Scheme 4. Generality of Seven-Membered Ring Glycal
Scheme 6. Attempted Cycloisomerization of Bis-silyl Ether
Diol 22
Formation from Various Diastereomersa
hydroxymethyl oxygen five atoms away from the C4-
hydrogen, which in turn is anti to the allylic silyloxy
substituent at C3. This previously unobserved limitation of
the cycloisomerization methodology can be avoided by use
of different protective group patterns, as described earlier
with substrate 4.
Classical methods for carbohydrate synthesis are well-
known to favor furanose and/or pyranose structures over
septanose (seven-membered ring sugar) isomers,8,9 and seven-
membered ring sugars can also be produced by multistep
routes involving selective protection of hexose sugar second-
ary alcohols10 or by rearrangement of partially protected
furanoside derivatives.11 Although other methods for the
formation of oxepins (seven-membered cyclic enol ethers)12,13
a Conditions: (a) 15% W(CO)6, Et3N, THF, h (350 nm) 55 °C,
6 h. (b) Ac2O, cat. DMAP.
(8) (a) Stevens, J. D. J. Chem. Soc., Chem. Commun. 1969, 1140. (b)
Ng, C. J.; Stevens, J. D. Carbohydr. Res. 1996, 284, 241.
(9) (a) Anet, E. F. L. J. Carbohydr. Res. 1968, 8, 164. (b) Grindley, T.
B.; Gulasekharan, V. J. Chem. Soc., Chem. Commun. 1978, 1073.
(10) (a) Micheel, F.; Suckfu¨ll, F. Ann. 1933, 502, 85. (b) Ward, D. E.;
Liu, Y.; Rhee, C. K. Can. J. Chem. 1994, 72, 1429. (c) McAuliffe, J. C.;
Hindsgaul, O. Synlett 1998, 307.
(11) Contour, M.-O.; Fayet, C.; Gelas, J. Carbohydr. Res. 1990, 201,
150.
(12) For formation of septanose glycals via ring-closing metathesis of
alkenes tethered to O-vinyl ethers, see: (a) Peczuh, M. W.; Snyder, N. L.
Tetrahedron Lett. 2003, 44, 4057. (b) Peczuh, M. W.; Snyder, N. L.; Fyvie,
W. S. Carbohydr. Res. 2004, 339, 1163.
the bis-silyl ether substrate 227 (Scheme 6), which is nearly
identical to the 6-deoxy substrate 20 that we have previously
established affords cycloisomerization product 21 in excellent
yield.1b,3a Surprisingly, neither cycloisomerization product 23
nor the seven-membered ring isomer was observed as a
product, and the only isolable compound was the unstable
dienyl ether 24.
(13) For representative other methods for formation of oxepins via: ring-
closing metathesis-isomerization: (a) Chatterjee, A. K.; Morgan, J. P.;
Scholl, M.; Grubbs, R. H. J. Am. Chem. Soc. 2000, 122, 3783. (b) Rainier,
J. D.; Allwein, S. P.; Cox, J. M. J. Org. Chem. 2001, 66, 1380. (c) Sutton,
A. E.; Seigal, B. A.; Finnegan, D. F.; Snapper, M. L. J. Am. Chem. Soc.
2002, 124, 13390. (d) Schmidt, B. Eur. J. Org. Chem. 2003, 816.
Oxidation-dehydration of 1,6-hexanediol: (e) Larkin, D. R. J. Org. Chem.
1965, 30, 335. (f) Oakes, F. T.; Yang, F.-A.; Sebastian, J. F. J. Org. Chem.
1982, 47, 3094. Via lactone enol phosphate or triflates: (g) Kane, V. V.;
Doyle, D. L.; Ostrowski, P. G. Tetrahedron Lett. 1980, 21, 2643. (h)
Tsushima, K.; Araki, K.; Murai, A. Chem. Lett. 1989, 1313. (i) Nicolaou,
K. C. J. Am. Chem. Soc. 1997, 119, 5469. Via anionic cyclization of allyl
glycidyl ether: (j) Ichikawa, Y.; Niitsuma, S.; Kato, K.; Takita, T. J. Chem.
Soc., Chem. Commun. 1988, 625. (k) Bird, C. W.; Hormozi, N. Tetrahedron
Lett. 1990, 31, 3501. Oxidative expansion with peroxides: (l) Krafft, G.
A.; Katzenellenbogen, J. A. J. Am. Chem. Soc. 1981, 103, 5459. (m)
Goodman, R. M.; Kishi, Y. J. Org. Chem. 1994, 59, 5125. [3.3]-
Rearrangements: (n) Wenkert, E.; Greenberg, R. S.; Kim, H. S. HelV. Chim.
Acta 1987, 70, 2159. (o) Clark, D. L.; Chou, W.-N.; White, J. B. J. Org.
Chem. 1990, 55, 3975. (p) Sugiyama, J.; Tanikawa, K.; Okada, T.; Noguchi,
K.; Ueda, M.; Endo, T. Tetrahedron Lett. 1994, 35, 3111. (q) Hofmann,
B.; Reissig, H.-U. Chem. Ber. 1994, 127, 2337. Conjugate oxacyclization
This compound can be envisioned to arise from hydroxyl-
assisted â-elimination via the intermediacy of expected
product 23, especially given the syn relationship of the
Scheme 5. Cycloisomerization of Substrate 18 with Two
Secondary Alcohols Also Gives Seven-Membered Ring
Product 19
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