Reactions of some 2- and 4-O-triflylglycopyranosides with MeLi, t-BuOK, and pyridine

Article abstract of DOI:10.1016/S0008-6215(00)00291-3

As an extension of our previous work on secondary triflates of carbohydrates [El Nemr, A.; Tsuchiya, T. Tetrahedron Lett. 1995, 36, 7665-7668. El Nemr, A.; Tsuchiya, T.; Kobayashi, Y. Carbohydr. Res. 1996, 293, 31-59. El Nemr, A.; Tsuchiya, T. Carbohydr. Res. 1997, 301, 77-87. El Nemr, A.; Tsuchiya, T. Carbohydr. Res. 1997, 303, 267-281], the reaction modes of several methyl 2- and 4-O-triflyl-D-glycopyranosides with MeLi (strong base), t-BuOK (moderately strong base), and pyridine (weak base) have been studied. This paper describes the reactions of 3-O-benzyl-4,6-O-benzylidene-2-O-triflyl-D-gluco and -mannopyranosides with MeLi to give mainly the corresponding 2-C-methyl derivatives through α-elimination, with t-BuOK to give either the 2,3-unsaturated compounds through β-elimination or detriflyl 2-ols, and with hot pyridine to give the corresponding 2-pyridinium salts with inversion (except for the 2-O-triflyl-α-D-mannopyranoside (8)). 2,3,6-Tri-O-benzyl-4-O-triflyl-α-D-gluco and -mannopyranosides were also examined similarly.

Full text of DOI:10.1016/S0008-6215(00)00291-3

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Carbohydrate Research 330 (2001) 205–214
Reactions of some 2- and 4-O-triflylglycopyranosides
with MeLi, t-BuOK, and pyridine
Ahmed El Nemr, Tsutomu Tsuchiya*
Institute of Bioorganic Chemistry, 3-34-17 Ida, Nakahara-ku, Kawasaki 211-0035, Japan
Received 13 October 2000; accepted 20 October 2000
Abstract
As an extension of our previous work on secondary triflates of carbohydrates [El Nemr, A.; Tsuchiya, T.
Tetrahedron Lett. 1995, 36, 7665–7668. El Nemr, A.; Tsuchiya, T.; Kobayashi, Y. Carbohydr. Res. 1996, 293, 31–59.
El Nemr, A.; Tsuchiya, T. Carbohydr. Res. 1997, 301, 77–87. El Nemr, A.; Tsuchiya, T. Carbohydr. Res. 1997, 303,
267–281], the reaction modes of several methyl 2- and 4-O-triflyl-
t-BuOK (moderately strong base), and pyridine (weak base) have been studied. This paper describes the reactions of
3-O-benzyl-4,6-O-benzylidene-2-O-triflyl- -gluco and -mannopyranosides with MeLi to give mainly the correspond-
D-glycopyranosides with MeLi (strong base),
D
ing 2-C-methyl derivatives through a-elimination, with t-BuOK to give either the 2,3-unsaturated compounds
through b-elimination or detriflyl 2-ols, and with hot pyridine to give the corresponding 2-pyridinium salts with
inversion (except for the 2-O-triflyl-a-
D
-mannopyranoside (8)). 2,3,6-Tri-O-benzyl-4-O-triflyl-a-D-gluco and
-mannopyranosides were also examined similarly. © 2001 Elsevier Science Ltd. All rights reserved.
Keywords: Triflate; MeLi; t-BuOK; Pyridine; Deuterated compound; a-Elimination; b-Elimination; Pyridinium salt; Nucleophilic
substitution
We have recently reported1–3 a new reaction
with some carbohydrate triflates when they
are treated with MeLi or BuLi in diethyl ether
giving C-methyl (or butyl) or unsaturated
compounds, both through a-elimination with
removal of a hydrogen (or deuterium) atom at
the carbon bearing a CF3SO3 group as a
proton (deuteron). To clarify the reaction
modes for these compounds when the strongly
basic Me(Bu)Li is changed to a weaker base
triflyl-
sponding
compounds through a-elimination, and the 3-
O-triflyl- -allopyranosides gave the corre-
sponding unsaturated compounds through
b-elimination.4 When pyridine was used, how-
ever, most of the compounds readily gave the
corresponding 3-pyridinium derivatives with
inversion;4 it should be emphasized that
D
-glucopyranosides afforded the corre-
2,3- and/or 3,4-unsaturated
D
methyl
triflyl-a-
2-O-benzyl-4,6-O-benzylidene-3-O-
such as t-BuOK or pyridine, 3-O-triflyl- -
D
D
-glucopyranoside readily gave the
gluco- and - -allo-furanoses and the corre-
D
corresponding 3-deoxy-3-pyridinium- -allo-
D
sponding pyranosides were examined. It was
pyranoside, even though the steric and electro-
static 1,3-diaxial interactions5 between MeO-1
and the pyridine molecule approaching C-3
would be expected, in the transition state, to
hinder the reaction. The reaction should thus
be facilitated by pyridine, a noncharged,5,6
which may generate only weak electrostatic
found that, when t-BuOK was used, the 3-O-
* Corresponding author.
E-mail
address:
seiyuken@mx1.alpha-web.ne.jp
(T.
Tsuchiya).
0008-6215/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0008-6215(00)00291-3

206
A. El Nemr, T. Tsuchiya / Carbohydrate Research 330 (2001) 205–214
repulsion between its slightly negative-charged
nitrogen and MeO-1. This paper is an exten-
sion of our previous work and describes the
D
-manno structure (13 and 17, respectively)
were produced as the sole products in high
yields (Table 1). This means that the SN2
reactions by pyridine proceed as smoothly as
those by such anionic nucleophiles as N−3 and
F− or by the strongly basic hydrazine.6,9,12
reactions of 2- and 4-O-triflyl- -glycopyran-
D
osides with MeLi, t-BuOK, and pyridine to
clarify the limitation of the foregoing
reactions.
The
next. When the 2-O-triflyl-a-
noside (8) was treated with MeLi, the C-2-
methyl-
-gluco derivative (12)2 was obtained
D
-mannopyranosides were examined
D
-mannopyra-
Synthesis of triflates
D
in high yield unaccompanied by the
D
-manno
isomer, along with the detriflyl 2-ol (7)13 and a
trace amount of unsaturated compounds 11.14
It is noteworthy that the abstraction of H-2 by
Me(Bu)Li occurs readily, although, in 8, the
SN2 reaction at C-2 is quite difficult.5,6,15 In
Methyl 3-O-benzyl-4,6-O-benzylidene-2-O-
triflyl-b-
-(2-2H)mannopyranoside (10%)† was
D
prepared by the usual Swern oxidation–
(NaBD4) reduction procedure for methyl 3-O-
benzyl-4,6-O-benzylidene-b- -glucopyranoside
D
(5),7 followed by triflation (5“2“9%“10%; 2
was prepared in high yield through a different
route already reported8). Likewise, the 2-
the reactions of 8 and the corresponding
D
-2-
derivative (8%) with t-BuOK, the 2,3-unsatu-
rated compounds, 11 and 11%, respectively,
were mainly produced as observed for 4, 6,
and 10%, through b-(H-3) [but not a-(H- or
D-2)] elimination, as indicated by the reten-
tion of deuterium at C-2 in 11%.
deuterated 2-O-triflyl-a-
10% was prepared from methyl 3-O-benzyl-4,6-
O-benzylidene-a-
-glucopyranoside (3)7 via a
D
anomer (8%) of
D
similar route involving oxidation–(NaBD4)
reduction reactions (3“1“3%), with triflation
of the resulting HO-2 group (to give 4%), inver-
sion of the C-2 function (with NaOBz–DMF),
subsequent debenzoylation (to give 7%), and
triflation of the epi-HO-2 group.
Compound 8 was next heated in pyridine.
In this case, no pyridinium compound was
produced and three 2,3-unsaturated products
[11, 18, and 1916 (major)] were formed. Com-
pound 18 was assigned to be an a,b-unsatu-
1
rated aldehyde based on the H NMR (CHO,
l 9.98, J1,2 7 Hz), C NMR (CHO, l 190.5),
Reactions of undeuterated and deuterated 2-
and 4-triflates with MeLi, t-BuOK, and
pyridine
13
and mass spectra. Compound 19 was assigned
to be the 2-eno-1,5-lactone16 having possibly
1
an E5 conformation based on the H NMR
At first, unlabeled methyl 3-O-benzyl-4,6-
(H-2, l 5.46; H-3, l 7.30) and mass spectra.
As observed in many other 2-sulfonylated a-
O-benzylidene-2-O-triflyl-a- (4)9–11 and -b-
-
D
glucopyranosides (6)9 were treated with
t-BuOK in diethyl ether, whereupon only the
detriflyl 3-ols 37 and 57 were produced, in 76
and 68% yields, respectively (this suggests that
the process can be used for detriflation in
some cases). As previously reported, com-
pounds 4 and 6 are known to give the C-2-al-
kyl derivatives when treated with the strongly
basic Me(Bu)Li in diethyl ether1,2 (Table 1).
Compounds 4 and 6 were next treated with
hot pyridine (ꢀ80 °C, 7 h). In this case, the
2-deoxy-2-pyridinium compounds having the
D-mannopyranosides, the SN2 reactions at C-2
occur with difficulty,5,6 possibly because of the
steric repulsion between MeO-1 and the ap-
proaching nucleophiles to C-2 from the lower
side in their transition states; in this case,
however, electrostatic repulsion between
MeO-1 and pyridine will be negligible, and the
steric interaction should be the sole cause.
Even so, the weakly basic, noncharged pyri-
dine molecule can not attack at C-2 of 8 and
instead attacks H-3 (to produce 11 by b-elimi-
nation) or H-1 (to produce 19 by b-elimina-
tion), as shown in Scheme 1. Compound 18
may be produced by hydrolysis of 11 with
contaminant water in the pyridine, catalyzed
by the CF3SO3H liberated during the reaction.
† Compounds with a primed number are for the deuterated
derivatives of the corresponding nondeuterated compounds
throughout this paper.

A. El Nemr, T. Tsuchiya / Carbohydrate Research 330 (2001) 205–214
207
Summarizing all our data for the secondary
triflates hitherto studied [Refs. 1–4 with this
paper], it is concluded that, in treatment with
Me(Bu)Li in diethyl ether, all 2-O-triflylglyco-
pyranosides tested gave the 2-C-methyl (or
butyl) derivatives, mainly through a-elimina-
tion, and the 3-1,2 and 4-O-triflyl analogs gave
mainly the corresponding unsaturated com-
pounds through a-elimination or the detriflyl
alcohols. In the reactions with t-BuOK, all
compounds gave mainly the corresponding un-
saturated compounds through b-elimination or
the detriflyl alcohols. The foregoing results are
therefore contradictory to the generally ac-
cepted concept that double bonds formed by
removal of a sulfonyloxy group always arise
through b-elimination, and, instead, indicate
that double bonds are formed through either a-
or b-elimination, depending upon the structures
of the starting materials and the reaction con-
ditions. In the case of pyridine, all compounds,
Next, the 2-labeled 2-O-triflyl-b- -manno-
D
pyranoside (10%) was examined. Treatment of
10% with MeLi (this reaction is not reported in
Refs. 1–4) gave a mixture of four compounds:
14,15 14%, 15,2 and 16,2 the ratio of the non-
labeled (14) and 2-labeled 2,3-unsaturated com-
pounds (14%) being 3:2 (20% in total). Com-
pound 14 was considered to be produced by
initial D-2 abstraction by MeLi (a-elimination)
followed by 3“2 proton migration with subse-
quent removal of the 2-OTf group1,2 (the whole
reaction pattern closely resembles b-elimina-
tion and is liable to be so misjudged, in the
absence of D-2 labeling). The 2-C-methyl-
D
-
gluco (15) and - -manno (16) derivatives (2:3,
D
76% in total) were considered to be produced
by initial D-2 abstraction (a-elimination) fol-
lowed by formation of the 2-oxo intermediate
(by removal of the F3CSO−2 group) and rapid
reaction of the intermediate with excess
MeLi.1,2 The difference in the ratio of product-
species between 8 and 10% may be ascribed to
the difference in anomeric configuration.
except 2-O-triflyl-a- -mannopyranoside (8),
D
gave the corresponding pyridinium salts in high
yields with inversion.
Compound 10% was next treated with t-
BuOK, whereupon a 2-labeled compound 14%
was exclusively produced by b-elimination; its
1H NMR spectrum showed a very clear pattern,
due to the absence of H-2, as compared with
that obtained from the treatment of 10% with
MeLi (to give a mixture of 14 and 14%; see
Section 2). When 10% was heated in pyridine, the
2-deoxy-2-pyridinium compound 20% with the
D-gluco structure was produced with inversion,
in high yield and unaccompanied by any unsat-
urated or ring-contracted product17 (Table 1).
The 4 - deuterated - 4 - O - triflyl - a - - gluco-
D
(21%3) and -galactopyranosides (25%2) were next
examined. As shown in Table 1, reactions of
21%3 and 25%2 with MeLi or t-BuOK gave the
corresponding 3,4- (26%) and/or 4,5-unsaturated
(22,2 22%) compounds, or the detriflyl 4-ol (23%2),
respectively; the reaction pattern (a- or b-elim-
ination) and the product-species are fundamen-
tally similar to that for the 3-O-triflyl-a- -
D
glycopyranosides already reported1,2 (see Table
1). When 21 and 25 were treated with hot
pyridine, the corresponding 4-deoxy-4-pyri-
dinium compounds, 24 and 27,2 respectively
were produced readily under inversion in high
yields.
1. Experimental
General methods.—Optical rotations were
determined with a Perkin–Elmer 241 polarime-
ter. Mass spectra were measured by the fast-
atom bombardment method with a JEOL

208
A. El Nemr, T. Tsuchiya / Carbohydrate Research 330 (2001) 205–214
tion of 2 (1.50 g) in MeOH (40 mL) was
added NaBD4 (0.22 g, 5.27 mmol) and the
solution was kept for 2 h at rt. Excess CO2
(dry ice) was added, the solution was concen-
trated, and the residue was chromatographed
(1:1 hexane–EtOAc) to give, from the faster-
moving fractions, compound 5% as needles (97
mg, 6% based on 5), mp 182–183 °C (unla-
beled compound, lit.7 184–185 °C); [h]2D2
−
45° (c 0.5, CHCl3), (unlabeled, lit.7 [h]D −48°
(CHCl3)); m/z 374.27 (M++1); Anal. Calcd
Scheme 1.
1
for C21H23DO6: m/z 373.16 for M+; H NMR
SX-102 spectrometer. NMR spectra (1H at
250 or 500 MHz, 13C at 125.8 MHz, and 19F
at 235.35 MHz) were recorded with Bruker
AC-250P or AMX-500 spectrometers, using
(CDCl3): l 2.45 (s, 1 H, OH), 3.46 (dt, 1 H,
J4,5:J5,6 10.5, J5,6% 5.0 Hz, H-5), 3.57 (s, 3 H,
OCH3), 3.68 (dd, 1 H, H-4), 3.69 (d, 1 H, J3,4
8.0 Hz, H-3), 3.80 (t, 1 H, H-6), 4.33 (s, 1 H,
H-1), 4.36 (dd, 1 H, H-6%), 4.88 (ABq, 2 H, J
12 Hz, CH2Ph), 5.58 (s, 1 H, CHPh). From
the slower-moving fractions compound 9% was
obtained as needles (1.38 g, 85% based on 5),
mp 116–118 °C (lit.8 no data reported); [h]2D2
−30° (c 0.5, CHCl3), (lit.8 no data reported);
m/z 374.24 (M++1); Anal. Calcd for
19
Me4Si and CFCl3 (for F) as the internal and
external references, respectively. TLC was per-
formed on Silica Gel 60 F254 (E. Merck 5715
and 5717), and detected by charring with aq
50% H2SO4. Column chromatography was
performed on Wakogel C-200.
Preparation of starting materials
1
C21H23DO6: m/z 373.16 for M+; H NMR
Methyl 3-O-benzyl-4,6-O-benzylidene-i-
(2-2H)glucopyranoside (5%) and methyl 3-O-
benzyl-4,6-O-benzylidene-i-
-(2-2H)manno-
pyranoside (9%). To a cold (−78 °C) solution
of oxalyl chloride (0.94 mL, 10.7 mmol) in
CH2Cl2 (20 mL) was added Me2SO (1.52 mL,
21.5 mmol) and after 15 min, methyl 3-O-ben-
D-
(CDCl3): l 2.55 (s, 1 H, OH), 3.35 (ddd, 1 H,
J4,5 9.5, J5,6 10, J5,6% 4.5 Hz, H-5), 3.56 (s, 3 H,
OCH3), 3.65 (d, 1 H, J3,4 9.5 Hz, H-3), 3.89 (t,
1 H, H-6), 4.14 (t, 1 H, H-4), 4.34 (dd, 1 H,
H-6%), 4.41 (s, 1 H, H-1), 4.81 (ABq, 2 H, J 12
Hz, CH2Ph) 5.61 (s, 1 H, CHPh), no H-2
signal was observed.
D
zyl-4,6-O-benzylidene-b- -glucopyranoside
D
(5)7 (2.0 g, 5.37 mmol) in CH2Cl2 (15 mL) was
added dropwise and the mixture was stirred
for 30 min. After the addition of Et3N (3 g),
the mixture was warmed to rt and kept for 1
h. Water (20 mL) was added, and the organic
layer separated was washed with water, dried
(Na2SO4), and concentrated. The residue was
recrystallized from MeOH to give 2 as needles
(1.85 g), mp 179–180 °C (lit.8 no data re-
ported), [h]2D2 −76° (c 1, CHCl3) (lit.8 no data
reported); m/z 371.22 (M++1); Anal. Calcd
Methyl 3-O-benzyl-4,6-O-benzylidene-h- -
D
(2-2H)glucopyranoside (3%). A solution of 37
(1.5 g, 4.03 mmol) in CH2Cl2 (10 mL) was
oxidized as described for 2 to give 1 as needles
(1.42 g), mp 146–147 °C, [h]2D2 +11° (c 1,
CHCl3); m/z 369.10 (M+−1), 371.12 (M++
1); Anal. Calcd for C21H22O6: m/z 370.16 for
1
M+; H NMR (CDCl3): l 3.47 (s, 3 H,
OCH3), 3.81 (t, 1 H, H-6), 3.87 (dd, 1 H, H-4),
4.19 (dt, 1 H, J4,5 :J5,6 10.5, J5,6% 5.0 Hz, H-5),
4.38 (dd, 1 H, H-6%), 4.53 (d, 1 H, J3,4 10.5 Hz,
H-3), 4.75 (s, 1 H, H-1), 4.82 (ABq, 2 H, J 12
Hz, CH2Ph), 5.56 (s, 1 H, CHPh). A solution
of 1 (1.2 g) in MeOH (30 mL) was treated
with NaBD4 as described for 9% to give 3%
as needles (1.16 g, 91% based on 3),
mp 186–188 °C (unlabeled compound, lit.7
187–188 °C), [h]D22 +76° (c 1, CHCl3) (unla-
beled, lit.7 [h]D +78° (CHCl3)); m/z 372.16
(M+−1), 374.19 (M++1); Anal. Calcd for
for C21H22O6: m/z 370.14 for M+; H NMR
1
(CDCl3): l 3.59 (s, 3 H, OCH3), 3.75 (dt, 1 H,
J4,5 :J5,6 10, J5,6% 4.3 Hz, H-5), 3.85 (t, 1 H,
J6,6% 10 Hz, H-6), 3.94 (dd, 1 H, H-4), 4.23 (dd,
1 H, J1,3 ꢀ1, J3,4 9.5 Hz, H-3), 4.45 (dd, 1 H,
H-6%), 4.76 (d, 1 H, H-1), 4.86 (ABq, 2 H, J 12
Hz, CH2Ph), 5.58 (s, 1 H, CHPh); 13C NMR
(CDCl3): l 58.01, 66.49, 68.58, 73.31, 81.92,
82.09, 101.11, 101.58, 196.45 (C-2). To a solu-

A. El Nemr, T. Tsuchiya / Carbohydrate Research 330 (2001) 205–214
209
1
C21H23DO6: m/z 373.19 for M+; H NMR
(CDCl3): l 2.33 (s, 1 H, OH), 3.45 (s, 3 H,
OCH3), 3.64 (t, 1 H, H-6), 3.75 (t, 1 H,
H-4), 3.82 (d, 1 H, J3,4 10 Hz, H-3), 3.84
(dt, 1 H, J4,5:J5,6ꢀ10, J5,6% 4 Hz, H-5),
4.30 (dd, 1 H, H-6%), 4.80 (s, 1 H, H-1), 4.87
(ABq, 2 H, J 11.5 Hz, CH2Ph), 5.57 (s, 1 H,
CHPh); no H-2 signal was observed.
Methyl 3-O-benzyl-4,6-O-benzylidene-2-O-
triflyl-h-
-(2-2H)glucopyranoside (4%). Pre-
D
pared from 3% (1.0 g, 2.68 mmol) as
described in the general procedure for trifla-
tion to give 4% as needles (1.21 g, 89%), mp
82–84 °C (unlabeled compound, lit.9 83–
85 °C), [h]2D2 +34° (c 1, CHCl3) (unlabeled,
lit.9 [h]D +35.7° (CHCl3)); m/z 504.14 (M+
Table 1

210
A. El Nemr, T. Tsuchiya / Carbohydrate Research 330 (2001) 205–214
Table 1 (Continued)
−1), 506.16 (M++1); Anal. Calcd for
C22H22DF3O8S: m/z 505.11 for M+; 1H
NMR (CDCl3): l 3.47 (s, 3 H, OCH3), 3.69
(t, 1 H, H-4), 3.76 (t, 1 H, H-6), 3.88 (dt, 1
H, J4,5 9, J5,6 10, J5,6% 4.5 Hz, H-5), 4.12 (d, 1
H, J3,4 9 Hz, H-3), 4.31 (dd, 1 H, H-6%), 4.81
(ABq, 2 H, J 11.5 Hz, CH2Ph), 4.96 (s, 1 H,
H-1), 5.56 (s, 1 H, CHPh); no H-2 signal was
observed.
Methyl 3-O-benzyl-4,6-O-benzylidene-h-
D-
mannopyranoside (7). A mixture of methyl 3-
O-benzyl-4,6-O-benzylidene-2-O-triflyl-a- -
D
glucopyranoside (4)9–11 (2.1 g, 4.17 mmol) and
NaOBz (1.81 g, 12.6 mmol) in DMF (50 mL)

A. El Nemr, T. Tsuchiya / Carbohydrate Research 330 (2001) 205–214
211
Anal. Calcd for C22H23F3O8S: m/z 504.11 for
was heated at 80 °C for 8 h. Water (50 mL)
was added and the mixture was extracted
with CHCl3 (70 mL×3). The extracts com-
bined were washed with water, dried
(Na2SO4), and concentrated in vacuo to give
the crude 2-O-Bz derivative of 7 as a syrup
(1.98 g). A mixture of the syrup and
NaOMe in MeOH was allowed to stand for
1 h. After excess CO2 (dry ice) was added,
the mixture was concentrated and the
residue was chromatographed (1:1 hexane–
EtOAc) to give 7 as a syrup (1.21 g, 78%),
[h]2D2 +50° (c 1, CHCl3), (lit.13 [h]2D5 +51°
1
M+; H NMR (CDCl3): l 3.40 (s, 3 H,
OCH3), 3.82 (m, 1 H, H-5), 3.87 (t, 1 H,
H-6), 4.03 (m, 2 H, H-3,4), 4.26 (dd, 1 H,
H-6%), 4.78 (ABq, 2 H, J 12 Hz, CH2Ph),
4.84 (d, 1 H, H-1), 5.08 (t, 1 H, J1,2:J2,3 ꢀ
1.5 Hz, H-2), 5.62 (s, 1 H, CHPh). Anal.
Calcd for C22H23F3O8S: C, 52.38; H, 4.60.
Found: C, 52.29; H, 4.59.
Methyl 3-O-benzyl-4,6-O-benzylidene-2-O-
triflyl-h-
-(2-2H)mannopyranoside (8%). Pre-
D
pared from 7% as needles (81%), mp
91–93 °C (unlabeled compound, 90–91 °C),
1
(CHCl3)); H NMR (CDCl3): l 2.74 (s, 1 H,
[h]2D2 +18° (c 1, CHCl3) (unlabeled, [h]2D2
+
18° (CHCl3)); m/z 504.02 (M+−1), 506.02
(M++1); Anal. Calcd for C22H22DF3O8S:
OH), 3.36 (s, 3 H, OCH3), 3.75–3.93 (m, 3
H, H-4,5,6), 4.02 (m, 1 H, H-2), 4.08 (m, 1
H, H-3), 4.27 (dd, 1 H, H-6%), 4.74 (d, 1 H,
J1,2 1.5 Hz, H-1), 4.78 (ABq, 2 H, J 11.5
Hz, CH2Ph), 5.61 (s, 1 H, CHPh).
1
m/z 505.11 for M+; H NMR (CDCl3): l
3.39 (s, 3 H, CH3), 3.81 (dt, 1 H, J4,5:J5,6
10, J5,6% 4 Hz, H-5), 3.85 (t, 1 H, H-6), 4.03
(m, 2 H, H-3,4), 4.26 (dd, 1 H, H-6%), 4.78
(ABq, 2 H, J 12 Hz, CH2Ph), 4.84 (s, 1 H,
H-1), 5.08 (br s, 0.06 H, H-2), 5.62 (s, 1 H,
CHPh).
Methyl 3-O-benzyl-4,6-O-benzylidene-h- -
D
(2-2H)mannopyranoside (7%). A mixture of 4%
(1.05 g, 2.08 mmol) and NaOBz (0.91 g,
6.32 mmol) in DMF (30 mL) was heated as
described for 7 to give the crude 2-O-Bz
derivative of 7% as a syrup (1.12 g). Deben-
zoylation (cat. NaOMe in MeOH) followed
by chromatography (1:1 hexane–EtOAc)
Methyl 3-O-benzyl-4,6-O-benzylidene-2-O-
triflyl-i-
-(2-2H)mannopyranoside (10%). Pre-
D
pared from 9% as needles (93%), mp
98–99 °C (unlabeled compound, lit.15 99 °C),
[h]2D2 −35° (c 1, CHCl3), (unlabeled, lit.15
[h]D −36° (CHCl3)); m/z 506.23 (M++1);
Anal. Calcd for C22H22DF3O8S: m/z 505.11
gave 7% as a syrup (582 mg, 75%), [h]D22
+
49° (c 1, CHCl3), (unlabeled compound, lit.13
[h]2D5 +51° (CHCl3)); m/z 372.17 (M+−1),
374.19
(M++1);
Anal.
Calcd
for
1
for M+; H NMR (CDCl3): l 3.37 (ddd, 1
1
C21H23DO6: m/z 373.19 for M+: H NMR
H, J4,5 9.5, J5,6 10.3, J5,6% 5 Hz, H-5), 3.55 (s,
3 H, OCH3), 3.75 (d, 1 H, H-3), 3.90 (t, 1
H, H-6), 4.00 (t, 1 H, J3,4 :J4,5 9.5 Hz, H-
4), 4.33 (dd, 1 H, H-6%), 4.51 (s, 1 H, H-1),
4.80 (ABq, 2 H, J 12 Hz, CH2Ph), 5.62 (s, 1
H, CHPh).
General procedure for the reactions of tri-
flates with MeLi.—To a cold (−50 °C) so-
lution of a triflate (0.2 mmol) in dry Et2O (5
mL) was added MeLi (0.8 mmol, as a 1.4 M
solution in Et2O), and the solution was kept
for 1 h at rt. Aq 2 M NH4Cl (5 mL) and
CHCl3 (50 mL) were stirred in and the or-
ganic layer separated was washed with wa-
ter, dried (Na2SO4), concentrated, and the
reside was chromatographed.
(CDCl3): l 2.74 (s, 1 H, OH), 3.36 (s, 3 H,
OCH3), 3.79 (dt, 1 H, J4,5 :J5,6 ꢀ10, J5,6%
4
Hz, H-5), 3.86 (t, 1 H, H-6), 3.92 (t, 1 H,
H-4), 4.08 (d, 1 H, J3,4 10 Hz, H-3), 4.27
(dd, 1 H, H-6%), 4.74 (s, 1 H, H-1), 4.78
(ABq, 2 H, J 11.5 Hz, CH2Ph), 5.61 (s, 1 H,
CHPh).
General procedure for preparation of tri-
flates.—To a cold (−10 °C) solution of an
alcohol (1 mmol) in 2:1 CH2Cl2–pyridine (6
mL) was added (CF3SO2)2O (1.3 mmol) and
the solution was kept for 2 h at 0 °C. After
addition of water (0.5 mL), the mixture was
concentrated, and the residue was purified
by chromatography (3:1 hexane–EtOAc).
Methyl 3-O-benzyl-4,6-O-benzylidene-2-O-
Reaction of 8 with MeLi. After the general
procedure followed by chromatography (1:1
hexane–EtOAc), 8 (100 mg) gave 122 (59
mg) and 713 (13 mg) as syrups, respectively.
triflyl-h- -mannopyranoside (8). Prepared
D
from 7, needles (83%), mp 90–91 °C, [h]D22
+18° (c 1, CHCl3); m/z 505.15 (M++1);

212
A. El Nemr, T. Tsuchiya / Carbohydrate Research 330 (2001) 205–214
mp 119–121 °C (unlabeled compound, lit.14
120–121 °C), [h]D22 +57° (c 1, CHCl3) (unla-
beled, lit.14 [h]D +59° (c 0.6, CHCl3)); m/z
354.13 (M+−1), 356.13 (M++1); Anal.
Reaction of 10% with MeLi. After the general
procedure, 10% (100 mg) gave, on chromatog-
raphy (5:1 hexane–EtOAc), a 3:2 mixture of
149 and 14% as needles (14 mg, 20%), mp
82–84 °C (unlabeled compound, lit.15 83 °C),
[h]2D2 −108° (c 0.5, CHCl3) (unlabeled, lit.15
1
Calcd for C21H21DO5: m/z 355.15 for M+; H
NMR (CDCl3): l 3.41 (s, 3 H, OCH3), 3.83 (t,
1 H, H-6), 4.11 (dt, 1 H, J4,5 9, J5,6 10, J5,6% 4.5
Hz, H-5), 4.26 (dd, 1 H, J1,4 ꢀ1 J4,5 9 Hz,
H-4), 4.30 (dd, 1 H, H-6%), 4.74 (dd, 0.06 H,
H-2), 4.87 (ABq, 2 H, J 12 Hz, CH2Ph), 5.02
(s, 1 H, H-1), 5.59 (s, 1 H, CHPh).
1
[h]D −110° (CHCl3)); H NMR (CDCl3): l
3.42 (s, 3 H, OCH3), 3.81 (dt, 1 H, J4,5 8.5, J5,6
10, J5,6% 4 Hz, H-5), 3.91 (t, 1 H, H-6), 4.32
(dd, 1 H, H-6%), 4.44 (d with narrow multi-
plets, 1 H, H-4), 4.70 (t, 0.6 H, J1,2 :J2,4ꢀ1.5
Hz, H-2), 4.88 (ABq, 2 H, J 12 Hz, CH2Ph),
5.39 (dd, 0.6 H; d, 0.4 H, J1,4ꢀ2.5 Hz, H-1),
5.62 (s, 1 H, CHPh). Further development
with 1:1 hexane–EtOAc gave, from the faster-
moving fractions, compound 15 as a syrup (24
mg, 31%), [h]2D2 −41° (c 1, CHCl3), (unla-
Reaction of 10% with t-BuOK. After the gen-
eral procedure, 14% was obtained as needles
(84%), mp 83–84 °C (unlabeled compound,
lit.15 83 °C), [h]2D2 −109° (c 1, CHCl3), (unla-
beled, lit.15 [h]D −110° (CHCl3)); m/z 354.21
(M+−1); Anal. Calcd for C21H21DO5: m/z
355.15 for M+; 1H NMR (CDCl3): l 3.42 (s, 3
H, OCH3), 3.81 (dt, 1 H, J4,5 8.5, J5,6 10, J5,6%
4 Hz, H-5), 3.90 (t, 1 H, H-6), 4.32 (dd, 1 H,
H-6%), 4.44 (dd, 1 H, H-4), 4.70 (t, ꢀ0.06 H,
H-2), 4.88 (ABq, 2 H, J 12 Hz, CH2Ph), 5.39
(d, 1 H, J1,4 2.5 Hz, H-1), 5.62 (s, 1 H, CHPh).
Reaction of 21%3 with t-BuOK to gi6e methyl
1
beled, lit.2 [h]D24 −43° (CHCl3)); H NMR
(CDCl3): all signals are identical with those
reported.2 From the slower-moving fractions
compound 16 was obtained as a solid (34 mg,
45%), [h]2D2 −37° (c 1, CHCl3), (unlabeled,
1
lit.2 [h]2D4 −35° (CHCl3)); H NMR (CDCl3):
all signals are identical with those reported.2
General procedure for the reactions of tri-
flates with t-BuOK.—To a solution of a trifl-
ate (0.2 mmol) in dry ether (3 mL) was added
t-BuOK (0.6 mmol), and the mixture was
stirred for 3 h at rt. Water (7 mL) was added
and the resulting mixture was extracted with
CHCl3 (20 mL×3). The combined organic
solution was washed with water, dried
(Na2SO4), and concentrated. The residue was
chromatographed on silica gel with 1:1
hexane–EtOAc.
2,3,6-tri-O-benzyl-4-deoxy-i-
enopyranoside (222), methyl 2,3,6-tri-O-benzyl-
4-deoxy-i-
-(4-2H)threo-hex-4-enopyranoside
(22%) and methyl 2,3,6-tri-O-benzyl-h- -(4-
L
-threo-hex-4-
L
D
2H)glucopyranoside (23%2). Chromatography as
described in the general procedure gave a 1:4.5
mixture of 22 and 22% as a syrup (14%), [h]D22
+79° (c 0.5, CHCl3) (unlabeled compound,
lit.2 [h]2D2 +78° (c 1, CHCl3)); 1H NMR
(CDCl3): l 3.49 (s, 3 H, OCH3), 3.78 (dd, 1 H,
J1,2 2.5, J2,3 7 Hz, H-2), 3.92 (sl. br s, 2 H,
H-6,6%), 4.23 (ꢀdt, 1 H, J2,3 7, J3,6:J3,6%ꢀ1
Hz, H-3); 4.54, 4.63, and 4.77 (each ABq,
2 H, J 12 Hz, CH2Ph×3), 4.85 (d, 1 H, H-1),
5.04 (d, 0.18 H, J3,4 3 Hz, H-4). Further
development gave 23% as a syrup (81%), [h]D22
+11.5° (c 0.6, CHCl3) (lit.2 [h]D22 +12°
(CHCl3)).
Reaction of 8 with t-BuOK. After the gen-
eral procedure, 11 was obtained as needles
(93%), mp 121–122 °C (lit.14 120–121 °C),
[h]2D2 +56° (c 1, CHCl3) (lit.14 [h]2D2 +59° (c
0.6, CHCl3)); m/z 353.17 (M+−1), 355.17
(M++1); Anal. Calcd for C21H22O5: m/z
354.15 for M+; 1H NMR (CDCl3): l 3.41 (s, 3
H, OCH3), 3.83 (t, 1 H, H-6), 4.11 (dt, 1 H,
J4,5 :J5,6 10, J5,6% 4.5 Hz, H-5), 4.26 (dd, 1 H,
H-4), 4.30 (dd, 1 H, H-6%), 4.74 (dd, 1 H, J1,2
3.2, J2,4 ꢀ1.6 Hz, H-2), 4.86 (ABq, 2 H, J 12
Hz, CH2Ph), 5.01 (d, 1 H, H-1), 5.58 (s, 1 H,
CHPh).
Reaction of 25%2 with t-BuOK to gi6e methyl
2,3,6-tri-O-benzyl-4-deoxy-i-
hex-4-enopyranoside (22%) and 2,3,6-tri-O-ben-
zyl - 4 - deoxy - h -
- (4 - 2H)erythro - hex - 3 -
L
-(4-2H)threo-
D
enopyranoside (26%). Chromatography as de-
scribed in the general procedure gave 22% as a
syrup (34%), [h]D22 +79° (c 1.2, CHCl3) (unla-
beled compound, lit.2 [h]D22 +78° (c 1, CHCl3);
Reaction of 8% with t-BuOK to gi6e methyl 3
-O-benzyl-4,6-O-benzylidene-2-deoxy-h- -(2-
D
2H)erythro-hex-2-enopyranoside (11%). Needles,

A. El Nemr, T. Tsuchiya / Carbohydrate Research 330 (2001) 205–214
213
1H NMR (CDCl3): l 3.49 (s, 3 H, OCH3),
3.78 (dd, 1 H, J1,2 2.5, J2,3 7 Hz, H-2), 3.92
(sl. br s, 2 H, H-6,6%), 4.23 (dt, 1 H, J2,3 7,
J3,6 :J3,6%ꢀ1 Hz, H-3); 4.54, 4.63, and 4.77
(each ABq, 2 H, J 12 Hz, CH2Ph×3), 4.85
(d, 1 H, H-1). Further development gave 26%
as a syrup (54%), [h]2D2 −40° (c 1.1, CHCl3);
m/z 446.30 (M+−1); Anal. Calcd for
1 H, J1,2 2.8, J2,3 5.5 Hz, H-2), 7.92, 8.31 and
9.06 (m of 2, 1, and 2 H, respectively,
C5H5N). Anal. Calcd for C27H28F3NO8S·H2O:
C, 53.90; H, 5.03; N, 2.33. Found: C, 54.03;
H, 5.06; N, 2.38.
Reaction of 8 with pyridine to gi6e 1114,
3-O-benzyl-4,6-O-benzylidene-2-deoxy- -ery-
D
thro-hex-2-enal (18), and 4,6-O-benzylidene-
2,3-dideoxy- -erythro-hex-2-eno-1,5-lactone
1
C28H29DO5: m/z 447.22 for M+; H NMR
D
(19)16. Heating 8 (120 mg, 0.24 mmol) in
pyridine (4 mL) at 60 °C for 12 h followed
by concentration of the solution in vacuo
gave a residue, which was chromatographed
(1:1 hexane–EtOAc) to give, from the faster-
moving fractions, compound 1114 as needles
(7 mg, 8%) and, from the second-moving
fractions, compound 19 as a solid (25 mg,
45%), mp 135–136 °C (lit.16 136–137 °C),
[h]2D2 +32° (c 1, CHCl3) (lit.16 [h]2D7 +33° (c
1, CHCl3)); m/z 233.15 (M++1); Anal.
(acetone-d6): l 3.45 (s, 3 H, OCH3), 3.50 (dd,
1 H, H-6), 3.58 (dd, 1 H, H-6%), 4.16 (dd, 1
H, J1,2 4.0, J2,5 2.5 Hz, H-2), 4.40 (dt, 1 H,
J2,5 2.5, J5,6 5.0, J5,6% 6.0 Hz, H-5), 4.58, 4.75
and 4.82 (each ABq, 2 H, J 12 Hz, CH2Ph×
3), 4.94 (d, 1 H, H-1).
General procedure for the reactions of tri-
flates with pyridine.—A solution of a triflate
(0.2 mmol) in pyridine (2 mL) was heated at
80 °C for 7 h, except for 8. After excess pyri-
dine has been evaporated in vacuo, the
residue dissolved in CHCl3 (20 mL) was
washed with water, dried (Na2SO4), and con-
centrated. The residue was chromatographed
on silica gel (5:1 CHCl3–MeOH) to give the
pyridinium trifluoromethanesulfonate.
1
Calcd for C13H12O4: m/z 332.09 for M+; H
NMR (CDCl3): l 4.04 (unresolved m, 1 H,
H-6; signals are complex due to virtual cou-
plings involving H-4), 4.38–4.53 (unresolved
m, 3 H, H-4,5,6%), 5.46 (d, 1 H, H-2), 5.60 (s,
1 H, CHPh), 7.30 (d, 1 H, H-3); J2,3 6 Hz;
13C NMR (CDCl3): l 67.91 (C-6), 73.08 (C-4
or 5), 77.52 (C-5 or 4), 102.35 (CHPh);
106.32 (C-2), 126.45, 128.34, 129.47 and
136.23 (Ph), 161.36 (C-3), 188.07 (C-1), which
were confirmed by the CꢀH correlation spec-
trum; the H-4,5, and 6% could not be resolved
even in the spectrum in pyridine-d5. From the
slowest-moving fractions compound 18 was
Reaction of 49–11 with pyridine to gi6e
methyl
3-O-benzyl-4,6-O-benzylidene-2-de-
oxy-2-(pyridinium-1-yl)-h- -mannopyranoside
D
triflate (13). Syrup, [h]2D2 −41° (c 0.5,
1
CHCl3); H NMR (CDCl3): l 3.45 (s, 3 H,
OCH3), 3.80 (t, 1 H, J5,6:J6,6% 10 Hz, H-6),
4.06 (dt, 1 H, J4,5 :J5,6 10, J5,6% 5.5 Hz, H-5),
4.10 (t, 1 H, J3,4 10 Hz, H-4), 4.32 (dd, 1 H,
H-3), 4.38 (dd, 1 H, H-6%), 4.78 (ABq, 2 H, J
12 Hz, CH2Ph), 5.22 (d, 1 H, J1,2 B0.5, J2,3
5.8 Hz, H-2), 5.39 (s, 1 H, H-1), 5.61 (s, 1 H,
CHPh), 8.00, 8.40 and 8.97 (each m of 2, 1,
and 2 H, respectively, C5H5N); 19F NMR
(CDCl3): l −78.54 (s, CF3SO3).
obtained as a syrup (18 mg, 20%), [h]D22
+
0.2° (c 1, CHCl3); m/z 339.16 (M+−1),
341.16 (M++1); Anal. Calcd for C20H20O5:
1
m/z 340.13 for M+; H NMR (CDCl3): l
2.61 (d, 1 H, OH), 3.73 (dd, 1 H, J5,6 10, J6,6%
11 Hz, H-6), 4.20 (m, 1 H, H-5), 4.40 (dd, 1
H, J5,6% 5.5 Hz, H-6%), 4.90 (d, 1 H, J4,5 9.2
Hz, H-4), 4.95 (ABq, 2 H, J 11.5 Hz,
CH2Ph), 5.59 (s, 1 H, CHPh), 5.66 (d, 1 H,
Reaction of 69 with pyridine to gi6e methyl
3-O-benzyl-4,6-O-benzylidene-2-deoxy-2-(pyri-
dinium-1-yl)-i- -mannopyranoside triflate (17).
D
Needles, mp 73–75 °C, [h]2D3 +38° (c 1,
13
J1,2 7 Hz, H-2), 9.98 (d, 1 H, H-1); C NMR
CHCl3); m/z 434.16 (M+); Anal. Calcd for
(CDCl3): l 63.33 (C-5), 71.28 (C-6), 71.38
(C-4), 79.66 (CH2Ph), 101.81 (CHPh), 108.33
(C-2), 190.50 (C-1).
1
C26H28NO5: m/z 434.20 for M+; H NMR
(CDCl3): l 1.70 (s, 2 H, H2O), 3.50 (s, 3 H,
OCH3), 3.63 (dt, 1 H, J5,6% 5 Hz, H-5), 3.83
(t, 1 H, H-6), 4.01 (t, 1 H, J3,4 :J4,5 10 Hz,
H-4), 4.38 (dd, 1 H, H-6%), 4.41 (dd, 1 H,
H-3), 4.82 (ABq, 2 H, J 12 Hz, CH2Ph), 5.16
(d, 1 H, H-1), 5.60 (s, 1 H, CHPh), 5.78 (dd,
Reaction of 10% with pyridine to gi6e methyl
3-O-benzyl-4,6-O-benzylidene-2-deoxy-2-(pyri-
dinium-1-yl)-i-
-(2-2H)glucopyranoside tri-
D
flate (20%). Syrup, [h]2D3 +38° (c 1, CHCl3);
m/z 435.42 (M+); Anal. Calcd for C26H27-

214
A. El Nemr, T. Tsuchiya / Carbohydrate Research 330 (2001) 205–214
DNO5: m/z 435.20 for M+; 1H NMR
(CDCl3): l 3.37 (s, 3 H, OCH3), 3.83 (t, 1 H,
J5,6 :J6,6% 10.2 Hz, H-6), 3.87 (dd, 1 H, J3,4
8.0, J4,5 9.5 Hz, H-4), 4.04 (dt, 1 H, H-5), 4.45
(dd, 1 H, J5,6% 4.5 Hz, H-6%), 4.57 (ABq, 2 H, J
12 Hz, CH2Ph), 4.58 (d, 1 H, H-3), 5.36 (s, 1
H, H-1), 5.63 (s, 1 H, CHPh), 7.87, 8.34 and
8.83 (each m of 2, 1, and 2 H, respectively,
C5H5N); 19F NMR (CDCl3): l −78.62 (s,
CF3SO3).
preparation of some compounds and other
valuable advice.
References
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1
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10.5 Hz, H-6), 3.71 (dd, 1 H, J1,2 3.8, J2,3 10.5
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H), 8.14 (m, 1 H) and 9.03 (d, 6 Hz, 2 H)
(C5H5N).
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Acknowledgements
We express deep thanks to Dr Hiroshi Na-
ganawa of Institute of Microbial Chemistry,
Ms Yoshiko Koyama and Ms Miwa Arai of
our institute for measurements of mass spec-
tra, NMR spectra, and assistance in preparing
the manuscript, respectively. We are also
grateful to Dr Yoshihiko Kobayashi for
19. Doboszewski, B.; Hay, G. W.; Szarek, W. A. Can. J.
Chem. 1987, 65, 412–419.
.