4114
D. O. Arbelo, J. A. Prieto / Tetrahedron Letters 43 (2002) 4111–4114
Chem. 1983, 48, 5083; (d) Myers, A. G.; Widdowson, K.
L. Tetrahedron Lett. 1988, 6389.
0.834 mmol, 1 equiv.) were added to the reaction flask.
The flask was flame-dried under nitrogen while stirring to
remove moisture from the solids. Dry toluene (15 mL)
and 0.05 mL (0.834 mmol, 1 equiv.) of acetic acid were
added and the mixture was vigorously stirred. When the
solids dispersed, 0.17 g (0.83 mmol) of epoxide 25 [h]2D2=
−26.6° (c 0.03, ether) was added. The system was
heated to reflux for 160 h (monitored by TLC). Work-up
and solvent evaporation yielded the crude product mix-
ture. The unreacted starting material and ester regioiso-
mers were separated by flash chromatography (4:1
hexane/ethyl acetate) yielding 0.13 g (57%) of a 4:1
mixture of regioisomers 29; (b) General procedure for the
mesylation of alcohols: 3-[(2S,3S)-1-benzyloxy-2-methane-
sufonyloxyhexyl] propionate (31). To the reaction flask
was added 0.03 g (0.1 mmol) of the corresponding
hydroxy ester mixture 29, 5 mL of CH2Cl2, 0.2 g (0.2
mmol) of DMAP and 0.05 mL (0.28 mmol) of N,N-diiso-
propylethylamine. The reaction mixture was cooled to
−10°C with a water/NaCl/ice bath. After 30 min, 0.02
mL (0.19 mmol) of mesyl chloride was added dropwise
via syringe. The reaction was completed in 30 min (TLC)
at which time, water (1 mL) was added dropwise while
keeping the system cold. Work-up and solvent evapora-
tion yielded the crude regioisomeric mesylate mixture,
which could be used without further purification; (c)
General procedure for the methanolysis of propionates:
(+)-(2R,3S)-1-benzyloxy-2,3-epoxyhexane (30). The mesyl-
ate mixture (0.03 g, 0.1 mmol), 5 mL of MeOH and 0.01
g (0.04 mmol) of K2CO3 were added to the reaction flask
and stirred for 3 h (TLC). Work-up and solvent evapora-
tion yielded a crude oil, which was purified by column
chromatography (29:1 hexane/ethyl acetate) yielding
8. For cesium carboxylate mediated hydroxyl inversion, see:
(a) Hawryluk, N. A.; Snider, B. B. J. Org. Chem. 2000,
65, 8379; (b) Shimizu, T.; Hiranuma, S.; Nakata, T.
Tetrahedron Lett. 1996, 37, 6145; (c) Senanayake, C. H.;
Singh, S. B.; Bill, T. J.; DiMichelle, L. M.; Liu, J.;
Larsen, R. D.; Verhoeven, T. R. Tetrahedron Lett. 1993,
34, 2425; (d) Torisawa, Y.; Okabe, H.; Ikegami, S. Chem.
Lett. 1984, 1555; (e) Willis, C. L. Tetrahedron Lett. 1987,
28, 6705; (f) Kruizinga, W. H.; Strijtveen, B; Kellogg, R.
M. J. Org. Chem. 1981, 46, 4321.
9. For discussions of the ‘cesium effect’, see: (a) Salvatore,
R. N.; Nagle, A. S.; Schmidt, S. E.; Jung, K. W. Org.
Lett. 1999, 1, 1893; (b) Ostrowicki, A.; Koepp, E.;
Vo¨gtle, F. Top. Curr. Chem. 1991, 161, 38; (c) Dijkstra,
G.; Kruizinga, W. H.; Kellogg, R. M. J. Org. Chem.
1987, 52, 4230; (d) Kruizinga, W. H.; Kellogg, R. M. J.
Am. Chem. Soc. 1981, 101, 4230.
10. All products in this study were characterized by 1D/2D
1H and 13C NMR methods.
11. The regiochemistry for each system was established by
1D and 2D NMR. For example, the major regioisomer
18, arising from attack of the propionate nucleophile at
C-5 (epoxide 16), produced a correlation in the COSY
spectra between the resonance at 5.09 ppm (dq, J=6.4,
2.9 Hz) for the proton at the carboxylate bearing carbon
and the terminal methyl at 1.29 ppm (d, J=6.4 Hz).
Similar analyses allowed easy discrimination among each
pair of regioisomers.
12. (a) Chong, J. M.; Sharpless, K. B. J. Org. Chem. 1985,
50, 1560; (b) Behrens, C. H.; Ko, S. Y.; Sharpless, K. B.;
Walker, F. J. J. Org. Chem. 1985, 50, 5687.
13. For the application of 13C NMR spectroscopy for stereo-
chemical analysis in acyclic highly substituted alcohol,
see: (a) Stahl, M.; Schopfer, U.; Frenking, G.; Hoffmann,
R. W. J. Org. Chem. 1996, 61, 4975; (b) Whitesell, J. K.;
Hildebrandt, B. J. Org. Chem. 1985, 50, 4975.
1
0.018 g (90%) of epoxide product 30. H NMR (CDCl3):
l 7.30 (m, 5H), 4.57 (d, J=12.0 Hz, 1H), 4.55 (d, J=12.0
Hz, 1H), 3.72 (dd, J=11.4, 3.3 Hz, 1H), 3.47 (dd, J=
11.4, 5.6 Hz, 1H), 2.95 (m, 1H), 2.83 (m, 1H), 1.55 (m,
4H), 0.98 (t, J=7.3 Hz, 3H); 13C NMR (CDCl3): l 138.0,
128.4, 127.7, 127.7, 73.3, 70.5, 57.0, 56.0, 33.7, 19.3, 13.9;
HREIMS for C13H18O2 [M+]; calcd 206.1306, found
206.1306; [h]2D3=+25.0° (c 0.02, ether).
14. (a) General procedure for epoxide cleavage with cesium
propionate:
(2S,3S)-3-(1-benzyloxy-2-hydroxyhexyl)
propanoate (29). Cesium propionate/2% propionic acid
(1.17 g, 4.17 mmol, 5 equiv.) and 18-crown-6 (1.10 g,