Studies on the Total Synthesis of (2R,4'R,8'R)-α-Tocopherol (Vitamin E). Stereospecific Cyclizations Leading to Optically Active Chromans

Journal of Organic Chemistry

Volumn 46, Issue 12, 1981, Pages 2445-2450

  Cohen, Noal ^a   Lopresti, Rocco J ^a   Neukom, Christian ^a  

^a HOFFMANN LA ROCHE INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA TOCOPHEROL;

2 CHROMANCARBOXYLIC ACID DERIVATIVE; DRUG ANALYSIS; DRUG STRUCTURE; DRUG SYNTHESIS; IN VITRO STUDY; INFRARED SPECTROMETRY; METHODOLOGY; THEORETICAL STUDY; ULTRAVIOLET SPECTROPHOTOMETRY;

EID: 0019511531     PISSN: 00223263     EISSN: 15206904     Source Type: Journal    
DOI: 10.1021/jo00325a004     Document Type: Article

References (20)

1. Scott, J. W.; Cort, W. M.; Harley, H.; Parrish, D. R.; Saucy, G. J. Am. Oil Chem. Soc. 1974, 51, 200-3.
2. Mayer, H.; Schudel, P.; Rüegg, R.; Isler, O. Helv. Chim. Acta 1963,46, 650-71.
3. Bamer, R.; Schmid, M. Helv. Chim. Acta. 1979, 62, 2384-99.
4. Schmid, M.; Bamer, R. Helv. Chim. Acta. 1979,62, 464-73.
5. Zell, R. Helv. Chim. Acta. 1979,62, 474-80.
6. Chan, K.-K.; Cohen, N.; De Noble, J. P.; Specian, A. C., Jr.; Saucy, G. J. Org. Chem. 1976,41, 3497-505.
7. Cohen, N.; Lopresti, R. J.; Saucy, G. J. Am. Chem. Soc. 1979, 101, 6710-6.
8. Fugan ti, C.; Grasselli, P. J. Chem. Soc., Chem. Commun. 1979, 995-7.
9. Fischli, A. Chimia 1976, 30, 4-9.
10. Mayer, H.; Vetter, W.; Metzger, J.; Rüegg, R.; Isler, O. Helv. Chim. Acta 1967, 50, 1168-78.
11. Schudel, P.; Mayer, H.; Metzger, J.; Rüegg, R.; Isler, O. Helv. Chim. Acta. 1983, 46, 333-43.
12. Scott, J. W.; Bizzarre, F. T.; Parrish, D. R.; Saucy, G. Helv. Chim. Acta 1976,59, 290-306 [mp 124.5-128 °C; [a]25,) +14.78° (c 1, C2H5OH)].
13. The racemic modification of 11a has been prepared previously: Cort, W. M.; Scott, J. W.; Araujo, M.; Mergens, W. J.; Cannalonga, M. A.; Osadca, M.; Harley, H.; Parrish, D. R.; Pool, W. R. J. Am. Oil Chem. Soc. 1975, 52, 174-8.
14. Dr. John W. Scott of our laboratories has informed us that, in another study, attempted cyclodehydration of the racemic chlorophenol acid 25 under a variety of acidic conditions (p-TsOH, benzene reflux; concentrated HC1, reflux; 18 N H2S04-dioxane, reflux; H2S04-Ac20,115 °C) failed to produce the desired chroman-2-carboxylic acid 26. Similarly, the phenolic hydroxy ester 27 could be induced to cyclize only under conditions which first cleaved the benzyl ether protecting group (p-TaOH, toluene, reflux) in which case the 6-hydroxychroman-2-acetic acid ester 28 was the observed product. These results support the catalytic redox mechanism delineated in Scheme VI since neither 25 nor 27 can be converted to the corresponding quinone by air oxidation under the cyclization conditions. Thus in these substrates, the pathway shown in Scheme VI is blocked while that in Scheme V would, presumably, still be available. The failure to cyclize when the 6-hydroxyl moiety is protected or replaced strongly implicates the quinone 18 as a key intermediate in these transformations
15. Nakao, H.; Arakara, M. Chem. Pharm. Bull. 1972, 20, 1962-7.
16. Crossland, R. K.; Servis, K. L. J. Org. Chem. 1970, 35, 3195-6.
17. Treatment of this substance with p-toluenesulfonic acid in refluxing benzene failed to produce chroman, further suggesting that, under these conditions, cyclization involves attack of the free tertiary hydroxyl function on the aromatic ring as shown in Schemes V and VI.
18. It should be noted that this inversion sequence could not be carried out without initial esterification of 4 since attempted mesylation of quinone acid 11a led to an extremely complex mixture of products. The added esterification step is no inconvenience, however, since the ester 22 is required for subsequent conversion to (21Z,4'fi,8'fi)-a-tocopherol.2f
19. Cf.: (a) Baird, K. J.; Grundon, M. F. J. Chem. Soc., Perkin Trans. 1 1980,1820-5.
20. Silverman, R. B. J. Am. Chem. Soc. 1980,102,5421-3.