Synthesis of isochroman-3-ylacetates and isochromane-γ-lactones through rearrangement of aryldioxolanylacetates

Abstract

Lewis acid catalysed rearrangement of methyl 4,5-trans-4-aryldioxolan-5-ylacetates 1 provides a convenient route to substituted methyl isochroman-3-ylacetates 2 and isochromane-γ-lactones 3. The choice of Lewis acid is determined by the substitution pattern of the aromatic ring. The two contiguous isochromane stereocentres are transferred unchanged from the parent dioxolanes, while the configuration of the isochromane methyl group is dependent upon the aryl substitution, the reagent and the reaction conditions. Thus treatment of the C-2 epimeric 3′,5′-dimethoxyphenyldioxolanes 4 and 5 with camphorsulfonic acid afforded a mixture of the C-5 epimeric isochromane lactones 26 and 29, the former being favoured at lower acid concentrations, the latter at higher concentrations. Titanium tetrachloride isomerised the analogous 2′-chloro-5′-methoxyphenyldioxolanes 6 and 7 into the methyl isochroman-3-ylacetate 38, which could be lactonised to the isochromane lactone 27. Phosphoric acid converted the 2′,5′-dimethoxyphenyldioxolanes 8 and 9 into a mixture of the isochromane lactones 28 and 31, while similar treatment of the hydroxylactone 22 in the presence of acetaldehyde afforded the isochromane lactone 28 directly and with complete diastereoselectivity. Oxidative demethylation and annulation of this isochromane lactone 28 afforded 5-epi-7-deoxykalafungin 41.

References

1. R. G. F. Giles, I. R. Green, L. S. Knight, V. R. Lee Son and S. C. Yorke, J. Chem. Soc., Perkin Trans. 1, 1994, 1, 865.
2. (a) T. Mukaiyama, Org. React., 1982, 28, 203; (b) T. Mukaiyama, Angew. Chem., Int. Ed. Engl., 1977, 16, 817.
3. R. G. F. Giles, R. W. Rickards and B. S. Senanayake, J. Chem. Soc., Perkin Trans. 1, 1996, 2241.
4. R. G. F. Giles, R. W. Rickards and B. S. Senanayake, J. Chem. Soc., Perkin Trans. 1, 1997, 3361.
5. (a) R. H. Thomson, Naturally Occurring Quinones, 2nd edn., Academic Press, London, 1971; (b) R. H. Thomson, Naturally Occurring Quinones III, Recent Advances, Chapman and Hall, London, 1987; (c) R. H. Thomson, Naturally Occurring Quinones IV, Recent Advances, Blackie Academic and Professional, Chapman and Hall, London, 1997.
6. (a) V. Van Rheenen, R. C. Kelly and D. Y. Cha, Tetrahedron Lett., 1976, 17, 1973; (b) R. Ray and D. S. Matteson, Tetrahedron Lett., 1980, 21, 449.
7. R. G. F. Giles, P. R. K. Mitchell, G. H. P. Roos and J. M. M. Strümpfer, J. Chem. Soc., Perkin Trans. 1, 1981, 2091.
8. S. Tennant and D. Wege, J. Chem. Soc., Perkin Trans. 1, 1989, 2089.
9. W. Eisenhuth and H. Schmid, Helv. Chim. Acta, 1958, 41, 2021.
10. T. Li and R. H. Ellison, J. Am. Chem. Soc., 1978, 100, 6263.
11. P. Jacob III, P. S. Callery, A. T. Shulgin and N. Castagnoli, Jr., J Org. Chem., 1976, 41, 3627.
12. M. Karplus, J. Chem. Phys., 1960, 33, 1842.
13. D. W. Cameron, D. G. I. Kingston, N. Sheppard and Lord Todd, J. Chem. Soc., 1964, 98.
14. T. Kometani and E. Yoshii, J. Chem. Soc., Perkin Trans. 1, 1981, 1191.
15. M. A. Brimble and S. J. Stuart, J. Chem. Soc., Perkin Trans. 1, 1990, 881.
16. J. E. Baldwin and M. J. Lusch, Tetrahedron, 1982, 38, 2939.
17. D. B. Denney and L. C. Smith, J. Org. Chem., 1962, 27, 3404.