give a methoxy diol in 59% yield. However, surprisingly,
the desired 1,2-diol 16 was not obtained, but rather the
unexpected 1,3-diol 17.11 Thus the steric hindrance of the
chain outweighs that of the hydroxymethyl group, and no
directing effect of the alcohol was observed with BF3. We
hypothesized that if we added another alcohol such as benzyl
or allyl alcohol to the diastereomeric epoxide, then after
methylation and removal of the benzyl or allyl group, the
desired methoxy diol would be produced (in a sense using
benzyl or allyl alcohol as a surrogate for water). The allylic
alcohol 14 was epoxidized with DMDO (formed in situ from
oxone and acetone) to give a 3:1 ratio favoring the desired
syn epoxide 18 (Scheme 5). Opening with benzyl alcohol
Scheme 6
Scheme 5
gave the desired carbonate 20 in 74% yield.15 No methyl
lactol ether deprotection was observed during the acidic
hydrolysis step. Formation of the anion of the alcohol of 20
with NaH, even in the presence of methyl iodide or triflate,16
gave only the product of carbonate migration 22 rather than
the desired methyl ether 21. However, alkylation with methyl
triflate in the presence of the very hindered base 2,6-di-tert-
butylpyridine in refluxing dichloromethane furnished the
desired methyl ether 21 in 43% yield.
To prepare the compound for regeneration of the trisub-
stituted alkene and methyl ketone formation, we first had to
adjust the protecting groups. Basic hydrolysis of the carbon-
ate 21 provided the diol 23 in 83% yield (Scheme 7). A tert-
was unsuccessful, but we were able to form the allyloxy diol
19 from 18 on treatment with allyl alcohol and BF3 etherate.12
However, because of the low yield we discontinued this
route.
The solution to the formation of the desired methoxy diol
involved an intramolecular strategy.13 Thus the nucleophilic
carbamate was attached to the hydroxyl group of 18 by
treatment with phenyl isocyanate in 95% yield (Scheme 6).
Treatment of this carbamate with 5% HClO4 in acetonitrile14
(4) (a) Jung, M. E.; D’Amico, D. C. J. Am. Chem. Soc. 1993, 115, 12208
and references therein. (b) Jung, M. E.; D’Amico, D. C. J. Am. Chem. Soc.
1995, 117, 7379. (c) Jung, M. E.; D’Amico, D. C. J. Am. Chem. Soc. 1997,
119, 12150. (d) D’Amico, D. C. Ph.D. Thesis, UCLA, Los Angeles, CA,
1995. (e) Jung, M. E.; Lee, W. S.; Sun, D. Org. Lett. 1999, 1, 307. (f)
Jung, M. E.; Sun, D. Tetrahedron Lett. 1999, 40, 8343. (g) Jung, M. E.;
Karama, U.; Marquez, R. J. Org. Chem. 1999, 64, 663. (h) Jung, M. E.;
Marquez, R. Tetrahedron Lett. 1999, 40, 3129. (i) Jung, M. E.; Marquez,
R. Org. Lett. 2000, 2, 1669.
Scheme 7
(5) Jung, M. E.; Lee, C. P. Tetrahedron Lett. 2000, 41, 9719.
(6) Cossy, J.; Ranaivosata, J.-L.; Bellosta, V.; Wietzke, R. Synth.
Commun. 1995, 25, 3109.
(7) The alcohol is too hindered to allow easy introduction of the TBS
ether.
(8) Johnson, M. R.; Nakata, T.; Kishi, Y. Tetrahedron Lett. 1979, 20,
4343. Johnson, M. R.; Kishi, Y. Tetrahedron Lett. 1979, 20, 4347.
(9) Caron, M.; Sharpless, K. B. J. Org. Chem. 1985, 50, 1557.
(10) Liu, Y.-J.; Chu, T.-Y.; Engel, R. Synth. Commun. 1992, 22, 2367.
(11) The position of the methyl ether was determined by constructing
two derivatives, the cyclic carbonate, which had the characteristic IR stretch
of a six-membered carbonate (1755 cm-1), and the p-methoxybenzylidene
acetal formed by oxidative cyclization with DDQ, which showed the
expected NOE between 1,3 diaxial protons.
(12) The structure of 19 was again inferred, since the cyclic carbonate
formed from it had the characteristic IR stretch of a six-membered carbonate
(1748 cm-1).
(13) (a) Dolle, R. E.; Nicolaou, K. C. J. Am. Chem. Soc. 1985, 107,
1691. (b) Wang, Z.; Schreiber, S. L. Tetrahedron Lett. 1990, 31, 31.
(14) Horita, K.; Nagato, S.; Oikawa, Y.; Yonemitsu, O. Chem. Pharm.
Bull. 1989, 37, 1705.
butyldiphenylsilyl (TPS) ether was then attached to the
primary alcohol in 72% yield, allowing the secondary alcohol
to be protected as its benzyl ether to give 24 in 50% yield,
along with the bisbenzyl ether formed presumably as a result
(15) The IR spectrum of 20 showed an absorption at 1798 cm-1
,
indicative of a five-membered carbonate.
(16) (a) Jin, J.; Weinreb, S. M. J. Am. Chem. Soc. 1997, 119, 2050. (b)
Jung, M. E.; Nichols, C. J. Tetrahedron Lett. 1998, 39, 4615.
Org. Lett., Vol. 3, No. 3, 2001
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