T.
Horneff et al.31 were studied a model related to the C-9 to C-15
fragment of Geldanamycin which is an antitumar active compound.32
Diols (26) appeared to be easily
accessible from the corresponding aldol addition products by reduction. Using
the well-established Evans methodology,33
aldol addition product 25 was
generated and subsequently reduced to diol 26b
(Scheme 7).
The relative configuration of compound (28) was established by single crystal X-ray crystallography. The crystallographic result was in line with the expectation for an auxiliary-controlled aldol addition with N-propionyl-(S)-4-benzyl-2-oxazolidinone (10).34 Diol (26b), however, was not identical to diol (26b) obtained in the crotylation studies nor was the corresponding 1, 3-dioxane (27b) identical with 27a. 1H NMR studies with dioxane (27b) resulted in the coupling constants typical for a syn-aldol product, that is, the coupling constants for H-4 and H-5 (3J = 2.3 Hz) as well as for H-5 and both protons at C-6 (1.6 and 2.4 Hz) were small. Since the anti, syn-diol (26b) was not identical with 26a and since the relative configuration of 26a is syn at the CHMe-CHOH part (vide infra), diol 26a must have the syn,syn-configuration. Additional proof for this assignment came from another aldol addition they conducted with the propionate equivalent 23 (Scheme 8). Under conditions earlier described by Heathcock et al.35 using two equivalents of Bu2BOTf a major addition product was isolated. It turned out to be the syn,-syn-diastereoisomer 28. Reduction of product 25 gave diol 26a and further acetal formation yielded 27a.
___________
The relative configuration of compound (28) was established by single crystal X-ray crystallography. The crystallographic result was in line with the expectation for an auxiliary-controlled aldol addition with N-propionyl-(S)-4-benzyl-2-oxazolidinone (10).34 Diol (26b), however, was not identical to diol (26b) obtained in the crotylation studies nor was the corresponding 1, 3-dioxane (27b) identical with 27a. 1H NMR studies with dioxane (27b) resulted in the coupling constants typical for a syn-aldol product, that is, the coupling constants for H-4 and H-5 (3J = 2.3 Hz) as well as for H-5 and both protons at C-6 (1.6 and 2.4 Hz) were small. Since the anti, syn-diol (26b) was not identical with 26a and since the relative configuration of 26a is syn at the CHMe-CHOH part (vide infra), diol 26a must have the syn,syn-configuration. Additional proof for this assignment came from another aldol addition they conducted with the propionate equivalent 23 (Scheme 8). Under conditions earlier described by Heathcock et al.35 using two equivalents of Bu2BOTf a major addition product was isolated. It turned out to be the syn,-syn-diastereoisomer 28. Reduction of product 25 gave diol 26a and further acetal formation yielded 27a.
___________
31. T. Horneff, E. Herdtweck, S. Randoll,
and T. Bach, Bioorg. Med. Chem., 2006, 14, 6223
32. a) L. Whitesell, S. D. Shifrin, G.
Schwab, L. Neckers, Cancer Res., 1992, 52, 1721; b) J. G. Supko,
R. L. Hickman, M. R. Grever, and L. Malspeis, Cancer Chemother. Pharmacol., 1995, 36, 305.
33. D. A. Evans, J. Bartroli, and T. L. Shih, J. Am. Chem. Soc., 1981, 103, 2127.
34. a) H. Danda, M. M. Hansen, C. H. Heathcock, J. Org. Chem., 1990, 55, 173; (b) M. A.Walker, and C. H. Heathcock, J. Org. Chem., 1991, 56, 5747; (c) B. C. Raimundo, and C. H. Heathcock, Synlett, 1995, 1213.
35 (a) S.-I. Kiyooka, and C. H. Heathcock, Tetrahedron Lett., 1983, 24, 4765; (b) M. T. Reetz, and K. Kesseler, Chem. Commun., 1984, 1079.
Next Page34. a) H. Danda, M. M. Hansen, C. H. Heathcock, J. Org. Chem., 1990, 55, 173; (b) M. A.Walker, and C. H. Heathcock, J. Org. Chem., 1991, 56, 5747; (c) B. C. Raimundo, and C. H. Heathcock, Synlett, 1995, 1213.
35 (a) S.-I. Kiyooka, and C. H. Heathcock, Tetrahedron Lett., 1983, 24, 4765; (b) M. T. Reetz, and K. Kesseler, Chem. Commun., 1984, 1079.