Stereoselective Aldol Reactions of Chlorotitanium Enolates. An Efficient Method for the Assemblage of Polypropionate-Related Synthons

Journal of the American Chemical Society

Volumn 113, Issue 3, 1991, Pages 1047-1049

  Evans, David A ^a   Rieger, Dale L ^a   Bilodeau, Mark T ^a   Urpi, Felix ^a  

^a HARVARD UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84958315401     PISSN: 00027863     EISSN: 15205126     Source Type: Journal    
DOI: 10.1021/ja00003a051     Document Type: Article

References (24)

1. Evans, D. A.; Nelson, J. V.; Taber, T. Top. Stereochem. 1982, 13, 1–115.
2. Heathcock, C. H. In Asymmetric Synthesis; Morrison, J. D., Ed.; Academic Press: New York, 1983; Vol. 3, Chapter 2, pp 111–212.
3. Lehnert, W. Tetrahedron Lett. 1970, 4723–4724.
4. Harrison, C. R. Tetrahedron Lett. 1987, 28, 4135–4138.
5. Brocchini, S. J.; Eberle, M.; Lawton, R. G. J. Am. Chem. Soc. 1988, 110, 5211–5212. This paper, which establishes the precedent that quantitative enolization prior to electrophile introduction can be achieved under similar conditions, was inadvertently not cited in the two previous studies from this laboratory (ref 3).
6. For representative reactions of these enolates, see:
7. Evans, D. A.; Urpi, F.; Somers, T. C.; Clark, J. S.; Bilodeau, M. T. J. Am. Chem. Soc. 1990, 112, 8215–8216.
8. Evans, D. A.; Clark, J. S.; Metternich, R.; Novack, V. J.; Sheppard, G. S. J. Am. Chem. Soc. 1990, 112, 866–868.
9. Siegel, C.; Thornton, E. R. J. Am. Chem. Soc. 1989, 111, 5722–5728 and references cited therein.
10. Nakamura, E.; Kuwajima, I. Tetrahedron Lett. 1983, 24, 3343–3346.
11. Reference 2b.
12. The studies relating to the characterization of these enolates will be reported at a later time.
13. Evans, D. A.; Nelson, J. V.; Vogel, E.; Taber, T. R. J. Am. Chem. Soc. 1981, 103. 3099–3111.
14. See ref 1 for leading references
15. Brown, H. C.; Dhar, R. K.; Bakshi, R. K.; Pandiarajan, P. K.; Singaram, B. J. Am. Chem. Soc. 1989, 111, 3441–3442 and references cited therein.
16. General procedure for titanium aldol reactions: TiCl4 (1.1 equiv) is added dropwise to a 0.2 M solution of 1.0 equiv of the ketone or carboxylic acid derivative in CH2Cl2 at −78 °C under N2, giving a yellow slurry. After 2 min, 1.2 equiv of either Et3N or EtN(i-Pr)2 is added dropwise, and the resulting deep red solution is stirred at −78 °C under N2 for 1.5 h. After the dropwise addition of isobutyraldehyde (1.2 equiv), stirring is continued at −78 °C for 1.5 h. The reaction is terminated by addition of 1:1 v/v of saturated aqueous NH4Cl, the mixture is warmed to ambient temperature, and the product is isolated by a conventional extraction.
17. McCarthy, P. A.; Kageyama, M. J. Org. Chem. 1987, 52, 4681–4686.
18. Paterson, I.; McClure, C. K. Tetrahedron Lett. 1987, 28, 1229–1232.
19. Masamune, S.; Choy, W.; Kerdesky, F. A. J.; Imperiali, B. J. Am. Chem. Soc. 1981,103,1566–1568.
20. Reference 4a.
21. Reference 10.
22. Enders, D.; Lohray, B. B. Angew. Chem., Int. Ed. Engl. 1988, 27, 581–583. Variations in the proposed models occur in the disposition of the pendant enolate stereogenic center.
23. Gage, J. R.; Evans, D. A. Org. Synth. 1989, 68, 83–91.
24. Oppolzer, W.; Blagg, J.; Rodriguez, I.; Walther, E. J. Am. Chem. Soc. 1990, 112, 2767–2772.