9107
Scheme 2. (i) H2/Pd/C; (ii) MnO2/benzene; (iii) 12–15 kbar
mixtures of acetals 10a, 10b or 10c and pyrone 11 were maintained at 12–15 kbar, adducts 12a–c
were formed quantitatively, and as single regio- and stereoisomers. Although not entirely
1
13
unambiguous, the H and C NMR spectra of the adducts suggest that they are endo products,
with the substituent orientation as shown in the Scheme.
Thermal cycloaddition was less efficient. Prolonged reaction of acetal 10a with 11 in refluxing
benzene resulted in an equilibrium mixture, from which adduct 12a could be isolated in 55%
yield. In higher boiling solvents there was evidence of extensive decomposition.
Attempts to eliminate carbon dioxide from the adducts thermally, or with acid or base
catalysis, led to retro-Diels–Alder reaction or to decomposition, although aromatisation of 12a
and 12b occurred cleanly in the mass spectrometer. These results, however, illustrate the
potential of this approach to palmarumycin analogues for structure–activity studies, and the
reaction of 12 and related acetals with a variety of dienes is under current investigation.
The significant anti-microbial activity of several of the acetals and derived adducts will be
reported separately.
References
1. Krohn, K.; Michel, A.; Florke, U.; Aust, H.-J.; Draeger, S.; Schulz, B. Liebigs Ann. Chem. 1994, 1093 and 1099.
2. (a) Coutts, I. G. C.; Humphreys, D. J.; Schofield, K. J. Chem. Soc. (C) 1969, 1982. (b) Coutts, I. G. C.; Hamblin,
M. R.; Welsby, S. E. J. Chem. Soc., Perkin Trans 1 1981, 493.
3. Coutts, I. G. C.; Bulpitt, P. C. A.; Cummins, P. J.; Buckley, G. A.; Mills, S. D. Pestic. Sci. 1997, 51, 99.
4. Barrett, A. G. M.; Hamprecht, D.; Meyer, T. Chem. Commun. 1998, 809.
5. Ragot, J. P.; Steeneck, C.; Alcaraz, M.-L.; Taylor, R. J. K. J. Chem. Soc., Perkin Trans. 1 1999, 1073.
6. Wipf, P.; Jung, J.-K. J. Org. Chem. 1998, 63, 3530.
7. Coutts, I. G. C.; Pavlidis, V. H.; Reza, K.; Southcott, M. R.; Wiley, G. Tetrahedron Lett. 1997, 38, 5563.
8. Hart, D. J.; Mannino, A. Tetrahedron 1996, 52, 3841.
9. Okamura, H.; Morishige, K.; Iwagawa, T.; Nakatani, M. Tetrahedron Lett. 1998, 39, 1211.
10. (a) Carreno, M. C.; Farina, F.; Galan, A.; Ruano, J. L. J. Chem. Res. 1979. (b) Carreno, M. C.; Farina, F.;
Galan, A.; Ruano, J. L. G. J. Chem. Res. 1981, 370.
11. Coutts, I. G. C.; Culbert, N. J.; Edwards, M.; Hadfield, J. A.; Musto, D. R.; Pavlidis, V. H.; Richards, D. J. J.
Chem. Soc., Perkin Trans. 1 1985, 1892.
12. (a) Kerr, M. A. Synlett 1995, 1165. (b) Jarvo, E. R.; Boothroyd, S. E.; Kerr, M. A. Synlett 1996, 897.
.
.