Stereochemistry in the synthesis and reaction of exo-glycals.

Article abstract of DOI:10.1021/jo0255227

Two general methods are explored for the stereoselective synthesis of exo-glycals. One method utilizes a nucleophilic addition of fully protected sugar lactones of gluco-, galacto-, and manno-types, followed by the subsequent dehydration, to give the desired exo-glycals with (Z)-configuration. The other method proceeds with selenylation of C-glycosides in a stereoselective manner. The subsequent selenoxide elimination also provides (Z)-exo-glycals. The prepared exo-glycal conjugated esters of either gluco- or manno-type react with allyl alcohol to give exclusively alpha-anomers.

Full text of DOI:10.1021/jo0255227

J . Org. Chem. 2002, 67, 3773-3782
3773
Ster eoch em istr y in th e Syn th esis a n d Rea ction of exo-Glyca ls
Wen-Bin Yang, Yu-Ying Yang, Yu-Feng Gu, Shwu-Huey Wang,† Che-Chien Chang, and
Chun-Hung Lin*
Institute of Biological Chemistry, Academia Sinica, No. 128, Academia Road Section 2,
Nan-Kang, Taipei 11529, Taiwan
chunhung@gate.sinica.edu.tw
Received J anuary 14, 2002
Two general methods are explored for the stereoselective synthesis of exo-glycals. One method
utilizes a nucleophilic addition of fully protected sugar lactones of gluco-, galacto-, and manno-
types, followed by the subsequent dehydration, to give the desired exo-glycals with (Z)-configuration.
The other method proceeds with selenylation of C-glycosides in a stereoselective manner. The
subsequent selenoxide elimination also provides (Z)-exo-glycals. The prepared exo-glycal conjugated
esters of either gluco- or manno-type react with allyl alcohol to give exclusively R-anomers.
In tr od u ction
ally require more laborious efforts. These preparations
include Ramburg-Ba¨cklund rearrangement of S-glyco-
sides,15,16 Wittig olefination of sugar lactones (for conju-
gated exo-glycal esters),17 Keck reaction of glycosyl
dihalides (sugar dienes),18 and [2,3]-Wittig sigmatropic
rearrangement (for the exo-glycal analogue of glycosyl
serine).19 Nevertheless, most of these procedures are
limited to some special types of exo-glycals. We recently
reported a two-step synthesis of various conjugated exo-
glycals from sugar lactones.20,21 This method is general
and stereoselective to give exclusively the (Z)-isomers of
exo-glycals.21 We present herein a detailed study of such
stereoselective reactions and provide some insight for the
interpretation underlying the exclusive stereochemistry.
endo-Glycals, 1,2-unsaturated sugars, have been shown
to be indispensable chiral synthons in the preparation
of various biomolecules. For instance, the reaction of
endo-glucals with the silyl enol ether of acetophenone is
catalyzed by Lewis acid to give C-glycosides in an
excellent yield.1 Allylation of endo-glycals with allyltri-
methylsilane2 provides the substrate applicable to the
construction of the ABC rings of brevetoxin B.3 Epoxi-
dation of endo-glycals leads to a myriad of complex
oligosaccharides and glycosylated natural products with
high stereoselectivity.4-9 Michael additions of 2-nitro-
galactal have been explored for the synthesis of TN and
sialyl TN antigens, as well as the O-glycans of core 1 and
core 7 structures.10-12
The chemistry with regard to exo-glycals is less ad-
dressed in the literature. 1-exo-Methylene sugars have
been obtained by methylenation of sugar lactones with
Tebbe reagent,13 or by elimination reaction of the ap-
propriate pyranoketosyl bromides.14 The reported prepa-
rations of substituted or functionalized exo-glycals usu-
Resu lts a n d Discu ssion
The fully protected benzylated gluconolactone (1) was
obtained in 95% yield from the commercially available
2,3,4,6-tetra-O-benzyl-D-glucopyranose by oxidation with
DMSO and acetic anhydride. The galacto- and manno-
type lactones 2 and 3 were prepared from D-galactose and
* To whom correspondence should be addressed. Phone: +886-2-
2789-0110. Fax: +886-2-2651-4705.
(13) (a) Wilcox, C. X.; Long, G. W.; Shu, H. Tetrahedron Lett. 1984,
25, 395. (b) Haudrechy, A.; Sinay, P. J . Org. Chem. 1992, 57, 4142. (c)
Ali, M. H.; Collins, P. M.; Overend, W. G. Carbohydr. Res. 1990, 205,
428. The methylenation was also achieved by modified titanocene
reagent; see: (d) Csuk, R.; Glanzer, B. I. Tetrahedron 1991, 47, 1655.
(e) Faivre-Buet, V.; Eynard, I.; Nga, H. N.; Descotes, G.; Grouiller, A.
J . Carbohydr. Chem. 1993, 12, 349.
(14) Hahn, S.; Flath, F.-J .; Lichtenthaler, F. W. Liebigs Ann. 1995,
2081.
(15) (a) Alcaraz, M.-L.; Griffin, F. K.; Paterson, D. E.; Taylor, R. J .
K. Tetrahedron Lett. 1998, 39, 8183. (b) Griffin, F. K.; Murphy, P. V.;
Paterson, D. E.; Taylor, R. J . K. Tetrahedron Lett. 1998, 39, 8179.
(16) For a detailed review, see: Taylor, R. J . K. J . Chem. Soc., Chem.
Commun. 1999, 217.
† Taipei Medical University, Taipei 11031, Taiwan.
(1) Dawe, R. D.; Fraser-Raid, B. J . Chem. Soc., Chem. Commun.
1981, 1180.
(2) Danishefsky, S. J .; Kerwin, J . F., J r. J . Org. Chem. 1982, 47,
3805.
(3) Nicolaou, K. C.; Duggan, M. E.; Hwang, C.-K.; Somers, P. K. J .
Chem. Soc., Chem. Commun. 1985, 1359.
(4) Williams, L. J .; Garbaccio, R. M.; Danishefsky, S. J . In Carbo-
hydrates in Chemistry and Biology; Ernst, B., Hart, G. W., Sinay, P.,
Eds.; Wiley-VCH Verlag GmbH: Weinheim, Germany, 2000; Vol. 1,
pp 61-92.
(5) Seeberger, P. H.; Danishefsky, S. J . Acc. Chem. Res. 1998, 31,
685.
(6) Seeberger, P. H.; Beebe, X.; Sukenick, G. D.; Pochapsky, S.;
Danishefsky, S. J . Angew. Chem., Int. Ed. Engl. 1997, 36, 491.
(7) Zheng, C.; Seeberger, P. H.; Danishefsky, S. J . Angew. Chem.,
Int. Ed. 1998, 37, 786.
(8) Zheng, C.; Seeberger, P. H.; Danishefsky, S. J . J . Org. Chem.
1998, 63, 1126.
(9) Seeberger, P. H.; Eckhardt, M.; Gutteridge, C. E.; Danishefsky,
S. J . J . Am. Chem. Soc. 1997, 119, 10064.
(10) Winterfeld, G. A.; Schmidt, R. R. Angew. Chem., Int. Ed. 2001,
40, 2654.
(17) (a) Xie, J .; Molina, A.; Czernecki, S. J . Carbohydr. Chem. 1999,
18, 481. (b) Molina, A.; Czernecki, S.; Xie, J . Tetrahedron Lett. 1998,
39, 7507.
(18) (a) Praly, J .-P.; Chen, G.-R.; Gola, J .; Hetzer, G.; Raphoz, C.
Tetrahedron Lett. 1997, 38, 8185. (b) Praly, J .-P.; Kharraf, Z. E.;
Descotes, G. Carbohydr. Res. 1992, 232, 117. (c) Praly, J .-P.; Chen,
G.-R.; Gola, J .; Hetzer, G. Eur. J . Org. Chem. 2000, 2831.
(19) Lay, L.; Meldal, M.; Nicotra, F.; Panza, L.; Russo, G. J . Chem.
Soc., Chem. Commun. 1997, 1469.
(20) Yang, W.-B.; Chang, C.-F.; Wang, S.-H.; Teo, C.-F.; Lin, C.-H.
Tetrahedron Lett. 2001, 42, 4657.
(21) Yang, W.-B.; Wu, C.-Y.; Chang, C.-C.; Wang, S.-H.; Teo, C.-F.;
Lin, C.-H. Tetrahedron Lett. 2001, 42, 6907.
(11) Winterfeld, G. A.; Ito, Y.; Ogawa, T.; Schmidt, R. R. Eur. J .
Org. Chem. 1999, 1167.
(12) Das, J .; Schmidt, R. R. Eur. J . Org. Chem. 1998, 1609.
10.1021/jo0255227 CCC: $22.00 © 2002 American Chemical Society
Published on Web 05/09/2002

3774 J . Org. Chem., Vol. 67, No. 11, 2002
Yang et al.
Sch em e 1. Ster eoselective Syn th esis of Va r iou s (Z)-exo-Glyca ls by a Nu cleop h ilic Ad d ition a n d a
Su bsequ en t Deh yd r a tion
D-mannose according to known procedures: (i) conversion
of the aldose to methyl glycoside (∼50% yield),22 (ii)
benzylation of all the hydroxyl groups by using benzyl
bromide and sodium hydride (∼80% yield),23 (iii) hydroly-
sis of methyl glycoside (∼80% yield),24 and (iv) oxidation
with DMSO/Ac2O (∼92% yield).25 The three sugar lac-
tones 1-326 reacted with a variety of organolithium and
Grignard reagents to give the pyranoketoses 4-17 in
good to excellent yields (Scheme 1).20,21 These products
existed dominantly as R-anomers (>90%) as shown by
the NMR analyses including the NOESY experiments.27
Such stereoselectivity was in accordance with the well-
known anomeric effect.
The subsequent dehydration of pyranoketoses 4-17
was realized by treatment with trifluoroacetic anhydride
(TFAA) and pyridine to give exo-glycals 18-31 as exclu-
sive (Z)-isomers,28 including all the gluco-, galacto-, and
manno-type precursors. Most of the dehydration reac-
tions were carried out in yields from 70% to 89% except
for the preparation of 1-exo-methylene sugars 18, 25, and
28. These molecules further reacted with TFAA under
dehydration conditions and were found labile in silica gel
chromatography. The configuration of the reaction prod-
ucts was rigorously determined by comparison with the
reported NMR spectral data14-19,29 along with NOE
studies. For instance, a 10.7% enhancement of H1′ (at δ
5.41) in compound 31 was observed upon irradiation of
H2 (at δ 4.01). A 7.4% enhancement of H2 was found by
irradiation of H1′. The NOESY spectrum of sugar diene
31 also showed the correlation between H1′ and H2.
Direct dehydration of molecules 4-17 is less feasible
as the C1′ protons are not acidic especially when the
compounds (4, 5, 11, 12, 14, and 15) lack an electron-
withdrawing group. Thus, formation of (Z)-exo-glycals is
considered to proceed with an intermediary oxonium ion.
For example, the anomeric hydroxyl group of compound
5 would be activated by treatment with TFAA, and
facilitated to form oxonium intermediate A, which con-
ceivably has C1′ protons with a substantially lower pKa
value (Scheme 2). Once the anomeric carbon became sp2
hybridized, the conformer B would be disfavored due to
the 1,3-allylic strain between the C2 benzyloxy and C1′
ethyl groups. Thus, the preorganized intermediate A
having a C-H bond antiperiplanar to the p-orbitals of
oxocarbonium would readily undergo a deprotonation to
give the observed (Z)-exo-glycal 19.
Other evidence to support the existence of oxocar-
bonium intermediate is shown by the preparation of
furanosyl exo-glycals (Scheme 3). The 1:1 anomeric
mixture of 33, obtained by the addition of allylmagnesium
chloride to lactone 32, was treated with TFAA and
pyridine to give sugar diene 34 with (Z)-configuration.
Likewise, ozonolysis of 33 (1:1 anomeric mixture) followed
by dehydration also produces a single product, 35, with
(Z)-configuration. The stereochemistry is in agreement
with a common intermediate of oxonium ion similar to
that delineated in Scheme 2.
(22) (a) Voiland, A.; Michel, G. Carbohydr. Res. 1985, 141, 285. (b)
Medgyes, A.; Farkas, E.; Liptak, A.; Pozsgay, V. Tetrahedron 1997,
53, 4159.
(23) (a) Tennant-Eyles, R. J .; Davis, B. G.; Fairbanks, A. J .
Tetrahedron: Asymmetry 2000, 11, 231. (b) Lin, C.-C.; Shimazaki, M.;
Heck, M.-P.; Aoki, S.; Wang, R.; Kimura, T.; Ritzan, H.; Takayama,
S.; Wu, S.-H.; Weitz-Schmidt, G.; Wong, C.-H. J . Am. Chem. Soc. 1996,
118, 6826.
(24) Hardick, D. J .; Hutchinson, D. W.; Trew, S. J .; Wellington, E.
M. H. Tetrahedron 1992, 48, 6285.
(25) (a) Overkleeft, H. S.; van Wiltenburg, J .; Pandit, U. K.
Tetrahedron 1994, 50, 4215. (b) Mahmud, T.; Tornus, I.; Egelkrout,
E.; Wolf, E.; Uy, C.; Floss, H. G.; Lee, S. J . Am. Chem. Soc. 1999, 121,
6973.
(26) (a) Yang, W.-B.; Tsai, C.-H.; Lin, C.-H. Tetrahedron Lett. 2000,
41, 2569 (b) Yang, Y.-Y.; Yang, W.-B.; Teo, C.-F.; Lin, C.-H. Synlett
2000, 1634.
(27) For instance, the NOESY spectrum of ester 13 indicated the
cross-peaks between H1′ (δ 2.35 and 2.81) and H2 (δ 3.79), and thus
supported their close correlation in space.
It was noted that Xie and co-workers have reported a
synthesis of compound 30 by Wittig reaction of manno-
type lactone 3 with phosphorane Ph3PdCHCO2Et.17
However, their reported 1H NMR data are similar to
those of the gluco-type exo-glucal, but different from our
data for the manno-type exo-glycal 30. We repeated their
experiment and found the actual product was the gluco-
type exo-glucal 20 (20% yield, similar to the reported
yield). It is evident that Xie and co-workers have ne-
(28) We reported previously that ester 20 was synthesized in 75%
yield in company with the other isomer in 15% yield (see ref 20). The
yield of 20 can be improved to 90%.
(29) Dondoni, A.; Marra, A.; Pasti, C. Tetrahedron: Asymmetry 2000,
11, 305. (b) Borbas, A.; Szabovik, G.; Antal, Z.; Herczegh, P.; Agocs,
A.; Liptak, A. Tetrahedron Lett. 1999, 40, 3639.

Synthesis and Reaction of exo-Glycals
J . Org. Chem., Vol. 67, No. 11, 2002 3775
Sch em e 2. P r op osed F or m a tion of a n Oxoca r bon iu m Ion To Exp la in th e Resu ltin g Ster eoselectivity in
th e exo-Glyca l Syn th esis
of C-mannosides 3731 and 4131, respectively. Upon oxida-
Sch em e 3. P r ep a r a tion of F u r a n osyl exo-Glyca ls
34 a n d 35 a s Exclu sive (Z)-Isom er s fr om a Mixtu r e
of r- a n d â-An om er ic P r ecu r sor s
tion of 40 with NaIO4, the resulting selenide underwent
elimination consecutively to give exo-glycal 30. When a
mixture of 38 and 40 (1:4) was treated with NaIO4, a
single product, 30, was also obtained in a high yield. By
mechanistic considerations, selenide 40 likely exhibited
the (1R,1′R) configuration to account for the formation
of (Z)-exo-glycal via transition state E.
exo-Glycals are potentially versatile building blocks in
organic synthesis. The Michael addition reactions to
conjugated esters 20 and 30 have been investigated.
Treatment of the gluco-type exo-glycal 20 with allyl
alcohol in the presence of BF3‚OEt2 gave a single product
that was determined to have a C-substituent on the
â-position and an O-allyl group on the R-position. By a
similar procedure, Michael reaction of the manno-type
exo-glycal 30 with allyl alcohol also afforded a single
isomer with the R-O-allyl group by analogy to the
aforementioned stereochemical outcome that often oc-
curred in the reactions of manno-type sugars. The
detailed results will be published in due course. The
products of Michael addition with two tethers on ano-
meric centers can be elaborated for other applications.
For example, Schmidt et al. recently reported the syn-
thesis of R(1,3)-galactosyltransferase inhibitors based on
a new type of disubstrate analogue,32 which relied on the
buildup of quaternary carbon in the anomeric center.33
glected the possible epimerization at the C-2 position
during the Wittig reaction.
We also explored an alternative route to the synthesis
of exo-glycals (Scheme 4). C-Mannoside 36, prepared by
the known procedure,30 was subjected to ozonolysis. The
resulting ozonide was treated with NaOEt to give ester
37 in 83% yield. Lithiation of 37, followed by treatment
with phenylselenyl chloride, afforded the desired product
38 as a single isomer (27% yield) accompanied by the
ring-opening product 39 (56% yield) with (E)-configura-
tion (J 2,3 ) 15.6 Hz). Oxidation of 38 with NaIO4, followed
by an in situ selenoxide elimination, provided a 75% yield
of the conjugated ester 30 with (Z)-configuration, which
is identical to that prepared by the previous two-step
synthesis from lactone 3 (Scheme 1). We propose the
transition state D to account for the syn elimination of
selenoxides, giving the observed (Z)-double bond. Thus,
selenide 38 was deduced to have the (1S,1′S) chirality.
The stereochemistry might result from an attack of
PhSeCl from the exo face of the chelated transition state
C. On the other hand, treatment of 39 with PhSeCl led
to two ring-closure products (Scheme 5), R-isomer 38
(16%) and â-isomer 40 (65%). Two isomers were sepa-
rated by silica gel chromatography with elution of EtOAc/
hexanes (1:10). Reductions of 38 and 40 with NiCl2‚6H2O
were individually carried out to give quantitative yields
In conclusion, we have established two different meth-
ods to prepare exo-glycals. The two-step synthesis via
addition and elimination procedures (Scheme 1) is gen-
eral for preparation of the exo-glycals with five- and six-
membered rings. The exclusive formation of (Z)-isomers
suggests an oxocarbonium ion intermediate, which adapts
a preferable conformation during the process of dehydra-
tion. The alternative synthesis (Schemes 4 and 5) incor-
porates selenylation of C-glycosides and the subsequent
selenoxide elimination to give exo-glycals. This method
also affords exclusively the (Z)-isomers of exo-glycals. Our
preliminary study on the reactions of exo-glycals indi-
cated that Michael additions occurred in a highly stereo-
selective manner. Further application of exo-glycals to
(31) Allevi, P.; Ciuffreda, P.; Colombo, D.; Monti, D.; Speranza, G.;
Manitto, P. J . Chem. Soc., Perkin Trans. 1 1989, 1281.
(32) Waldscheck, B.; Streiff, M.; Notz, W.; Kinzy, W.; Schmidt, R.
R. Angew. Chem., Int. Ed. 2001, 40, 4007.
(33) For other examples, please see: (a) Koviach, J .; Chappell, M.
D.; Halcomb, R. L. J . Org. Chem. 2001, 66, 2318. (b) Panza, L.; Lay,
L. In Carbohydrates in Chemistry and Biology; Ernst, B., Hart, G. W.,
Sinay, P., Eds.; Wiley-VCH Verlag GmbH: Weinheim, Germany, 2000;
Vol. 1, pp 197-206.
(30) (a) Hosomi, A.; Sakata, Y.; Sakurai, H. Tetrahedron Lett. 1984,
25, 2383. (b) Bertozzi, C.; Bednarski, M. Carbohydr. Res. 1992, 223,
243.

3776 J . Org. Chem., Vol. 67, No. 11, 2002
Yang et al.
Sch em e 4. Syn th esis of Ester 30 a s a (Z)-Isom er by th e Selen yla tion of C-Glycosid e 37 a n d a Su bsequ en t
Selen oxid e Elim in a tion
Sch em e 5. Syn th esis of Ester 30 a s a (Z)-Isom er by th e Tr ea tm en t of Rin g-Op en in g Ester 39 w ith P h SeCl
a n d a Su bsequ en t Selen oxid e Elim in a tion
were prepared from direct protection of free lactones (com-
mercially available)26 or according to the reported proce-
dures.22-25 In a typical reaction, a fully protected lactone (1.0
mmol) in anhydrous THF (10 mL) was stirred at -78 °C under
N2 and subjected to the dropwise addition of Grignard reagent
or organolithoum (1.2 mmol). After another 3 h of stirring until
the disappearance of starting material, the reaction was
stopped by the addition of water and then extracted with
EtOAc (100 mL × 3). The combined organic layer was dried
over Na2SO4, and the filtrate was evaporated to give a dry
residue which was purified by silica gel column chromatogra-
phy with an appropriate eluent. The resulting product was
dissolved in THF (anhydrous, 10 mL) and treated with a
mixture of pyridine (10 mmol) and trifluoroacetic anhydride
(5.0 mmol) at 0 °C. After 4 h, the reaction mixture was
subjected to saturated NaHCO3 solution and extracted with
EtOAc (100 mL × 3). The combined organic layer was dried
over Na2SO4 and evaporated to provide the crude residue,
which was further purified by silica gel chromatography.
2,3,4,6-Tetr a-O-ben zyl-1-m eth yl-r-D-glu copyr an ose (4).34
The purification was carried out by silica gel chromatography
with hexanes/EtOAc (2:1) to give compound 4 in 90% yield
(of the nucleophilic addition): the 1H NMR data were con-
sistent with those reported previously;34 13C NMR (100 MHz,
CDCl3) δ 26.56, 68.84, 71.54, 73.41, 74.84, 75.57, 75.68, 78.45,
83.21, 83.62, 97.38, 127.58 (2×), 127.64, 127.74, 127.81,
the synthesis of uncommon carbohydrates is currently
under investigation.
Exp er im en ta l Section
Gen er a l Meth od s. All reactions were conducted under an
argon atmosphere. THF and diethyl ether were distilled from
sodium benzophenone ketyl. Dichloromethane was distilled
from calcium hydride. Methanol was distilled from magne-
sium. Solutions of compounds in organic solvents were dried
over sodium sulfate prior to rotary evaporation. DMF was
99.5% pure and anhydrous. Benzyl bromide was filtered
through alumina prior to use. TLC plates (layer thickness, 250
µm) were Kieselgel 60 F254. Carbohydrate compounds were
visualized with TLC by the stain solution p-anisaldehyde/
H2SO4/EtOH (6:1:100), phosphomolybdic acid (PMA)/EtOH
(1:20), and H2SO4/EtOH/H2O (1:10:10). Column chromatogra-
phy was carried out with silica gel 60 (70-230 mesh);
gradients of EtOAc/hexanes and gradients of MeOH/CHCl3
were used as eluents. Optical rotations were measured on a
digital polarimeter with a cuvette of 10 cm length. 1H NMR
spectra were recorded at 400 or 500 MHz with CHCl3 (δH 7.24)
or CD3OD [δH 3.30 (central line of a quintet)] as the internal
standard; 13C NMR spectra were recorded at 100 or 125 MHz
with CDCl3 [δc 77.0 (central line of a triplet)] or CD3OD [δc
49.0 (central line of a septet)] as the internal standard. Mass
spectra were recorded at an ESI or FAB ionization.
Gen er a l P r oced u r e for P r ep a r in g exo-Glyca ls. Sugar
lactones in fully protective forms of benzyl or TBDMS groups
(34) Lay, L.; Nicotra, F.; Panza, L.; Russo, G. Caneva, E. J . Org.
Chem. 1992, 57, 1304.

Synthesis and Reaction of exo-Glycals
J . Org. Chem., Vol. 67, No. 11, 2002 3777
127.85, 127.90, 128.29, 128.33, 128.35, 128.40 (2×), 137.87,
138.19, 138.26, 138.65; ESI-MS m/z (rel intens) 537.2 (M -
H2O + H+, 2), 429 (100); FAB-MS m/z (rel intens) 537.3 (M -
H2O + H+, 4), 307.1 (31), 154 (100); HRMS (FAB) m/z calcd
for C35H37O5 (M - H2O + H+) 537.2641, found 537.2657.
H2), 3.76 (dd, 1H, J ) 11.0, 3.9 Hz, H6b), 3.97 (ddd, 1H, J )
9.3, 3.9, 2.0 Hz, H5), 4.02 (t, 1H, J ) 9.3 Hz, H3), 4.53 (d, 1H,
J ) 12.3 Hz, PhCH2), 4.60 (d, 1H, J ) 10.8 Hz, PhCH2), 4.61
(d, 1H, J ) 12.3 Hz, PhCH2), 4.69 (d, 1H, J ) 11.1 Hz, PhCH2),
4.83 (d, 1H, J ) 10.8 Hz, PhCH2), 4.87 (d, 1H, J ) 11.0 Hz,
PhCH2), 4.91 (d, 1H, J ) 11.0 Hz, PhCH2), 4.93 (d, 1H, J )
11.1 Hz, PhCH2), 5.13 (dd, 1H, J ) 17.3, 2.0 Hz, H3′a), 5.19
(dd, 1H, J ) 10.2, 2.0 Hz, H3′b), 5.88 (ddd, 1H, J ) 17.3, 10.2,
7.5 Hz, H2′), 7.19-7.21 (m, 2H, Ph), 7.24-7.33 (m, 18H, Ph);
13C NMR (100 MHz, CDCl3) δ 42.82, 68.75, 71.58, 73.31, 74.84,
75.30, 75.55, 78.45, 81.48, 83.74, 97.59, 120.04, 127.47, 127.54,
127.59, 127.61, 127.69, 127.80, 127.81, 127.85, 128.14, 128.28,
128.32, 128.37, 132.20, 137.97, 138.27, 138.39, 138.60. FAB-
MS m/z (rel intens) 563 (M - H2O + H+, 5), 455 (40), 253 (30),
181 (100); HRMS (FAB) m/z calcd for C37H39O5 (M - H2O +
H+) 563.2797, found 563.2772.
2,3,4,6-Tetr a -O-ben zyl-1-p r op yl-r-D-glu cop yr a n ose (5).
To a stirred solution of gluconolactone 1 (247 mg, 0.5 mmol)
in anhydrous THF (10 mL) at -78 °C was added C3H7MgBr
(1.0 M in THF, 0.6 mL, 0.6 mmol). The resulting mixture was
warmed from -78 to -20 °C in a 3 h period, quenched by
addition of NH4Claq, and extracted with EtOAc (50 mL × 3).
The organic phase was washed with brine, dried over anhy-
drous Na2SO4, and concentrated under reduced pressure. The
residue was purified by silica gel chromatography with hex-
anes/EtOAc (3:1) to give 268 mg of product 5 as a colorless
syrup in 92% yield: Rf 0.4 (EtOAc/hexanes, 1:3; PMA); [R]25
D
+10° (c 5.7, CHCl3); 1H NMR (400 MHz, CDCl3) δ 0.85 (t, 3H,
J ) 7.3 Hz, H3′) 1.25-1.47 (m, 2H, H2′), 1.62 (t, 2H, J ) 8.8
Hz, H1′), 3.41 (d, 1H, J ) 9.2 Hz, H2), 3.63 (t, 1H, J ) 9.3 Hz,
H3), 3.65 (dd, 1H, J ) 10.8, 1.7 Hz, H6a), 3.75 (dd, 1H, J )
10.8, 3.9 Hz, H6b), 3.96 (ddd, 1H, J ) 9.3, 3.9, 1.7 Hz, H5), 3.98
(t, 1H, J ) 9.3 Hz, H4), 4.52 (d, 1H, J ) 12.3 Hz, PhCH2), 4.60
(d, 1H, J ) 10.7 Hz, PhCH2), 4.61 (d, 1H, J ) 12.3 Hz, PhCH2),
4.67 (d, 1H, J ) 11.1 Hz, PhCH2), 4.81 (d, 1H, J ) 10.7 Hz,
PhCH2), 4.85 (d, 1H, J ) 11.0 Hz, PhCH2), 4.88 (d, 1H, J )
11.0 Hz, PhCH2), 4.91 (d, 1H, J ) 11.1 Hz, PhCH2), 7.6∼7.1
(m, 20H, Ph); 13C NMR (100 MHz, CDCl3) δ 14.23, 15.86, 40.86,
68.85, 71.59, 73.32, 74.87, 75.41, 75.60, 78.46, 81.48, 83.87,
98.84, 127.47, 127.59, 127.61, 127.65, 127.74, 127.81, 127.84,
127.88, 128.21, 128.27, 128.29, 128.37, 137.96, 138.30, 138.31,
138.64; ESI-MS m/z (rel intens) 583 (M + H+, 22), 555 (39),
457 (100); FAB-MS m/z (rel intens) 565.3 (M - H2O + H+,
31), 457.2 (66), 391.2 (9); HRMS (FAB) m/z calcd for C37H41O5
(M - H2O + H+) 565.2954, found 565.2961.
2,3,4,6-Tetr a-O-ben zyl-1-(dim eth oxyph osph or yl)m eth yl-
r-D-glu cop yr a n ose (8).29a The purification was carried out
by silica gel chromatography with hexanes/EtOAc (1:1) to give
compound 8 as a white solid in 92% yield (of the nucleophilic
addition): Rf 0.44 (EtOAc/hexanes, 1/1; PMA); [R]25 -13.3°
D
(c 6.2, CHCl3); 1H NMR (400 MHz,CDCl3) δ 1.68 (dd, 1H, J )
18.5,15.2 Hz, H1′a), 2.30 (dd, 1H, J ) 17.6, 15.2 Hz, H1′b), 3.27
(dd, 1H, J ) 9.4,1.1 Hz, H2), 3.60 (dd, 1H, J ) 10.7, 2.0 Hz,
H
6a), 3.61 (d, 3H, J ) 11.1 Hz, OCH3), 3.66 (d, 3H, J ) 11.1
Hz, OCH3), 3.70 (dd, 1H, J ) 10.0, 9.4 Hz, H4), 3.73 (dd, 1H,
J ) 10.7, 3.6 Hz, H6b), 4.08 (ddd, 1H, J ) 10.0, 3.6, 2.0 Hz,
H5), 4.12 (t, 1H, J ) 9.4 Hz, H3), 4.47 (s, 2H, PhCH2), 4.58 (d,
1H, J ) 11.0 Hz, PhCH2), 4.64 (d, 1H, J ) 11.7 Hz, PhCH2),
4.85 (d, 1H, J ) 11.0 Hz, PhCH2), 4.91 (s, 2H, PhCH2), 4.96
(d, 1H, J ) 11.7 Hz, PhCH2), 5.73 (s, 1H, OH), 7.18∼7.21 (m,
2H, Ph), 7.22-7.34 (m, 18H, Ph); 13C NMR (100 MHz, CDCl3)
δ 32.54 (d, J P,C1 ) 536.8 Hz), 51.73 (d, J P,OMe ) 25.2 Hz), 53.25
(d, J P,OMe ) 24.8 Hz), 68.46, 71.00, 73.26, 74.78, 75.08, 75.55,
78.31, 82.55 (d, J P-C ) 53.2 Hz), 83.10 (d, J P-C ) 12.8 Hz),
96.61 (d, J P-C3 ) 32.0 Hz), 127.53, 127.57, 127.65, 127.68,
127.76, 127.90, 127.93, 128.27 (2×), 128.33, 128.38, 128.59,
137.75, 137.84, 138.20, 138.50; ESI-MS m/z (rel intens) 663
(M + H+, 26), 645 (M - H2O + H+, 62), 537 (100), 429 (55);
FAB-MS m/z (rel intens) 663 (M + H+, 7), 645 (M - H2O +
H+, 3), 537 (30), 154 (100); HRMS (FAB) m/z calcd for
2,3,4,6-Tetr a -O-ben zyl-1-(eth oxyca r bon yl)m eth yl-r-D-
glu cop yr a n ose (6).35 The purification was carried out by
silica gel chromatography with hexanes/EtOAc (5:1) to give
compound 6 as a colorless syrup in 95% yield (of the nucleo-
1
philic addition): Rf 0.5 (EtOAc/hexanes, 1/3; PMA); H NMR
(400 MHz, CDCl3) δ 1.22 (t, 3H, J ) 7.1 Hz, OCH2CH3), 2.33
(d, 1H, J ) 15.4 Hz, H1′a), 2.76 (d, 1H, J ) 15.4 Hz, H1′b), 3.32
(d, 1H, J ) 9.4 Hz, H2), 3.61 (dd, 1H, J ) 11.1, 1.5 Hz, H6a),
3.69 (t, 1H, J ) 9.9 Hz, H4), 3.73 (dd, 1H, J ) 11.1, 3.8 Hz,
C
C
37H45O9P (M + H+) 663.2722, found 663.2711; calcd for
37H43O8P (M -H2O + H+) 645.2617, found 645.2603. Anal.
Calcd for C37H43O9P: C, 67.06; H, 6.54. Found C, 67.11; H,
6.70.
H
6b), 4.01 (ddd, 1H, J ) 9.9, 3.8, 1.5 Hz, H5), 4.12 (dd, 1H, J
) 9.9, 9.4 Hz, H3), 4.14 (q, 2H, J ) 7.1 Hz, OCH2CH3), 4.49 (d,
1H, J ) 12.2 Hz, PhCH2), 4.57 (d, 1H, J ) 12.2 Hz, PhCH2),
4.59 (d, 1H, J ) 10.9 Hz, PhCH2), 4.65 (d, 1H, J ) 11.5 Hz,
PhCH2), 4.84 (d, 1H, J ) 10.9 Hz, PhCH2), 4.90 (s, 2H, PhCH2),
4.96 (d, 1H, J ) 11.5 Hz, PhCH2), 5.32 (s, 1H, OH), 7.18-7.21
(m, 2H, Ph), 7.24-7.32 (m, 18H, Ph); 13C NMR (100 MHz,
CDCl3) δ 14.01, 40.45, 61.01, 68.53, 71.42, 73.26, 74.84, 75.19,
75.61, 78.45, 81.88, 83.15, 97.09, 127.51, 127.59, 127.62,
127.70, 127.73, 127.79, 127.91, 128.27, 128.33, 128.40, 128.42
(2×), 137.81, 138.22, 138.26, 138.52, 172.39; ESI-MS m/z (rel
intens) 650 (M + Na + H+, 100), 609 (M - H2O + H+, 30), 563
(6); HRMS (FAB) m/z calcd for C38H41O7 (M - H2O + H+)
609.2852, found 609.2857.
1-Allyl-2,3,4,6-tetr a -O-ben zyl-r-D-glu cop yr a n ose (7). To
a stirred solution of gluconolactone 1 (280 mg, 0.52 mmol) in
anhydrous THF (12 mL) at -78 °C was added allylmagnesium
chloride (2.0 M in THF, 0.3 mL, 0.6 mmol). The resulting
mixture was warmed from -78 to -20 °C in a 1 h period,
quenched by addition of NH4Claq, and extracted with EtOAc
(50 mL × 3). The organic phase was washed with brine, dried
over anhydrous Na2SO4, and concentrated under reduced
pressure. The residue was purified by silica gel chromatogra-
phy with hexanes/EtOAc (3:1) to give 247 mg of product 7 as
a colorless syrup in 82% yield: Rf 0.19 (CHCl3, PMA); 1H NMR
(400 MHz, CDCl3) δ 2.42 (dd, 1H, J ) 13.8, 7.5 Hz, H1′a), 2.47
(dd, 1H, J ) 13.8, 7.5 Hz, H1′b), 3.44 (d, 1H, J ) 9.1 Hz, H4),
3.65 (dd, 1H, J ) 11.0, 2.0 Hz, H6a), 3.68 (d, 1H, J ) 9.1 Hz,
2,3,4,6-Tet r a -O-b en zyl-1-(et h oxysu lfon yl)m et h yl-r-D-
glu cop yr a n ose (9).29b The purification was carried out by
silica gel chromatography with hexanes/EtOAc (5:1, 3:1) to give
compound 9 as a colorless syrup in 81% yield (of the nucleo-
philic addition): Rf 0.75 (EtOAc/hexanes, 1:1; PMA); [R]25
D
-9.2° (c 4.1, CHCl3); 1H NMR (400 MHz, CDCl3) δ 1.26 (t, 3H,
J ) 7.0 Hz, OCH2CH3), 2.98 (d, 1H, J ) 14.5 Hz, H1′a), 3.39
(d, 1H, J ) 14.5 Hz, H1′b), 3.39 (d, 1H, J ) 9.4 Hz, H2), 3.64
(dd, 1H, J ) 11.0, 1.0 Hz, H6a), 3.73 (t, 1H, J ) 9.4 Hz, H4),
3.74 (d, 1H, J ) 11.0 Hz, H6b), 4.03 (dm, 1H, J ) 9.4 Hz, H5),
4.10 (t, 1H, J ) 9.4 Hz, H3), 4.20 (q, 2H, J ) 7.0 Hz, OCH2-
CH3), 4.48 (d, 1H, J ) 12.0 Hz, PhCH2), 4.53 (d, 1H, J ) 12.0
Hz, PhCH2), 4.59 (d, 1H, J ) 11.5 Hz, PhCH2), 4.61 (s, 1H,
OH), 4.64 (d, 1H, J ) 11.5 Hz, PhCH2), 4.84 (d, 1H, J ) 10.9
Hz, PhCH2), 4.89 (d, 1H, J ) 10.9 Hz, PhCH2), 4.93 (d, 1H, J
) 11.7 Hz, PhCH2), 4.96 (d, 1H, J ) 11.7 Hz, PhCH2), 7.18-
7.22 (m, 2H, Ph), 7.25-7.37 (m, 18H, Ph); 13C NMR (100 MHz,
CDCl3) δ 14.89, 55.30, 67.83, 68.39, 71.90, 73.39, 74.92, 75.11,
75.64, 77.97, 80.92, 82.86, 95.75, 127.64, 127.67, 127.71,
127.72, 127.74, 127.76, 128.28, 128.33, 128.36, 128.42, 128.63,
128.72, 137.36, 137.90, 138.01, 138.27; ESI-MS m/z (rel intens)
685 (M + Na+, 100), 627 (2), 357 (2), 339 (4). Anal. Calcd for
C
37H42O9S: C, 67.05; H, 6.39. Found C, 67.14; H, 6.32.
2,3,4,6-Te t r a -O-b e n zyl-1-(p h e n yl)m e t h yl-r-D-glu co-
p yr a n ose (10). To a stirred solution of gluconolactone 1 (540
mg, 1.0 mmol) in anhydrous THF (20 mL) at -78 °C was added
PhCH2MgBr (1.0 M in diethyl ether, 3.0 mL, 3.0 mmol). The
resulting mixture was warmed from -78 to -40 °C in a 2 h
period, quenched by addition of NH4Claq, and extracted with
EtOAc (100 mL × 3). The organic phase was washed with
(35) Lewis, M. D.; Cha, J . K.; Kishi, Y. J . Am. Chem. Soc. 1982,
104, 4976.

3778 J . Org. Chem., Vol. 67, No. 11, 2002
Yang et al.
brine, dried over anhydrous Na2SO4, and concentrated under
reduced pressure. The resulting residue was purified by silica
gel chromatography with hexanes/EtOAc (5:1, 3:1) to give 599
mg of product 10 as a colorless syrup in 95% yield: Rf 0.5
(EtOAc/hexanes, 1:3; PMA); [R]25D +13° (c 3.0, CHCl3); 1H NMR
(400 MHz, CDCl3) δ 2.56 (s, 1H, OH), 2.86 (d, 1H, J ) 13.6
Hz, H1′a), 3.04 (d, 1H, J ) 13.6 Hz, H1′b), 3.43 (d, 1H, J ) 9.3
Hz, H2), 3.62 (dd, 1H, J ) 10.8, 1.8 Hz, H6a), 3.67 (t, 1H, J )
9.6 Hz, H4), 3.74 (dd, 1H, J ) 10.8, 3.8 Hz, H6b), 3.89 (ddd,
1H, J ) 10.0, 3.8, 1.8 Hz, H5), 4.06 (t, 1H, J ) 9.3 Hz, H3),
4.53 (d, 1H, J ) 12.3 Hz, PhCH2), 4.58 (d, 1H, J ) 12.3 Hz,
PhCH2), 4.61 (d, 1H, J ) 10.9 Hz, PhCH2), 4.64 (s, 1H, OH),
4.70 (d, 1H, J ) 11.3 Hz, PhCH2), 4.83 (d, 1H, J ) 10.9 Hz,
PhCH2), 4.87 (d, 1H, J ) 11.0 Hz, PhCH2), 4.92 (d, 1H, J )
11.0 Hz, PhCH2), 4.98 (d, 1H, J ) 11.3 Hz, PhCH2), 7.21-
7.37 (m, 25H, Ph); 13C NMR (100 MHz, CDCl3) δ 43.81, 65.24,
68.87, 71.35, 73.32, 74.89, 75.31, 75.59, 78.49, 81.43, 83.89,
97.87, 126.91, 126.96, 127.49, 127.56, 127.58, 127.65, 127.74,
127.83, 127.86, 128.20, 128.23, 128.30, 128.35, 128.40, 128.43,
131.11, 134.68, 138.07, 138.28, 138.42, 138.56; ESI-MS m/z (rel
intens) 653 (M + Na+, 100), 545 (85), 505 (15); HRMS (FAB)
m/z calcd for C41H41O5 (M - H2O + H+) 613.2955, found
613.2962.
2,3,4,6-Tet r a -O-b en zyl-1-m et h yl-r-D-ga la ct op yr a n ose
(11). To a stirred solution of galactonolactone 2 (600 mg, 1.1
mmol) in anhydrous THF (20 mL) at -78 °C was added
CH3MgCl (3.0 M in THF, 0.4 mL, 1.2 mmol). The resulting
mixture was warmed from -78 to -20 °C in a 2 h period,
quenched by addition of 1 N AcOH, and extracted with EtOAc
(50 mL × 3). The collected organic layers were washed with
saturated NaHCO3, dried over Na2SO4, and evaporated in
vacuo. The resulting residue was purified by silica gel chro-
matography with hexanes/EtOAc (3:1) to give 554 mg of
product 11 in 91% yield: Rf 0.4 (EtOAc/hexanes, 1:3, PMA);
1H NMR (400 MHz, CDCl3) δ 1.41 (s, 3H, CH3), 2.52 (s, 1H,
OH), 3.53 (dd, 1H, J ) 9.0, 5.8 Hz, H6a), 3.57 (dd, 1H, J ) 9.0,
7.6 Hz, H6b), 3.82 (d, 1H, J ) 9.7 Hz, H2), 3.89 (dd, 1H, J )
9.7, 2.7 Hz, H3), 4.01 (dd, 1H, J ) 2.7, 1.0 Hz, H4), 4.11 (ddd,
1H, J ) 7.6, 5.8, 1.0 Hz, H5), 4.43 (d, 1H, J ) 11.9 Hz, PhCH2),
4.48 (d, 1H, J ) 11.9 Hz, PhCH2), 4.62 (d, 1H, J ) 11.6 Hz,
PhCH2), 4.68 (d, 1H, J ) 11.6 Hz, PhCH2), 4.70 (d, 1H, J )
11.1 Hz, PhCH2), 4.74 (d, 1H, J ) 11.6 Hz, PhCH2), 4.73 (d,
1H, J ) 11.6 Hz, PhCH2), 4.98 (d, 1H, J ) 11.0 Hz, PhCH2),
7.25-7.38 (m, 20H, Ph); 13C NMR (100 MHZ, CDCl3) δ 26.60,
68.84, 70.18, 72.39, 73.40, 74.33, 74.45, 75.74, 79.77, 80.92,
97.78, 127.47, 127.49, 127.55, 127.68, 127.74, 127.88, 128.02,
128.16, 128.29, 128.34 (2×), 128.38, 138.02, 138.16, 138.45,
138.83; ESI-MS m/z (rel intens) 555 (M + H+, 15), 537 (12),
429 (100); FAB-MS m/z (rel intens) 555.3 (M + H+, 2), 537.3
(10), 459.3 (2), 391.3 (5); HRMS (FAB) m/z calcd for C35H37O5
(M - H2O + H+) 537.2641, found 537.2648.
127.59, 127.67, 127.72, 127.76, 128.08, 128.21, 128.24, 128.28,
128.32, 138.15, 138.26, 138.50, 138.91; HRMS (FAB) m/z calcd
for C37H41O5 (M - H2O + H+) 565.2955, found 565.2961.
2,3,4,6-Tetr a -O-ben zyl-1-(eth oxyca r bon yl)m eth yl-r-D-
ga la ct op yr a n ose (13). To a stirred solution of galactono-
lactone 2 (250 mg, 0.46 mmol) in anhydrous THF (10 mL) at
-78 °C were added a THF (3 mL) solution containing EtOAc
(230 µL, 2.3 mmol) and LHMDS (1.0 M in THF, 2.07 mL, 2.7
mmol). The reaction was warmed from -78 to -50 °C in a 2
h period, quenched by addition of saturated NH4Claq, and
extracted with EtOAc (100 mL × 3). The organic phase was
washed with brine, dried over Na2SO4, and concentrated under
reduced pressure. The residue was purified by silica gel
chromatography with hexanes/EtOAc (5:1) to give 274 mg of
product 13 in 95% yield: Rf 0.34 (EtOAc/hexanes, 1:3, anis-
aldehyde); [R]25D -3° (c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3)
δ 1.19 (t, 3H, J ) 7.0 Hz, OCH2CH3), 2.35 (d, 1H, J ) 15.6 Hz,
H
1′a), 2.81 (d, 1H, J ) 15.6 Hz, H1′b), 3.47 (dd, 1H, J ) 9.3, 5.5
Hz, H6a), 3.59 (dd, 1H, J ) 9.3, 7.7 Hz, H6b), 3.79 (dd, 1H, J )
9.8, 1.3 Hz, H2), 4.02 (dd, 1H, J ) 2.7, 1.4 Hz, H4), 4.04-4.14
(m, 3H, OCH2CH3, H3), 4.16 (ddd, 1H, J ) 7.7, 5.5 Hz, H5),
4.41 (d, 1H, J ) 11.8 Hz, PhCH2), 4.47 (d, 1H, J ) 11.8 Hz,
PhCH2), 4.60 (d, 1H, J ) 11.4 Hz, PhCH2), 4.67 (d, 1H, J )
11.4 Hz, PhCH2), 4.73 (d, 1H, J ) 11.6 Hz, PhCH2), 4.76 (d,
1H, J ) 11.6 Hz, PhCH2), 4.93 (d, 1H, J ) 11.4 Hz, PhCH2),
4.99 (d, 1H, J ) 11.4 Hz, PhCH2), 5.34 (d, 1H, J ) 1.3 Hz,
OH), 7.25-7.38 (m, 20H, Ph); 13C NMR (125 MHZ, CDCl3) δ
13.99, 40.59, 60.59, 68.65, 70.15, 72.59, 73.36, 74.67, 74.81,
75.23, 78.40, 80.42, 97.64, 127.54 (2×), 127.58, 127.66, 127.77,
127.80, 128.11, 128.20, 128.35, 128.36, 128.41, 128.56, 138.11
(2×), 138.45, 138.83, 172.55; HRMS (FAB) m/z calcd for
C
38H41O7 (M - H2O + H+) 609.2852, found 609.2859.
2,3,4,6-Tetra-O-benzyl-1-methyl-r-D-mannopyranose (14).
To a stirred solution of mannolactone 3 (270 mg, 0.5 mmol) in
anhydrous THF (10 mL) at -78 °C was added CH3MgCl (3.0
M in THF, 0.2 mL, 0.6 mmol). The resulting mixture was
warmed to 0 °C in a 2 h period, quenched by addition of 1 N
AcOH, and extracted with EtOAc (50 mL × 3). The collected
organic layers were washed with saturated NaHCO3, dried
over Na2SO4, and evaporated in vacuo. The resulting residue
was purified by silica gel chromatography with hexanes/EtOAc
(3:1) to give 238 mg of product 14 in 86% yield: Rf 0.3 (EtOAc/
hexanes, 1:3, PMA); 1H NMR (400 MHz, CDCl3) δ 1.42 (s, 3H,
CH3), 2.25 (s, 1H, OH), 3.63-3.72 (m, 2H, H6a, H6b), 3.72 (d,
1H, J ) 2.7 Hz, H2), 3.85 (t, 1H, J ) 9.7 Hz, H4), 3.94-3.99
(m, 1H, H5), 4.12 (dd, 1H, J ) 9.4, 2.7 Hz, H3), 4.51 (d, 1H, J
) 10.8 Hz, PhCH2), 4.55 (d, 1H, J ) 12.6 Hz, PhCH2), 4.60 (d,
1H, J ) 12.6 Hz, PhCH2), 4.68 (d, 1H, J ) 11.6 Hz, PhCH2),
4.75 (s, 2H, PhCH2), 4.86 (d, 1H, J ) 10.8 Hz, PhCH2), 4.97
(d, 1H, J ) 11.6 Hz, PhCH2), 7.14-7.38 (m, 20H, Ph); 13C NMR
(100 MHZ, CDCl3) δ 26.58, 69.81, 72.64, 72.80, 73.35, 74.74,
74.98, 75.11, 78.01, 81.45, 98.18, 127.47, 127.55 (3×), 127.75,
127.88, 128.04, 128.10, 128.20, 128.30 (2×), 128.40, 138.44,
138.50, 138.57, 138.58; ESI-MS m/z (rel intens) 555 (M + H+,
15), 537 (12), 429 (100); FAB-MS m/z (rel intens) 555.3 (M +
H+, 2), 537.3 (10), 459.3 (2), 391.3 (5); HRMS (FAB) m/z calcd
for C35H37O5 (M - H2O + H+) 537.2641, found 537.2648.
2,3,4,6-Tetr a -O-ben zyl-1-p r op yl-D-m a n n op yr a n ose (15).
To a stirred solution of mannolactone 3 (225 mg, 0.42 mmol)
in anhydrous THF (10 mL) at -78 °C was added C3H7MgBr
(1.0 M in THF, 0.84 mL, 0.84 mmol). The resulting mixture
was warmed from -78 to -20 °C in a 3 h period, quenched by
addition of NH4Claq, and extracted with EtOAc (100 mL × 3).
The organic phase was washed with brine, dried over anhy-
drous Na2SO4, and concentrated under reduced pressure. The
residue was purified by silica gel chromatography with toluene/
EtOAc (12:1) to give 189 mg of product 15 as a colorless syrup
in 80% yield: Rf 0.2 (EtOAc/hexanes, 1:5, PMA); 1H NMR (400
MHz, CDCl3) δ 0.88 (t, 3H, J ) 7.2 Hz, CH3), 1.11-1.22 (m,
1H, H2′a), 1.37-1.49 (m, 1H, H2′b), 1.59-1.69 (m, 1H, H1′a),
1.76-1.85 (m, 1H, H1′b), 3.67 (dd, 1H, J ) 10.8, 5.5 Hz, H6a),
3.71 (dd, 1H, J ) 10.8, 2.0 Hz, H6b), 3.78 (d, 1H, J ) 2.6 Hz,
H2), 3.89 (t, 1H, J ) 9.7, Hz, H4), 3.96 (ddd, 1H, J ) 9.5, 5.5,
2.0 Hz, H5), 4.41 (dd, 1H, J ) 9.3, 2.6 Hz, H3), 4.53 (d, 1H, J
) 10.9 Hz, PhCH2), 4.54 (d, 1H, J ) 12.3 Hz, PhCH2), 4.60 (d,
2,3,4,6-Tet r a -O-b en zyl-1-p r op yl-r-D-ga la ct op yr a n ose
(12). To a stirred solution of galactonolactone 2 (90 mg, 1.17
mmol) in anhydrous THF (5 mL) at -78 °C was added C3H7-
MgCl (1.0 M in THF, 0.2 mL, 0.2 mmol). The resulting mixture
was warmed from -78 to -20 °C in a 2 h period, quenched by
addition of NH4Claq, and extracted with EtOAc (50 mL × 3).
The organic phase was washed with brine, dried over anhy-
drous Na2SO4, and concentrated under reduced pressure. The
resulting residue was purified by silica gel chromatography
with toluene/EtOAc (8:1) to give 89 mg of product 12 as a
colorless syrup in 90% yield: Rf 0.4 (EtOAc/toluene, 1:8;
1
anisaldehyde); H NMR (400 MHz, CDCl3) δ 0.84 (t, 3H, J )
7.3 Hz, CH3), 1.31-1.45 (m, 2H, H2′), 1.57-1.69 (m, 2H, H1′),
2.36 (s, 1H, OH), 3.52 (dd, 1H, J ) 9.0, 5.5 Hz, H6a), 3.59 (dd,
1H, J ) 9.0, 7.8 Hz, H6b), 3.85 (d, 1H, J ) 9.5 Hz, H2), 3.92
(dd, 1H, J ) 9.5, 2.5 Hz, H3), 4.02 (dd, 1H, J ) 2.5, 0.9 Hz,
H4), 4.09 (ddd, 1H, J ) 7.8, 5.5, 0.9 Hz, H5), 4.43 (d, 1H, J )
11.8 Hz, PhCH2), 4.47 (d, 1H, J ) 11.8 Hz, PhCH2), 4.62 (d,
1H, J ) 11.7 Hz, PhCH2), 4.67 (d, 1H, J ) 11.6 Hz, PhCH2),
4.69 (d, 1H, J ) 11.4 Hz, PhCH2), 4.75 (d, 1H, J ) 11.6 Hz,
PhCH2), 4.94 (d, 1H, J ) 11.7 Hz, PhCH2), 5.00 (d, 1H, J )
11.4 Hz, PhCH2), 7.15-7.41 (m, 20H, Ph); 13C NMR (100 MHZ,
CDCl3) δ 14.10, 15.51, 40.85, 68.68, 70.00, 72.19, 73.31, 73.98,
74.22, 75.50, 78.29, 81.14, 98.69, 127.30, 127.43, 127.47,

Synthesis and Reaction of exo-Glycals
J . Org. Chem., Vol. 67, No. 11, 2002 3779
1H, J ) 12.3 Hz, PhCH2), 4.64 (d, 1H, J ) 11.5 Hz, PhCH2),
4.75 (d, 1H, J ) 11.8 Hz, PhCH2), 4.78 (d, 1H, J ) 11.8 Hz,
PhCH2), 4.86 (d, 1H, J ) 10.9 Hz, PhCH2), 5.02 (d, 1H, J )
11.5 Hz, PhCH2), 7.17-7.38 (m, 20H, Ph); 13C NMR (100 MHz,
CDCl3) δ 14.21, 16.04, 40.09, 69.84, 72.68, 72.78, 73.35, 74.61,
74.99, 75.38, 76.55, 81.97, 99.38, 127.43 (2×), 127.48, 127.50,
127.52, 127.83, 127.94, 128.02, 128.17, 128.25, 128.27, 128.37,
138.47, 138.53, 138.68, 138.75; HRMS (FAB) m/z calcd for
7.15 (m, 2H, Ph), 7.24-7.37 (m, 18H, Ph); 13C NMR (100 MHz,
CDCl3) δ 68.77, 72.78, 73.54, 74.41, 74.47, 77.53, 78.54, 78.95,
84.72, 94.70, 127.63, 127.67, 127.69, 127.77, 127.85, 127.87
(2×), 127.90, 128.34, 128.36, 128.38, 128.43, 137.87, 138.04,
138.10, 138.34, 156.33; ESI-MS m/z (rel intens) 554.8 (M +
H2O + H+, 8), 429 (M - PhCH2O + H+, 100), 391.0 (35); HRMS
m/z calcd for C35H37O5 (M + H+) 537.2641, found 537.2638.
(1(1′)Z)-2,3,4,6-Tetr a -O-ben zyl-1-d eoxy-1-p r op ylid en e-
D-glu cop yr a n ose (19). To a solution of 5 (212 mg, 0.36 mmol)
in anhydrous THF (10 mL) at 0 °C were added pyridine (0.72
mL, 9.0 mmol) and trifluoroacetic anhydride (0.21 mL, 1.5
mmol). The resulting reaction was stirred at 0 °C for 2 h,
stopped by adding saturated NaHCO3, and extracted with
EtOAc (100 mL). The resulting organic layer was dried over
Na2SO4 and concentrated at reduced pressure. The purification
by silica gel chromatography with hexanes/EtOAc (10:1)
afforded 148 mg of product 19 in 72% yield as a white solid:
Rf 0.5 (EtOAc/hexanes, 1:3; PMA); 1H NMR (400 MHz, CDCl3)
δ 0.96 (t, 3H, J ) 7.6 Hz, CH3), 2.09-2.23 (m, 2H, H2′), 3.65
(ddd, 1H, J ) 9.9, 3.8, 1.9 Hz, H5), 3.65 (t, 1H, J ) 7.5 Hz,
H3), 3.73 (dd, 1H, J ) 10.8, 3.8 Hz, H6a), 3.76 (dd, 1H, J ) 9.9,
7.5, Hz, H4), 3.78 (dd, 1H, J ) 10.8, 1.9 Hz, H6b), 3.90 (dd, 1H,
J ) 7.4, 1.1 Hz, H2), 4.50 (d, 1H, J ) 11.0 Hz, PhCH2), 4.54
(d, 1H, J ) 12.2 Hz, PhCH2), 4.59 (d, 1H, J ) 11.6 Hz, PhCH2),
4.65 (d, 1H, J ) 12.2 Hz, PhCH2), 4.69 (d, 1H, J ) 11.6 Hz,
PhCH2), 4.72 (d, 1H, J ) 12.2 Hz, PhCH2), 4.77 (d, 1H, J )
11.0 Hz, PhCH2), 4.85 (d, 1H, J ) 11.2 Hz, PhCH2), 4.99 (td,
1H, J ) 7.3, 1.1 Hz, H1′), 7.14-7.17 (m, 2H, Ph), 7.23-7.37
(m, 18H, Ph); 13C NMR (100 MHz, CDCl3) δ 17.78, 29.87, 68.93,
72.60, 73.53, 74.44, 74.56, 77.84, 78.47, 79.37, 85.41, 112.64,
127.63, 127.69, 127.74, 127.76, 127.80, 127.83, 127.85, 127.97,
128.37, 128.39, 128.43, 128.47, 138.26, 138.30 (2×), 138.52,
147.56; ESI-MS m/z (rel intens) 587.3 (M + Na+, 100), 565.4
(M + H+, 11), 457.3 (18); FAB-MS m/z (rel intens) 565.3 (M +
H+, 20), 457.2 (67), 391.2 (40), 307.2 (100); HRMS (FAB) m/z
calcd for C37H41O5 (M + H+) 565.2954, found 565.2955.
(1(1′)Z)-2,3,4,6-Tet r a -O-b en zyl-1-d eoxy-1-(et h oxyca r -
bon yl)m eth ylid en e-D-glu cop yr a n ose (20).17a The purifica-
tion was carried out by silica gel chromatography with
hexanes/EtOAc (5:1) to give compound 20 as a colorless syrup
in 90% yield (of the dehydration). The other isomer was
sometimes obtained as the minor product. Data for compound
C
37H41O5 565.2954 (M - H2O + H+), found 565.2956.
2,3,4,6-Tetr a-O-ben zyl-1-(eth oxycar bon yl)m eth yl-D-m an -
n op yr a n ose (16). To a stirred solution of mannolactone 3 (338
mg, 0.63 mmol) in anhydrous THF (20 mL) at -78 °C were
added a THF (3 mL) solution containing EtOAc (0.37 mL, 3.77
mmol) and LHMDS (1.0 M in THF, 5.65 mL, 5.65 mmol). The
reaction was warmed from -78 to -20 °C in a 1 h period,
quenched by addition of saturated NH4Claq, and then extracted
with EtOAc (100 mL × 3). The organic phase was washed with
brine, dried over Na2SO4, and concentrated under reduced
pressure. The residue was purified by silica gel chromatogra-
phy with hexanes/EtOAc (3:1) to give 373 mg of product 16 as
a colorless syrup in 95% yield: Rf 0.35 (EtOAc/hexanes, 1:3;
anisaldehyde); [R]31D +7.6° (c 1.3, CHCl3); 1H NMR (400 MHz,
CDCl3) δ 1.24 (t, 3H, J ) 7.2 Hz, OCH2CH3), 2.33 (d, 1H, J )
15.7 Hz, H1′a), 3.00 (d, 1H, J ) 15.7 Hz, H1′b), 3.67 (dd, 1H, J
) 11.2, 2.0 Hz, H6a), 3.75 (d, 1H, J ) 11.2, 4.0 Hz, H6b), 3.78
(d, 1H, J ) 2.5 Hz, H2), 3.90-4.02 (m, 2H, H4, H5), 4.09-4.20
(m, 3H, OCH2CH3, H3), 4.50 (d, 1H, J ) 12.0 Hz, PhCH2), 4.57
(d, 1H, J ) 10.9 Hz, PhCH2), 4.64 (d, 1H, J ) 12.1 Hz, PhCH2),
4.65 (d, 1H, J ) 11.5 Hz, PhCH2), 4.77 (m, 2H, PhCH2), 4.86
(d, 1H, J ) 10.9 Hz, PhCH2), 5.01 (d, 1H, J ) 11.5 Hz, PhCH2),
7.21-7.38 (m, 20H, Ph); 13C NMR (100 MHz, CDCl3) δ 14.05,
40.45, 60.98, 69.27, 72.90, 73.05, 73.26, 74.44, 74.92, 75.00,
77.62, 81.37, 97.41, 127.31, 127.51, 127.55, 127.56, 127.60,
127.79, 127.92, 128.11, 128.23, 128.29, 128.32, 128.38, 138.40,
138.57, 138.63, 138.74, 172.61; ESI-MS m/z (rel intens) 609.0
(M - H2O + H+, 100); HRMS (FAB) m/z calcd for C38H41O7
(M - H2O + H+) 609.2852, found 609.2854.
1-Allyl-2,3,4,6-tetr a -O-ben zyl-D-m a n n op yr a n ose (17).
To a stirred solution of mannolactone 3 (108 mg, 0.2 mmol) in
anhydrous THF (5 mL) at -78 °C was added allylmagnesium
chloride (2.0 M in THF, 0.12 mL, 2.4 mmol). The resulting
mixture was warmed from -78 to -20 °C in a 4-h period,
quenched by addition of NH4Claq, and extracted with EtOAc
(50 mL × 3). The organic phase was washed with brine, dried
over anhydrous Na2SO4, and concentrated under reduced
pressure. The residue was purified by silica gel chromatogra-
phy with hexanes/EtOAc (3:1) to give 99 mg of product 17 as
a colorless syrup in 85% yield: Rf 0.6 (EtOAc/hexanes, 1:2;
20: Rf 0.5 (EtOAc/hexanes, 1:3); [R]25 +50.1° (c 2.8, CHCl3);
D
1H NMR (400 MHz, CDCl3) δ 1.27 (t, 3H, J ) 7.1 Hz,
OCH2CH3), 3.82 (dd, 1H, J ) 11.8, 3.5 Hz, H6a), 3.83-3.89 (m,
3H, H2, H3, H4), 3.89 (dd, 1H, J ) 11.8, 2.0 Hz, H6b), 4.16 (q,
2H, J ) 7.1 Hz, OCH2CH3), 4.32 (ddd, 1H, J ) 9.6, 3.5, 2.0
Hz, H5), 4.51 (d, 1H, J ) 11.8 Hz, PhCH2), 4.53 (d, 1H, J )
11.2 Hz, PhCH2), 4.54 (d, 1H, J ) 12.1 Hz, PhCH2), 4.61 (d,
1H, J ) 11.8 Hz, PhCH2), 4.63 (d, 1H, J ) 12.3 Hz, PhCH2),
4.66 (d, 1H, J ) 11.2 Hz, PhCH2), 4.72 (d, 1H, J ) 12.1 Hz,
PhCH2), 4.75 (d, 1H, J ) 12.3 Hz, PhCH2), 5.20 (s, 1H, H1′),
7.16-7.8 (m, 2H, Ph), 7.23-7.38 (m, 18H, Ph); 13C NMR (100
MHz, CDCl3) δ 14.32, 59.64, 68.28, 71.43, 72.82, 73.50, 73.64,
77.25, 77.34, 77.75, 82.76, 99.88, 127.48, 127.72, 127.77,
127.85, 127.88 (3×), 127.96, 128.28, 128.30, 128.41, 128.48,
137.08, 137.56, 137.81, 138.26, 161.82, 164.73; ESI-MS m/z (rel
intens) 609 (M + H+, 100), 563 (25), 531 (7), 415 (5); FAB-MS
m/z (rel intens) 609 (M + H+, 10), 391 (4), 307 (33), 289 (18),
154 (100); HRMS (FAB) m/z calcd for C38H41O7 (M + H+)
1
PMA); H NMR (400 MHz, CDCl3) δ 2.22 (dd, 1H, J ) 13.7,
9.5 Hz, H1′a), 2.50 (s, 1H, OH), 2.78 (dd, 1H, J ) 13.7, 5.3 H1′b),
3.68∼3.74 (m, 2H, H6a, H6b), 3.75 (d, 1H, J ) 2.7 Hz, H2), 3.91-
3.95 (m, 1H, H5), 3.95 (t, 1H, J ) 9.1 Hz, H4), 4.14 (dd, 1H, J
) 9.1, 2.7 Hz, H3), 4.54 (d, 1H, J ) 12.2 Hz, PhCH2), 4.55 (d,
1H, J ) 10.8 Hz, PhCH2), 4.64 (d, 1H, J ) 12.2 Hz, PhCH2),
4.66 (d, 1H, J ) 11.5 Hz, PhCH2), 4.75 (d, 1H, J ) 11.8 Hz,
PhCH2), 4.78 (d, 1H, J ) 11.8 Hz, PhCH2), 4.87 (d, 1H, J )
10.8 Hz, PhCH2), 5.03 (d, 1H, J ) 11.5 Hz, PhCH2), 5.14 (d,
1H, J ) 17.1 Hz, H3′a), 5.23 (dd, 1H, J ) 10.2, 1.8 Hz, H3′b),
5.77-5.89 (m, 1H, H2_), 7.17-7.39 (m, 20H, Ph); 13C NMR (100
MHz, CDCl3) δ 42.60, 69.64, 72.66, 72.96, 73.34, 74.58, 75.02,
75.22, 77.55, 81.82, 97.85, 120.92, 127.38, 127.47, 127.50,
127.53, 127.76, 127.95, 128.01, 128.21, 128.25 (2×), 128.28,
128.39, 132.26, 138.49, 138.63 (3×); HRMS (FAB) m/z calcd
for C37H39O5 (M - H2O + H+) 563.2797, found 663.2787.
2,3,4,6-Tetr a -O-ben zyl-1-d eoxy-1-m eth ylid en e-D-glu co-
p yr a n ose (18).34 The purification was carried out by silica
gel chromatography with hexanes/EtOAc (10:1) to give com-
pound 18 as a colorless syrup in 45% yield (of the dehydra-
tion): 1H NMR (400 MHz, CDCl3) δ 3.69-3.78 (m, 5H, H3, H4,
H5, H6a, H6b), 3.96 (d, 1H, J ) 7.2 Hz, H2), 4.51 (d, 1H, J )
11.1 Hz, PhCH2), 4.53 (d, 1H, J ) 12.1 Hz, PhCH2), 4.62 (s,
1H, H1′a), 4.63 (d, 1H, J ) 12.1 Hz, PhCH2), 4.64 (d, 1H, J )
11.6 Hz, PhCH2), 4.71 (d, 1H, J ) 11.2 Hz, PhCH2), 4.76 (s,
1H, H1′b), 4.77 (d, 1H, J ) 11.6 Hz, PhCH2) 4.77 (d, 1H, J )
11.2 Hz, PhCH2), 4.86 (d, 1H, J ) 11.1 Hz, PhCH2), 7.12-
609.2852, found 609.2851. Data for the other isomer: [R]25
D
1
+24.4° (c 0.9, CHCl3); H NMR (400 MHz, CDCl3) δ 1.26 (t,
3H, J ) 7.1 Hz, OCH2CH3), 3.68 (dd, 1H, J ) 11.2, 4.7 Hz,
H
6a), 3.70 (dd, 1H, J ) 10.2, 4.0 Hz, H4), 3.77 (dd, 1H, J )
11.2, 1.9 Hz, H6b), 3.94 (dd, 1H, J ) 4.0, 1.8 Hz, H3), 4.14 (q,
2H, J ) 7.1 Hz, OCH2CH3), 4.40 (d, 1H, J ) 11.5 Hz, PhCH2),
4.42 (d, 1H, J ) 11.4 Hz, PhCH2), 4.53 (d, 1H, J ) 11.4 Hz,
PhCH2), 4.54 (d, 1H, J ) 12.2 Hz, PhCH2), 4.60 (d, 1H, J )
12.2 Hz, PhCH2), 4.61 (d, 1H, J ) 11.7 Hz, PhCH2), 4.62 (ddd,
1H, J ) 10.2, 4.7, 1.9 Hz, H5), 4.67 (d, 1H, J ) 11.5 Hz, PhCH2),
4.69 (d, 1H, J ) 11.7 Hz, PhCH2), 5.67 (s, 1H, H1′), 5.95 (d,
1H, J ) 1.8 Hz, H2), 7.14-7.16 (m, 2H, Ph), 7.25-7.36 (m,
18H, Ph); 13C NMR (100 MHz, CDCl3) δ 14.32, 59.71, 68.75,
69.42, 70.79, 71.05, 72.34, 73.34, 74.88, 76.68, 80.55, 100.91,
127.56, 127.66, 127.68, 127.81, 127.87, 127.91, 128.27, 128.29

3780 J . Org. Chem., Vol. 67, No. 11, 2002
Yang et al.
(2×), 128.31 (2×), 128.40, 137.33, 137.76, 137.98, 138.08,
165.56, 167.54; ESI-MS m/z (rel intens) 639 (72), 609 (M +
H+, 100), 531 (15), 415 (20); FAB-MS m/z (rel intens) 639 (7),
609 (M + H+, 10), 471 (15), 289 (20), 147 (100); HRMS (FAB)
m/z calcd for C38H41O7 (M + H+) 609.2852, found 609.2846.
(1(1′)Z)-1-Allylid en e-2,3,4,6-tetr a -O-ben zyl-1-d eoxy-r-
D-glu cop yr a n ose (21). To compound 7 (145 mg, 0.25 mmol)
in anhydrous THF (10 mL) were added pyridine (0.4 mL, 5.0
mmol) and trifluoroacetic anhydride (0.3 mL, 2.0 mmol) at 0
°C, and the mixture was stirred for 1 h. The reaction mixture
was quenched with saturated NaHCO3 and extracted with
EtOAc (100 mL × 3). The organic layer was washed with brine,
dried over anhydrous Na2SO4, and concentrated under reduced
pressure. The residue was purified by silica gel chromatogra-
phy with hexanes/EtOAc (10:1) to give 119 mg of product 21
128.65, 136.54, 137.38, 137.58, 137.93, 161.97; ESI-MS m/z (rel
intens) 645 (M + H+, 57), 549 (30), 415 (27), 341 (18); FAB-
MS m/z (rel intens) 645 (M + H+, 5), 627 (1), 537 (3), 307 (20),
154 (100); HRMS (FAB) m/z calcd for C37H41O8S (M + H+)
645.2522, found 645.2523.
(1(1′)Z)-2,3,4,6-Tetr a-O-ben zyl-1-deoxy-1-(ph en yl)m eth -
ylid en e-D-glu cop yr a n ose (24).15a The purification was car-
ried out by silica gel chromatography with hexanes/EtOAc (3:
1) to give compound 24 as a colorless syrup in 87% yield (of
the dehydration): Rf 0.6 (EtOAc/hexane, 1:3); [R]25 +59.1° (c
D
1
1.86, CHCl3); H NMR (400 MHz, CDCl3) δ 3.79 (dd, 1H, J )
10.8, 4.3 Hz, H6a), 3.82-3.86 (m, 2H, H3, H4), 3.88 (dd, 1H, J
) 10.8, 1.9 Hz, H6b), 4.03 (d, 1H, J ) 4.7 Hz, H2), 4.11 (ddd,
1H, J ) 9.5, 4.3, 1.9 Hz, H5), 4.56 (d, 1H, J ) 11.3 Hz, PhCH2),
4.59 (d, 1H, J ) 12.3 Hz, PhCH2), 4.62 (d, 1H, J ) 11.8 Hz,
PhCH2), 4.66 (d, 1H, J ) 12.3 Hz, PhCH2), 4.67 (d, 1H, J )
11.0 Hz, PhCH2), 4.76 (d, 1H, J ) 11.0 Hz, PhCH2), 4.78 (d,
1H, J ) 11.8 Hz, PhCH2), 4.79 (d, 1H, J ) 11.3 Hz, PhCH2),
5.73 (s, 1H, H1′), 7.20-7.39 (m, 23H, Ph), 7.68 (dd, 2H, J )
7.3, 1.3 Hz, Ph); 13C NMR (100 MHz, CDCl3) δ 69.09, 71.68,
73.41, 73.45, 73.99, 76.83, 77.80, 79.17, 84.48, 109.45, 126.33,
127.58, 127.68 (2×), 127.71, 127.79, 127.84, 127.87, 127.97,
128.14, 128.32, 128.35, 128.39, 128.47, 128.69, 135.09, 137.82,
138.08, 138.12, 138.14, 148.97; HRMS (FAB) m/z calcd for
as a colorless syrup in 85% yield: Rf 0.47 (EtOAc/hexanes, 1:3;
1
PMA); [R]21 +61° (c 2.0, CHCl3); H NMR (400 MHz, CDCl3)
D
δ 3.73 (dd, 1H, J ) 9.7, 6.3 Hz, H4), 3.75 (t, 1H, J ) 6.3 Hz,
H3), 3.78 (dd, 1H, J ) 11.3, 3.6 Hz, H6a), 3.81 (dd, 1H, J )
11.3, 1.9 Hz, H6b), 3.86 (ddd, 1H, J ) 9.7, 3.6, 1.9 Hz, H5), 3.96
(d, 1H, J ) 6.3 Hz, H2), 4.53 (d, 1H, J ) 11.2 Hz, PhCH2),
4.56 (d, 1H, J ) 12.2 Hz, PhCH2), 4.59 (d, 1H, J ) 11.8 Hz,
PhCH2), 4.65 (d, 1H, J ) 12.2 Hz, PhCH2), 4.67 (d, 1H, J )
11.3 Hz, PhCH2), 4.74 (d, 1H, J ) 11.8 Hz, PhCH2), 4.76 (d,
1H, J ) 11.2 Hz, PhCH2), 4.80 (d, 1H, J ) 11.3 Hz, PhCH2),
4.99 (dd, 1H, J ) 10.6, 1.8 Hz, H3′a), 5.16 (dd, 1H, J ) 17.3,
1.8 Hz, H3′b), 5.60 (d, 1H, J ) 10.6 Hz, H1′), 6.76 (dt, 1H, J )
17.3, 10.6 Hz, H2′), 7.15-7.37 (m, 20H, Ph); 13C NMR (100
MHz, CDCl3) δ 68.69, 72.35, 73.47, 74.01, 74.27, 77.54, 77.95,
78.77, 84.61, 111.15, 115.18, 127.60, 127.67, 127.69, 127.74
(2×), 127.76, 127.83, 127.87, 128.31, 128.35, 128.37, 128.43,
129.90, 137.79, 138.05, 138.07, 138.17, 149.59; ESI-MS m/z (rel
intens) 563 (M + H+, 60), 555 (100), 455 (51), 359 (10); HRMS
(FAB) m/z calcd for C37H39O5 (M + H+) 563.2797, found
563.2772.
C
41H40O5 (M+) 612.2876, found 612.2889.
2,3,4,6-Tetr a-O-ben zyl-1-deoxy-1-m eth yliden e-D-galacto-
p yr a n ose (25). To a solution of 11 (200 mg, 0.36 mmol) in
anhydrous THF (10 mL) at 0 °C were added pyridine (0.87
mL, 10.8 mmol) and trifluoroacetic anhydride (0.26 mL, 1.8
mmol). The reaction was stirred for 2 h at 0 °C, stopped by
addition of NaHCO3, and extracted with EtOAc (100 mL). The
organic layer was washed with brine, dried over Na2SO4, and
concentrated. The purification by silica gel chromatography
with hexanes/EtOAc (10:1) afforded 103 mg of product 25 as
a colorless syrup in 53% yield: Rf 0.63 (EtOAc/hexanes, 1:3;
PMA); 1H NMR (400 MHz, CDCl3) δ 3.62 (dd, 1H, J ) 9.6, 6.5
Hz, H6a), 3.66 (d, 1H, J ) 9.0, 2.7 Hz, H3), 3.70 (dd, 1H, J )
9.6, 6.0 Hz, H6b), 3.82 (ddd, 1H, J ) 6.5, 6.0, 2.0 Hz, H5), 4.05
(t, 1H, J ) 2.5 Hz, H4), 4.36 (d, 1H, J ) 9.0 Hz, H2), 4.45 (d,
1H, J ) 11.9 Hz, PhCH2), 4.52 (d, 1H, J ) 11.9 Hz, PhCH2),
4.60 (d, 1H, J ) 11.5 Hz, PhCH2), 4.70 (d, 1H, J ) 1.4 Hz,
(1(1′)Z)-2,3,4,6-Tet r a -O-b en zyl-1-d eoxy-1-(d im et h oxy-
p h osp h or yl)m eth ylid en e-D-glu cop yr a n ose (22).29a The pu-
rification was carried out by silica gel chromatography with
hexanes/EtOAc (1:1) to give compound 22 as a colorless syrup
in 81% yield (of the dehydration): Rf 0.17 (EtOAc/hexanes, 1:1;
PMA); [R]25D +52.5° (c 8.3, CHCl3); 1H NMR (400 MHz, CDCl3)
δ 3.67 (d, 3H, J P-OCH3 ) 5.0 Hz, OCH3), 3.70 (d, 3H, J P-OCH3
)
H1′a), 4.71 (d, 1H, J ) 11.8 Hz, PhCH2), 4.72 (d, 1H, J ) 11.8
5.0 Hz, OCH3), 3.75-3.89 (m, 4H, H3, H4, H6a, H6b), 3.95 (d,
1H, J ) 5.8 Hz, H2), 4.11 (ddd, 1H, J ) 9.8, 3.1, 2.0 Hz, H5),
4.52-4.74 (m, 8H, PhCH2), 5.06 (d, 1H, J P-H1 ) 12.0 Hz, H1_),
7.17-7.19 (m, 2H, Ph), 7.24-7.34 (m, 18H, Ph); 13C NMR (100
Hz, PhCH2), 4.73 (d, 1H, J ) 11.9 Hz, PhCH2), 4.74 (d, 1H, J
) 1.4 Hz, H1′b), 4.77 (d, 1H, J ) 11.9 Hz, PhCH2) 4.92 (d, 1H,
J ) 11.5 Hz, PhCH2), 7.25-7.37 (m, 20H, Ph); 13C NMR (100
MHz, CDCl3) δ 68.62, 72.79, 73.53, 73.73, 74.38, 74.56, 77.35,
78.38, 82.07, 95.11, 127.47, 127.58, 127.60, 127.66, 127.77,
127.91, 127.93, 128.01, 128.21, 128.28, 128.37, 128.43, 138.00,
138.21, 138.52, 138.88, 157.39; ESI-MS m/z (rel intens) 554.8
(M + H2O + H+, 18), 429 (M - PhCH2O + H+, 100), 391.0
(35); HRMS (FAB) m/z calcd for C35H37O5 (M + H+) 537.2639,
found 537.2635.
MHz, CDCl3) δ 52.18 (d, J P-OMe ) 21.7 Hz), 52.52 (d, J P-OMe
)
21.7 Hz), 68.19, 72.55, 73.47, 73.73, 74.02, 76.96, 78.22, 78.40
(d, J P-C ) 54.0 Hz), 83.26, 94.02 (d, J P-C ) 630 Hz), 127.67,
127.76, 127.80, 127.83, 127.90, 127.92, 127.94, 128.06, 128.37
(2×), 128.46, 128.56, 137.06, 137.72, 137.84, 137.96, 165.37
(d, J P-C ) 30 Hz); ESI-MS m/z (rel intens) 1289 (2M + H+,
18), 645 (M + H+, 100), 537 (3), 429 (3); FAB-MS m/z (rel
intens) 645 (M + H+, 55), 537 (5), 307 (25), 154 (100); HRMS
(FAB) m/z calcd for C37H42O8P (M + H+) 645.2618, found
645.2609.
(1(1′)Z)-2,3,4,6-Tetr a -O-ben zyl-1-d eoxy-1-p r op ylid en e-
D-ga la ctop yr a n ose (26). To compound 12 (69 mg, 0.12 mmol)
in anhydrous THF (5 mL) were added pyridine (0.29 mL, 3.6
mmol) and trifluoroacetic anhydride (0.85 mL, 0.6 mmol) at 0
°C. The reaction was stirred for 3 h at 0 °C, stopped by addition
of saturated NaHCO3, and extracted with EtOAc (50 mL). The
organic layer was dried over Na2SO4 and concentrated. The
purification by silica gel chromatography with hexanes/EtOAc
(10:1) afforded product 26 (47 mg) in 70% yield: Rf 0.84
(1(1′)Z)-2,3,4,6-Tetr a-O-ben zyl-1-deoxy-1-(eth oxysu lfon -
oyl)m eth ylid en e-D-glu cop yr a n ose (23).29b The purification
was carried out by silica gel chromatography with hexanes/
EtOAc (1:1) to give compound 23 as a colorless syrup in 83%
yield (of the dehydration): Rf 0.78 (EtOAc/hexanes, 1:1; PMA);
[R]25 +76.8° (c 1.64, CHCl3); 1H NMR (400 MHz, CDCl3) δ
(EtOAc/hexanes, 1:2; PMA); [R]25 +27.6° (c 4.7, CHCl3); 1H
D
D
1.23 (t, 3H, J ) 7.0 Hz, OCH2CH3), 3.78 (dd, 1H, J ) 11.5, 3.2
Hz, H6a), 3.83 (dd, 1H, J ) 5.9, 5.0 Hz, H3), 3.87 (dd, 1H, J )
11.5, 2.1 Hz, H6b), 3.90 (dd, 1H, J ) 9.5, 5.9 Hz, H4), 3.91 (d,
1H, J ) 5.0 Hz, H2), 4.14 (q, 2H, J ) 7.0 Hz, OCH2CH3), 4.29
(ddd, 1H, J ) 9.5, 3.2, 2.1 Hz, H5), 4.55 (d, 1H, J ) 11.0 Hz,
PhCH2), 4.56 (d, 1H, J ) 11.2 Hz, PhCH2), 4.57 (d, 1H, J )
11.8 Hz, PhCH2), 4.58 (d, 1H, J ) 12.0 Hz, PhCH2), 4.60 (d,
1H, J ) 11.0 Hz, PhCH2), 4.63 (d, 1H, J ) 12.0 Hz, PhCH2),
4.69 (d, 1H, J ) 11.2 Hz, PhCH2), 4.70 (d, 1H, J ) 11.8 Hz,
PhCH2), 5.65 (s, 1H, H1′), 7.20-7.36 (m, 20H, Ph); 13C NMR
(100 MHz, CDCl3) δ 14.82, 66.71, 67.86, 72.38, 73.33, 73.51,
73.73, 76.68, 76.87, 78.50, 82.31, 104.22, 127.64, 127.72, 127.88
(2×), 127.90, 127.99, 128.03, 128.28, 128.36, 128.40, 128.49,
NMR (400 MHz, CDCl3) δ 0.95 (t, 3H, J ) 7.5 Hz, CH3), 2.07-
2.21 (m, 2H, H2′), 3.66 (dd, 1H, J ) 8.1, 2.7 Hz, H3), 3.67 (dd,
1H, J ) 9.8, 6.0 Hz, H6a), 3.75 (dd, 1H, J ) 9.8, 6.4 Hz, H6b),
3.86 (ddd, 1H, J ) 6.4, 6.0, 2.5 Hz, H5), 4.07 (t, 1H, J ) 2.7
Hz, H4), 4.24 (dd, 1H, J ) 8.1, 1.0 Hz, H2), 4.45 (d, 1H, J )
11.8 Hz, PhCH2), 4.52 (d, 1H, J ) 11.8 Hz, PhCH2), 4.60 (d,
1H, J ) 11.6 Hz, PhCH2), 4.64 (d, 1H, J ) 11.5 Hz, PhCH2),
4.70 (d, 1H, J ) 11.9 Hz, PhCH2), 4.71 (d, 1H, J ) 11.5 Hz,
PhCH2), 4.75 (d, 1H, J ) 11.9 Hz, PhCH2), 4.88 (d, 1H, J )
11.6 Hz, PhCH2), 5.07 (dt, 1H, J ) 7.4, 1.0 Hz, H1_), 7.24-
7.36 (m, 20H, Ph); 13C NMR (100 MHz, CDCl3) δ 14.46, 17.85,
68.80, 72.94, 73.47, 73.91, 74.52, 74.57, 77.10, 78.12, 81.59,
114.38, 127.43, 127.47, 127.49, 127.56, 127.58, 127.82, 127.89,

Synthesis and Reaction of exo-Glycals
J . Org. Chem., Vol. 67, No. 11, 2002 3781
127.95, 127.97, 128.25, 128.32, 128.37, 138.34, 138.54, 138.66,
138.66, 147.40; ESI-MS m/z (rel intens) 564.7 (M + H+, 20),
457.0 (100), 349.0 (21); HRMS (FAB) m/z calcd for C37H41O5
4.18 (t, 1H, J ) 9.4 Hz, H4), 4.40 (d, 1H, J ) 12.6 Hz, PhCH2),
4.52 (d, 1H, J ) 12.0 Hz, PhCH2), 4.56 (d, 1H, J ) 10.9 Hz,
PhCH2), 4.58 (d, 1H, J ) 12.4 Hz, PhCH2), 4.61 (d, 1H, J )
12.0 Hz, PhCH2), 4.70 (d, 1H, J ) 12.4 Hz, PhCH2), 4.73 (d,
1H, J ) 12.6 Hz, PhCH2), 4.77 (t, 1H, J ) 7.3 Hz, H1′), 4.95 (d,
1H, J ) 10.9 Hz, PhCH2), 7.18-7.40 (m, 20H, Ph); 13C NMR
(100 MHz, CDCl3) δ 14.41, 18.11, 68.91, 69.50, 71.15, 73.40,
74.09, 74.45, 75.16, 80.26, 82.25, 118.93, 127.42, 127.50,
127.56, 127.72, 127.74, 127.84, 127.94, 127.96, 128.20, 128.27,
128.30, 128.32, 138.31 (2×), 138.46, 138.58, 147.41; HRMS
(FAB) m/z calcd for C37H41O5 (M + H+) 565.2954, found
565.2960.
(M
+
H+) 565.2954, found 565.2963. Anal. Calcd for
C
37H40O5: C, 78.69; H, 7.14. Found C, 78.36; H, 7.35.
(1(1′)Z)-2,3,4,6-Tetr a-O-ben zyl-1-deoxy-1-(eth oxycar bon -
yl)m eth ylid en e-D-ga la ctop yr a n ose (27). The preparation
used 13 as the starting material as was described for the
synthesis of 20. Compound 13 (274 mg, 0.44 mmol) in
anhydrous THF (10 mL) was treated with pyridine (0.35 mL,
0.44 mmol) and trifluoroacetic anhydride (0.31 mL, 2.2 mmol)
at 0 °C. The reaction was stirred for 2 h and stopped by
addition of saturated NaHCO3. The organic layer was dried
over Na2SO4 and concentrated to give a residue which was
puried by silica gel chromatography with hexanes/EtOAc (9:
1) to give 27 (216 mg) in 81% yield: Rf 0.67 (EtOAc/hexanes,
(1(1′)Z)-2,3,4,6-Tet r a -O-b en zyl-1-d eoxy-1-(et h oxyca r -
bon yl)m eth ylid en e-D-m a n n op yr a n ose (30). The prepara-
tion used 16 as the starting material as was described for the
synthesis of 20. Compound 16 (266 mg, 0.43 mmol) in
anhydrous THF (20 mL) was treated with pyridine (1.5 mL,
18.5 mmol) and trifluoroacetic anhydride (0.6 mL, 4.3 mmol)
at 0 °C. The reaction was stirred for 2 h and stopped by
addition of saturated NaHCO3. After extraction with EtOAc
(100 mL), the organic layer was dried over Na2SO4 and
concentrated to give a dry residue. The purification by silica
gel chromatography with hexanes/EtOAc (5:1) generated 30
(232 mg) as a colorless syrup in 89% yield: Rf 0.3 (EtOAc/
1:5; PMA); [R]25 -20° (c 3.0, CHCl3); 1H NMR (400 MHz,
D
CDCl3) δ 1.23 (t, 3H, J ) 7.2 Hz, OCH2CH3), 3.73 (dd, 1H, J
) 9.3, 2.8 Hz, H3), 3.78 (dd, 1H, J ) 9.3, 6.0 Hz, H6a), 3.79
(dd, 1H, J ) 9.3, 7.2 Hz, H6b), 3.99 (ddd, 1H, J ) 7.2, 6.0, 1.0
Hz, H5), 4.12 (q, 2H, J ) 7.2 Hz, OCH2CH3), 4.13 (dd, 1H, J )
2.8, 1.0 Hz, H4), 4.44 (dd, 1H, J ) 9.3, 1.4 Hz, H2), 4.45 (d, 1H,
J ) 11.6 Hz, PhCH2), 4.54 (d, 1H, J ) 11.6 Hz, PhCH2), 4.61
(d, 1H, J ) 11.4 Hz, PhCH2), 4.71 (s, 2H, PhCH2), 4.73 (d, 1H,
J ) 11.2 Hz, PhCH2), 4.78 (d, 1H, J ) 11.2 Hz, PhCH2), 4.94
(d, 1H, J ) 11.4 Hz, PhCH2), 5.78 (d, 1H, J ) 1.4 Hz, H1′),
7.25-7.34 (m, 20H, Ph); 13C NMR (100 MHz, CDCl3) δ 14.30,
59.59, 67.93, 72.60, 73.59, 73.59, 74.39, 74.66, 76.46, 78.48,
81.77, 100.02, 127.53, 127.59, 127.74, 127.79, 127.82 (2×),
127.96, 127.98, 128.25, 128.42 (2×), 128.44, 137.63, 137.80,
137.99, 138.39, 164.91, 165.12; FAB-MS m/z (rel intens) 609.1
(M + H+, 100), 563 (10), 517 (8); HRMS (FAB) m/z calcd for
hexanes, 1:3; anisaldehyde); [R]24 +1.65° (c 3.61, CHCl3); 1H
D
NMR (400 MHz, CDCl3) δ 1.25 (t, 3H, J ) 7.2 Hz, OCH2CH3),
3.77 (dd, 1H, J ) 6.0, 2.5 Hz, H3), 3.78-3.84 (m, 2H, H6a, H6b),
3.98 (m, 1H, H5), 4.08∼4.13 (m, 2H, H2, H4), 4.14 (q, 2H, J )
7.2 Hz, OCH2CH3), 4.44 (d, 1H, J ) 12.2 Hz, PhCH2), 4.45 (d,
1H, J ) 11.1 Hz, PhCH2), 4.58 (d, 1H, J ) 12.2 Hz, PhCH2),
4.59 (d, 1H, J ) 11.9 Hz, PhCH2), 4.63 (d, 1H, J ) 11.1 Hz,
PhCH2), 4.64 (d, 1H, J ) 11.8 Hz, PhCH2), 4.67 (d, 1H, J )
11.8 Hz, PhCH2), 4.70 (d, 1H, J ) 11.9 Hz, PhCH2), 5.27 (s,
1H, H1_), 7.14-7.36 (m, 20H, Ph); 13C NMR (100 MHz, CDCl3
δ 14.32, 59.66, 69.05, 71.13, 72.13, 73.49, 73.53, 74.77, 77.22,
78.03, 79.47, 99.86, 127.49, 127.75, 127.78, 127.84 (2×), 127.88
(2×), 128.28, 128.36 (2×), 128.45 (2×), 137.25, 137.79, 137.90,
138.24, 162.64, 164.80; FAB-MS m/z (rel intens) 609.3 (M +
H+, 80), 563.3 (15), 519.3 (10), 501.3 (15), 391.3 (10); HRMS
(FAB) m/z calcd for C38H41O7 (M + H+) 609.2852, found
609.2858.
C
38H41O7 (M + H+) 609.2852, found 609.2852.
2,3,4,6-Tetr a-O-ben zyl-1-deoxy-1-m eth yliden e-D-m an n o-
p yr a n ose (28). To a solution of 11 (83 mg, 0.15 mmol) in
anhydrous THF (10 mL) at 0 °C were added pyridine (0.36
mL, 4.5 mmol) and trifluoroacetic anhydride (0.11 mL, 0.75
mmol). The reaction was stirred at 0 °C for 1 h and warmed
to room temperature, THF was removed, and the reaction was
diluted with EtOAc (100 mL) and extracted with saturated
NaHCO3. The organic layer was washed with brine, dried over
Na2SO4, and concentrated. The purification by silica gel
chromatography with hexanes/EtOAc (10:1) afforded 41 mg
of product 28 as a colorless syrup in 51% yield: Rf 0.60 (EtOAc/
(1(1′)Z)-1-Allylid en e-2,3,4,6-tetr a -O-ben zyl-1-d eoxy-d -
m a n n op yr a n ose (31). To a solution of 17 (70 mg, 0.12 mmol)
in anhydrous THF (5 mL) at 0 °C were added pyridine (0.24
mL, 3.0 mmol) and trifluoroacetic anhydride (0.1 mL, 0.5
mmol). The reaction was stirred for 1.5 h and quenched by
addition of saturated NaHCO3. After extraction with EtOAc
(50 mL × 3), the organic layer was dried over Na2SO4 and
concentrated to give a dry residue. The purification by silica
gel chromatography with hexanes/EtOAc (5:1) generated 31
1
hexanes, 1:3; PMA); H NMR (400 MHz, CDCl3) δ 3.62 (ddd,
1H, J ) 9.2, 4.4, 2.5 Hz, H5), 3.66 (dd, 1H, J ) 9.2, 3.2 Hz,
H3), 3.77 (dd, 1H, J ) 10.7, 2.5 Hz, H6a), 3.80 (dd, 1H, J )
10.7, 4.4 Hz, H6b), 4.07 (d, 1H, J ) 3.2 Hz, H2), 4.16 (t, 1H, J
) 9.2 Hz, H4), 4.37 (s, 1H, H1′a), 4.42 (d, 1H, J ) 12.5 Hz,
PhCH2), 4.53 (d, 1H, J ) 10.8 Hz, PhCH2), 4.54 (d, 1H, J )
11.9 Hz, PhCH2), 4.57 (d, 1H, J ) 12.2 Hz, PhCH2), 4.62 (d,
1H, J ) 11.9 Hz, PhCH2), 4.66 (d, 1H, J ) 12.2 Hz, PhCH2),
4.76 (d, 1H, J ) 12.5 Hz, PhCH2), 4.83 (s, 1H, H1′b), 4.92 (d,
1H, J ) 10.8 Hz, PhCH2), 7.16-7.40 (m, 20H, Ph); 13C NMR
(100 MHz, CDCl3) δ 69.35, 69.41, 71.40, 73.44, 73.63, 74.12,
75.07, 80.22, 81.50, 99.55, 127.53, 127.59, 127.64, 127.73 (2×),
127.80, 127.98, 128.15 (2×), 128.31, 128.33, 128.35, 138.03,
138.19, 138.28, 138.39, 154.87; ESI-MS m/z (rel intens) 554.8
(M + H2O + H+, 18), 429 (M - PhCH2O + H+, 100), 391.0
(35); HRMS (FAB) m/z calcd for C35H37O5 (M + H+) 537.2639,
found 537.2635.
(52 mg) in 76% yield as a colorless syrup: Rf 0.75 (EtOAc/
1
hexanes, 1:2; PMA); [R]25 +15° (c 2.1, CHCl3); H NMR (400
D
MHz, CDCl3) δ 3.64 (dt, 1H, J ) 9.2, 3.4 Hz, H5), 3.65 (dd, 1H,
J ) 9.2, 3.3 Hz, H3), 3.82 (dd, 1H, J ) 10.0, 3.4 Hz, H6a), 3.86
(dd, 1H, J ) 10.0, 3.4 Hz, H6b), 4.01 (d, 1H, J ) 3.3 Hz, H2),
4.22 (t, 1H, J ) 9.2 Hz, H4), 4.39 (d, 1H, J ) 12.5 Hz, PhCH2),
4.54 (d, 1H, J ) 11.7 Hz, PhCH2), 4.56 (d, 1H, J ) 10.9 Hz,
PhCH2), 4.57 (d, 1H, J ) 11.7 Hz, PhCH2), 4.62 (d, 1H, J )
12.0 Hz, PhCH2), 4.70 (d, 1H, J ) 12.0 Hz, PhCH2), 4.74 (d,
1H, J ) 12.5 Hz, PhCH2), 4.93 (d, 1H, J ) 10.9 Hz, PhCH2),
5.05 (dd, 1H, J ) 10.4, 1.8 Hz, H3′a), 5.19 (dd, 1H, J ) 17.3,
1.8 Hz, H3′b), 5.41 (d, 1H, J ) 10.7 Hz, H1′), 6.75 (dt, 1H, J )
17.3, 10.5 Hz, H2′), 7.19-7.41 (m, 20H, Ph); 13C NMR (125
MHz, CDCl3) δ 69.32, 71.41, 73.42, 74.11, 74.23, 74.39, 75.04,
80.31, 81.53, 116.20, 116.38, 127.50, 127.57, 127.59, 127.62,
127.73 (2×), 127.85, 127.91, 128.10, 128.30 (2×), 128.33,
129.93, 138.04, 138.14, 138.32, 138.42, 148.54; ESI-MS m/z (rel
intens) 563.2 (M + H+, 72), 555.2 (100), 415.2 (20), 359.2 (10);
FAB-MS m/z (rel intens) 563.2 (M + H+, 23), 455.2 (17), 391.2
(16); HRMS (FAB) m/z calcd for C37H39O5 (M + H+) 563.2720,
found 563.2733.
(1(1′)Z)-2,3,4,6-Tetr a -O-ben zyl-1-d eoxy-1-p r op ylid en e-
D-m a n n op yr a n ose (29). To a solution of 15 (60 mg, 0.1 mmol)
in anhydrous THF (5 mL) were added pyridine (0.25 mL, 3.1
mmol) and trifluoroacetic anhydride (0.73 mL, 0.5 mmol) at 0
°C. The reaction was stirred for 2 h at 0 °C. The reaction was
quenched by addition of saturated NaHCO3 solution and
extracted with EtOAc (50 mL × 3). The organic layer was dried
over Na2SO4 and concentrated. The purification by silica gel
chromatography with hexanes/EtOAc (10:1) gave 50 mg of
product 29 in 85% yield: Rf 0.38 (EtOAc/hexanes, 1:6.5;
anisaldehyde); [R]25D +5.7° (c 1.5, CHCl3); 1H NMR (400 MHz,
CDCl3) δ 0.98 (t, 3H, J ) 7.5, Hz, H3′), 2.10-2.25 (m, 2H, H2_),
3.53 (ddd, 1H, J ) 9.4, 3.8, 3.0 H5), 3.62 (dd, 1H, J ) 9.2, 3.3
Hz, H3), 3.78-3.87 (m, 2H, H6), 3.97 (d, 1H, J ) 3.3 Hz, H2),
(1(1′)Z)-1-Allylid en e-2,3,5,6-tetr a -O-ter t-bu tyld im eth yl-
sily-1-d eoxy-D-glu con ofu r a n ose (34). Compound 34 was
prepared as described in two steps (64% overall yield)20
starting from 32:26b colorless syrup; [R]23D -3.85° (c 2.1, CHCl3);

3782 J . Org. Chem., Vol. 67, No. 11, 2002
Yang et al.
Rf 0.6 (EtOAc/hexanes, 1:50); UV λmax ) 255 nm; IR (KBr, cm-1
)
for C44H47O780Se 767.2487 (M + H+) found 767.2484; calcd
for C44H47O778Se (M + H+) 765.2495, found 765.2504. Data
for compound 39: colorless syrup; Rf 0.3 (EtOAc/hexanes, 1:2;
1
2931, 2858, 1699, 1472, 1255, 1097, 835, 777; H NMR (400
MHz, CDCl3) δ 0.07 (s, 6H, SiCH3), 0.76 (s, 3H, SiCH3), 0.92
(s, 9H, SiCH3), 0.11 (s, 3H, SiCH3), 0.13 (s, 3H, SiCH3), 0.86
(s, 18H, C(CH3)3), 0.88 (s, 9H, C(CH3)3), 0.90 (s, 9H, C(CH3)3),
3.78 (dd, 1H, J ) 11.0, 5.4 Hz, H6a), 3.89 (dd, 1H, J ) 11.0,
2.4 Hz, H6b), 4.03 (dd, 1H, J ) 2.8, 1.7 Hz, H3), 4.08 (ddd, 1H,
J ) 7.2, 5.4, 2.4 Hz, H5), 4.22 (d, 1H, J ) 1.7 Hz, H2), 4.37 (dd,
1H, J ) 7.2, 2.8 Hz, H4), 4.85 (dd, 1H, J ) 10.5, 2.0 Hz, H3′a),
5.01 (dd. 1H, J ) 17.2, 2.0 Hz, H3′b), 5.09 (d, 1H, J ) 10.5 Hz,
H1′), 6.59 (dt, 1H, J ) 17.2, 10.5 Hz, H2′); 13C NMR (100 MHz,
CDCl3) δ -5.38, -5.33, -4.56, -4.48, -4.26, -4.22, -4.03,
-3.55, 17.90, 18.04, 18.30, 18.44, 25.62, 25.83, 25.96, 25.99,
65.06, 71.62, 76.47, 77.62, 84.20, 102.15, 112.09, 131.20,
157.28; ESI-MS m/z (rel intens) 659.6 (M + H+, 65), 529.5 (25),
397.4 (27), 661.5 (100); HRMS (FAB) m/z calcd for C33H71O5Si4
(M + H+) 659.4378, found 659.4359.
anisaldehyde); [R]25 +28.9° (c 9.0, CHCl3); IR (cm-1) 1656.5,
D
1716.9, 3490.3 (-OH); 1H NMR (400 MHz, CDCl3) δ 1.28 (t, J
) 7.1 Hz, 3H, OCH2CH3), 2.56 (d, J ) 5.4 Hz, 1H, OH), 3.57
(dd, J ) 9.6, 5.3 Hz, 1H, H8a), 3.62 (dd, J ) 9.6, 3.4 Hz, 1H,
H
8b), 3.81 (dd, J ) 7.7, 2.8 Hz, 1H, H6), 3.88 (dd, J ) 6.9, 2.9
Hz, 1H, H5), 3.98 (m, 1H, H7), 4.16-4.22 (m, 3H, OCH2CH3,
PhCH2), 4.26 (t, J ) 6.8 Hz, 1H, H4), 4.46-4.59 (m, 7H,
PhCH2), 6.13 (d, J ) 15.6 Hz, 1H, H2), 7.05 (dd, J ) 15.6, 6.6
Hz, 1H, H3), 7.15-7.32 (m, 20H, Ph); 13C NMR (100 MHz,
CDCl3) δ 14.24, 60.47, 70.01, 71.08, 71.14, 73.37, 73.84, 74.57,
78.41, 78.53, 80.99, 124.03, 127.60, 127.70, 127.74, 127.82,
127.84, 127.87 (2×), 128.29 (2×), 128.41 (2×), 128.46, 137.73,
137.84, 137.89, 138.24, 146.04, 165.98; FAB-MS m/z (rel intens)
611.1 (M + H+, 100); HRMS (FAB) m/z calcd for C38H43O7
611.3008 (M + H+), found 611.3005.
(1(1′)Z)-2,3,5,6-Tetr a -O-ter t-bu tyld im eth ylsily-1-d eoxy-
1-(ca r bon yl)m eth ylid en e-D-glu con ofu r a n ose (35). Com-
pound 35 was prepared as described in three steps (61% overall
yield)20 starting from 32:26b colorless syrup; Rf 0.2 (EtOAc/
hexanes, 1:50); [R]25D +14.0° (c 1.0, CHCl3); UV λmax ) 260 nm;
1H NMR (400 MHz, CDCl3) δ 0.06 (s, 6H, SiCH3), 0.09 (s, 3H,
SiCH3), 0.10 (s, 3H, SiCH3), 0.11 (s, 3H, SiCH3), 0.13 (s, 3H,
SiCH3), 0.14 (s, 3H, SiCH3), 0.15 (s, 3H, SiCH3), 0.86 (s, 9H,
C(CH3)3), 0.87 (s, 9H, C(CH3)3), 0.88 (s, 9H, C(CH3)3), 0.90 (s,
9H, C(CH3)3), 3.80 (dd, 1H, J ) 11.1, 4.6 Hz, H6a), 3.91 (dd,
1H, J ) 11.1, 3.0 Hz, H6b), 4.13 (dd, 1H, J ) 3.1, 2.1 Hz, H3),
4.13 (ddd, 1H, J ) 7.0, 4.6, 3.0 Hz, H5), 4.42 (d, 1H, J ) 2.1
Hz, H2), 4.65 (dd, 1H, J ) 7.0, 3.1 Hz, H4), 5.18 (d, 1H, J ) 8.4
Hz, H1′), 9.96 (d, 1H, J ) 8.4 Hz, CHO); 13C NMR (100 MHz,
CDCl3) δ -5.49, -5.32, -4.59, -4.55, -4.41, -4.19, -4.10,
-3.66, 17.81, 17.94, 18.22, 18.34, 25.36, 25.48, 25.86, 26.00,
64.39, 77.14, 75.33, 78.53, 86.69, 103.43, 175.62, 189.67; FAB-
MS m/z (rel intens) 661.3 (M + H+, 100), 529.3 (12), 387.3 (8);
HRMS (FAB) m/z calcd for C32H69O6Si4 (M + H+) 661.4267,
found 661.4269.
2,3,4,6-Te t r a -O-b e n zyl-1-d e oxy-1-(e t h oxyca r b on yl)-
m et h ylid en e-1′(R)-(p h en yl)selen yl-â-D-m a n n op yr a n ose
(40). Compound 39 (128.4 mg, 0.21 mmol) in anhydrous
CH2Cl2 (10 mL) was treated with PhSeCl (48.4 mg, 0.25 mmol)
at room temperature. After 12 h, the reaction was mixed with
CSA (48.9 mg, 0.21 mmol) and stirred for 6 days. The reaction
mixture was quenched with saturated NaHCO3, extracted with
EtOAc (100 mL × 3), washed with brine, and dried over
Na2SO4. The filtrate was concentrated and purified by silica
gel chromatography with hexanes/EtOAc (6:1, 4:1) to give 108
mg of product 40 (71%) as a colorless syrup: Rf 0.30 (EtOAc/
hexanes, 1:4; anisaldehyde); 1H NMR (400 MHz, CDCl3) δ 1.11
(t, 3H, J ) 7.1 Hz, OCH2CH3), 3.42 (ddd, 1H, J ) 9.7, 2.8, 2.8
Hz, H5), 3.62 (dd, 1H J ) 9.5, 2.7 Hz, H3), 3.64-3.68 (m, 4H,
H1′, H2, H6a, H6b), 3.97 (t, 1H, J ) 9.3 Hz, H4), 4.00∼4.08 (m,
2H, OCH2CH3), 4.38 (d, 1H, J ) 10.9 Hz, PhCH2), 4.16 (d, 1H
J ) 2.4 Hz, H1), 4.45 (d, 1H, J ) 11.9 Hz, PhCH2), 4.58 (d,
2H, J ) 11.8 Hz, PhCH2), 4.77 (d, 1H, J ) 11.8 Hz, PhCH2),
4.81 (d, 1H, J ) 11.8 Hz, PhCH2), 4.85 (d, 1H, J ) 10.8 Hz,
PhCH2), 5.07 (d, 1H, J ) 11.0 Hz, PhCH2), 7.20-7.37 (m, 23H,
Ph), 7.49-7.52 (m, 2H, Ph); 13C NMR (100 MHz, CDCl3) δ
13.94, 43.60, 60.95, 69.21, 72.68, 73.29, 73.89, 74.44, 75.06,
75.13, 78.08, 80.42, 85.25, 127.28, 127.58, 127.66, 127.70,
127.73, 127.79, 127.99, 128.13, 128.16, 128.28, 128.30, 128.47,
128.54, 129.17, 134.89, 135.00, 138.28, 138.39, 138.62, 138.83,
171.47; FAB-MS m/z (rel intens) 767.2 (M + H+, 100),
765.2(60), 675.1(5), 673.1(3), 569.1(3), 567.1(2); HRMS (FAB)
m/z calcd for C44H47O780Se 767.2487 (M + H+), found 767.2502;
calcd for C44H47O778Se 765.2494 (M + H+), found 765. 2491.
2,3,4,6-Te t r a -O-b e n zyl-1-d e oxy-1-(e t h oxyca r b on yl)-
m et h ylid en e-1′(S)-(p h en yl)selen yl-r-D-m a n n op yr a n ose
(38) a n d (Z)-4,5,6,8-Tetr a -O-ben zyl-7-h yd r oxy-D-m a n n o-
oct-2-en oic Acid Eth yl Ester (39). To a THF solution
(anhydrous 20 mL) of compound 37 (497 mg, 0.79 mmol) were
added at -78 °C LHMDS (1.0 M in THF, 1.57 mL, 1.57 mmol)
dropwise in a 10 min period and PhSeCl (526 mg, 2.75 mmol)
in THF. The color of the solution changed from orange to
yellow. The reaction was then warmed to -60 °C. H2O workup
and diluting with EtOAc(100 mL) gave 38 (150 mg, 27%) and
39 (518 mg, 56%). Data for compound 38: colorless syrup; Rf
0.3 (EtOAc/hexanes, 1:4; anisaldehyde); [R]25 +7.60° (c 3.3,
Ack n ow led gm en t. We are indebted to Prof. J im-
Min Fang at the National Taiwan University for his
critical reading of this manuscript and Dr. Chuan-Fa
Chang for all the graphic assistance. We acknowledge
the financial support from the National Science Council
(Grant NSC-90-2113-M-001-028), National Health Re-
search Institute (Grant NSC-90-2323-B-001-004), and
Academia Sinica.
D
CHCl3); 1H NMR (400 MHz, CDCl3) δ 1.19 (t, J ) 6.9 Hz, 3H,
OCH2CH3), 3.31 (dd, J ) 9.1, 3.0 Hz, 1H, H3), 3.64 (dd, J )
10.3, 1.8 Hz, 1H, H6a), 3.70-3.78 (m, 2H, H5, H6b), 3.84-3.91
(m, 3H, H1′, PhCH2), 3.95 (t, 1H, J ) 9.1 Hz, H4), 4.13 (q, J )
7.0 Hz, 2H, OCH2CH3), 4.19 (t, 1H, J ) 2.5 Hz, H2), 4.46 (d,
1H, J ) 10.6 Hz, PhCH2), 4.47 (d, 1H, J ) 12.1 Hz, PhCH2),
4.57 (dd, 1H, J ) 11.8, 1.8 Hz, H1), 4.61 (d, 1H, J ) 11.6 Hz,
PhCH2), 4.63 (d, 1H, J ) 12.3 Hz, PhCH2), 4.76 (d, 1H, J )
12.6 Hz, PhCH2), 4.78 (d, 1H, J ) 10.6 Hz, PhCH2), 7.10∼7.37
(m, 25H, Ph); 13C NMR (100 MHz, CDCl3) δ 13.94, 44.61, 61.51,
69.28, 71.01, 71.14, 71.39, 73.27, 73.86, 74.37, 75.02, 76.51,
79.61, 127.25, 127.36, 127.40, 127.62, 127.77, 127.97, 128.15,
128.21 (2×), 128.30 (3×), 128.54, 129.46, 134.83, 138.13 (3×),
138.17, 138.34, 170.32; EI-MS m/z (rel intens) 767.2 (M + H+,
100), 765.4 (57), 609.4 (M - SePh+, 55); HRMS (FAB) m/z calcd
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra of compounds 18-31, 34, 35, and 37-41 and NOESY
spectra of compounds 26, 30, and 31 to indicate the correlation
of H1′ and H2 in space. This material is available free of charge
via the Internet at http://pubs.acs.org.
J O0255227