Aldol reactions of ketal-protected tartrate ester enolates. Asymmetric syntheses and absolute stereochemical assignments of phospholipase A2 inhibitors cinatrin C1 and C3

Tetrahedron

Volumn 53, Issue 26, 1997, Pages 8779-8794

  Evans, David A ^a   Trotter, B Wesley ^a   Barrow, James C ^a  

^a HARVARD UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CINATRIN; PHOSPHOLIPASE A2 INHIBITOR; UNCLASSIFIED DRUG;

ARTICLE; CHIRALITY; DRUG DESIGN; ENZYME INHIBITION; ENZYME SYNTHESIS; NUCLEAR MAGNETIC RESONANCE; PRIORITY JOURNAL; REACTION ANALYSIS; STEREOCHEMISTRY; STRUCTURE ANALYSIS;

EID: 0030803002     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4020(97)90390-2     Document Type: Article

References (23)

1. Seebach, D. In Modern Synthetic Methods; R. Scheffold, Ed.; Verlag: Frankfurt, 1980; Vol. 2; pp 93-171.
2. For examples, see Johnson, R. A.; Sharpless, K. B. In Catalytic Asymmetric Synthesis; I. Ojima, Ed.; VCH: New York, 1993; pp 103-158 (asymmetric epoxidation) and Maruoka, K.; Yamamoto, H. In Catalytic Asymmetric Synthesis; I. Ojima, Ed.; VCH: New York, 1993; pp 413-440 (Lewis acid-mediated reactions).
3. For examples, see Johnson, R. A.; Sharpless, K. B. In Catalytic Asymmetric Synthesis; I. Ojima, Ed.; VCH: New York, 1993; pp 103-158 (asymmetric epoxidation) and Maruoka, K.; Yamamoto, H. In Catalytic Asymmetric Synthesis; I. Ojima, Ed.; VCH: New York, 1993; pp 413-440 (Lewis acid-mediated reactions).
4. Itazaki, H.; Nagashima, K.; Kawamura, Y.; Matsumoto, K.; Nakai, H.; Terui, Y. Journal of Antibiotics 1992, 45, 38-49.
5. Naef, R.; Seebach, D. Angew. Chem. Int. Ed. Eng. 1981, 20, 1030-1031. For the related alkylation of threonine-derived ketals see: Seebach, D.; Aebi, J. D.; Gander-Coquoz, M.; Naef, R. Helv. Chim. Acta 1987, 70, 1194-1216.
6. Naef, R.; Seebach, D. Angew. Chem. Int. Ed. Eng. 1981, 20, 1030-1031. For the related alkylation of threonine-derived ketals see: Seebach, D.; Aebi, J. D.; Gander-Coquoz, M.; Naef, R. Helv. Chim. Acta 1987, 70, 1194-1216.
7. (a) Evans, D. A.; Barrow, J. C.; Leighton, J. L.; Robichaud, A. J. J. Am. Chem. Soc. 1994, 116, 12111-12112.
8. (b) Evans, D. A.; Barrow, J. C.; Leighton, J. L.; Sefkow, M.; Robichaud, A. J. J. Am. Chem. Soc. 1997, manuscript in preparation.
9. Silylketene acetal 5 is formed as a 2:1 mixture of (E) and (Z) isomers (reference 5). A single isomer is arbitrarily depicted in the illustrations in this paper.
10. Proof of stereochemistry for adduct 6d is detailed in reference 5.
11. Details of the X-ray crystal structure have been provided.
12. Similar models have been proposed for aldol reactions of silylketene acetals: (a) Gennari, C.; Bernardi A.; Colombo, L.; Scolastico, C. J. Am. Chem. Soc. 1985, 107, 5812-5813 (titanium enolates) and (b) Kobayashi, S.; Hachiya, I. J. Org. Chem. 1992, 57, 1324-1326 (tin-mediated aldols).
13. Similar models have been proposed for aldol reactions of silylketene acetals: (a) Gennari, C.; Bernardi A.; Colombo, L.; Scolastico, C. J. Am. Chem. Soc. 1985, 107, 5812-5813 (titanium enolates) and (b) Kobayashi, S.; Hachiya, I. J. Org. Chem. 1992, 57, 1324-1326 (tin-mediated aldols).
14. 1H, for example) of the approach of the electrophile. While we have not rigorously investigated the implication that the titanium enolate isomers can equilibrate under the reaction conditions, work in these laboratories has shown that titanium enolate isomers obtained via transmetallation of silyl enol ethers will equilibrate (Duffy, Joseph L. Ph.D. Thesis, Harvard University, 1996).
15. Tanaka, K.; Itazaki, H.; Yoshida, T. Journal of Antibiotics 1992, 45, 50-55.
16. Williams, K.; Halpern, B. Synthesis 1974, 727-728. We prepared benzyl myristate in 95% yield via acid-catalyzed esterification of myristic acid (benzyl alcohol, p-toluenesulfonic acid, refluxing benzene, Dean-Stark apparatus).
17. Davis, F. A.; Vishwakarma, L. C.; Billmers, J. M.; Finn, J. J. Org. Chem. 1984, 49, 3241-3243.
18. 1H NMR). Analytically pure material (which reproducibly gives yields and selectivities identical to the crude material in the ensuing aldol reaction) can be obtained by recrystallization from hexanes.
19. 3 reported by Itazaki and coworkers (reported as -86.1° in reference 3); our measurements of the natural sample provided by Dr. Kamigauchi gave the positive optical rotation reported here.
20. 1H NMR spectrum identical to that of the natural sample.
21. 1 to measure an optical rotation with our instrumentation.
22. Kelly, T. R.; Schmidt, T. E.; Haggerty, J. G. Synthesis 1972, 544-545.
23. Uray, G.; Lindner, W. Tetrahedron 1988, 44, 4357-4362.