Total synthesis of (-)-xyloketal A

Organic Letters

Volumn 8, Issue 7, 2006, Pages 1427-1429

  Pettigrew, Jeremy D ^a   Wilson, Peter D ^a  

^a SIMON FRASER UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

BIOLOGICAL PRODUCT; PYRAN DERIVATIVE; XYLOKETAL A;

ARTICLE; CATALYSIS; CHEMICAL STRUCTURE; CHEMISTRY; STEREOISOMERISM; SYNTHESIS; XYLARIALES;

BIOLOGICAL PRODUCTS; CATALYSIS; MOLECULAR STRUCTURE; PYRANS; STEREOISOMERISM; XYLARIALES;

EID: 33645908503     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol060266w     Document Type: Article

References (24)

1. Lin, Y.; Wu, X.; Feng, S.; Jiang, G.; Luo, S.; Zhou, S.; Vrijmoed, L. L. P.; Jones, E. B. G.; Krohn, K.; Steingrover, K.; Zsila, F. J. Org. Chem. 2001, 66, 6252.
2. Wu, X. Y.; Liu, X. H.; Lin, Y. C.; Luo, J. H.; She, Z. G.; Houjin, L.; Chan, W. L.; Antus, S.; Kurtan, T.; Elsässer, B.; Krohn, K. Eur. J. Org. Chem. 2005, 4061.
3. Wu, X.; Liu, X.; Jiang, G.; Lin, Y.; Chan, W.; Vrijmoed, L. I., P. Chem. Nat. Compd. 2005, 41, 27.
4. We have previously reported a racemic synthesis of the two possible diastereoisomers of a tris-demethyl analogue of xyloketal A and a racemic synthesis of a demethyl analogue of xyloketal D. We have also reported the first total synthesis of (±)-xyloketal D which is, in a structural sense, one of the simpler members of this family of natural products, see: (a) Pettigrew, J. D.; Bexrud, J. A.; Freeman, R. P.; Wilson, P. D. Heterocycles 2004, 62, 445.
5. We have also described an asymmetric total synthesis of (-)-xyloketal D and its enantiomer, see: (b) Pettigrew, J. D.; Freeman, R. P.; Wilson, P. D. Can. J. Chem. 2004, 82, 1640. These syntheses featured the cycloaddition reactions of appropriately functionalized o-quinone methides and dihydrofurans as a key step. The further application of this chemistry, to complete the total synthesis of xyloketal A (1), has not been successful.
6. We have recently described an alternative approach to the synthesis of the xyloketal A (1) based on a novel phenylboronic acid-mediated triple condensation reaction of α,β-unsaturated aldehydes and phloroglucinol, see: Pettigrew, J. D.; Cadieux, J. A.; So, S. S. S.; Wilson, P. D. Org. Lett. 2005, 7, 467.
7. Krohn and co-workers have attempted the synthesis of xyloketal A (1) from racemic 5-hydroxy-4-methyl-3-methylenepentan-2-one and phloroglucinol. In this instance, the desired tris-adducts were isolated in 6% yield as a mixture of eight diastereoisomers. see: (a) Krohn, K.; Riaz, M.; Flörke, U. Eur. J. Org. Chem. 2004, 1261.
8. In this paper, an asymmetric synthesis of (-)-xyloketal D via a conjugate addition reaction of 2,4-dihydroxyacetophenone to the (4R)-enantiomer of the aforementioned ketone was also described. In addition. Krohn and co-workers reported the synthesis of demethyl analogues of the xyloketal natural products in this paper. For a preliminary communication of this work, see: (b) Krohn, K.; Riaz, M. Tetrahedron Lett. 2004, 45, 293.
9. We have established, in simplified model systems, that this novel triple electrophilic aromatic substitution reaction and subsequent bicyclic acetal formation process can be promoted with a variety of acidic reagents in the presence of anhydrous magnesium sulfate, see: Pettigrew, J. D.; Wilson, P. D. J. Org. Chem. 2006, 71, 1620.
10. Gage, J. R.; Evans, D. A. Org. Synth. 1990, 68, 83.
11. For reports on the use of HMPA in alkylation reactions of derivatives of oxazolidinone chiral auxiliaries, see: (a) Fadel, A. Tetrahedron: Asymmetry 1994, 5, 531.
12. (b) Versteeg, M.; Bezuidenhoudt, B. C. B.; Ferreira, D.; Swart, K. J. J. Chem. Soc., Chem. Commun. 1995, 1317.
13. (c) Versteeg, M.; Bezuidenhoudt, B. C. B.; Ferreira, D. Tetrahedron 1999, 55, 3365.
14. Evans, D. A.; Ennis, M. D.; Mathre, D. J. J. Am. Chem. Soc. 1982, 104, 1737.
15. For an alternative synthesis (employing a resolution procedure) and proof of absolute stereochemistry of the chiral nonracemic alcohol 7. see ref 4b.
16. The final reaction product was contaminated with a small amount of the corresponding exo-cyclic dihydrofuran (<7%).
17. (a) Hojo, M.; Masuda, R.; Sakaguchi, S.; Takagawa, M. Synthesis 1986, 1016.
18. (b) Colla, A.; Martins, M. A. P.; Clar, G.; Krimmer, S.; Fischer, P. Synthesis 1991, 483.
19. A direct one-step procedure for the synthesis of dihydrofuran esters from the corresponding dihydrofurans has been reported, see: Stetter, H.; Lorenz, G. Chem. Ber. 1985, 118, 1115. However, in our hands, a complex mixture of reaction products was obtained when the dihydrofuran 8 was employed as a reaction substrate.
20. The trichloroketone 10 was isolated as a single geometrical isomer. The geometry of the double bond was not determined but it is reasonable to assume, based on electronic and steric considerations, that it is trans.
21. For a related procedure, see: de Buyck, L.; de Footer, H.; Schamp, N. Bull. Soc. Chim. Belg. 1988, 97, 371.
22. Herein, the numbering scheme is based on that described by Lin and co-workers (see ref 1).
23. 1H NMR spectrum.
24. The reaction was also repeated at 0 °C with 4 equiv of the alcohol 3. In this instance, a mixture of xyloketal A(1) and 2,6-epi-xyloketal A (2,6-epi-1) was isolated in 14% yield (dr = 5:2). In addition, no evidence for the formation of mono- or bis-addition products was recorded. This reflects the relative instability of the alcohol 3 and the increased reactivity of the more electron-rich mono- and bis-addition products toward electrophilic aromatic substitution processes.