyclohexanone (cf.A. G. Schultz and J. P. Dittami, J. Org. Chem., 1984, 49, 2615) by a Finkelstein reaction (NaI, acetone, 90%).
8. Iodo ketone 2 was prepared from 4-(2-hydroxyethyl) cyclohexanone (M. A. Ciufolini and N. E. Byrne, J. Am. Chem. Soc., 1991, 113, 8016) using PPh₃ and I₂(60%).
9. The amine is available commercially as the hydrochloride salt.
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12. The absolute stereochemistry of bicyclic ketones 3 and 4 was determined using the CD Octant rule. For a good discussion, see: E. L. Eliel and S. H. Wilen, Stereochemistry of Organic Compounds, Wiley, New York, 1994, p. 1022.
13. Racemic ketone 3 is commercially available. Racemic 4: E. N. Marvell, D. Sturmer and C. Rowell, Tetrahedron, 1966, 22, 861.
14. K. Sugasawa, M. Shindo, H. Noguchi and K. Koga, Tetrahedron Lett., 1996, 37, 7377.