The synthesis of polyoxygenated, enantiopure cyclopentene derivatives using the Ramberg-B?cklund rearrangement

Article abstract of DOI:10.1016/S0040-4039(00)02209-7

A novel approach to polyoxygenated enantiopure cyclopentenes, α-chlorocyclopentenones and cyclopentenones is described which utilizes the Ramberg-Ba?cklund rearrangement of thiosugar-derived sulfones. A formal synthesis of the natural aminocyclopentitol, trehazolamine is also reported.

Full text of DOI:10.1016/S0040-4039(00)02209-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 1197–1200
The synthesis of polyoxygenated, enantiopure cyclopentene
derivatives using the Ramberg–Ba¨cklund rearrangement
Graeme D. McAllister and Richard J. K. Taylor*
Department of Chemistry, University of York, Heslington, York YO10 5DD, UK
Received 10 November 2000; accepted 29 November 2000
Abstract—A novel approach to polyoxygenated enantiopure cyclopentenes, a-chlorocyclopentenones and cyclopentenones is
described which utilizes the Ramberg–Ba¨cklund rearrangement of thiosugar-derived sulfones. A formal synthesis of the natural
aminocyclopentitol, trehazolamine is also reported. © 2001 Elsevier Science Ltd. All rights reserved.
A wide range of compounds containing polyoxygenated
cyclopentenes or their derivatives exist in nature.1 These
include prostaglandins,2 mannostatins,3 trehazolamine4
and cyclopentitols.5 In an ongoing study to investigate
synthetic applications of the Ramberg–Ba¨cklund Rear-
rangement (RBR),6 we now report the use of thiosugar-
derived sulfones as precursors to enantiopure
cyclopentenes (Scheme 1). Cere` et al. recently demon-
strated the use of mannose-derived sulfones in the
synthesis of conduritols,7 but to date there have been
no reported syntheses of cyclopentenes via the RBR of
oxidized thiosugars.
of 1 and 2 by m-chloroperbenzoic acid gave the novel
sulfones 3 and 4 in a reasonable overall yield (Scheme
2).9
The Ramberg–Ba¨cklund Rearrangement of 3 under
Meyers’ conditions (KOH/CCl4/tBuOH),10 gave a 5:1
mixture of enol ethers 5 and 6 (Table 1, entry i). The
major product, 5 results from double chlorination fol-
lowed by episulfone formation and loss of sulfur diox-
ide. These enol ethers are easily separated by
chromatography and have a reasonable stability on
silica. Similarly (entry ii), RBR of ribose-derived sul-
fone 4 gave enol ethers 7 and 8 (ca. 3:1) in 69% overall
yield.11
We first investigated the use of pentose sugars and
prepared benzyl-protected methyl 5-thio-D-xylopyrano-
side 1 and methyl 5-thio-
D
-ribopyranoside 2 following
Treatment of enol ethers 5–8 with aqueous acid re-
sulted in the formation of enones 9–12 in good yields
the methods of Whistler8a and Hughes.8b Oxidation
Scheme 1. (X=H or OMe).
* Corresponding author. E-mail: rjkt1@york.ac.uk
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(00)02209-7

1198
G. D. McAllister, R. J. K. Taylor / Tetrahedron Letters 42 (2001) 1197–1200
Scheme 2.
Table 1. Ramberg–Ba¨cklund Rearrangement of sulfones 3 and 4a
a 3:2 CCl4-tBuOH, KOH, 60°C. b Yields are of isolated enol ethers after column chromatography.
Scheme 3.

G. D. McAllister, R. J. K. Taylor / Tetrahedron Letters 42 (2001) 1197–1200
1199
Scheme 4.
Scheme 5.
(Scheme 3). In the case of enones 10 and 12, optical
rotation values are in good agreement with the litera-
ture {10: [h]D +63.9 (c. 0.84, CHCl3): Lit.12 (enant.):
[h]D −61.7 (c. 1.5, CHCl3). 12: [h]D +21.0 (c. 0.2,
CHCl3): Lit.12 (enant.): [h]D −22.1 (c. 0.5, CHCl3)}.
should prove useful for the preparation of analogues of
cyclopentitols, and in addition, we have completed a
formal synthesis of the aglycone trehazolamine in good
yield from thioglucose. Further research is currently
underway to extend this methodology and utilize the
cyclopentene/cyclopentenone products for the synthesis
of more complex natural products.
As a natural extension to the work with pentose sugars,
we next investigated the RBR of a thioglucose-derived
sulfone. Compound 13 has previously been synthesized
by Chiara and co-workers,4 and is an advanced inter-
mediate in the synthesis of trehazolamine, the aglycone
of the trehalase inhibitor, trehazolin. We therefore
explored the RBR route to 13 illustrated retrosyntheti-
cally in Scheme 4.
Acknowledgements
We thank the EPSRC for postdoctoral funding
(G.D.M.).
Benzylated methyl 5-thio-
prepared from diacetone
D
-glucopyranoside 14 was
-glucose following the
D
References
method of Yuasa et al.13 Treatment of 14 with ZnCl2/
dichloromethyl methyl ether (DCMME)14 gave the cor-
responding anomeric chloride which was immediately
oxidized to chlorosulfone 15 in 40% overall yield
1. Berecibar, A.; Grandjean, C.; Siriwardena, A. Chem. Rev.
1999, 99, 779–844.
2. Suzuki, M.; Yanagisawa, A.; Noyori, R. J. Am. Chem.
t
(Scheme 5). Treatment of 15 with BuOK in THF at
Soc. 1988, 110, 4718–4726.
−78°C to effect the RBR gave cyclopentene 13 in 40%
overall yield after chromatography. The chlorination/
oxidation/RBR sequence could also be carried out
without purification of the chlorosulfone 15: in this
case, the overall yield for the 3-step sequence was 33%.
The optical rotation of 13 was in good agreement with
the literature value {[h]D +38.5 (c. 1.95, CHCl3). Lit.4
[h]D +37.5 (c. 1.7, CHCl3)}.
3. Aoyagi, T.; Yamamoto, T.; Kojiri, K.; Morishima, H.;
Nagai, M.; Hamada, M.; Takeuchi, T.; Umezawa, H. J.
Antibiot. 1989, 42, 883–889.
4. Storch de Gracia, I.; Dietrich, H.; Bobo, S.; Chiara, J. L.
J. Org. Chem. 1998, 63, 5883–5889.
5. (a) Seepersaud, M.; Al-Abed, Y. Tetrahedron Lett. 2000,
41, 4291–4293; (b) Maezaki, N.; Sakamoto, A.; Tanaka,
T.; Iwata, C. Tetrahedron: Asymmetry 1998, 9, 172–182.
6. (a) Taylor, R. J. K. J. Chem. Soc., Chem. Commun. 1999,
217–227, and references therein; (b) Griffin, F. K.; Patter-
son, D. E.; Taylor, R. J. K. Angew. Chem., Int. Ed. Eng.
1999, 38, 2939–2942; (c) Campbell, A. D.; Patterson, D.
E.; Raynham, T. M.; Taylor, R. J. K. J. Chem. Soc.,
Chem. Commun. 1999, 1599–1600.
In conclusion, we have demonstrated that enantiopure,
polyoxygenated cyclopentenes can be easily synthesized
by the Ramberg–Ba¨cklund rearrangement of sulfones
prepared from readily-available thiosugars. Enones 9–
12 are suitable precursors for the synthesis of
prostaglandin-type molecules, and a-chloroenones 9
and 11 have potential application in Pd-catalyzed cou-
7. (a) Cere`, V.; Mantovani, G.; Peri, F.; Pollicino, S.; Ricci,
A. Tetrahedron 2000, 56, 1225–1231; (b) Cer, V.; Peri, F.;
Pollicino, S. Tetrahedron Lett. 1997, 37, 7797–7800.
pling reactions. Cyclopentenes derived from thioglucose
.

1200
G. D. McAllister, R. J. K. Taylor / Tetrahedron Letters 42 (2001) 1197–1200
8. (a) Ingles, D.; Whistler, R. L. J. Org. Chem. 1962, 27,
12. Johnson, C. R.; Nerurkar, B. M.; Golebiowski, A.; Es-
ker, J. L. J. Chem. Soc., Chem. Commun. 1995, 1139–
1140.
13. Yuasa, H.;Tamura, J.;Hashimoto, H. J. Chem. Soc., Perkin
Trans. 1 1990, 2763–2769.
14. For additional examples of this reaction see: Ziegler, T.;
Pavliak, V.; Lin, T.-H.; Kovac, P.; Glaudemans, C. P. J.
Carbohydr. Res. 1990, 204, 167-189; Withers, S. G.; Per-
cival, M. D.; Street, I. P. Carbohydr. Res. 1989, 187, 43–66;
Nashed, E. M.; Glaudemans, C. P. J. J. Org. Chem. 1987,
52, 5255–5260.
3896–3898; (b) Hughes, N. A.; Munkombwe, N. M.
Carbohydr. Res. 1985, 136, 397–409 and 411–418; (c)
Hughes, N. M.; Kuhajda, K.-M.; Miljovic, D. A. Carbo-
hydr. Res. 1994, 257, 299–304.
9. All new compounds were fully characterized spectroscop-
ically and by HRMS or elemental analysis.
10. Meyers, C. Y.; Malte, A. M.; Matthews, W. S. J. Am. Chem.
Soc. 1969, 91, 7510–7512.
11. We also attempted the RBR directly on sulfones 3 and 4,
but only isolated an optically inactive sulfone resulting from
elimination of the benzyloxy groups in positions 3 and 5.
.
.