Highly cis- or trans-selective oxygen to carbon rearrangements of anomerically linked 6-substituted tetrahydropyranyl enol ethers

Abstract

Low temperature Lewis acid catalysed oxygen to carbon rearrangements of anomerically linked 6-substituted tetrahydropyranyl enol ethers lead to the corresponding trans-ketones in a highly diastereoselective manner, whereas at higher temperatures the cis-ketones are formed with a high degree of selectivity under thermodynamic control.

References

1. For excellent reviews see: (a) D. Levy and C. Tang, The Chemistry of C-Glycosides, Pergamon, 1995; (b) M. H. D. Postema, Tetrahedron, 1992, 48, 8545.
2. M. F. Buffet, D. J. Dixon, G. L. Edwards, S. V. Ley and E. W. Tate, Synlett, 1997, 1055.
3. For related examples see: (a) J. Herscovici, S. Delatre and K. Antonakis, J. Org. Chem., 1987, 52, 5691; (b) K. Mikami and H. Kishino, Tetrahedron Lett., 1996, 37, 3705.
4. For related rearrangements at benzylic positions see: (a) J. Wennerberg, L. Eklund, M. Polla and T. Frejd, Chem. Commun., 1997, 445; (b) J. Wennerberg and T. Frejd, Acta Chem. Scand., 1998, 52, 95.
5. M. F. Buffet, D. J. Dixon, S. V. Ley and E. W. Tate, Synlett, 1998, 1091.
6. D. J. Dixon, S. V. Ley and E. W. Tate, Synlett, 1998, 1093.
7. D. J. Dixon, S. V. Ley and E. W. Tate, J. Chem. Soc., Perkin Trans. 1, 1998, 3125.
8. For related examples see: (a) M. Takahashi, H. Suzuki, Y. Moro-oka and T. Ikawa, Tetrahedron Lett., 1982, 23, 4031; (b) R. Menicagli, C. Malanga, M. Dell'Innocenti and L. Lardicci, J. Org. Chem., 1987, 52, 5700; (c) H. Frauenrath and J. Runsink, J. Org. Chem., 1988, 53, 1860; (d) A. Ricci, A. Degl'Innocenti, A. Capperucci, C. Faggi, G. Seconi and L. Favaretto, Synlett, 1990, 471; (e) D. G. Bourke, D. J. Collins, A. I. Hibbered and M. D. McLeod, Aust. J. Chem., 1996, 49, 425; (f) M. Sollogoub, J.-M. Mallet and P. Sinaÿ, Tetrahedron Lett., 1998, 39, 3471.
9. Fresh Tebbe reagent (purchased from Sigma-Aldrich Chemical Co.) is required for this reaction to proceed smoothly. It was found that if an older batch of Tebbe reagent was used the Lewis acidity of the degraded reagent was sufficient to cause some decomposition during the methylenation reaction.
10. Typical experimental procedure for the transformation of 5 into 8 and 9: To a stirred solution of 5(0.100 g, 0.44 mmol) in dichloro-methane (1.5 mL) at –78 °C was added TMSOTf (0.004 mL, 0.022 mmol). After stirring at –78 °C for 5 min the reaction mixture was quenched by the addition of phosphate buffer (pH 7.4, 3 mL), the aqueous layer extracted with diethyl ether (3 × 5mL) and the combined organic extracts dried (MgSO₄), filtered and evaporated in vacuo to give a slightly yellow oil. ¹H NMR spectroscopic analysis of this crude product showed a 3:97 ratio of 9:8. Purication by silica column chromatography, eluting with 20% diethyl ether–light petroleum (bp 40–60 °C), gave 9(0.002 g, 2%) and 8(0.070 g, 70%) as colourless oils. Characterisation data for 9: ν_max(thin film)/cm^–1 2930, 2858, 1717, 1458, 1356, 1197, 1080; δ_H(400 MHZ; CDCl₃) 3.74–3.68 (1H, m, OCHCH₂CO), 3.26–3.22 (1H, m, CHOCHCH₂CO), 2.64 (1H, dd, J 15.1 and 8.1, CHHCOCH₃), 2.38 (1H, dd, J15.1 and 4.8, CHHCOCH₃), 2.16 (3H, s, COCH₃), 1.82–1.11 (16H, m, 8 × CH₂), 0.86 (3H, t, J7.0, CH₂CH₃); δ_C(100 MHZ; CDCl₃) 207.8 (COCH₃), 78.0 (OCHCH₂CO), 74.4 (CHOCHCH₂CO), 50.4 (CH₂CO), 36.4, 31.8, 31.6, 31.3, 31.0 (COCH₃), 29.3, 25.5, 23.5, 22.6, 14.0 (CH₂CH₃); m/z(FAB) 109 (62%), 113 (53%), 136 (60%), 154 (54%), 169 (100%), 227 (40%)(Found: MH⁺, 227.2015. C₁₄H₂₇O₂ requires 227.2011)(Found: C, 74.79; H, 11.58. C₁₄H₂₆O₂ requires: C, 74.96; H, 11.60%). Characterisation data for 8: ν_max(thin film)/cm^–1 2930, 2858, 1715, 1460, 1357, 1203, 1162, 1095, 1041; δ_H(400 MHZ; CDCl₃) 4.42–4.19 (1H, m, OCHCH₂CO), 3.69–3.61 (1H, m, CHOCHCH₂CO), 2.75 (1H, dd, J 15.1 and 8.3, CHHCOCH₃), 2.42 (1H, dd, J 15.1 and 7.4, CHHCOCH₃), 2.17 (3H, s, COCH₃), 1.71–1.26 (16H, m, 8 × CH₂), 0.87 (3H, t, J 6.4, CH₂CH₃); δ_C(100 MHZ; CDCl₃) 207.4 (COCH₃), 71.7 (OCHCH₂CO), 67.5 (CHOCHCH₂CO), 48.2 (CH₂CO), 33.0, 31.8, 30.5 (COCH₃), 30.2, 29.6, 29.3, 25.7, 22.6, 18.4, 14.0 (CH₂CH₃); m/z(FAB) 109 (71%), 169 (100%), 227 (78%)(Found: MH⁺, 227.2016. C₁₄H₂₇O₂ requires 227.2011)(Found: C, 74.86; H, 11.57. C₁₄H₂₆O₂ requires: C, 74.96; H, 11.60%).
11. For a transition-state discussion of this phenomenon, see P. Deslongchamps, Pure Appl. Chem., 1993, 65, 1161.
12. Base-induced reversible β-elimination as a method for forming cis-tetrahydropyrans is well-established in synthesis for example: E. D. Bergman, D. Ginsburg and R. Pappo, Org. React. (N.Y.), 1959, 10, 179.