A study of the epoxidation of 6-deoxyhex-5-enopyranosides. 1,5-Dicarbonyl derivatives and novel synthetic routes to D-xylo-hexos-5-ulose and D-lyxo-hexos-5-ulose

Article abstract of DOI:10.1021/jo016378c

The work described deals with the isolation and characterization of epoxides from 6-deoxyhex-5-enopyranosides and preliminary exploration of their synthetic potential. Prolonged epoxidation reaction times led to their hydrolysis in situ and gave novel protected D-hexos-5-ulose derivatives (sugar 1,5-dicarbonyls). Some reactions of the hexos-5-uloses were studied, and in some cases septanoside (seven-membered-ring saccharide) derivatives were isolated. Novel routes to D-xylohexos-5-ulose and D-lyxo-hexos-5-ulose, of interest as intermediates in the synthesis and biosynthesis of inositols and aza sugars, are also described. The structures of the epoxides and novel hexos-5-uloses were established by NMR and X-ray crystallographic methods.

Full text of DOI:10.1021/jo016378c

J . Org. Chem. 2002, 67, 3733-3741
3733
A Stu d y of th e Ep oxid a tion of 6-Deoxyh ex-5-en op yr a n osid es.
1,5-Dica r bon yl Der iva tives a n d Novel Syn th etic Rou tes to
D-xylo-Hexos-5-u lose a n d D-lyxo-Hexos-5-u lose
Philomena M. Enright,† Manuela Tosin,† Mark Nieuwenhuyzen,‡ Linda Cronin,† and
Paul V. Murphy*,†
Department of Chemistry, Centre for Synthesis and Chemical Biology, Conway Institute of Biomolecular
and Biomedical Research, University College Dublin, Belfield, Dublin 4, Ireland, and School of
Chemistry, Queen’s University, Belfast BT9 5AG, Antrim, Northern Ireland
paul.v.murphy@ucd.ie
Received December 15, 2001
The work described deals with the isolation and characterization of epoxides from 6-deoxyhex-5-
enopyranosides and preliminary exploration of their synthetic potential. Prolonged epoxidation
reaction times led to their hydrolysis in situ and gave novel protected D-hexos-5-ulose derivatives
(sugar 1,5-dicarbonyls). Some reactions of the hexos-5-uloses were studied, and in some cases
septanoside (seven-membered-ring saccharide) derivatives were isolated. Novel routes to D-xylo-
hexos-5-ulose and D-lyxo-hexos-5-ulose, of interest as intermediates in the synthesis and biosynthesis
of inositols and aza sugars, are also described. The structures of the epoxides and novel hexos-5-
uloses were established by NMR and X-ray crystallographic methods.
Sch em e 1
In tr od u ction
Much recent interest has focused on the synthetic
potential of glycals as their epoxides and other deriva-
tives can be used in the preparation of oligosaccharides,
glycoconjugates, and a variety of other carbohydrate
derivatives of biological and medical interest.1 6-Deoxy-
hex-5-enopyranosides 1, which are further enol ethers
with “exo-glycal” functionality, have proven to be useful
intermediates in synthesis, as illustrated by the prepara-
tion of carbacycles by Ferrier and other rearrangement
(Sinay) reactions.2 Despite these and other successes,
there is little work reported in the literature on the
synthesis and reactions of their epoxides3 or other small
ring adducts. Reactions of epoxides 2 with reducing
reagents or nucleophiles (Scheme 1) could provide useful
intermediates for the synthesis of a range of biologically
interesting carbohydrate derivatives for the synthesis of
novel glycosaminoglycan derivatives,4 novel aminoglyco-
sides with potential as RNA binding agents,5 or other
glycomimetics.6 We have recently shown that they can
be used in the synthesis of the glycosidase inhibitor
deoxymannojirimycin.7 In this paper we provide a full
account8 concerning the isolation of the epoxides from
6-deoxyhex-5-enopyranosides, their hydrolysis to give
novel protected D-hexos-5-ulose derivatives, and the
synthesis of the parent hexos-5-uloses D-xylo-hexos-5-
ulose and D-lyxo-hexos-5-ulose.9 These hexos-5-uloses are
of interest as they have been postulated as intermediates
† University College Dublin.
‡ Queen’s University.
(1) For reviews see: (a) Danishefsky, S. J .; Bilodeau, M. T. Angew.
Chem., Int. Ed. Engl. 1996, 35, 1380. (b) Ferrier, R. J . Top. Curr. Chem.
2001, 215, 153.
(2) (a) Ferrier, R. J .; Middleton, S. Chem. Rev. 1993, 93, 2779. (b)
Dalko, P.; Sinay¨, P. Angew. Chem., Int. Ed. 1999, 38, 773. (c) Ferrier,
R. J . Top. Curr. Chem. 2001, 215, 277.
(3) As far as we are aware only one synthesis of their epoxides had
been reported previously: Defaye, J . C. R. Hebd. Seances Acad. Sci.
1962, 255, 794.
(4) Lander, A. D. Chem. Biol. 1994, 1, 73.
(5) Alper, P. B.; Hendrix, M.; Sears, P.; Wong, C.-H. J . Am. Chem.
Soc. 1998, 120, 1965.
(6) Wong, C.-H. Acc. Chem. Res. 1999, 32, 376.
(7) O’Brien, J .; Tosin, M.; Murphy, P. V. Org. Lett. 2001, 3, 3353.
(8) Parts of the work described herein have been communicated
recently; see: Enright, P. M.; O’Boyle, K. M.; Murphy, P. V. Org. Lett.
2000, 2, 3929. See also ref 7.
(9) For previous syntheses of protected and unprotected hexos-5-
uloses see: (a) Heusinger, H. Carbohydr. Res. 1988, 181, 67. (b) Kiely,
D. E.; Fletcher, H. G., J r. J . Org. Chem. 1969, 34, 1386. (c) Helferich,
B.; Bigelow, N. M. Z. Physiol. Chem. 1931, 200. (d) Blattner, R.; Ferrier,
R. J . J . Chem. Soc., Perkin Trans. 1 1980, 1523. (e) Ferrier, R. J .; Tyler,
P. C. J . Chem. Soc., Perkin Trans. 1 1980, 1528. (f) Barili, P. L.;
Bergonzi, M. C.; Berti, G.; Catelani, G.; D’Andrea, F.; De Rensis, F. J .
Carbohydr. Chem. 1999, 18, 1037. (g) Barili, P. L.; Berti, G.; Catelani,
G.; D’Andrea, F.; De Rensis, F.; Goracci, G. J . Carbohydr. Chem. 1998,
17, 1167-1180. (h) Barili, P. L.; Berti, G.; Catelani, G.; D’Andrea, F.;
DeRensis, F. Tetrahedron 1997, 53, 8665.
10.1021/jo016378c CCC: $22.00 © 2002 American Chemical Society
Published on Web 04/30/2002

3734 J . Org. Chem., Vol. 67, No. 11, 2002
Enright et al.
20 at 60 °C in acetonitrile (entry 14) led to the formation
of 1,5-dicarbonyl derivatives (hexos-5-uloses). The most
efficient formation of the hexos-5-uloses was observed
when methyl(trifluoromethyl)dioxirane was again used.
Lower yields and conversions were observed for reactions
with dimethyldioxirane and other epoxidizing agents.18
The galactose derivative 28/29 was isolated (48%) from
the reaction of methyl(trifluoromethyl)dioxirane with 15.
Efforts to obtain the epoxides from the TMS-protected
10, by careful monitoring of the reaction carried out at
room temperature, were not successful and surprisingly
gave the hemiketal 17 (71%); attempts to purify this
material further by distillation led to its efficient conver-
sion to 18 (75%).19 A hemiketal related to 17 was also
observed previously by Chapleur and co-workers from the
dihydroxylation of methyl 2,3-di-O-benzyl-4-O-methane-
sulfonyl-6-deoxy-R-D-xylo-hex-5-enopyranoside (using
RuCl3/NaIO4); this compound eliminated methanol dur-
ing chromatography, and the product thus obtained also
had a bicyclic structure, 6.20 In our hands the dihydroxy-
lation of TMS-protected and acetyl-protected hex-5-
enopyranosides using similar conditions did not proceed
in good yields to give the hexos-5-uloses.
F igu r e 1. Use of NOE experiments to assign the stereochem-
istry of epoxides.
in the biosynthesis10 of inositols and aza sugars and are
also synthetic prescursors to both aza sugars11 and
inositols.12
Resu lts a n d Discu ssion
Syn th esis a n d Str u ctu r e of Ep oxid es. A series of
epoxidation reactions of 9-1513 were investigated (Table
1), and epoxides could be isolated in high yields from
acetylated and benzylated hex-5-enopyranosides (entries
4, 7, and 10) using methyl(trifluoromethyl)dioxirane,
generated in situ.14 Epoxidation with MCPBA in dichlo-
romethane15 in the presence of aqueous sodium bicarbon-
ate buffer16 also worked well (entries 6 and 9). Attempts
to separate the epoxides by silica gel chromatography led
to depleted yields (entries 3 and 8). However, the crude
product is sufficiently pure that it can be used for further
synthetic transformations (entry 14), and the epoxides
It was generally noted that the epoxides with their
oxygen atom in an equatorial orientation (S configura-
tion) were more susceptible to hydrolysis during chro-
matography; this is consistent with the greater reactivity
of equatorial pyranosides. The formation of hexos-5-
uloses in these reactions is explained by the hydrolysis
of the initially formed epoxide, giving a hemiketal, 3a ,
or possibly a hemiacetal, 3b, that ultimately loses
methanol (Scheme 1). The formation of 17 from 10 would
suggest attack by water at C-5 is favored. However, this
does not preclude the possible attack of water at C-1 in
other cases to give 3b, which would ultimately have the
same consequences. The relatively facile hydrolysis of the
epoxides formed in these reactions can be compared with
that of similarly reactive epoxides derived from 4-deoxy-
L-threo-hex-4-enopyranoside, which have been shown to
give bisglycosides when reacted with methanol.21
1
are stable once isolated.17 The H NMR spectral data for
19 were in good agreement with those reported previ-
ously by Defaye.3 The stereochemical configuration at C-5
(R) of this product, previously not determined, was
established by X-ray crystallography. The configuration
at C-5 can also be determined using NOE experiments.
The isomer 22 showed an NOE enhancement between
H-6a and H-4 but not between H-6a and H-3, whereas
23 showed enhancements between H-6a and H-4 and also
between H-6a and H-3 (Figure 1).
F or m a tion of Hexos-5-u loses fr om Ep oxid es. Pro-
longed reaction times (Table 1) in the epoxidation of 9-15
(entries 1, 2, 5, and 11-13), the attempted separation of
epoxides by chromatography, and the hydrolysis of 19/
Str u ctu r e of Hexos-5-u loses. The hexos-5-uloses
isolated could adopt the structure of one or more of the
tautomers 4-7 or possibly that of hydrated compound 8
(Scheme 1). However, the bicyclic structure 6, which
disguises both carbonyl groups and has the pyranose ring
in a 4C1 conformation, is favored in all cases.22 It is
adopted exclusively by the protected 5-keto-D-glucose and
5-keto-D-mannoses (16, 18, 21, 26, 27, and 30) in CDCl3.
There is no evidence in the NMR or IR spectra to support
the presence of open chain 4 or septanos-5-ulose struc-
tures 5 in any of the equilibrium product mixtures.23
However, there is evidence for a dynamic equilibrium
between 28 and 29 which presumably occurs via a
(10) (a) Wong, Y.-H. H.; Sherman, W. R. J . Biol. Chem. 1981, 256,
7077. (b) Eisenberg, F., J r.; Maeda, T. In Inositols and Phosphoinositi-
des; Bleasdale, J . E., Eichberg, J ., Hauser, G., Eds.; Humana: Totowa,
NJ , 1985; p 3. (c) Hardick, D. J .; Hutchinson, D. W.; Trew, S. J .;
Wellington, E. M. H. Chem. Commun. 1991, 729.
(11) For the synthesis of aza sugars using 1,5-dicarbonyl sugars,
see: (a) Baxter, E. W.; Reitz, A. B. J . Org. Chem. 1994, 59, 3175. (b)
D’Andrea, F.; Catelani, G.; Mariani, M.; Vecchi B. Tetrahedron Lett.
2001, 42, 1139. (c) Barili, P. L.; Berti, G.; Catelani, G.; D’Andrea, F.;
DeRensis, F.; Puccioni, L. Tetrahedron 1997, 53, 3407.
(12) Hexos-5-uloses have also been used in a synthesis of inositols;
see: Pistara, V.; Barili, P. L.; Catelani, G., D’Andrea, F.; Fisichella, S.
Tetrahedron Lett. 2000, 41, 3253.
1
(13) Modifications of literature methods were used for the synthesis
of 9-15. Full details are provided in the Supporting Information. (a)
Semeria, D.; Phillipe, M.; Delaumeny, J .-M.; Sepulchre, A.-M.; Gero,
S. D. Synthesis 1983, 710. (b) Sakairi, N.; Kuzuhara, H. Tetrahedron
Lett. 1982, 23, 50, 5327. (c) Takeo, K.; Fukatsu, T.; Yasato, T.
Carbohydr. Res. 1982, 107, 71. (d) Ferrier, R. J .; Prasit, P. Carbohydr.
Res. 1980, 82, 263-272. (e) Sugawara, F.; Kuzuhara, H. Agric. Biol.
Chem. 1981, 45, 301. (f) Defaye, J .; Gadelle, A.; Wong, C. C. Carbohydr.
Res. 1981, 94, 131. (g) Bernet, B.; Vasella, A. Helv. Chim. Acta 1979,
62, 2411. (h) Lehmann, Carbohydr. Res. 1966, 2, 1. (i) Das, S. K.;
Mallet, J .-M.; Sinay¨, P. Angew. Chem., Int. Ed. Engl. 1997, 36, 493.
(14) Yang, D.; Wong, M.-K.; Yip, Y.-C. J . Org. Chem. 1995, 60, 3887.
(15) Hydrolysis of the epoxides was more pronounced if diethyl ether
was used as a solvent.
septanos-5-ulose intermediate; the H NMR of the prod-
uct recorded directly after silica chromatography indi-
cated a 60:40 mixture of 28 and 29, and this ratio
(18) Further details are provided in the Supporting Information.
(19) Some conversion of 17 to 18 was also observed in CDCl3 by
NMR.
(20) Taillefumier, C., Lakhrissi, M., Chapleur, Y. Synlett 1999, 697.
(21) Barili, P. L.; Berti, G.; Catelani, G.; D’Andrea, F.; De Rensis,
F. Tetrahedron 1997, 8665.
(22) The spectra were recorded in CDCl3 and also DMSO-d6 and
acetone-d6.
(16) Anderson, W. K.; Veysoglu, T. J . Org. Chem. 1973, 38, 12, 2267.
(17) Decomposition did not occur after storage in a freezer for 3
weeks.
(23) The 1H NMR spectra were recorded in CDCl3, and the IR
spectra were obtained by liquid film method, by KBr method, or for a
solution in CHCl3.

Epoxidation of 6-Deoxyhex-5-enopyranosides
J . Org. Chem., Vol. 67, No. 11, 2002 3735
Ta ble 1. Syn th esis of Ep oxid es a n d Hexos-5-u loses
a
Reagents and conditions: (A) MCPBA, CH2Cl2, 0.5 M NaHCO3, chromatography; (B) MCPBA, CH2Cl2, 0.5 M NaHCO3, no
chromatography; (C) 1,1,1-trifluoroacetone, oxone, NaHCO3, Na2EDTA, CH3CN, H2O, no chromatography; (D) 1,1,1-trifluoroacetone, oxone,
b
NaHCO3, Na2EDTA, CH3CN, H2O, chromatography; (E) H2O, MeCN, 60 °C, chromatography. Prolonged exposure to chromatography
reduces the yield.

3736 J . Org. Chem., Vol. 67, No. 11, 2002
Enright et al.
as would have been expected for a compound with
structure 8.25 2D NOESY spectra were also obtained for
31-35, 37, and 39 to confirm that tautomerization to
compounds with glucose configuration did not occur
during the course of the reactions (Table 2). It was
interesting to observe the formation of septanoside
products 36 and 38 as byproducts in two cases; the
stereochemical configuration of these compounds was
assigned on the basis of cross-peaks observed between
H-1 and H-3 in 2D NOESY spectra. The reduction of 36
and 38 with NaBH4 was also investigated to aid the
stereochemical assignment; reduction of 38 gave two
diastereoisomeric alcohols, whereas reduction of 36 gave
a single alcohol. The coupling constants for the anomeric
protons (J 1,2) of these alcohols were between 6.2 and 7.6
Hz; these values are consistent with those described for
related septanosides that have a 1,2-trans configura-
tion.26 The acetylation of the galactose derivative 28/29
unexpectedly gave as the major products a compound
with talose configuration 40 (20%) and the septanoside
41 (48%). The structure assigned to 40 was strongly
supported by the analysis of coupling constants in the
1H NMR spectrum and NOESY experiments.27 The
formation of the septanosides can be rationalized (Scheme
2) by trapping of the more nucleophilic seven-membered-
ring tautomer 43, possibly present in small amounts in
solution, or directly from 6.
F igu r e 2. Use of NOE experiments to determine the hexos-
5-ulose structure.
Sch em e 2
Sch em e 3
Syn t h esis of D-xylo-H exos-5-u lose a n d D-lyxo-
Hexos-5-u lose. The preparation of D-xylo-hexos-5-ulose
(46) and D-lyxo-hexos-5-ulose (47) (5-keto-D-glucose and
5-keto-D-mannose) was investigated as these compounds
have, respectively, been used in the synthesis of the
glycosidase inhibitors28 1-deoxynojirimycin (48) and
1-deoxymannojirimycin (49) and they have also been
postulated as intermediates in the biosynthesis of inosi-
tols. Attempts to directly remove the protecting groups
from 21 and 26 were not successful, but the labile TMS
groups were easily removed, using methanol, from 16 to
give 46, and from 17 or 18 to give 47 (Scheme 3).
Alternatively, the benzyl protecting groups were removed
from 33 and 35 by catalytic hydrogenation using Pd-C
in ethanol to give the unprotected glycosides 44 and 45,
respectively. The TBS group can be removed from 45 to
give 46 by treatment with TBAF in THF (Scheme 3),
illustrating that this is a strategy that could be utilized
for the protection of the 1,5-dicarbonyl products.29 Selec-
tive manipulation of the hydroxyl groups of 45 (or 44)
could be possible, and the resulting products could be
investigated for the synthesis of oligosaccharides contain-
ing aza sugars.
changed to 25:75 over 3 days.24 The coupling constants
in the 1H NMR spectra and 2D NOESY experiments were
used to confirm the structures proposed for all of the
products in CDCl3; the rationale used is illustrated for
1
26 (Figure 2). Thus, the H and 13C NMR spectra of the
product obtained from the reaction of 13 (Table 1, entry
11) indicated the preferred structure for the product to
be either one with idose configuration 26 or one with
glucose configuration 42b, which has the pyranose ring
in a twist boat conformation; the tautomer with glucose
configuration 42a , with its pyranose ring in a 1C4
conformation, is excluded on the basis of the coupling
1
constants for the ring protons in the H NMR spectrum.
(25) Detailed studies on equilibrium product mixtures in aqueous
solutions of unprotected hexos-5-uloses have been carried out, and
hydrated structures are observed under these conditions. See: (a)
Kiely, D. E.; Harry-O’Kuru, R. E.; Morris, J r., P. E.; Morton, D. W.;
Riordan, J . M. J . Carbohydr. Chem. 1997, 16, 1159. (b) Riordan, J .
M.; Morris, P. E., J r.; Kiely, D. E. J . Carbohydr. Chem. 1993, 12, 865.
(26) Compounds with a 1,2-trans configuration that are known are
derivatives of methyl â-D-glucoseptanoside and methyl R-L-idoseptano-
side. Derivatives of septanosides with a 1,2-cis configuration (methyl
R-D-glucoseptanoside and methyl â-L-idoseptanoside) have J 1,2 values
of 2-3 Hz. See: (a) Stevens, J . D. Aust. J . Chem. 1975, 28, 525. (b)
Ng, C. J .; Stevens, J . D., Carbohydr. Res. 1996, 284, 241. (c) Ng. C. J .;
Craig, D. C.; Stevens, J . D. Carbohydr. Res. 1996, 284, 249.
(27) NOE cross-peaks were not observed between H-3 and H-6
protons as would be expected for the compound with galactose
configuration.
The 2D NOESY experiments showed cross-peaks, pos-
sible only for structure 26, between H-3 and one of the
H-6 protons; cross-peaks were not observed between H-2
and H-6 or between H-4 and H-6 as would have been
expected for 42b. A similar rationale was used in assign-
ing all structures described herein. Crystals (needles)
were obtained for 26, and its structure was determined
by X-ray crystallographic methods; the structure in the
solid state was the same as that observed in solution.
Rea ction s of Hexos-5-u loses. Some reactions of the
hexos-5-uloses were studied (Table 2). The reaction of 26
with excess acetic anhydride and pyridine gave the
monoacetate 32 rather than a product with three acetates
(28) (a) Hughes, A. B.; Rudge, A. J . Nat. Prod. Rep. 1994, 135. (b)
Fleet, G. W. J . Glycobiology 1992, 2, 199 and references therein.
(29) The use of more than 1 equiv of TBAF leads to formation of
unidentified products.
(24) The NMR spectra were obtained in CDCl3.

Epoxidation of 6-Deoxyhex-5-enopyranosides
J . Org. Chem., Vol. 67, No. 11, 2002 3737
Ta ble 2. Rea ction s of Hexos-5-u loses
reagents and
conditionsa
entry
reactant
product (yield, %)
R1, R2
1
2
3
4
5
6
7
8
9
21
26
26
26
26
26
26
26
D
A
B
C
D
E
F
G
A
31 (63)
32 (58)
Ac, TBS
Bn, Ac
Bn, Me
33 (78)
34 (66)b
Bn, Tf
35 (48)
Bn, TBS
Bn, TBS
Bn, 2-BrBz
Bn, Ms
35 (38), 36 (16)
37 (45), 38 (16)
39 (63)
28/29
a
Reagents and conditions: (A) Ac2O, Py, DMAP (cat.), 25 °C, 15 h; (B) NaH (2 equiv), MeI (2 equiv), DMF, 25 °C, 12 h; (C) Tf2O (2
equiv), 2,6-lutidine (4 equiv), CH2Cl2, -40 to +25 °C, 15 h; (D) TBSOTf (1.5 equiv), 2,6-lutidine (2 equiv), CH2Cl2; (E) TBSOTf (2 equiv),
pyridine, -40 to +25 °C, 15 h; (F) 2-bromobenzoyl chloride (2 equiv), DMAP (cat.), pyridine, 0-25 °C, 15 h; (G) MsCl (2 equiv), DMAP,
b
pyridine, 2.5 h. Yield based on the amount of recovered starting material.
1
solid (0.56 g, 27%): [R]20 +92.1° (c 0.152, CHCl3); H NMR
Con clu sion s
D
(CDCl3, 270 MHz) δ 5.76 (apt t, 1H, J ) 9.9 Hz), 5.53 (d, 1H,
In summary we have described the preparation and
isolation of epoxides in high yields from hex-5-enopyra-
nosides. Hydrolysis of these epoxides gives novel pro-
tected hexos-5-uloses with interesting bicyclic structures.
Some novel reactions of the protected hexos-5-uloses were
studied, and these gave, in some cases, septanoside
derivatives. Application of the methodology to the syn-
thesis of unprotected D-hexos-5-uloses, which are of
interest as intermediates in the synthesis and biosyn-
thesis of aza sugars and inositols, has been achieved, and
the methodology has potential for the synthesis of other
1,5-dicarbonyl derivatives. Current work is concerned
with further exploration of the synthetic potential of the
hex-5-enopyranosides and their epoxides. In particular
the syntheses of aza sugars and iduronic acids are being
explored, and the biological activity of these compounds
will be reported in due course.
J ) 9.9 Hz), 5.00 (m, 2H), 3.43 (s, 3H), 2.84 (d, 1H J ) 4.2
Hz), 2.53 (d, 1H, J ) 4.2 Hz), 2.10, 2.04, 2.03 (each s, each
3H); 13C NMR (CDCl3) δ 170.4, 170.1, 169.7 (each s, each OAc),
98.5 (d), 79.1 (s), 71.1, 68.3, 66.8 (each d), 56.7 (q), 45.7 (t),
20.9, 20.8, 20.7 (each q); IR (KBr disk) ν 2940, 1750, 1372,
1217, 1040, 730 cm-1; CI-HRMS m/z found 319.1029, required
319.1029 [M + H]+.
(ii) 1,1,1-Trifluoroacetone (0.96 mL, 13 mmol), Na2EDTA
(7.5 mL of a 0.4 mM aq solution), 11 (0.4 g), oxone (2.8 g, 6.5
mmol), and NaHCO3 (0.64 g) were treated as described above,
and reaction was carried out for 2 h and gave a 50:50 mixture
of 19 and 20 (0.416 g, 99%) as a colorless syrup. Selected 1H
NMR data for isomer 20: δ (CDCl3) 3.46 (s, 3H), 3.01 (d, 1H,
J ) 4.5 Hz), 2.86 (d, 1H, J ) 4.5 Hz).
Meth yl 2,3,4-Tr i-O-a cetyl-5,6-a n h yd r o-5-h yd r oxy-r-D-
m a n n op yr a n osid e (22/23). (i) Alkene 12 (2.0 g, 6.62 mmol)
was dissolved in a mixture of dichloromethane (66 mL) and
0.5 M aqueous sodium bicarbonate (20 mL); solid m-chlorop-
erbenzoic acid (2.07 g, 6.62 mmol) was slowly added, and the
solution was stirred at room temperature for 2 h, after which
time the reaction did not proceed further (TLC analysis). The
two phases were separated, and the organic phase was washed
with 1 N sodium hydroxide (20 mL) and water (20 mL) and
then dried (Na2SO4); the solvent was removed at room tem-
perature under reduced pressure to yield a white clear oil (2.08
g) which NMR analysis revealed to be a mixture of 22 (61%),
23 (13%), and 12 (25%). TLC analysis indicated the epoxides
had identical Rf values (0.7; EtOAc/petroleum ether, 1:1).
Chromatography (silica gel prepacked with EtOAc/petroleum
ether/Et3N, 100:10:1; eluant EtOAc/petroleum ether gradient,
1:10 to 1:0) gave recovered 12 (0.5 g, 25%) and 22 (clear oil,
0.74 g, 35%): [R]D +19.0° (c 0.45, CHCl3); 1H NMR (300 MHz,
CDCl3) δ 5.81 (d, 1H, J ) 10.5 Hz), 5.59 (dd, 1H, J ) 3.2, 10.5
Hz), 5.41 (dd, 1H, J ) 1.9 Hz), 4.78 (d, 1H, J ) 1.9 Hz), 3.42
(s, 3H), 2.85 (d, 1H, J ) 4.0 Hz), 2.57 (d, 1H, J ) 4.0 Hz),
2.17, 2.05, 2.01 (each s, each 3H); 13C NMR (CDCl3) δ 170.4,
170.1, 169.7 (each s), 100.4 (d), 79.9 (s), 70.1, 67.4, 64.3 (each
d), 56.4 (q), 46.4 (t), 21.0, 20.8, 20.7 (each q); IR (CH2Cl2
solution) ν 2937, 1751, 1489, 1433, 1373, 1246, 1221, 1162,
1118, 1071, 1020, 981, 957, 884, 844, 789, 728 cm-1; CI-HRMS
m/z found 336.1294, required 336.1294 [M + NH4]+. Anal.
Calcd for C13H18O9: C, 49.06; H, 5.70. Found: C, 48.76; H,
5.63.
Exp er im en ta l Section
Epoxidation s with Meth yl(tr iflu or om eth yl)dioxir an e.21
1,1,1-Trifluoroacetone (10 equiv) and Na2EDTA (50 mL of a
4.0 × 10-4 M aq solution, 0.01 mol) were added to a cooled
solution (0 °C) of the hex-5-enopyranoside (1 equiv) in MeCN.
A mixture of oxone (5 equiv) and NaHCO3 (7 equiv) was added
in portions every 5 min for 1 h. The reaction was then stirred
for the indicated time or worked up immediately and was
poured into ice-cold water. The products were extracted with
CH2Cl2 (3×). The combined extracts were dried (MgSO4) and
filtered, and the solvent was removed under diminished
pressure.
Meth yl 2,3,4-Tr i-O-a cetyl-5,6-a n h yd r o-5-h yd r oxy-r-D-
glu cop yr a n osid e (19/20). (i) m-Chloroperbenzoic acid (1.196
g, 5.3 mmol) was added over 30 min in small portions to a
stirred mixture of 11 (2 g, 5.3 mmol) and 0.5 M NaHCO3 (16.8
mL) in CH2Cl2 (120 mL).16 The mixture was stirred at room
temperature overnight, and the two phases were separated.
The organic phase was dried (Na2SO4) and the solvent removed
under diminished pressure. The residue was purified by
chromatography using an EtOAc/petroleum ether gradient (1:4
to 1:1) to give recovered 11 (0.7 g) followed by 19 as a white

3738 J . Org. Chem., Vol. 67, No. 11, 2002
Enright et al.
(ii) Alkene 12 (0.66 g, 2.18 mmol) was dissolved in aceto-
nitrile (20 mL) and Na2EDTA (0.4 mM, 11 mL). To this
solution, vigorously stirred in an ice bath, was added 1,1,1-
trifluoroacetone (2 mL, 10 equiv) through a precooled syringe,
and then a mixture of oxone (6.7 g, 5 equiv) and sodium
hydrogen carbonate (1.28 g, 7 equiv) was added in small
portions over 60 min. After 1 h and 45 min, no more starting
material was detected by TLC and the solution was worked
up as described above and gave a white clear oil (0.65 g, 94%)
which was a mixture of 22 (54%) and 23 (40%). The crude
product was slowly eluted (EtOAc/petroleum ether gradient,
1:4 to 1:0) through a column of silica gel (prepacked with
EtOAc/petroleum ether/NEt3, 100:20:1) in an attempt to
separate the two epoxides. However, only a 2:1 mixture of 22
and 23 was recovered (0.21 g, 30%).
mmol) was slowly added to a stirred mixture of 9 (0.25 g, 0.5
mmol) and 0.5 M NaHCO3 (1.9 mL) in CH2Cl2 over 30 min.
The mixture was stirred at room temperature overnight, and
then the two phases were separated. The organic phase was
washed successively with 1 M NaOH and water and dried (Na2-
SO4), the solvent removed under diminished pressure, and the
residue purified by chromatography (EtOAc/petroleum ether,
1:10, as eluant) to give the title compound (0.055 g, 22%):
1
[R]20 -3.57° (c 0.224, CHCl3); H NMR (CDCl3, 500 MHz) δ
D
5.20 (d, 1H, J ) 1.8 Hz), 4.14 (d, 1H, J ) 7.8 Hz), 3.65 (dd,
1H, J ) 1.8, 7.3 Hz), 3.59 (apt t, 1H, J ) 7.3 Hz), 3.54 (dd, J
) 7.3, 1.8 Hz), 3.26 (dd, 1H, J ) 1.8, 7.8 Hz); 13C NMR δ 103.2
(s), 101.0 (d), 77.5, 77.4 (each d), 68.6 (t), 0.5, 0.4, 0.2 (each q);
IR (liquid film) ν 3396, 2957, 1642, 1391, 1252, 1094, 888, 844,
751 cm-1; CI-HRMS m/z found 412.2007, required 412.2010
[M + NH4]+.
NMR data for 23: 1H NMR (300 MHz, CDCl3) δ 5.48-5.44
(overlapping signals, 2 H), 5.29 (dd, 1H, J ) 3.6, 2.7 Hz), 4.87
(d, 1H, J ) 3.6 Hz), 3.47 (s, 3H), 2.97 (d, 1H, J ) 4.8 Hz), 2.87
(d, 1H, J ) 4.8 Hz), 2.15 (s, 3H), 2.06 (s, 6H); 13C NMR (CDCl3)
δ 170.3, 169.9, 169.3 (each s), 99.8 (d), 80.3 (s), 69.1, 68.6, 66.3
(each d), 57.0 (q), 49.9 (t), 20.8-20.7 (3 s, each q).
Meth yl 2,3,4-Tr i-O-tr im eth ylsilyl-r-D-m an n o-5-h ydr ato-
5-u lo-1,5-p yr a n osid e (17). Alkene 10 (0.5 g, 1.27 mmol) was
dissolved in acetonitrile (9.5 mL) and aqueous Na2EDTA (4.0
× 10-4 M, 6.4 mL), the solution was cooled to 0 °C, and cold
1,1,1-trifluoroacetone (1.27 mL, 10 equiv) was added through
a precooled syringe. To this vigorously stirred were added
mixture oxone (3.81 g, 5 equiv) and sodium hydrogen carbonate
(0.83 g, 7 equiv) in small portions over 60 min. After 30 min
the TLC plate showed that 11 had been consumed and a
unique spot (Rf ) 0.5; EtOAc/petroleum ether, 1:4). The
reaction was quenched with ice-cold water (30 mL) at the end
of the addition, and the product was extracted in dichlo-
romethane (30 mL) and washed twice with cold water and
dried (MgSO4). The solvent was removed at room temperature
under reduced pressure to yield a colorless oil identified as 17
(0.385 g, 71%): 1H NMR (300 MHz, CDCl3) δ 5.83 (d, 1H, J )
1.8 Hz), 4.77 (d, 1H, J ) 8.2 Hz), 3.94 (apt t, 1H, J ) 2.9 Hz),
3.83 (dd, 1H, J ) 2.9, 8.2 Hz), 3.81 (d, 1H, J ) 3.9 Hz), 3.50
(s, 3H), 3.47 (d, 1H, J ) 3.9 Hz), 2.00-1.60 (2 br s, 2H), 0.21,
0.17, 0.14 (each s, each 9H); 13C NMR (CDCl3) δ 99.4 (s), 97.8
(d), 76.2, 69.9, 68.9 (each d), 64.5 (t), 56.8 (q), 0.3, 0.2, 0.0 (9
signals, each q).
Meth yl 2,3,4-Tr i-O-ben zyl-5,6-a n h yd r o-5-h yd r oxy-r-D-
glu cop yr a n osid e (24/25). (i) Compound 13 (1.0 g, 2.23 mmol)
was dissolved and vigorously stirred in dichloromethane (22
mL) and 0.5 M aqueous sodium bicarbonate (6.6 mL); m-
chloroperbenzoic acid (0.7 g, 2.23 mmol) was slowly added, and
after 45 min, no more starting material was detected by TLC
and the two phases were separated. The organic phase was
washed with 1 N sodium hydroxide (7 mL) and water (7 mL)
and dried (Na2SO4); removing the solvent at room temperature
under reduced pressure gave a white oily residue (1.04 g,
100%). NMR analysis of this crude product indicated it
contained 24 (70%) and 25 (30%). TLC analysis revealed one
spot (Rf ) 0.42; EtOAc/petroleum ether, 1:4). Chromatography
(silica gel packed with EtOAc/petroleum ether/NEt3, 10:100:
1; gradient elution with EtOAc/petroleum ether, 1:10 to 1:1)
gave a white solid which was a 10:1 mixture 24 and 25 (0.23
g, 24%): IR (KBr) ν 3086, 3062, 3030, 2906, 1879, 1742, 1605,
1496, 1453, 1360, 1285, 1210, 1167, 1099, 1036, 1003, 914, 740,
696 cm-1; ES-HRMS m/z found 480.2389, required 480.2386
[M + NH4]+. Anal. Calcd for C28H30O6: C, 72.71; H, 6.54.
Found: C, 72.41; H, 6.46.
2,3,4-Tr i-O-tr im eth ylsilyl-1,6-an h ydr o-â-L-gu lopyr an os-
5-u lo-5-h yd r a te (18). Kugelrohr distillation of 17 (0.068 g,
0.16 mmol) at 0.1 mmHg in the bp range 100-110 °C gave
the title compound (0.051 g, 0.12 mmol, 75%): [R]20 -0.4° (c
D
NMR data for 24: 1H NMR (300 MHz, CDCl3) δ 7.39-7.24
(ms, 15H, aromatic H), 4.99, 4.85 (each d, 2H, J ) 10.8 Hz),
4.90, 4.61 (each d, 2H, J ) 11.6 Hz), 4.83, 4.69 (each d 1H, J
) 12.1 Hz), 4.64 (d, 1H, J ) 3.4 Hz), 4.29 (apt t, 1H, J ) 9.6
Hz), 3.89 (d, 1H, J ) 9.6 Hz), 3.61 (dd, 1H, J ) 9.6, 3.4 Hz),
3.40 (s, 3H), 2.65 (AB d, 2H, J ) 4.9 Hz); 13C NMR (CDCl3) δ
138.8, 138.3, 137.9 (each s), 128.8, 128.3, 128.2 (each d), 99.9
(d), 80.5 (s), 80.0, 79.9, 75.8 (each d), 76.1, 75.4, 73.8 (each t),
56.6 (q), 45.7 (t).
0.5, CHCl3); 1H NMR (CDCl3, 270 MHz) δ 5.04 (d, 1H, J ) 2.4
Hz), 3.86 (d, 1H, J ) 7.7 Hz), 3.70 (dd, 1H, J ) 1.5, 7.7 Hz),
3.58 (dd, 1H, J ) 4.2, 2.4 Hz), 3.49 (dd, 1H, J ) 7.7, 4.2 Hz),
3.08 (dd, 1H, J ) 7.7, 1.7 Hz), 0.01, -0.02 (each s, each 3H);
13C NMR (CDCl3) δ 102.2 (d), 100.8 (s), 74.5, 72.9, 71.8 (each
d), 66.4 (t), 0.5, 0.4, 0.2 (each q); IR (liquid film) ν 3424, 1957,
2902, 1735, 1251, 1122, 896, 841, 754 cm-1; CI-HRMS m/z
found 412.2006, required 412.2006 [M + NH4]+.
2,3,4-Tr i-O-a cetyl-1,6-a n h yd r o-â-L-id op yr a n os-5-u lo-5-
h yd r a te (21). Reaction of 11 (0.38 g, 1 mmol), 1,1,1-trifluo-
NMR data for 25: 1H NMR (300 MHz, CDCl3) δ 7.36-7.23
(m, 15H, aromatic H), 4.88-4.80 and 4.72-4.58 (each m, each
2H), 4.83 and 4.66 (AB d, 2H, J ) 11.6 Hz), 4.61 (d, 1H, J )
3.8 Hz), 4.01 (apt t, 1H, J ) 9.5 Hz), 3.81 (d, 1H, J ) 9.4 Hz),
3.64 (dd, 1H, J ) 3.8 Hz), 3.42 (s, 3H), 3.15 (d, 1H, J ) 5.2
Hz), 2.81 (d, 1H, J ) 5.2 Hz); 13C NMR (CDCl3) δ 138.9, 138.3,
138.2 (each s), 128.8-127.9 (15 signals, each d), 99.7 (d), 81.8
(s), 80.3, 79.5, 77.7 (each d), 76.2, 75.3, 74.0 (each t), 56.2 (q),
50.5 (t).
(ii) The alkene 13 (1.0 g, 2.23 mmol) was dissolved in
acetonitrile (20 mL) and Na2EDTA (0.4 mM, 11 mL) and
vigorously stirred in an ice bath; cold 1,1,1-trifluoroacetone
(2 mL, 10 equiv) was poured into the solution through a
precooled syringe, and then a mixture of oxone (6.83 g, 5 equiv)
and sodium hydrogen carbonate (1.30 g, 7 equiv) was added
in small portions over 60 min. After 1 h, no more starting
material was detectable by TLC and the reaction was im-
mediately worked up as described above and gave a white oil
(1.1 g, 100%) which NMR analysis confirmed to be a mixture
of 24 (30%) and 25 (70%). After column chromatography, only
a 7:3 mixture of 24 and 25 was recovered (0.1 g, 10%), as well
as 26 (white solid, 0.57 g, 57%).
roacetone (1 mL, 0.01 mol), Na2EDTA (5 mL of a 4.0 × 10-4
M
aq solution), oxone (3 g, 5 mmol), and NaHCO3 (0.65 g, 7 mmol)
in MeCN (7.5 mL) for 15 h gave the title compound after
chromatography using a short column of silica gel (0.152 g,
50%): [R]20 +34.8° (c 0.046, CHCl3); 1H NMR (CDCl3, 270
D
MHz) δ 5.46 (d, 1H, J ) 2.0 Hz), 5.40 (apt t, 1H, J ) 8.5 Hz),
5.14 (dd, 1H, J ) 2.0, 8.5 Hz), 4.91 (dd, 1H, J ) 2.0, 8.5 Hz),
4.60 (s), 4.16 (d, 1H, J ) 8.5 Hz), 3.51 (dd, 1H, J ) 8.5, 2.0
Hz), 2.04, 2.08, 2.12 (each s); 13C NMR δ 173.1, 170.9, 170.6
(each s), 103.1 (s), 99.0 (d), 74.7, 74.6, 74.5 (each d), 70.7 (t),
21.4, 21.3 (each q); IR (liquid film) ν 3379, 2917, 1731, 1369,
1225, 1041 cm-1; CI-HRMS m/z found 322.1138, required
322.1140 [M + NH4]+.
2,3,4-Tr i-O-a cetyl-1,6-a n h yd r o-â-L-gu lop yr a n os-5-u lo-
5-h yd r a te (30). A mixture of epoxides 19 and 20 (0.36 g, 1.13
mmol) was stirred in acetonitrile (15 mL) and deionized water
(15 mL) at 60 °C for 90 min. The solvent was removed under
reduced pressure (azeotroping with toluene). The crude prod-
uct was purified by column chromatography (EtOAc/petroleum
ether gradient, 1:1 to 1:0; silica gel prepacked with EtOAc/
petroleum ether/NEt3, 50:50:1) and gave 30 (0.30 g, 87%): Rf
) 0.6 (EtOAc/petroleum ether, 1:1); [R]D -20.0° (c 0.2, CHCl3);
1H NMR (300 MHz, CDCl3) δ 5.45 (d, 1H, J ) 2.3 Hz), 5.35
2,3,4-Tr i-O-tr im eth ylsilyl-1,6-a n h yd r o-â-L-id op yr a n os-
5-u lo-5-h yd r a te (16). m-Chloroperbenzoic acid (0.129 g, 0.5

Epoxidation of 6-Deoxyhex-5-enopyranosides
J . Org. Chem., Vol. 67, No. 11, 2002 3739
(dd, 1H, J ) 4.8, 9.7 Hz), 5.25 (dd, 1H, J ) 1.5 Hz), 5.22 (dd,
1H, J ) 4.8, 2.3 Hz), 4.07 (d, 1H, J ) 8.3 Hz), 3.43 (dd, 1H, J
) 8.3 Hz), 2.14, 2.13, 2.01 (each s, each 3H); 13C NMR (CDCl3)
δ 172.7, 170.2, 169.8 (each s), 102.1 (s), 99.2 (d), 73.2, 69.5,
68.0 (each d), 66.7 (t), 21.0, 20.9, 20.7 (each q); IR (CH2Cl2
solution) ν 3588, 3053, 2987, 1754, 1423, 1373, 1265, 1230,
1056, 738, 705 cm-1; CI-HRMS m/z found 322.1136, required
322.1138 [M + NH4]+.
affording the title compound as a clear syrup (0.17 g, 63%):
[R]20 +12.3° (c 1.46, CHCl3); 1H NMR (CDCl3, 270 MHz) δ
D
5.43 (d, 1H, J ) 1.8 Hz), 5.26 (apt t, 1H, J ) 8.4 Hz), 5.13
(dd, 1H, J ) 1.8 Hz), 4.89 (dd, 1H, J ) 1.8, 8.4 Hz), 4.18 (d,
1H, J ) 8.4 Hz), 3.39 (dd, 1H, J ) 1.8, 8.4 Hz), 2.06, 2.03,
1.99 (each s, each 3H), 0.82 (s, 9H), 0.16 (s, 6H); 13C NMR
(CDCl3) δ 170.3, 170.2, 169.7 (each s), 102.7 (s), 98.2 (d), 74.2,
73.7, 71.0 (each d), 69.7 (t), 25.4 (s), 17.7 (q), 0.43, 0.24 (each
q); IR (liquid film) ν 2960, 2860, 1748, 1473, 1369, 1227, 1130,
1042, 842, 685 cm-1; CI-HRMS m/z found 436.2004, required
436.2002 [M + NH4]+.
2,3,4-Tr i-O-b en zyl-1,6-a n h yd r o-â-L-id op yr a n os-5-u l-
ose (26). 13 (4.5 g, 0.01 mol), 1,1,1-trifluoroacetone (10 mL,
0.1 mol), Na2EDTA (50 mL of a 4.0 × 10-4 M aq solution),
oxone (30 g, 0.05 mol), and NaHCO3 (6.51 g, 0.07 mol) in MeCN
(70 mL) were reacted as described above for 12 h. Chroma-
tography (EtOAc/petroleum ether gradient, 1:4 to 1:1) gave the
2,3,4-Tr i-O-ben zyl-5-O-a cetyl-1,6-a n h yd r o-â-L-id op yr a -
n os-5-u lose (32). A catalytic quantity of DMAP (10 mg) was
added to a solution of 26 (0.1 g, 0.2 mmol) in acetic anhydride
(5 mL) and pyridine (5 mL). The mixture was stirred overnight.
Water and EtOAc were added and the layers separated. The
aq layer was further extracted with EtOAc. The combined
organic extracts were washed with aq NaHCO3 and water and
dried (MgSO4), and the solvent was removed under diminished
pressure. Chromatography (EtOAc/petroleum ether gradient,
1:8 to 1:4) gave 26 as a clear syrup (0.073 g, 67%): [R]20D +42.3°
title compound as a white solid (4.36 g, 95%): [R]20 +34.5° (c
D
1.0, CHCl3); mp 98-99 °C; 1H NMR (CDCl3, 270 MHz) δ 7.22-
7.34 (ms, 15H, aromatic), 5.26 (d, 1H, J ) 2.0 Hz), 4.61-4.94
(ms, 6H), 4.19 (d, 1H, J ) 8.0 Hz), 3.79 (apt t, 1H, J ) 8.0
Hz), 3.68 (dd, 1H, J ) 2.0, 8.0 Hz), 3.53 (dd, 1H, J ) 8.0, 2.0
Hz), 3.31 (dd, 1H, J ) 8.0, 2.0 Hz); 13C NMR δ 138.4, 138.2,
137.7 (each s, each aromatic C), 128.8-127.7 (18C, each d, each
aromatic CH), 103.5 (s), 98.4 (d), 82.6 (d), 82.0 (d), 75.6, 74.7,
73.0 (each t), 68.5 (t); IR (solution in CHCl3) ν 3356, 2323, 1453,
1344, 1208, 1067, 1003, 836, 754 cm-1; CI-HRMS m/z found
466.2290, required 466.2291 [M + NH4]+.
1
(c 1.0, CHCl3); H NMR (CDCl3, 270 MHz) δ 7.31-7.24 (ms,
15H), 5.35 (d, 1H, J ) 2.0 Hz), 4.89-4.62 (m, 6H), 4.35 (d,
1H, J ) 8.0 Hz), 4.31 (dd, 1H, J 2.0, J ) 8.0 Hz), 3.83 (apt t,
1H, J ) 8.0 Hz), 3.80 (dd, 1H, J ) 8.0, 2.0 Hz), 3.63 (dd, 1H,
J ) 8.0, 2.0 Hz), 2.00 (s, 3H); 13C NMR δ 168.0 (s), 138.3, 138.0,
137.7 (each s), 128.6-127.7 (18C, each d), 104.2 (s), 99.3, 82.5,
82.4, 80.4 (each d), 75.5, 74.9, 73.1 (each t), 68.1 (t), 21.6 (q);
2,3,4-Tr i-O-b e n zyl-1,6-a n h yd r o-L-gu lop yr a n os-5-u l-
ose (27). Reaction of 1,1,1-trifluoroacetone (2 mL, 20 mmol),
Na2EDTA (10 mL of a 4.0 × 10-4 M aq solution), 14 (0.899 g,
2 mmol), oxone (6 g, 10 mmol), and NaHCO3 (1.3 g, 14 mmol)
in MeCN (15 mL) for 15 h gave 27 as a clear syrup (0.432 g,
48%) after chromatography (EtOAc/petroleum ether, 1:4):
IR (liquid film) ν 2923, 1761, 1454, 1363, 1219, 1074, 737 cm-1
;
CI-HRMS m/z found 508.2346, required 508.2335 [M + NH4]+.
2,3,4-Tr i-O-b en zyl-5-O-m et h yl-1,6-a n h yd r o-â-L-id op y-
r a n os-5-u lose (33). Iodomethane (0.16 g, 1.6 mmol) was
added dropwise to a solution of 26 (0.35 g, 0.8 mmol) and
sodium hydride (62 mg, 1.6 mmol) in anhydrous DMF at 0 °C
under a N2 atmosphere. The reaction mixture was stirred for
15 h. Water and EtOAc were added and the layers separated.
The aq layer was further extracted with EtOAc. The organic
extracts were combined and dried (MgSO4), and the solvent
was removed under diminished pressure. Chromatography
(EtOAc/petroleum ether, 1:4) gave the title compound as a
[R]20 +14.2° (c 0.8, CHCl3); 1H NMR (CDCl3, 270 MHz) δ
D
7.32-7.27 (ms, 15H), 5.28 (d, 1H, J ) 2.0 Hz), 4.72 (m, 6H),
3.99 (d, 1H, J ) 9.0 Hz), 3.99 (dd, 1H, J ) 1.0, 9.0 Hz), 3.73
(dd, 1H, J ) 4.5, 9.0 Hz, H-3), 3.66 (dd, 1H, J ) 4.5, 2.0 Hz),
3.24 (dd, 1H, J ) 1.0, 9.0 Hz); 13C NMR (CDCl3) δ 138.5, 138.0,
137.8 (each s), 128.8-127.5 (18C, each d), 102.6 (s), 99.4 (d),
81.4 (d), 78.5 (d), 75.0 (d), 75.2, 73.1, 73.0 (each t), 66.9 (t);
IR (liquid film) ν 3421, 2929, 1454, 1364, 1260, 1112, 799,
697 cm-1; CI-HRMS m/z found 466.2230, required 466.2220
[M + NH4]+.
clear syrup (0.284 g, 79%): [R]20 +17.4° (c 0.26, CHCl3);
D
2-O-Ben zyl-3,4-d i-O-isop r op ylid en e-1,6-a n h yd r o-â-L-ta -
lop yr a n os-5-u lose (28) a n d 2-O-Ben zyl-3,4-d i-O-isop r o-
pyliden e-1,6-an h ydr o-r-D-galactopyr an os-5-u lose (29). Re-
action of 1,1,1-trifluoroacetone (1.63 mL, 16.3 mmol), Na2EDTA
(8.15 mL of a 4.0 × 10-4 M aq solution), 15 (0.50 g, 1.63 mmol),
oxone (4.9 g, 8.1 mmol), and NaHCO3 (1.06 g, 11.4 mmol) in
MeCN (11.4 mL) for 15 h gave an interconverting mixture of
the title compounds as a clear syrup (0.27 g, 48%) after
chromatography (EtOAc/petroleum ether, 1:5 to 1:1, gradient
elution); CI-HRMS m/z found 326.1606, required 326.1603
[M + NH4]+.
1H NMR (CDCl3, 500 MHz) δ 7.18-7.28 (ms, 15H), 5.18 (d,
1H, J ) 2.0 Hz), 4.83-4.56 (ms, 6H), 3.93 (d, 1H, J ) 8.0 Hz),
3.71 (apt t, 1H, J ) 8.0 Hz), 3.68 (dd, 1H, J ) 2.0, 8.0 Hz),
3.56 (dd, 1H, J ) 8.0, 2.0 Hz), 3.47 (dd, 1H, J ) 8.0, 2.0 Hz),
3.42 (s, 3H, OMe); 13C NMR (CDCl3) δ 138.5, 137.9 (each s),
129.6-127.6 (18C, each d), 106.3 (s), 98.3, 82.7, 82.3, 81.3 (each
d), 75.5, 74.4, 73.0, 63.5 (each t), 50.6 (q); IR (liquid film)
ν 1651, 1453, 1365, 1260, 1098 cm-1; CI-HRMS m/z found
480.2387, required 480.2386 [M + NH4]+.
2,3,4-Tr i-O-ben zyl-5-tr iflu or om eth a n esu lfon yl-1,6-a n -
h yd r o-â-L-id op yr a n os-5-u lose (34). Trifluoromethanesulfon-
ic anhydride (0.054 mL, 0.32 mmol) was added dropwise to a
stirred solution of 26 (0.072 g, 0.16 mmol) and 2,6-lutidine
(0.075 mL, 0.64 mmol) in CH2Cl2 (2 mL) at -40 °C under N2.
The reaction mixture was allowed to attain room temperature
and stirred for a further15 h. The mixture was then diluted
with CH2Cl2, washed successively with 5% CuSO4 and water
(2×), and dried (Na2SO4) and the solvent removed under
diminished pressure. Chromatography (EtOAc/petroleum ether,
1:6, as eluant) gave recovered 26 (22 mg) followed by the title
Selected NMR data for 28: 1H NMR (CDCl3, 270 MHz) δ
7.26-7.36 (ms, 5H), 5.38 (s, 1H), 3.36 (d, J ) 7.9 Hz), 1.53,
1.33 (each s, each 3H); 13C NMR (CDCl3) δ 137.1 (s), 127.9-
128.5 (3 d), 109.0 (s), 102.0 (s), 100.9 (d), 77.5, 76.6, 75.2 (each
d), 72.2, 66.3 (each t), 26.0, 24.2, 21.9 (each q).
Selected NMR data for 29: 1H NMR (CDCl3, 270 MHz) δ
7.26-7.36 (ms, 5H, aromatic H), 5.42 (d, 1H, J ) 2.6 Hz), 4.71,
4.61 (each d, each 1H, J ) 12.2 Hz) 3.47 (dd, 1H, J ) 4.6, 2.6
Hz), 1.47, 1.40 (each s, each 3H); 13C NMR (CDCl3) δ 137.4
(s), 127.9-128.5 (3 d), 111.7 (s), 101.1 (s), 100.1 (d), 78.7, 78.2,
77.5 (each d), 71.5, 69.1 (each t), 27.4, 26.2, 21.9 (each q).
2,3,4-Tr i-O-a cetyl-5-O-ter t-bu tyld im eth ylsilyl-1,6-L-a n -
h yd r oid op yr a n os-5-u lose (31). tert-Butyldimethylsilyl tri-
fluoromethanesulfonate (0.59 mL, 2.4 mmol) was added drop-
wise to a solution of 21 (0.196 g, 0.65 mmol) and 2,6-lutidine
(0.52 mL, 4.2 mmol) in anhydrous CH2Cl2 at -40 °C under a
N2 atmosphere. The reaction mixture was allowed to warm to
room temperature and stirred for a further 1.5 h. Water and
CH2Cl2 were then added, and the two phases were separated.
The organic phase was washed with 5% CuSO4 and water (2×)
and dried (Na2SO4) and the solvent removed under diminished
pressure. The residue was purified using column chromatog-
raphy (gradient elution, EtOAc/petroleum ether, 1:10 to 1:4),
compound as a clear syrup (45 mg, 48%): [R]20 +15.4° (c 1.0,
D
CHCl3); 1H NMR (CDCl3, 270 MHz) δ 7.25-7.32 (ms, 15H),
5.42 (d, 1H, J ) 2.0 Hz), 4.87-4.56 (m, 6H), 4.37 (d, 1H, J )
8.0 Hz), 4.08 (dd, 1H, J ) 2.0, 8.0 Hz), 3.94 (dd, 1H), 3.78 (apt
t, 1H, J ) 8.0 Hz), 3.63 (dd, 1H, J ) 2.0, 8.0 Hz); 13C NMR δ
137.8, 137.3, 137.0 (each s, each aromatic C), 128.7-127.8
(18C, each d, each aromatic CH), 111.0 (s), 100.1, 82.1, 82.0,
81.5 (each d), 75.6, 75.3, 73.3 (each t), 67.5 (t); IR (liquid film)
2922, 1601, 1420, 1215, 1091, 799 cm-1; CI-HRMS m/z found
598.1728, required 598.1722 [M + NH4]+.
2,3,4-Tr i-O-b en zyl-5-O-ter t-b u t yld im et h ylsilyl-1,6-a n -
h yd r o-â-L-id op yr a n os-5-u lose (35). tert-Butyldimethylsilyl
trifluoromethanesulfonate (0.23 mL, 1 mmol) was added
dropwise to a stirred solution of 26 (0.3 g, 0.67 mmol) and 2,6-

3740 J . Org. Chem., Vol. 67, No. 11, 2002
Enright et al.
lutidine (0.15 mL, 1.3 mmol) in CH2Cl2 (5 mL) under N2 at
-40 °C. The reaction mixture was allowed to warm to room
temperature and stirred for a further 2 h. The solution was
then diluted with CH2Cl2, washed with 5% CuSO4 and water
(2×), and dried (Na2SO4) and the solvent removed under
diminished pressure. The title compound (0.22 g, 58%) was
(2.5 mL) under a N2 atmosphere. The mixture was cooled to 0
°C, and methanesulfonyl chloride (0.086 mL, 1.1 mmol) was
added dropwise. The reaction mixture was allowed to warm
to room temperature and stirred for 2 h. Water and CH2Cl2
were added and the layers separated. The aq layer was further
extracted with CH2Cl2 (3×). The combined organic extracts
were washed with 5% CuSO4 (2×) and water (3×) and dried
(Na2SO4), and the solvent was removed under diminished
pressure. Chromatography (EtOAc/petroleum ether, 1:4) gave
obtained as a clear syrup after chromatography (EtOAc/
1
petroleum ether, 1:10); [R]20 +15.4° (c 1.0, CHCl3); H NMR
D
(CDCl3, 270 MHz) δ 7.23-7.13 (ms, 15H, aromatic), 5.23 (d,
1H, J ) 2.0 Hz), 4.91-4.55 (m, 6H), 4.10 (d, 1H, J ) 8.0 Hz),
3.65 (apt t, 1H, J ) 8.0 Hz), 3.53 (dd, 1H, J ) 2.0, 8.0 Hz),
3.45 (dd, 1H, J ) 8.0, 2.0 Hz), 3.31 (dd, 1H, J ) 8.0, 2.0 Hz),
0.82 (s, 9H), 0.09 (s, 6H); 13C NMR (CDCl3) δ 139.0, 138.4 (each
s), 128.9-128.0 (18C, each d), 105.1 (s), 98.8, 84.9, 82.9, 82.4
(each d), 76.0, 75.3, 73.4, 73.3 (each t), 26.2 (q), 18.3 (q), 1.44,
0.43 (q); IR (liquid film) ν 2928, 1454, 1364, 1274, 1205, 1091,
859 cm-1. CI-HRMS m/z found 580.3101, required 580.3094
[M + NH4]+.
the title compound as a clear syrup (0.184 g, 63%): [R]20
D
+12.8° (c 0.25, CHCl3); 1H NMR (CDCl3, 300 MHz) δ 7.20-
7.35 (ms, 15H), 5.39 (d, 1H, J ) 2.0 Hz), 4.60-4.94 (m, 6H),
4.31 (d, 1H, J ) 8.0 Hz), 4.20 (dd, 1H, J ) 2.0, 8.0 Hz), 3.90
(dd, 1H, J ) 2.0, 8.0 Hz), 3.75 (apt t, 1H, J ) 8.0 Hz), 3.59
(dd, 1H, J ) 2.0, 8.0 Hz), 3.15 (s, 3H); 13C NMR (CDCl3) δ
138.5, 138.0, 138.9 (each s), 128.9-128.0 (18C, each d), 108.1
(s), 100.4, 82.9, 82.5, 82.3 (each d), 75.9, 75.3, 73.5 (each t),
68.4 (t), 42.2 (q); IR (film) ν 2952, 1454, 1371, 1191, 1069,
787 cm-1; CI-HRMS m/z found 544.2005, required 544.2002
[M + NH4]+.
1-O-ter t-Bu tyld im eth ylsilyl-2,3,4-tr i-O-ben zyl-â-D-xylo-
h exosep t a n osid -5-u lose (36). tert-Butyldimethylsilyl tri-
fluoromethanesulfonate (0.2 mL, 0.88 mmol) was added drop-
wise to a solution of 26 (0.2 g, 0.44 mmol) in pyridine (5 mL)
at -40 °C under a N2 atmosphere. After 3 h, water and EtOAc
were added and the layers were separated. The aq layer was
further extracted with EtOAc (2×), the combined organic
layers were subsequently washed with 5% CuSO4 (2×) and
water (3×) and dried (Na2SO4), and the solvent was removed
under diminished pressure. The residue was purified by
chromatography using EtOAc/petroleum ether (1:10) to give
35 (97 mg, 38%) followed by the title compound as a clear syrup
(40 mg, 16%): [R]20D +8.23° (c 0.158, CHCl3); 1H NMR (CDCl3,
270 MHz) δ 7.35-7.24 (ms, 15H), 4.79 (d, 1H, J ) 5.3 Hz),
4.77-4.44 (m, overlapping signals, 7H), 4.26 (d, 1H, J ) 18.0
Hz), 4.09 (d, 1H, J ) 18.0 Hz), 3.79 (apt t, 1H, J ) 7.3 Hz),
3.66 (dd, 1H, J ) 7.3, 5.3 Hz), 0.89 (s, 9H), 0.07 (s, 6H); 13C
NMR (CDCl3) δ 208.0 (s), 138.3, 137.9, 137.5 (each s), 128.5-
127.7 (15C, each d), 100.3, 85.7, 83.1, 81.8 (each d), 74.7, 74.6,
72.9, 71.3 (each t), 25.7, 18.0, 1.11, 0.09 (each q); IR (liquid
film) ν 2927, 1736, 1454, 1259, 1094, 837, 698 cm-1; CI-HRMS
m/z found 580.3091, required 580.3094 [M + NH4]+.
2-O-Ben zyl-3,4-d i-O-isop r op ylid en e-5-O-a cetyl-1,6-a n -
h yd r o-r-D-ga la ctop yr a n os-5-u lose (40) a n d 1-O-(Acetyl)-
O-b en zyl-3,4-d i-O-isop r op ylid en e-r-L-a r a b in o-h exosep -
ta n osid -5-u lose (41). Hexos-5-ulose 28/29 (0.22 g, 0.7 mmol)
was dissolved in acetic anhydride (1 mL) and pyridine (1 mL),
and the mixture was allowed to stand for 24 h. Excess reagents
were removed using a rotary evaporator, and xylene (2 × 25
mL) was distilled from the residue. Chromatography (EtOAc/
petroleum ether, 1:10 to 1:5, gradient elution) gave in order
of elution 40 (50 mg, 20%) and 41 (0.12 g, 48%). A third fraction
1
(70 mg, 28%) was obtained. H NMR spectral data indicated
this fraction was a 1.5:1.0:0.5 mixture of 2-O-benzyl-3,4-di-O-
isopropylidene-5-O-acetyl-1,6-anhydro-â-D-talopyranos-5-ul-
ose (δ 6.12, d, J ) 3.5 Hz), 40, and 1-O-(acetyl)-O-benzyl-3,4-
di-O-isopropylidene-â-L-arabino-hexoseptanosid-5-ulose (δ 5.41,
d, J ) 1.6 Hz).
Analytical data for 40: 1H NMR (CDCl3, 300 MHz); δ 7.26-
7.36 (ms, 5H), 6.04 (d, 1H, J ) 7.8 Hz), 5.11 (d, 1H, J ) 8.5
Hz), 4.71 (dd, 1H, J ) 9.2 Hz), 4.88, 4.62 (each d, each 1H, J
) 11.7 Hz), 4.12, 4.27 (each d, each 1H, J ) 18.8 Hz), 3.63
(dd, J ) 9.2, 7.8 Hz), 2.02, 1.60, 1.44 (each s, each 3H); 13C
NMR (CDCl3) δ 206.2 (s), 169.6 (s), 137.9 (s), 128.6, 128.2, 128.1
(each d), 111.6 (s), 93.5, 80.8, 80.0, 77.8 (each d), 74.8, 68.4
(each t), 27.2, 25.2, 21.1 (each q); CI-HRMS m/z found
368.1708, required 368.1709 [M + NH4]+.
2,3,4-Tr i-O-ben zyl-5-O-(2-br om oben zoyl)-1,6-a n h yd r o-
â-L-id op yr a n os-5-u lose (37) a n d 1-O-(2-Br om oben zoyl)-
2,3,4-tr i-O-ben zyl-â-D-xylo-h exosep ta n osid -5-u lose (38).
2-Bromobenzoyl chloride (0.27 mL, 2.6 mmol) was added to a
solution of 26 (0.29 g, 0.66 mmol) in pyridine (5 mL) at 0 °C
under a N2 atmosphere. After 12 h, water and EtOAc were
added and the layers separated. The aq layer was further
extracted with EtOAc (2×), the combined organic phases were
subsequently washed with 5% CuSO4 (2×) and water (3×) and
dried (Na2SO4), and the solvent was removed under diminished
pressure. Chromatography (EtOAc/petroleum ether, 1:10) gave
the title compounds 37 (0.19 g, 45%) and 38 (0.1 g, 16%).
Analytical data for 41: 1H NMR (CDCl3, 500 MHz) δ 7.26-
7.36 (ms, 5H, aromatic H), 5.54 (d, 1H, J ) 1.2 Hz), 4.67 (dd,
1H, J ) 7.2, 1.5 Hz), 4.69, 4.61 (each d, each 1H, J ) 12.0
Hz), 4.40 (dd, 1H, J ) 1.5 Hz), 4.33 (d, 1H, J ) 8.2 Hz), 3.78
(dd, 1H, J ) 8.2, 1.5 Hz), 3.61 (s, 1H), 2.12 (s, 3H), 1.56, 1.34
(each s, each 3H); 13C NMR (CDCl3) δ 168.0 (CdO), 137.4 (s),
128.8, 128.3, 128.1 (each d), 109.5, 104.6 (each s), 101.5 (d),
78.0, 77.2, 74.4 (each d), 72.5, 65.2 (each t), 26.1, 24.5, 21.9
(each q); CI-HRMS m/z found 368.1706, required 368.1709
[M + NH4]+.
1
Analytical data for 37: [R]D +50° (c 0.058, CHCl3); H NMR
(CDCl3 δ 7.64 (ms, 19H), 5.40 (d, 1H, J ) 1.8 Hz), 4.75 (m,
6H), 4.51 (d (J ) 7.9 Hz) and dd (J ) 7.9, 1.8 Hz) overlapping,
2H), 3.95 (dd, 1H, J ) 7.9, 1.8 Hz), 3.88 (apt t, 1H, J ) 7.9
Hz), 3.69 (dd, 1H, J ) 7.9, 1.8 Hz); 13C NMR (CDCl3) δ 162.8
(s), 138.3, 137.7, 137.6 (each s, each aromatic C), 134.7, 133.4,
131.9 (each d), 128.6-127.2 (20C, each d), 122.4 (s), 105.1 (s),
99.5, 82.5, 82.4, 80.4 (each d), 75.4, 74.9, 73.1 (each t), 68.19
(t); IR (liquid film) ν 2911, 1733, 1567, 1454, 1245, 1089,
740 cm-1; CI-HRMS m/z found 648.1573, required 648.1596
5-O-Met h yl-1,6-a n h yd r o-â-L-id op yr a n os-5-u lose (44).
Compound 33 (0.126 g, 0.27 mmol) and Pd-C (0.13 g) in EtOH
(10 mL) were stirred in a Parr hydrogenation apparatus at 40
psi for 12 h. The reaction mixture was then filtered and the
solvent removed under diminished pressure. Chromatography
(EtOAc/MeOH, 3:1) gave 44 (0.041 g, 79%): [R]20 +13.3° (c
D
1
0.6, CHCl3); H NMR (D2O, 270 MHz) δ 5.21 (d, 1H, J ) 1.6
[M + NH4]+.
Hz), 3.88 (d, 1H, J ) 7.4 Hz), 3.75 (d, 1H, J ) 7.4 Hz), 3.56-
3.42 (ms, 3H), 3.40 (s, 3H); 13C NMR (D2O) δ 108.4 (s), 103.4,
77.0, 74.2 (each d), 67.2 (t), 54.0 (q); IR (liquid film) ν 2924,
2853, 2359, 1453, 1362, 1270, 1094, 697 cm-1; CI-HRMS m/z
found 210.0977, required 210.0976 [M + NH4]+.
1
Analytical data for 38: [R]20 +17.7° (c 0.096, CHCl3); H
D
NMR (CDCl3, 270 MHz) δ 7.25 (ms, 19H), 5.82 (d, 1H, J ) 5.1
Hz), 4.77 (d, 1H, J ) 6.5 Hz), 4.74-4.40 (ms, 6H), 4.36, 4.25
(each d, each 1H, J ) 17.0 Hz), 3.93 (apt t, 1H, J ) 6.5 Hz),
3.82 (apt t, 1H, J ) 6.5 Hz); 13C NMR (CDCl3) δ 206.2, 163.9
(each s), 137.7, 137.2, 137.0 (each s), 134.6-127.2 (24C, each
d), 122.4 (s), 97.2, 85.5, 80.0 (each d), 74.8, 74.5, 73.2 (each t),
72.9 (t, C-6); IR (KBr) ν 2300, 1742, 1590, 1497 cm-1; ES-
HRMS m/ z found 648.1599, required 648.1596 [M + NH4]+.
2,3,4-Tr i-O-ben zyl-5-O-m eth a n esu lfon yl-1,6-a n h yd r o-
â-L-id op yr a n os-5-u lose (39). Compound 26 (0.25 g, 0.55
mmol) and DMAP (cat.) were dissolved in anhydrous pyridine
5-O-ter t-Bu tyld im eth ylsilyl-1,6-a n h yd r o-L-id op yr a n os-
5-u lose (45). Compound 35 (0.45 g, 0.8 mmol) and 10% Pd-C
(0.45 g) in EtOH (20 mL) were placed in a hydrogenation
apparatus overnight (50 psi). The resulting mixture was
filtered and the solvent removed under diminished pressure.
Chromatography of the residue (EtOAc/MeOH, 3:1) gave 45
as a white solid (0.165 g, 71%): [R]20 +45° (c 0.1, CHCl3); 1H
D
NMR (CDCl3, 270 MHz) δ 5.31 (s, 1H), 4.04 (d, 1H, J ) 7.6

Epoxidation of 6-Deoxyhex-5-enopyranosides
J . Org. Chem., Vol. 67, No. 11, 2002 3741
Hz), 3.60 (s, 3H), 3.31 (d, 1H, J ) 7.6 Hz), 0.89 (s, 9H), 0.19,
0.18 (each s, each 3H); 13C NMR (CDCl3) δ 103.7 (s), 100.7 (d),
75.9, 75.1, 74.7 (each d), 68.3 (t), 25.6 (q), 17.8 (q), -3.1, -3.2
(each q); IR (KBr disk) ν 3529, 3438, 2937, 1365, 1254, 1128,
857, 688 cm-1; CI-HRMS m/z found 310.1681, required 310.1682
[M + NH4]+.
stirred at room temperature for 3 days, after which the solvent
was removed under reduced pressure to yield 47 as a white
solid (0.110 g, 94%): [R]D -19.89° (c 0.19, H2O); ES-LRMS m/z
found 177 [M - H]-, 355 [2M - H]-. The 1H and 13C NMR
(300 MHz, D2O) data are in excellent agreement with those
previously reported. The NMR data are complex due to
interconverting isomers and have been assigned and discussed
in detail previously.25a
D-xylo-Hexos-5-u lose (46). (i) Tetrabutylammonium fluo-
ride (0.5 mL, 0.5 mmol, 1 M in THF) was added to a solution
of 5-O-tert-butyldimethylsilyl-1,6-anhydro-L-idopyranos-5-ulose
(0.14 g, 0.5 mmol) in THF (10 mL), and the resulting yellow
solution was stirred for 1 h. The solvent was then removed
under diminished pressure and the residue purified by chro-
matograhy using a short column of silica gel (EtOAc/MeOH,
3:1, as eluant). The title compound was obtained as a clear oil
Ack n ow led gm en t. We thank Professor Richard J .
K. Taylor, the NMR Centre UCD, Enterprise Ireland
(Grants Sc/97/547 and Sc/00/182), Limerick Co. Council
(scholarship to P.M.E.), Dublin Corp. (scholarship to
M.T.), and University College Dublin (Presidents award)
for support, and the Health Research Board (Ireland)
and Wellcome Trust for an equipment grant.
(0.085 g, 100%): [R]20 -10.5° (c 0.43, H2O); ES-LRMS m/z
D
found 177, required 177 [M - H]-. The H and 13C NMR (300
1
MHz, D2O) data are in excellent agreement with those previ-
ously reported. The NMR data are complex due to intercon-
verting isomers and have been assigned and discussed in detail
previously.25b
Su p p or tin g In for m a tion Ava ila ble: Full details of the
synthesis of hex-5-enopyranosides 9-15, other epoxidations
investigated, analytical data for alcohols obtained from reduc-
(ii) The title compound was also prepared by heating a
solution of 16 (30 mg, 0.08 mmol) in MeOH (3 mL) at reflux
for 5 h. The solvent was removed under diminished pressure,
and subsequent chromatography of the residue (EtOAc/MeOH,
3:1, as eluant) gave the title compound (13 mg, 85%).
D-lyxo-Hexos-5-u lose (47). Hemiketal 17 (0.280 g, 0.66
mmol) was dissolved in methanol (5 mL), and the solution was
1
tion of 36 and 38, H and 13C NMR and selected NOE spectra
for all new compounds, and X-ray crystal structures of 19 and
26. This material is available free of charge via the Internet
at http://pubs.acs.org.
J O016378C