C-Glycosylmethylene carbenes: Synthesis of anhydro-aldose tosylhydrazones as precursors; generation and a new synthetic route to exo-glycals

Article abstract of DOI:10.1039/b307378e

Acylated anhydro-aldononitriles (glycosyl cyanides) were transformed into anhydro-aldose tosylhydrazones by Raney-nickel reduction in the presence of tosylhydrazine in a one-pot reaction. The configuration of the C=N double bond in these hydrazones was E as proven by ¹⁵N-¹H coupling constants as well as X-ray crystallography. Thermolysis in refluxing 1,4-dioxane of the sodium salts of the tosylhydrazones obtained by sodium hydride (generally 10 eq.) resulted in the formation of anhydro-1-deoxy-ald-1-enitols (exo-glycals). "Dimeric" N-glycosyl-methyl anhydro-aldose tosylhydrazones could also be isolated when the use of less base caused incomplete deprotonation of the starting compounds. This two-step procedure constitutes a novel, reasonably short synthetic pathway to acylated exo-glycals from the readily available glycosyl cyanides.

Full text of DOI:10.1039/b307378e

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C-Glycosylmethylene carbenes: synthesis of anhydro-aldose
tosylhydrazones as precursors; generation and a new synthetic
route to exo-glycals
Marietta Tóth,a Katalin E. Kövér,b Attila Bényeic and László Somsák*a
a Department of Organic Chemistry, University of Debrecen, Debrecen, Hungary.
E-mail: somsak@tigris.klte.hu; Fax: ϩ36-52-453-836; Tel: ϩ36-52-512-900/2348
b Department of Inorganic and Analytical Chemistry, University of Debrecen, Debrecen,
Hungary
c Department of Physical Chemistry, Laboratory for X-Ray Diffraction,
University of Debrecen, Debrecen, Hungary
Received 30th June 2003, Accepted 12th September 2003
First published as an Advance Article on the web 13th October 2003
Acylated anhydro-aldononitriles (glycosyl cyanides) were transformed into anhydro-aldose tosylhydrazones by
Raney–nickel reduction in the presence of tosylhydrazine in a one-pot reaction. The configuration of the C᎐N
᎐
double bond in these hydrazones was E as proven by 15N–1H coupling constants as well as X-ray crystallography.
Thermolysis in refluxing 1,4-dioxane of the sodium salts of the tosylhydrazones obtained by sodium hydride
(generally 10 eq.) resulted in the formation of anhydro-1-deoxy-ald-1-enitols (exo-glycals). “Dimeric” N-glycosyl-
methyl anhydro-aldose tosylhydrazones could also be isolated when the use of less base caused incomplete
deprotonation of the starting compounds. This two-step procedure constitutes a novel, reasonably short
synthetic pathway to acylated exo-glycals from the readily available glycosyl cyanides.
rearrangement of glycosylsulfonyl methanes;5i–k oxidation of
Introduction
C-glycosyl phenylselenyl methane followed by elimination;5l
Keck-reaction of glycosylidene dihalides5m and hydrogen halo-
genide eliminations from C-glycosyl iodomethanes.5n–p With
the exception of the last two methods the applied (generally
strongly basic) reaction conditions require O-benzyl (or other
base stable) protecting groups. On the other hand, O-acylated
exo-glycals, which can be more advantageous e.g. for radical-
mediated transformations, are accessible only via laborious
preparation of precursors.5m–p
Recognition of the essential roles of carbohydrates in various
biological events has brought about an enormous development
in synthetic carbohydrate chemistry.1 To get a better insight into
the action of carbohydrate derivatives in living organisms, mole-
cules of natural origin as well as their counterparts with simi-
lar biological effects and/or chemical structure (the so-called
mimetics) need to be prepared in large amounts by chemical
synthesis. The design of glycomimetics2 comprises a variety of
structural modifications, among others introduction of double
bonds into carbohydrate derivatives to modify conformation,
replacement of either or both oxygens in the ring or attached to
the anomeric carbon by other atoms to modify chemical prop-
erties or stability and changing the ring size, just to mention a
few.
Unsaturated carbohydrates, especially glycals (1,4- or 1,5-
anhydro-2-deoxypent- or hex-1-enitols, Chart 1 A and B) and
exo-glycals (2,5- or 2,6-anhydro-1-deoxyhex- or hept-1-enitols,
Chart 1 D) play a central role in the aforementioned efforts
being themselves glycomimetics on one hand, and offering
many elegant synthetic possibilities for further transformations
on the other. Syntheses and synthetic uses of glycals3 are well
documented and reviewed, however, seven-membered ring
glycals (1,6-anhydro-2-deoxy-hex- or hept-1-enitols, Chart 1 C)
are scarcely mentioned in the literature.4 Several synthetic
protocols are known for the preparation of exo-glycals5: olefin-
ation of sugar lactones by using the Tebbe reagent,5a,b di-
methyltitanocene,5c–e the Wittig methodology,5f,g or addition of
C-nucleophiles followed by dehydration;5h Ramberg–Bäcklund
A not yet studied possibility for the formation of septanose
glycals/exo-glycals may be the rearrangement of a carbene
attached to the anomeric carbon of a sugar derivative (Scheme
1, I). To this end one has to find access to suitable precursors of
such intermediates and to study the possibilities of their trans-
formations outlined in Scheme 1. 1,2-O and 1,2-C shifts might
result in seven-membered ring glycals III and IV, and the prod-
ucts of the two routes would be indistinguishable from each
other if R1 = R2. Shift of the R2 substituent (1,2-H shift if R2 =
H) should lead to exo-glycal derivatives II. Other pathways
than substituent shifts may also be operative and should be
considered depending on the structure of the products.6
Chart 1
Scheme 1
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 3
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 4 0 3 9 – 4 0 4 6
4039

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Scheme 2 a: Raney-Ni, NaH2PO2, PhNHCH2CH2NHPh, pyridine, AcOH, H2O; b: p-TsOHؒH2O, acetone, CH2Cl2; c: Raney-Ni, NaH2PO2,
TsNHNH2, pyridine, AcOH, H2O; d: Raney-Ni, NaH2PO2, pyridine, AcOH, H2O; e: NaH, abs. 1,4-dioxane, reflux; f: TsNHNH2, p-TsOH, molecular
sieves (3 Å) abs. 1,4-dioxane.
In this paper we present a full account of our investigations
into the preparation of 2,5- and 2,6-anhydro-aldose tosyl-
hydrazones as precursors of C-glycosylmethylene carbenes
(I, R1 = R2 = H) whose generation and ensuing transformation
lead to exo-glycals II.7
and sodium hypophosphite in aqueous acetic acid and pyrid-
ine.17 Under these conditions the product should be trapped as
an imidazolidine derivative 2 by 1,2-dianilinoethane, because,
in the absence of a trapping agent, the reaction gave e.g. 2,6-
anhydro-ald-2-enose 4 (1-formyl-galactal) as the ultimate
product.18 C-Glycosyl aldehyde 3 can be obtained from 2 by
acid catalyzed hydrolysis in moderate yields.
The conversion of nitriles to aldehydes with Raney-nickel in
aqueous alcohols under hydrogen atmosphere was studied in
some details and trapping the intermediate with a carbonyl
reagent proved advantageous to prevent formation of the corre-
sponding methylamine derivative.19 While 1,2-dianilinoethane
mentioned above and semicarbazide were very effective,
phenylhydrazine was less efficient, and tosyl- and benzoyl-
hydrazine as well as hydroxylamine were reported to give no
useful results.20
In keeping with the above reports we have found that the
reduction of 1 with Raney-nickel and sodium hypophosphite in
aqueous acetic acid and pyridine in the presence of semicarb-
azide gave anhydro-aldose semicarbazones.21 In our hands,
contrary to the reported failure, tosylhydrazine proved also
effective and besides several non-sugar aldehyde tosylhydra-
zones22 anhydro-aldose tosylhydrazones 5 were isolated in
acceptable to good yields (Table 1).
As little as 10% excess reagent tosylhydrazine was sufficient
to obtain the expected hydrazone (entry 2), and the crude
products were generally pure enough for further transform-
ations. The reaction of 1c led to a complex mixture at room
temperature, however, at 40 ЊC 5c could be isolated in an
acceptable yield (entry 6). Under the same conditions un-
saturated nitrile 9 gave a mixture of products which were not
separated. The corresponding tosylhydrazone 10 was obtained
by a conventional condensation of 1-formyl-galactal 4 with
tosylhydrazine.
Results and discussion
Precursors
From the classes of compounds known to be suitable for carb-
ene generation8 C-glycosyl derivatives of diazomethane,9
monohalomethanes,5n–p,10 oxirane,11 and tetrazole12 have so far
been described in the literature. Since C-glycosyl diazo-
methanes are extremely labile,13 and the preparation of
C-glycosyl halomethanes14 as well as oxiranes is rather lengthy,
and because carbene generation from the latter can be expected
to occur at the least substituted carbon, only 5-glycosyl
tetrazoles have been investigated as precursors of C-glyco-
sylmethylene carbenes. As these experiments were rather dis-
couraging (under several thermolytic or photolytic conditions
either decomposition or no reaction was observed) other
precursors have been sought for.
A widely used method for the generation of carbenes is the
aprotic Bamford–Stevens reaction: thermo- or photolysis of
tosylhydrazone salts.15 The corresponding precursors of
C-glycosylmethylene carbenes, i.e. anhydro-aldose tosylhydra-
zones (5 in Scheme 2) can expectedly be prepared from anhy-
dro-aldoses 3, however, these “C-glycosyl aldehydes”, although
known, are not readily accessible especially with pyranoid rings
mainly because of the lengthiness of the preparative pro-
cedures.16 One of the most straightforward ways to obtain
C-glycosyl aldehydes is reduction of the nitrile moiety in
anhydro-aldononitriles (glycosyl cyanides) 1 by Raney-nickel
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 4 0 3 9 – 4 0 4 6
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Table 1 Preparation of 2,5- and 2,6-anhydro-aldose tosylhydrazones at room temperature
Starting compound
Entry
1
mmol
TsNHNH2/mmol (eq.)
React. timea/h
Product
Isolated yieldb(%)
1
2
3
4
5
6
7
8
9
a
a
a
b
c
c
d
e
f
8.40
11.19
0.14
0.98
0.17
0.86
3.50
0.70
1.13
0.21
14.28 (1.7)
12.31 (1.1)
0.24 (1.7)
1.67 (1.7)
0.29 (1.7)
1.46 (1.7)
4.20 (1.2)
0.84 (1.2)
1.36 (1.2)
0.36 (1.7)
4
7
3
6
6
2f
4
5
5
4
5a
5a
5a
87c
90c
55
5b
60d
e
5c
5d
5e
5f
64
73g
69
58
h
10
g
5g
a The reaction time may depend on the quality of the Raney-nickel. b By column chromatography. c Crude product. d 94% conversion.
e Complex reaction mixture. f Reaction temperature: 40 ЊC. g By crystallization. h This product could not be isolated in pure state.
1
The H NMR spectra of compounds 5 exhibited resonances
for the 4-methylbenzenesulfonyl moiety (δ 2.2–2.4 ppm, 3H
singlets for CH3; 6.9–7.8 ppm, two 2H doublets, J = 7.9–8.1 Hz,
for the aromatic protons), the NH proton (δ 8.1–11.6 ppm, 1H
broad singlets), and H-1 (δ 7.0–7.3 ppm, 1H doublets, J1,2 = 6.3–
6.8 Hz for the 2,3-trans configurated 5a–d, 4.8 Hz for 5e, 5.5 Hz
for 5f, and 6.0 Hz for 5g). The vicinal couplings indicated that
the sugar moieties existed in the conformations depicted for
5a–d,f, with 5e undergoing a conformational change as com-
pared to the parent compound 1e to accommodate the bulky
tosylhydrazone moiety in an equatorial position. In the 13C
NMR spectra characteristic signals appeared for the 4-methyl-
benzenesulfonyl groups (δ 144–145, 135–137, 127–131 ppm for
the aromatic carbons, 21.4–21.8 ppm for CH3), for C-1 (δ 143–
146 ppm), and for the sugar carbons as expected.
Each of these spectra exhibited one set of resonances show-
ing that one diastereomer of 5 was present in the samples. From
the gradient enhanced 15N–1H long-range correlation experi-
ments (G-HSQMBC)23 all of the chemical shifts and coupling
constants of 15N have been obtained (Fig. 1). On the basis of the
sign and magnitude of two- and three-bond 15N–1H coupling
constants,24 the configuration of the carbon–nitrogen double
bond in the –CH ᎐N –N H moiety could unambiguously be
᎐
b
b
a
a
2
assigned. The value of 3.7 Hz measured for JNbHb suggests an
anti orientation of the lone-pair electrons on nitrogen (δNb
325.21 ppm) to the methine proton attached to the adjacent
=
carbon, i.e. E configuration around the C᎐N double bond. The
᎐
value of three-bond coupling constants, 3JNaHb = 7.9 Hz (where
δNa = 167.24 ppm), indicates a cis-arrangement of the relevant
atoms as well. This conclusion was corroborated by a single
crystal X-ray investigation of 5d (Fig. 2).
Generation of C-glycosylmethylene carbenes and isolation of
their ensuing products
According to the Bamford–Stevens protocol, generation of
carbenes can be effected by photo- or thermolysis of (usually
sodium) salts of tosylhydrazones in an aprotic solvent.15
Because of milder conditions photolysis of the sodium salt of
5a obtained with sodium hydride in 1,4-dioxane was tried first.
After 4.5 hours irradiation with a 150 W mercury lamp in a
quartz tube the starting material disappeared, and a complex
reaction mixture was obtained. The only product to be isolated
was 6a (8%). Use of other conditions, like tBuOK in tBuOH
did not give better results.
Thermolytic reactions (Table 2) were carried out by placing a
base into a solvent, which was heated to reflux and a solution of
5 in the same solvent was added dropwise to the vigorously
stirred refluxing mixture. A comparison of the conditions in
entries 1–5 indicates that NaH in 1,4-dioxane gave the best iso-
lated yields. Increasing the excess of the base enhanced the pro-
portion of 6a over 8a (Entries 6 and 7) and similar observations
Fig. 1 Expansion of the relevant parts of the 15N–1H HSQMBC
spectrum of 5d used to establish the configuration of the C᎐N double
᎐
bond.
were made in other cases, as well (Entries 8–13). The formation
of compounds 8 suggested that with incomplete deprotonation
of 5 the formed carbene (7) could insert into the NH bond of 5
(or, alternatively, the probable intermediate C-glycosyl diazo-
methane alkylated 5) as it was observed with other substrates as
well.25 Since compounds 6 formed in rather clean reactions
(in reactions of entries 7, 11, 13, and 15 TLC showed only the
product) and were isolated in fairly good yields, it can be con-
cluded that the main pathway for the transformation of carb-
enes 7 is the 1,2-H shift and the other possibilities shown in
Scheme 1 play only a subordinate role if any.
The Bamford–Stevens reaction of 10 gave isolable products
under neither photolytic nor thermolytic conditions.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 4 0 3 9 – 4 0 4 6
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Table 2 Generation of C-glycosylmethylene carbenes by thermolysis and isolation of their ensuing products
Isolated yielda (%)
Starting compound
Entry
5
mmol
Base (eq.)
Solvent
6
8
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
a
a
a
a
a
a
a
b
b
c
c
d
d
e
f
0.57
0.38
0.57
0.57
0.57
0.38
0.76
0.38
0.12
0.33
0.26
0.66
0.44
0.22
tBuOK (2.0)
NaOMe (3.0)
tBuOH
Diglyme
Diglyme
7
15
8
Not isolated
14
18
19
NaH
(2.4)
NaOMe (2.0)
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
1,4-Dioxane
26
52
59
82
11
39
16
72
25
86
18
74
25c
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
NaH
(1.2)
(5.0)
(10.0)
(1.7)
(10.0)
(2.2)
(10.0)
(1.2)
(10.0)
(2.0)
(10.0)
(∼2.0)
17
Not isolated
Not formed
59
22
45
Not formed
30
Not formed
Not observed
Not formed
Not observed
0.26
b
g
a By column chromatography. b From the crude product. c Yield from 1g.
Perkin-Elmer 16 PC FT-IR spectrometer. Routine NMR
spectra were recorded with Bruker WP 360 SY (360/90 MHz for
1H/13C) and Avance DRX 500 (500/125/50 MHz for 1H/13C/15N)
spectrometers, J values are quoted in Hz. Chemical shifts are
referenced to Me4Si (1H), to the residual solvent signals (13C), or
to NH4Cl as external standard (15N). TLC was performed on
DC-Alurolle Kieselgel 60 F254 (Merck); the plates were visual-
ized by gentle heating or with UV light. For column chromato-
graphy Kieselgel 60 (Merck) was used. Organic solutions were
dried on MgSO4, and concentrated in vacuo at 40–50 ЊC (water
bath).
15N NMR experimental
NMR experiments were performed on a Bruker DRX 500 spec-
trometer equipped with a triple resonance (1H/13C/15N) x,y,z-
gradient probe. The temperature for all measurements was set
to 300 K. All spectra were processed with XWINNMR 2.6.
Samples of 5–10 mg in 600 µl CDCl3 or C6D6 were used for all
experiments, except for the long range 1H–15N correlation
spectra of 5d (∼40–60 mg in 500 µl CDCl3).
Fig. 2 ORTEP drawing of 5d. Selected bond length (Å), angle (Њ) and
torsion angle (Њ) data: C1–C2 1.474(8), C1–N1 1.243(7), N1–N2
1.390(7), N2–S1 1.615(6), S1–O8 1.443(5), S1–O9 1.444(5), S1–C13
1.741(8); C2–C1–N1 120.9(7), C1–N1–N2 116.2(8), N1–N2–S1
118.8(6), N2–S1–O8 106.6(4), N2–S1–O9 104.8(4); O1–C2–C1–N1
125.2, C2–C1–N1–N2 Ϫ175.4.
1H NMR assignments were established on the basis of gradi-
ent enhanced DQF-COSY spectra.27 Proton chemical shifts
(referenced to internal TMS) and scalar coupling constants
were extracted from the resolution enhanced 1D proton
spectra. COSY spectra were recorded with 512 × 2k data
points, spectral widths 4000 Hz, number of transients 4 and
recycle delay of 1.8 s.
1
Exo-glycals 6 exhibited characteristic resonances in their H
NMR spectra26 for H-1 (δ 4.6–5.0 ppm) and H-1Ј (δ 4.2–4.7
ppm) which appeared as triplets (J1,1Ј = 1.5–2.1 Hz, J1,3 < 1 to
1.5 Hz, J1Ј,3 < 1 to 1.8 Hz). Signals for C-1 and C-2 were
observed around 95–97 ppm and 152–155 ppm for 6a–f and at
87.1 and 157.7 ppm for 6g, respectively. All other protons and
carbons resonated as expected. For 8d a complete assignment
of proton resonances was accomplished by COSY experiments.
In summary, the Raney-nickel–sodium-hypophosphite
reduction of the nitrile group in anhydro-aldononitriles (glyco-
syl cyanides) in the presence of tosylhydrazine constitutes a
simple method to obtain anhydro-aldose tosylhydrazones. The
scope and limitations of this reductive transformation as to
the preparation of other azomethine derivatives of anhydro-
aldoses have been described elsewhere.21 Aprotic Bamford–
Stevens reaction of these tosylhydrazones opens a new way to
exo-glycals which have thus become easily accessible with acyl
protecting groups as well.
Proton–nitrogen coupling constants were measured by the
recently proposed gradient enhanced HSQMBC experiment23
(heteronuclear single quantum multiple bond correlation) with
selective excitation of CHb and NaHa protons. Selective excit-
ation of proton resonances was achieved by a Gaussian pulse of
35 ms. Two HSQMBC spectra were acquired with 150 × 512
data points, spectral width of 100000 Hz in 15N and 500 Hz
1
in H dimension, number of transients 16 and recycle delay
of 2.0 s. The relevant two- and three-bond proton–nitrogen
coupling constants (Fig. 1) were determined from the pure
absorption phase multiplets after sufficient zero-filling during
processing to establish 0.3 Hz resolution in the F2 dimension.
In-phase splitting of the multiplets is due to proton–proton
coupling, while the heteronuclear coupling yields antiphase
multiplet structure (see Fig. 1).
Experimental
General experimental methods
General procedure for the synthesis of anhydro-aldose
tosylhydrazones 5
Melting points were measured on a Kofler hot-stage apparatus
and are uncorrected. Optical rotations were determined with a
Perkin-Elmer 241 polarimeter at room temperature. [α]D values
are given in 10Ϫ1deg cm2 gϪ1. IR spectra were taken with a
(For the actually used amounts of reagents see Table 1): Raney-
nickel (1.5 g per 1 mmol substrate, from an aqueous suspension,
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 4 0 3 9 – 4 0 4 6
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Merck) was added at room temperature to a vigorously stirred
solution of pyridine (5.7 mL per 1 mmol substrate), acetic acid
(3.4 mL per mmol substrate), and water (3.4 mL per 1 mmol
substrate). Then sodium hypophosphite (0.74 g, 8.4 mmol),
tosylhydrazine (0.20 g–0.32 g, 1.1–1.7 mmol), and the corre-
sponding anhydro-aldononitrile 1 (1 mmol) were added to the
mixture. When the reaction was complete (TLC, eluent: ethyl
acetate–hexane 1 : 1) the insoluble materials were filtered off
with suction, and washed with dichloromethane (10 mL). The
organic layer of the filtrate was separated, washed with water
(3 mL), 10% aqueous hydrogen chloride solution (2 × 3 mL),
cold, saturated sodium hydrogencarbonate solution (2 × 3 mL),
water (3 mL), and then dried on anhydrous magnesium sulfate.
The solution was concentrated under reduced pressure, and
traces of pyridine were removed by repeated co-evaporations
with toluene. The residue was purified by column chromato-
graphy (eluent: ethyl acetate–hexane 1 : 1 or 1 : 2) to give 5a–c,e,
and f, while 5d was obtained by crystallization from a mixture
of ethyl acetate and hexane.
3,4,5,7-Tetra-O-benzoyl-2,6-anhydro-D-glycero-D-gulo-
heptose tosylhydrazone (5c). Colourless syrup; [α]D ϩ 4 (c 1.00
in CHCl3); δH (360 MHz; CDCl3) 8.12 (1 H, br s, NH), 8.04–
7.74 (8 H, m, OBz), 7.58 (2 H, d, J 7.9, Ts), 7.57–7.21 (12 H, m,
OBz), 7.16 (1 H, d, J1,2 6.3, H-1), 6.90 (2 H, d, J 7.9, Ts), 5.93,
5.67, 5.41 (3 H, 3 pseudo t, J 9.5, H-3, H-4, H-5), 4.58 (1 H,
dd, J7,7Ј 12.1, H-7Ј), 4.43 (1 H, dd, H-7), 4.36 (1 H, dd, J2,3 9.5,
H-2), 4.15 (1 H, ddd, J6,7 5.3, J6,7Ј 2.1, H-6), 2.19 (3 H, s, CH3);
δC (90 MHz; CDCl ) 166.3, 165.9, 165.6, 165.3 (C᎐O), 144.1
᎐
3
(C-1), 143.7, 135.2 (Ts quaternary), 133.6, 133.4, 133.2, 129.8,
129.6, 129.3, 128.4, 127.3 (Ts, OBz), 128.7, 128.6 (OBz quater-
nary), 78.1, 76.2, 73.7, 70.7, 69.3 (C-2, C-3, C-4, C-5, C-6), 63.2
(C-7), 21.6 (CH3); IR νmax/cmϪ1 3200, 1732, 1452, 1268, 1166,
1094, 710 (Found: C, 64.82; H, 4.74; N, 3.72. Calc. for
C42H36N2O11S: C, 64.94; H, 4.67; N, 3.61%).
3,4,5-Tri-O-acetyl-2,6-anhydro-D-manno-hexose tosylhydra-
zone (5d). White crystals; mp 83–86 ЊC; [α]D Ϫ 35 (c 1.01 in
CHCl3); δH (360 MHz; CDCl3) 8.93 (1 H, br s, NH), 7.81 (2 H,
d, J 7.9, Ts), 7.33 (2 H, d, J 7.9, Ts), 7.03 (1 H, d, J1,2 6.8, H-1),
5.33 (1 H, br s, H-5), 5.18 (1 H, dd, J3,4 10.0, H-3), 5.09 (1 H, dd,
J4,5 3.1, H-4), 3.99 (1 H, d, J5,6 < 1, J6,6Ј 13.1, H-6), 3.89 (1 H, dd,
J2,3 9.5, H-2), 3.68 (1 H, d, J5,6Ј < 1, H-6Ј), 2.42 (CH3-Ts), 2.15,
2.01, 1.75 (9 H, 3 s, 3 × OAc); δC (90 MHz; CDCl3) 170.6, 170.2,
General method for the synthesis of exo-glycals 6
(For the actual amounts of reagents see Table 2): Sodium
hydride (0.24 g, 10 mmol, or the amount indicated in Table 2)
was added to dry 1,4-dioxane (25 mL). The suspension was
stirred and heated to reflux, and then a solution of a tosyl-
hydrazone 5 (1 mmol) in dry 1,4-dioxane (25 mL) was added
dropwise. When the reaction was complete (TLC, eluent: ethyl
acetate–hexane 1 : 1), the mixture was cooled down, and the
insoluble material filtered off. The solvent was removed under
diminished pressure, and the residue was purified by column
chromatography (eluent: gradient of ethyl acetate–hexane 1 : 2
to 1 : 1) to give exo-glycals 6a–d,f, and g.
170.0 (C᎐O), 144.3 (C-1), 144.0, 135.3 (Ts quaternary), 129.5,
᎐
127.9 (Ts), 78.5, 70.5, 68.4, 67.1 (C-2, C-3, C-4, C-5), 67.8 (C-6),
21.4 (CH3-Ts), 20.8, 20.5, 20.2 (CH3); IR νmax/cmϪ1 3202, 1748,
1372, 1224, 1166, 1050 (Found: C, 50.07; H, 5.39; N, 6.05. Calc.
for C19H24N2O9S: C, 49.99; H, 5.30; N, 6.14%).
3,4,5-Tri-O-acetyl-2,6-anhydro-D-gluco-hexose
tosylhydra-
zone (5e). Colourless syrup; [α]D Ϫ 4 (c 1.00 in CHCl3); δH (360
MHz; acetone-d6) 10.1 (1 H, br s, NH), 7.75 (2 H, d, J 8.1, Ts),
7.39 (2 H, d, J 8.1, Ts), 7.25 (1 H, d, J1,2 4.8, H-1), 5.31 (1 H, dd,
J4,5 3.8, H-4), 5.07 (1 H, ddd, J5,6 10.0, J5,6Ј 3.3, H-5), 4.99 (1 H,
dd, J2,3 2.2, H-2), 4.44 (1 H, dd, J3,4 4.5, H-3), 3.83 (1 H, dd, J6,6Ј
11.0, H-6Ј), 3.71 (1 H, dd, H-6), 2.41 (3 H, s, CH3-Ts), 2.11,
1.96, 1.94 (9 H, 3 s, 3 × OAc); δC (90 MHz; acetone-d6) 170.1,
Isolation of compounds 8
These compounds were obtained from reactions conducted
under conditions given above for exo-glycals 6 modified accord-
ing to the data shown in Table 2. Isolation of 8 was effected by
column chromatography (eluent: gradient of ethyl acetate–
hexane 1 : 2 to 1 : 1).
169.8 (C᎐O), 146.2 (C-1), 144.7, 137.2 (Ts quaternary), 130.4,
᎐
128.5 (Ts), 74.1, 69.9, 66.9, 66.3 (C-2, C-3, C-4, C-5), 64.0 (C-6),
21.4 (CH3-Ts), 20.7, 20.6, 20.5 (CH3); IR νmax/cmϪ1 3208, 1750,
1372, 1222, 1066 (Found: C, 49.88; H, 5.39; N, 6.22. Calc. for
C19H24N2O9S: C, 49.99; H, 5.30; N, 6.14%).
3,4,5,7-Tetra-O-acetyl-2,6-anhydro-D-glycero-L-manno-
heptose tosylhydrazone (5a). Colourless syrup; [α]D ϩ 6 (c 0.97
in CHCl3); δH (360 MHz; DMSO-d6) 11.62 (1 H, br s, NH), 7.67
(2 H, d, J 7.9, Ts), 7.42 (2 H, d, J 7.9, Ts), 7.00 (1 H, d, J1,2 6.7,
H-1), 5.29 (1 H, d, J5,6 < 1.0, H-5), 5.22 (1 H, dd, J4,5 3.1, H-4),
4.95 (1 H, dd, J3,4 10.4, H-3), 4.24–4.20 (1 H, m, H-6), 4.14 (1 H,
dd, J2,3 9.8, H-2), 4.00 (1 H, dd, J6,7Ј 4.9, J7,7Ј 11.6, H-7Ј), 3.93
(1 H, dd, J6,7 7.4, H-7), 2.37 (3 H, s, CH3-Ts), 2.11, 1.98, 1.90,
1.66 (12 H, 4 s, 4 × OAc); δC (90 MHz; CDCl3) 170.6, 170.5,
4,5,7-Tri-O-acetyl-2,6-anhydro-3-deoxy-3-phthalimido-D-
glycero-D-gulo-heptose tosylhydrazone (5f). White crystals; mp
207 ЊC dec.; [α]D ϩ 65 (c 1.01 in CHCl3); δH (360 MHz; DMSO-
d6) 11.48 (1 H, br s, NH), 7.90–7.80 (4 H, m, Phth), 7.34 (2 H, d,
J 7.9, Ts), 7.10 (1 H, d, J1,2 5.5, H-1), 7.07 (2 H, d, J 7.9, Ts),
5.62, 5.02, 4.30 (3 H, 3 pseudo t, J 9.5–10.0, H-3, H-4, H-5),
4.87 (1 H, dd, J2,3 10.4, H-2), 4.16 (1 H, dd, J7,7Ј 12.5, H-7),
4.07–4.03 (2 H, m, H-6, H-7Ј), 2.27 (3 H, s, CH3-Ts), 2.02, 1.99,
1.76 (9 H, 3 s, 3 × OAc); δC (90 MHz; CDCl3) 170.8, 170.3,
170.2, 170.1 (C᎐O), 144.1 (C-1), 144.1, 135.5 (Ts quaternary),
᎐
129.6, 127.9 (Ts), 78.2, 74.3, 71.0, 67.6, 66.9 (C-2, C-3, C-4, C-5,
C-6), 61.7 (C-7), 21.4 (CH3-Ts), 20.6, 20.2 (CH3); IR νmax/cmϪ1
3208, 1752, 1372, 1228, 1166, 1054 (Found: C, 49.91; H, 5.45;
N, 5.42. Calc. for C22H28N2O11S: C, 50.00; H, 5.34; N, 5.30%).
169.7, 168.0, 167.5 (C᎐O), 144.0 (C-1), 144.2, 135.1 (Ts quater-
᎐
nary), 131.6, 131.5 (Phth quaternary), 134.4, 123.9 (Phth),
129.6, 127.8 (Ts), 76.1, 73.9, 71.3, 68.9 (C-2, C-4, C-5, C-6), 62.3
3,4,5,7-Tetra-O-acetyl-2,6-anhydro-D-glycero-D-gulo-heptose
tosylhydrazone (5b). Colourless syrup; [α]D Ϫ 8 (c 1.33 in
CHCl3); δH (360 MHz; CDCl3) 9.16 (1 H, br s, NH), 7.80 (2 H,
d, J 7.9, Ts), 7.34 (2 H, d, J 7.9, Ts), 7.00 (1 H, d, J1,2 6.3, H-1),
5.26 (1 H, dd, J3,4 9.4, H-3), 5.05 (1 H, dd, J4,5 10.0, H-4), 5.01–
4.94 (1 H, m, H-5), 4.24 (1 H, dd, J7,7Ј 12.2, H-7), 4.07 (1 H, dd,
H-7Ј), 3.99 (1 H, dd, J2,3 9.5, H-2), 3.72 (1 H, ddd, J5,6 9.5, J6,7
5.3, J6,7Ј 1.8, H-6), 2.42 (3 H, s, CH3-Ts), 2.07, 2.03, 2.01, 1.72
(12 H, 4 s, 4 × OAc); δC (90 MHz; CDCl3) 170.8, 170.6, 170.2,
(C-7), 52.3 (C-3), 21.8 (CH3-Ts), 20.9, 20.7, 20.6 (CH3); IR νmax/
cmϪ1 3194, 1750, 1718, 1384, 1230, 1166, 1042 (Found: C,
54.72; H, 4.92; N, 6.95. Calc. for C28H29N3O11S: C, 54.63; H,
4.75; N, 6.83%).
3,4,6-Tri-O-benzoyl-2,5-anhydro-D-allo-hexose
tosylhydra-
zone (5g). Crude product, colourless syrup; δH (360 MHz;
CDCl3) 8.35 (1 H, br s, NH), 8.08–7.27 (15 H, m, Bz), 7.74 (2 H,
d, J 8.2, Ts), 7.16 (1 H, d, J1,2 6.0, H-1), 7.11 (2 H, d, J 8.2, Ts),
5.69 (1 H, dd, J4,5 3.8, H-4), 5.64 (1 H, dd, J3,4 5.5, H-3), 4.83
(1 H, t, J2,3 6.0, H-2), 4.64 (1 H, dd, J6,6Ј 11.4, H-6Ј), 4.58 (1 H,
dd, J5,6 3.8, J5,6Ј 3.2, H-5), 4.47 (1 H, dd, H-6), 2.27 (3 H, s,
169.6 (C᎐O), 144.3, 135.5 (Ts quaternary), 143.7 (C-1), 129.8,
᎐
128.0 (Ts), 77.8, 75.9, 73.1, 69.6, 68.3 (C-2, C-3, C-4, C-5, C-6),
62.1 (C-7), 21.6 (CH3-Ts), 20.8, 20.7, 20.3 (CH3); IR νmax/cmϪ1
3186, 1754, 1368, 1226, 1166, 1036 (Found: C, 50.15; H, 5.48;
N, 5.21. Calc. for C22H28N2O11S: C, 50.00; H, 5.34; N, 5.30%).
CH3); δC (90 MHz; CDCl ) 166.3, 165.4, 165.2 (C᎐O), 145.7
᎐
3
(C-1), 144.0, 135.2 (Ts quaternary), 135.5, 129.8, 129.6, 128.6,
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 4 0 3 9 – 4 0 4 6
4043

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128.5 (Ts, OBz), 128.9 (OBz quaternary), 80.5, 80.0, 73.4, 72.8
(C-2, C-3, C-4, C-5), 64.4 (C-6), 21.5 (CH3); IR νmax/cmϪ1 3208,
1728, 1452, 1270, 1168, 710.
H-3), 5.30 (1 H, ddd, J5,6 3.2, J5,6Ј 1.6, H-5), 5.10 (1 H, dd, J4,5
3.2, H-4), 4.69 (1 H, pseudo t, J1,1Ј 1.6, J1,3 1.6, H-1), 4.49 (1 H,
pseudo t, J1Ј,3 1.6, H-1Ј), 4.02 (1 H, dd, J6,6Ј 12.6, H-6), 3.92
(1 H, dd, H-6Ј), 2.12, 2.10, 1.99 (9 H, 3 s, 3 × OAc); δC (90 MHz;
4,5,7-Tri-O-acetyl-2,6-anhydro-3-deoxy-D-lyxo-hept-2-enose
tosylhydrazone (10). Formyl galactal 4 (200 mg, 0.66 mmol) was
dissolved in dry 1,4-dioxane (2 mL), molecular sieves (3 Å) and
then a solution of tosylhydrazine (150 mg, 0.78 mmol) in dry
1,4-dioxane (2 mL) were added in one portion, followed by
4-methylbenzenesulfonic acid (12 mg, 0.066 mmol). The mix-
ture was stirred at room temp. until disappearance of the start-
ing material (1–2 days). After filtration and evaporation of the
solvent the residue was dissolved in diethyl ether, washed with
water, dried, and the solvent removed. Attempted purification
by silica gel column chromatography resulted in partial decom-
position, therefore the crude product (282 mg, 90%) was used
for further experiments. Colourless syrup; δH (360 MHz; acet-
one-d6) 10.26 (1 H, br s, NH), 7.81 (2 H, d, J 7.9, Ts), 7.40 (2 H,
d, J 7.9, Ts), 7.39 (1 H, br s, H-1), 5.69 (1 H, dd, J4,5 3.0, H-4),
5.45 (1 H, d, J3,4 4.3, H-3), 5.15 (1 H, br s, H-5), 4.54 (1 H, m,
H-6), 4.32 (1 H, dd, J6,7 7.0, J7,7Ј 11.3, H-7), 4.22 (1 H, dd, J6,7Ј
5.8, H-7Ј), 2.40 (3 H, s, CH3-Ts), 2.06, 2.05, 1.96 (9 H, 3 s,
CDCl ) 170.3, 170.0, 169.5 (C᎐O), 154.5 (C-2), 96.9 (C-1), 70.3,
᎐
3
67.8, 67.7 (C-3, C-4, C-5), 68.3 (C-6), 21.0, 20.9, 20.8 (CH3); IR
νmax/cmϪ1 1748, 1662, 1372, 1218, 1070 (Found: C, 53.11; H,
5.84. Calc. for C12H16O7: C, 53.01; H, 5.92%).
4,5,7-Tri-O-acetyl-2,6-anhydro-1,3-dideoxy-3-phthalimido-D-
glycero-D-gluco-hept-1-enitol (6f). Colourless syrup; [α]D ϩ 29
(c 1.08 in CHCl3); δH (360 MHz; CDCl3) 7.88 (2 H, dd, Phth),
7.76 (2 H, dd, Phth), 5.92 (1 H, pseudo t, J4,5 9.7, H-4), 5.30
(1 H, pseudo t, J5,6 9.8, H-5), 5.07 (1 H, ddd, J3,4 9.8, H-3), 4.80
(1 H, dd, J1,1Ј 1.8, J1,3 1.5, H-1), 4.42 (1 H, dd, J7,7Ј 12.3, H-7),
4.24 (1 H, pseudo t, J1Ј,3 1.8, H-1Ј), 4.22 (1 H, dd, H-7Ј), 4.01
(1 H, ddd, J6,7 4.2, J6,7Ј 1.8, H-6), 2.06, 2.04, 1.87 (9 H, 3 s, 3 ×
OAc); δC (90 MHz; CDCl ) 170.7, 170.0, 169.5, 167.0 (C᎐O),
᎐
3
151.9 (C-2), 131.4 (Phth quaternary), 134.6, 123.8 (Phth), 95.7
(C-1), 75.8, 70.8, 68.3 (C-4, C-5, C-6), 61.8 (C-7), 51.4 (C-3),
20.7, 20.6, 20.5 (CH3); IR νmax/cmϪ1 1748, 1732, 1380, 1222,
1048, 722 (Found: C, 58.32; H, 5.04; N, 3.12. Calc. for
C21H21NO9: C, 58.47; H, 4.91; N, 3.25%).
3 × OAc); δC (90 MHz; acetone-d ) 170.6, 170.3 (C᎐O), 150.3
᎐
6
(C-2), 144.7, 137.2 (Ts quaternary), 142.1 (C-1), 130.3, 128.6,
128.4 (Ts), 105.4 (C-3), 74.2, 65.5, 63.8 (C-4, C-5, C-6), 62.3
(C-7), 21.4 (CH3-Ts), 20.6, 20.5 (CH3).
3,4,6-Tri-O-benzoyl-2,5-anhydro-1-deoxy-D-ribo-hex-1-enitol
(6g). Colourless syrup; [α]D ϩ 24 (c 0.90 in CHCl3); δH (360
MHz; CDCl3) 8.09–7.89 (6 H, m, OBz), 7.60–7.31 (9 H, m,
OBz), 6.20 (1 H, ddd, J3,4 5.3, H-3), 5.73 (1 H, t, J4,5 5.3, H-4),
4.89 (1 H, ddd, J5,6 4.2, J5,6Ј 3.7, H-5), 4.72 (1 H, dd, J6,6Ј 12.1,
H-6Ј), 4.67 (1 H, pseudo t, J1,1Ј 1.5, J1,3 1.5, H-1), 4.57 (1 H, dd,
H-6), 4.44 (1 H, pseudo t, J1Ј,3 1.5, H-1Ј); δC (90 MHz; CDCl3)
3,4,5,7-Tetra-O-acetyl-2,6-anhydro-1-deoxy-D-galacto-hept-
1-enitol (6a). Colourless syrup; [α]D ϩ 74 (c 1.45 in CHCl3);
(lit.,10a [α]2D5 ϩ 70 (c 1.10 in CHCl3); δH (360 MHz; CDCl3) 5.69
(1 H, ddd, J3,4 10.5, H-3), 5.52 (1 H, dd, J5,6 1.5, H-5), 5.06 (1 H,
dd, J4,5 3.1, H-4), 4.82 (1 H, dd, J1,1Ј 2.1, J1,3 1.5, H-1), 4.51 (1 H,
dd, J1Ј,3 1.6, H-1Ј), 4.21 (1 H, dd, J7,7Ј 11.5, H-7), 4.15 (1 H, dd,
H-7Ј), 4.02 (1 H, ddd, J6,7 6.8, J6,7Ј 6.4, H-6), 2.17, 2.14, 2.07,
2.01 (12 H, 4 s, 4 × OAc); δC (90 MHz; CDCl3) 170.5, 170.2,
165.4, 166.2 (C᎐O), 157.7 (C-2), 133.6, 133.5, 133.4, 133.3,
᎐
129.9, 128.6 (OBz), 129.3, 128.9 (OBz quaternary), 87.1 (C-1),
80.6, 72.0, 70.9 (C-3, C-4, C-5), 63.9 (C-6); IR νmax/cmϪ1 1728,
1266, 1118, 708 (Found: C, 70.80; H, 4.94. Calc. for C27H22O7:
C, 70.74; H, 4.84%).
170.0, 169.6 (C᎐O), 154.1 (C-2), 96.1 (C-1), 75.7, 71.3, 67.7,
᎐
67.0 (C-3, C-4, C-5, C-6), 61.7 (C-7), 20.8, 20.7 (CH3); IR
νmax/cmϪ1 2942, 1748, 1666, 1372, 1216, 1084 (Found: C, 52.39;
H, 5.98. Calc. for C15H20O9: C, 52.33; H, 5.85%).
3,4,5,7-Tetra-O-acetyl-2,6-anhydro-D-glycero-L-manno-
heptose-[N-(4-methylbenzenesulfonyl)-N-(2Ј,3Ј,4Ј,6Ј-tetra-O-
acetyl-ꢀ-D-galactopyranosylmethyl)] hydrazone (8a). Colourless
syrup; [α]D ϩ 25 (c 0.87 in CHCl3); δH (360 MHz; C6D6)
7.92 (2 H, d, J 8.4, Ts), 7.33 (1 H, d, J1,2 6.3, H-1), 6.79 (2 H, d,
J 7.8, Ts), 5.62–5.44 (4 H, m), 5.29–5.16 (2 H, m), 4.32–
4.23 (2 H, m), 4.19–4.02 (2 H, m), 4.01–3.84 (2 H, m), 3.68–
3.60 (2 H, m), 3.51–3.39 (1 H, m), 3.25 (1 H, t), 2.05 (3 H,
s, CH3-Ts) 1.94, 1.85, 1.83, 1.76, 1.70, 1.67, 1.64, 1.55 (24 H,
8 s, 8 × OAc); δC (90 MHz; CDCl3) 170.6, 170.3, 170.2, 170.1
3,4,5,7-Tetra-O-acetyl-2,6-anhydro-1-deoxy-D-gluco-hept-1-
enitol (6b). Colourless syrup; [α]D ϩ 41 (c 1.02 in CHCl3);
δH (360 MHz; CDCl3) 5.47 (1 H, d, J3,4 8.4, H-3), 5.22 (1 H, dd,
J5,6 9.4, H-5), 5.16 (1 H, pseudo t, J4,5 8.5, H-4), 4.84 (1 H, br s,
J1,1Ј < 1.0, J1,3 < 1.0, H-1), 4.56 (1 H, br s, J1Ј,3 < 1.0, H-1Ј), 4.29
(1 H, dd, J7,7Ј 12.6, H-7), 4.20 (1 H, dd, H-7Ј), 3.84 (1 H, ddd,
J6,7 4.2, J6,7Ј 2.1, H-6), 2.13, 2.11, 2.05, 2.04 (12 H, 4 s, 4 × OAc);
δC (90 MHz; CDCl ) 170.8, 170.1, 169.5, 169.3 (C᎐O), 153.2
(C᎐O), 144.4, 134.8 (Ts quaternary), 140.9 (C-1), 129.7, 128.3
᎐
᎐
3
(C-2), 96.7 (C-1), 76.4, 73.4, 69.3, 68.2 (C-3, C-4, C-5, C-6), 62.0
(C-7), 20.9, 20.8, 20.7 (CH3); IR νmax/cmϪ1 1748, 1668, 1372,
1216, 1038 (Found: C, 52.44; H, 5.72. Calc. for C15H20O9: C,
52.33; H, 5.85%).
(Ts), 79.2, 77.5, 74.4, 74.1, 72.1, 71.0, 67.8, 67.6, 67.4, 67.1 (C-2,
C-3, C-4, C-5, C-6, C-1Ј, C-2Ј, C-3Ј, C-4Ј, C-5Ј), 61.7, 60.9 (C-7,
C-6Ј), 48.4 (CH2-N), 21.7 (CH3-Ts), 21.0, 20.8, 20.7, 20.6
(CH3); IR νmax/cmϪ1 1748, 1372, 1228, 1050 (Found: C, 51.18;
H, 5.67, N, 3.11. Calc. for C37H48N2SO20: C, 50.91; H, 5.54; N,
3.21%).
3,4,5,7-Tetra-O-benzoyl-2,6-anhydro-1-deoxy-D-gluco-hept-1-
enitol (6c). Colourless syrup; [α]D ϩ 43 (c 0.98 in CHCl3);
δH (360 MHz; CDCl3) 8.08–8.03 (4 H, m, OBz), 7.93–7.87 (4 H,
m, OBz), 7.59–7.26 (12 H, m, Bz), 5.98–5.80 (3 H, m, H-3, H-4,
H-5 strongly coupled), 4.96 (1 H, pseudo t, J1,1Ј 1.5, J1,3 1.5,
H-1), 4.71 (1 H, pseudo t, J1Ј,3 1.5, H-1Ј), 4.71 (1 H, dd, J6,7Ј 3.1,
J7,7Ј 12.1, H-7Ј), 4.53 (1 H, dd, J6,7 4.7, H-7), 4.32–4.27 (1 H, m,
3,4,5,7-Tetra-O-acetyl-2,6-anhydro-D-glycero-D-gulo-heptose-
[N-(4-methylbenzenesulfonyl)-N-(2Ј,3Ј,4Ј,6Ј-tetra-O-acetyl-ꢀ-D-
glucopyranosylmethyl)] hydrazone (8b). Colourless syrup; [α]D ϩ
8 (c 1.02 in CHCl3); δH (360 MHz; CDCl3) 7.72 (2 H, d, J 7.9,
Ts), 7.31 (2 H, d, J 7.9, Ts), 7.05 (1 H, d, J1,2 6.4, H-1), 5.33–5.15
(2 H, m), 5.13–4.85 (4 H, m), 4.27–4.01 (4 H, m), 3.99–3.50
(6 H, m), 2.42 (3 H, s, CH3-Ts), 2.15–2.01 (21 H, m, 7 × OAc),
1.82 (3 H, s, OAc); δC (90 MHz; CDCl3) 170.6, 170.4, 170.3,
H-6); δC (90 MHz; CDCl ) 166.3, 165.7, 165.2, 165.1 (C᎐O),
᎐
3
153.3 (C-2), 133.7, 133.5, 133.3, 130.1, 129.9, 128.7, 128.6,
128.5 (OBz), 129.7, 129.1, 129.0, 128.9, (OBz quaternary), 97.3
(C-1), 77.0, 73.3, 69.9, 69.1 (C-3, C-4, C-5, C-6), 63.0 (C-7); IR
νmax/cmϪ1 1732, 1602, 1452, 1270, 1094, 708 (Found: C, 71.08;
H, 4.89. Calc. for C35H28O9: C, 70.94; H, 4.76%).
170.1, 169.5 (C᎐O), 144.4, 134.6 (Ts quaternary), 141.0 (C-1),
᎐
129.7, 128.4 (Ts), 78.7, 76.9, 75.9, 75.7, 74.2, 73.1, 70.3, 69.8,
68.4, 68.1 (C-2, C-3, C-4, C-5, C-6, C-1Ј, C-2Ј, C-3Ј, C-4Ј, C-5Ј),
62.2, 61.6 (C-7, C-6Ј), 48.3 (CH2-N), 21.6 (CH3-Ts), 20.9, 20.8,
20.7, 20.4 (CH3); IR νmax/cmϪ1 1748, 1366, 1226, 1034 (Found:
C, 51.02; H, 5.69; N, 3.35. Calc. for C37H48N2SO20: C, 50.91; H,
5.54; N, 3.21%).
3,4,5-Tri-O-acetyl-2,6-anhydro-1-deoxy-D-manno-hex-1-eni-
tol (6d). White crystals; mp 98–100 ЊC; [α]D Ϫ 94 (c 0.99 in
CHCl3); δH (360 MHz; DMSO-d6) 5.42 (1 H, ddd, J3,4 10.0,
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 4 0 3 9 – 4 0 4 6
4044

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2 Carbohydrate Mimics, Concepts and Methods, ed. Y. Chapleur,
3,4,5,7-Tetra-O-benzoyl-2,6-anhydro-D-glycero-D-gulo-
heptose-[N-(4-methylbenzenesulfonyl)-N-(2Ј,3Ј,4Ј,6Ј-tetra-O-
benzoyl-ꢀ-D-glucopyranosylmethyl)] hydrazone (8c). Colourless
syrup; δH (360 MHz; CDCl3) 8.14–7.75 (14 H, m), 7.60–7.27
(29 H, m), 6.80 (2 H, d, J 7.9, Ts), 5.95–5.83 (2 H, m), 5.66
(1 H, t), 5.53–5.43 (2 H, m), 5.12–5.03 (2 H, m), 4.74 (1 H, dd),
4.56 (1 H, dd), 4.45–4.31 (2 H, m), 4.28 (1 H, dd), 4.21–4.00
(2 H, m), 3.95–3.71 (2 H, m), 2.12 (3 H, s, CH3); δC (90 MHz;
Wiley-VCH, Weinheim, 1998; Glycoscience: Chemistry and Chemical
Biology, eds. B. O. Fraser-Reid, K. Tatsuta and J. Thiem, Springer,
Berlin, Heidelberg, 2001, vol III, pp. 2533–2752.
3 (a) L. Somsák, Chem. Rev., 2001, 101, 81–135; (b) W. Priebe,
G. Grynkiewicz, in Glycoscience: Chemistry and Chemical Biology,
eds. B. Fraser-Reid, K. Tatsuta, J. Thiem, Springer, Berlin,
Heidelberg, 2001, vol I, p. 749–784; (c) A. G. Tolstikov and G. A.
Tolstikov, Usp. Khim., 1993, 62, 621–643.
4 Z. Pakulski, Pol. J. Chem., 1996, 70, 667–707.
CDCl ) 166.3, 166.1, 166.0, 165.8, 165.6, 165.4, 165.3 (C᎐O),
᎐
3
5 Leading references for the preparation of exo-glycal derivatives:
(a) C. S. Wilcox, G. W. Long and H. Suh, Tetrahedron Lett., 1984,
25, 395–398; (b) T. V. RajanBabu and G. S. Reddy, J. Org. Chem.,
1986, 51, 5458–5461; (c) R. Csuk and B. I. Glänzer, Tetrahedron,
1991, 47, 1655–1664; (d ) C. R. Johnson and B. A. Johns, Synlett,
1997, 1406–1408; (e) X. Li, H. Ohtake, H. Takahashi and
S. Ikegami, Tetrahedron, 2001, 57, 4283–4295; ( f ) M. Lakhrissi and
Y. Chapleur, Angew. Chem., Int Ed. Engl., 1996, 35, 750–752; (g)
Y. Lakhrissi, C. Taillefumier, M. Lakhrissi and Y. Chapleur,
Tetrahedron: Asymmetry, 2000, 11, 417–421 and references therein;
(h) W.-B. Yang, Y.-Y. Yang, Y.-F. Gu, S.-H. Wang, C.-C. Chang and
C.-H. Lin, J. Org. Chem., 2002, 67, 3773–3782; (i) F. K. Griffin,
P. V. Murphy, D. E. Paterson and R. J. K. Taylor, Tetrahedron Lett.,
1998, 39, 8179–8182; (j) P. S. Belica and R. W. Franck, Tetrahedron
Lett., 1998, 39, 8225–8228; (k) F. K. Griffin, D. E. Paterson, P. V.
Murphy and R. J. K. Taylor, Eur. J. Org. Chem., 2002, 1305–1322;
(l ) J.-M. Lancelin, J.-R. Pougny and P. Sinaÿ, Carbohydr. Res., 1985,
136, 369–374; (m) J.-P. Praly, G.-R. Chen, J. Gola and G. Hetzer,
Eur. J. Org. Chem., 2000, 2831–2838; (n) M. Brockhaus and
J. Lehmann, Carbohydr. Res., 1977, 53, 21–31; (o) O. R. Martin and
F. Xie, Carbohydr. Res., 1994, 264, 141–146; (p) R. D. Guthrie,
I. D. Jenkins, J. J. Watters, M. W. Wright and R. Yamasaki,
Aust. J. Chem., 1982, 35, 2169–2173.
143.9, 134.1 (Ts quaternary), 142.3 (C-1), 78.6, 77.3, 76.2, 74.5,
73.6, 71.0, 69.5 (C-2, C-3, C-4, C-5, C-6, C-1Ј, C-2Ј, C-3Ј,
C-4Ј, C-5Ј), 63.6, 63.0 (C-7, C-6Ј), 49.3 (CH2-N), 21.6 (CH3); IR
νmax/cmϪ1 1732, 1452, 1270, 1094, 710.
3,4,5-Tri-O-acetyl-2,6-anhydro-D-manno-hexose-[N-(4-meth-
ylbenzenesulfonyl)-N-(2Ј,3Ј,4Ј-tri-O-acetyl-ꢁ-D-arabinopyrano-
sylmethyl)] hydrazone (8d). White crystals; mp 182–185 ЊC dec.;
[α]D Ϫ 65 (c 0.90 in CHCl3); δH (HSQMBC) (500 MHz; C6D6)
8.00 (2 H, d, J 8.2, Ts), 7.44 (1 H, d, J1,2 6.6, H-1), 6.86 (2 H, d,
J 8.2, Ts), 5.64 (1 H, dd, J3,4 10.2, H-3), 5.60 (1 H, t, J2Ј,3Ј 9.9,
H-2Ј), 5.32 (2 H, br s, H-5, H-4Ј), 5.28 (1 H, dd, J4,5 3.7, H-4),
5.22 (1 H, dd, J3Ј,4Ј 3.7, H-3Ј), 4.20 (1 H, d, JCH2a,1Ј 14.2, CH2a–
N), 3.90 (1 H, dd, J2,3 9.4, H-2), 3.77 (1 H, dd, J4Ј,5Јeq 2, J5Јeq,5Јax
13.3, H-5Јeq), 3.65 (1 H, dd, JCH2b,1Ј 5.8, CH2b–N), 3.63 (1 H, dd,
J1Ј,2Ј 9.0, H-1Ј), 3.58 (1 H, dd, J5,6eq 1.8, J6eq,6ax 13.3, H-6eq), 3.16
(1 H, d, J4Ј,5Јax 13.3, H-5Јax), 2.88 (1 H, d, J5,6ax 13.3, H-6ax), 2.16
(CH3-Ts), 1.96, 1.93, 1.86, 1.82, 1.76, 1.69 (18 H, 6 s, 6 × OAc);
δC (90 MHz; CDCl ) 170.6, 170.5, 170.3, 170.2, 170.1 (C᎐O),
᎐
3
144.3, 134.8 (Ts quaternary), 140.9 (C-1), 129.6, 128.2 (Ts),
79.6, 77.6, 71.7, 70.7, 68.7, 68.6, 68.2, 67.3 (C-2, C-3, C-4, C-5,
C-1Ј, C-2Ј, C-3Ј, C-4Ј), 68.1, 67.8 (C-6, C-5Ј), 48.6 (CH2–N),
21.6 (CH3-Ts), 21.1, 21.0, 20.9, 20.7, 20.5 (CH3); IR νmax/cmϪ1
1748, 1372, 1222. (Found: C, 51.22, H, 5.64, N, 3.72. Calc. for:
C31H40N2O16S: C, 51.10; H, 5.53; N, 3.84%).
6 S. Kim and J.-Y. Yoon, Synthesis, 2000, 1622–1630.
7 Part of this work has been published as a preliminary communi-
cation: M. Tóth and L. Somsák, J. Chem. Soc., Perkin. Trans.1,
2001, 942–943.
8 For a general account on carbene generation and precursors see:
M. Regitz, Methoden der organischen Chemie (Houben-Weyl),
Thieme, Stuttgart, 1989, vol E19b.
9 (a) J. Farkas and F. Sorm, Coll. Czech. Chem. Commun., 1972, 37,
2798–2803; (b) E. M. Acton, A. N. Fujiwara, L. Goodman and
D. W. Henry, Carbohydr. Res., 1974, 33, 135–151; (c) M. Brockhaus,
H. Fritz and J. Lehmann, Carbohydr. Res., 1979, 68, 225–230.
10 J. Lehmann and B. Schwesinger, Carbohydr. Res., 1982, 107,
43–53.
11 S. D. Shiyan, O. E. Lahtina, M. L. Shulman and A. Y. Khorlin, Izv.
Akad. Nauk SSSR, 1976, 197–199; S. Hanessian, T. J. Liak and
D. M. Dixit, Carbohydr. Res., 1981, 88, C14–C19.
12 I. Farkas, I. F. Szabó and R. Bognár, Carbohydr. Res., 1977, 56, 404–
406.
13 A study on the decomposition of 2,6-anhydro-1-deoxy-1-diazo--
glycero--manno-heptitol (C-galactopyranosyl diazomethane) under
X-Ray crystallographic structure determination of 5d†
Colourless block crystals (0.66 × 0.55 × 0.4 mm) of C19H24-
N2O9S, M = 456.46, orthorhombic, a = 9.939(7) Å, b = 12.907(5)
Å, c = 20.160(3) Å, V = 2586(2) Å3, Z = 4, space group: P212121,
ρcalc = 1.172 g cmϪ3. Data were collected at 293(1) K, Enraf
Nonius MACH3 diffractometer, Mo Kα radiation λ = 0.71073
Å, ω-2θ motion, θmax = 25.3Њ, 5867 measured reflections of
which 2786 reflections were unique with I > 2σ(I ), decay: 38%.
The structure was solved using the SIR-92 software28 and
refined on F2 using SHELX-97 program,29 publication material
was prepared with the WINGX-97 suite,30 R(F) = 0.0533 and
wR(F 2) = 0.1828 for 5867 reflections, 288 parameters. H atoms
were placed into geometric positions except N–H and hydrogen
on C1 which were found at the difference electron density
map and refined isotropically. Residual electron density: 0.269/
Ϫ0.196 e/Å3.
protic conditions showed the intermediacy of
a ”C-galacto-
pyranosyl methylium“ ion whose ensuing products contained exo-
glycal 8a (H instead of Ac) in less than 3% ratio. See ref. 9c.
14 These compounds have been directly transformed into the
corresponding exo-glycal derivatives by base induced hydrogen
halide elimination: see refs. 5n–p and 10.
15 K.-P. Zeller and H. Gugel in Methoden der organischen Chemie
(Houben-Weyl), ed. M. Regitz, Thieme, Stuttgart, 1989, vol E19b, p.
225–243; K. Maruoka, H. Yamamoto, in Comprehensive Organic
Synthesis, eds. B. M. Trost, I. Fleming, Pergamon, Oxford, 1991, vol
6, p. 776–779.
Acknowledgements
16 For leading references see ref. 3a (section III. C).
17 (a) H.-M. Dettinger, G. Kurz and J. Lehmann, Carbohydr. Res.,
1979, 74, 301–307; (b) H. P. Albrecht, D. B. Repke and J. G. Moffatt,
J. Org. Chem., 1973, 38, 1836–1840.
Financial support from the Hungarian Scientific Research
Fund (Grants: OTKA T032124, and OTKA T034515) is
gratefully acknowledged.
18 R. R. Schmidt and K. Frische, Bioorg. Med. Chem. Lett., 1993, 8,
1747–1750; K. Frische and R. R. Schmidt, Liebigs Ann., 1994, 297–
303.
19 M. Rabinovitz, in The chemistry of the cyano group,
ed. Z. Rappoport, John Wiley & Sons, London, 1970, p. 307–340.
20 H. Plieninger and G. Werst, Angew. Chem., 1955, 67, 156–157;
H. Plieninger and G. Werst, Chem. Ber., 1955, 88, 1956–1961;
H. Plieninger and B. Kiefer, Chem. Ber., 1957, 90, 617–623.
21 M. Tóth and L. Somsák, Carbohydr. Res., 2003, 338, 1319–
1325.
† CCDC reference number 213880. See http://www.rsc.org/suppdata/
ob/b3/b307378e/ for crystallographic data in .cif or other electronic
format.
References and notes
1 (a) Preparative Carbohydrate Chemistry, ed. S. Hanessian, Marcel
Dekker, New York, 1997; (b) Modern Methods in Carbohydrate
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Chemical Biology, eds. B. Fraser-Reid, K. Tatsuta and J. Thiem,
Springer, Berlin, Heidelberg, 2001, vol I–III.
22 M. Tóth and L. Somsák, Tetrahedron Lett., 2001, 42, 2723–
2725.
23 R. T. Williamson, B. L. Marquez, W. H. Gerwick and K. E. Kövér,
Magn. Reson. Chem., 2000, 38, 265–273.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 4 0 3 9 – 4 0 4 6
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24 G. J. Martin, M. L. Martin, J.-P. Gouesnard, in NMR Basic
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of this series, prepared by the dehydrohalogenation of the
corresponding acetylated β--galactopyranosyl iodomethane
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27 R. E. Hurd, J. Magn. Reson., 1990, 87, 422–428.
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29 G. M. Sheldrick, SHELXL-97, Universität Göttingen, Germany
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26 An exact correlation with the published data was observed
for the proton spectrum of 8a, the only known compound
30 L. J. Farrugia, WINGX-97 system, University of Glasgow, U.K.
1996.
O r g . B i o m o l . C h e m . , 2 0 0 3 , 1, 4 0 3 9 – 4 0 4 6
4046