Efficient stereocontrolled synthesis of C-glycosides using glycosyl donors substituted by propane 1,3-diyl phosphate as the leaving group

Article abstract of DOI:10.1016/S0957-4166(01)00305-6

α- and β-Glycosyl cyanides, per-O-acetyl-1,2-O-1-cyanoethylidenes and C-allyl glycopyranosides were efficiently prepared by treatment of 2,3,4-tri-O-acetyl-α,β-L-rhamno-, L-fuco- and 2,3,4,6-tetra-O-acetyl-α,β-D-galactopyranosyl propane-1,3-diyl phosphate

Full text of DOI:10.1016/S0957-4166(01)00305-6

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 1727–1735
Efficient stereocontrolled synthesis of C-glycosides using glycosyl
donors substituted by propane 1,3-diyl phosphate as the leaving
group
Gurdial Singh* and Hariprasad Vankayalapati
Department of Chemistry, University of Sunderland, Sunderland SR1 3SD, UK
Received 25 May 2001; accepted 29 June 2001
Abstract—a- and b-Glycosyl cyanides, per-O-acetyl-1,2-O-1-cyanoethylidenes and C-allyl glycopyranosides were efficiently
prepared by treatment of 2,3,4-tri-O-acetyl-a,b-
L
-rhamno-,
L
-fuco- and 2,3,4,6-tetra-O-acetyl-a,b-D-galactopyranosyl propane-1,3-
diyl phosphates with trimethylsilyl cyanide (TMSCN) and allyltrimethylsilane in the presence of trimethylsilyl triflate (TMSOTf).
-manno- and -glucopyranosyl propane-1,3-diyl phosphates were employed in the synthesis
Similarly 2,3,4,6-tetra-O-benzyl-a,b-
D
D
of C-glycosides. © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
Glycosyl cyanides are versatile intermediates as the
cyano group can be easily transformed into a variety of
other functionalities.5c Early methods for the prepara-
tion of cyanides involved the use of peracylated glyco-
syl halides with mercury(II)6a or silver cyanides,6b and
more recently via radical cyanation reactions.6c Other
approaches for the synthesis of these compounds
involve the cyanation of fluoroglycosides with
Me2AlCN and the reduction of C-glycopyranosyl
nitromethanes with PCl3 and pyridine.7
The fact that cell–cell interactions are dependant on the
interaction of oligosaccharides at the cell surface has
recently been accepted by the chemical and biological
communities. Binding of these oligosaccharides by
receptor proteins leads to cell adhesion1 and the biolog-
ical consequences of these events can be beneficial, as in
fertilisation, or detrimental, as in the case of bacterial2
or viral adhesion3 and inflammation.4 The development
of structures that can interrupt the binding of the
receptors of specific carbohydrates or that can be used
as probes becomes important in therapeutic regimes
and has been the impetus behind these areas of
research. However, the use of glycosides has been ham-
pered by the fact that the glycosidic bond is susceptible
towards hydrolysis and a plethora of enzymes exist to
accomplish such tasks in vivo. This liability has led to
the design and synthesis of glycomimetics with the aim
that the biological properties of naturally occurring
glycosides would be retained while being resistant
towards hydrolysis.
The allyl group can be simply converted to epoxypropyl
functions that are recognised as active site-directed
irreversible inhibitors of sugar processing enzymes.8
Furthermore, the double bond of the allyl group allows
a wide range of transformations that are centred on its
cleavage to an active aldehyde group that can be readily
elaborated.9 This strategy has been extended to incor-
porate the synthetic potential of C-vinyl and C-alkynyl
glycosides.10
The main approaches used for the synthesis of C-allyl
glycosides have involved the treatment of benzylated
glycolactones with allylmagnesium bromide followed by
stereoselective reduction of the resulting hemiketal
product with triethylsilane in the presence of boron
trifluoride etherate.11
The C-glycosides constitute such a class of compounds
and there are a number of reports of such naturally
occurring structures.5 Central among this class are gly-
cosyl cyanides and C-allyl glycosides, which are
regarded as being synthetically useful for the prepara-
tion of biologically important carbohydrate analogues.
The Keck reaction has also been employed using either
tri-n-butylallyltin or allylic sulphides or sulphones.12
Access to these C-allyl glycosides is most commonly
* Corresponding author. E-mail: gurdial.singh@sunderland.ac.uk
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00305-6

1728
G. Singh, H. Vankayalapati / Tetrahedron: Asymmetry 12 (2001) 1727–1735
1
achieved using protected glycosyl fluorides, 1-O-acetyl
glycopyranoses and other sugar derivatives with
allyltrimethylsilane13 in the presence of Lewis acids.
More recently there has been an approach that uses the
Keck radical allylation of protected sugar dihalides.14
One of the drawbacks of these approaches is that with
the exception of the Kishi method11 the reactions
invariably proceed in moderate yields and the stereose-
lectivity is usually in favour of the a-anomer.
contrast, the H NMR spectrum of 6b showed a dou-
blet (J 8.6 Hz) for C(1)H at l 5.49. The 13C NMR
spectra showed C(1) signals of 6a and 6b l 94.81 with
JC-H 183.8 Hz and l 93.46 with JC-H 162.3, respectively.
With these phosphates in hand we investigated their
displacement reaction with TMSCN and allyltrimethyl
silane in the presence of TMSOTf17 as an anomeric
activator, the findings are detailed in the Table 1. In the
case of O-acetyl glycosyl donors of
L-rhamno-, L-fuco-
and -galactopyranoses 6, 10 and 16 (Table 1) with
D
2. Results and discussion
TMSCN and TMSOTf in CH2Cl2 solvent at −78°C, to
our surprise we obtained 1,2-O-(1-cyanoethylidene)-gly-
coses as exo/endo mixture of 9a/9b, 15a/15b and 21a/
21b in yields of 79, 73 and 76%, respectively (Schemes
2 and 3).18
In our recent investigations we have introduced the
propane-1,3-diyl phosphate as the anomeric leaving
group at the anomeric centre of 2,3,4,6-tetra-O-benzyl-
a,-
D
-gluco-,
-fuco-
D
-mannopyranoses,15 2,3,4-tri-O-acetyl-
a,b-
L
and
2,3,4,6-tetra-O-acetyl-a,b-galacto-
In the case of the
L
-fucopyranosyl donor 10 we
pyranoses and successfully prepared a,b-O-glycosides
and fucosidase substrates.16 Herein, we report on our
findings targeted at the synthesis of C-glycosides
obtained exo isomer 15a as the major product (72%
yield) and its endo isomer 15b obtained in low yield of
1%. Prior to these findings similar compounds were
prepared by Meyers19 in poor yields ranging from
8–14% using mercury cyanide as the cyanide source.
The formation of these products can be readily
explained by trapping of the intermediate acetoxonium
employing
L-rhamno-, L-fuco-, D-galacto-, D-manno-
and -glucosyl donors having propane-1,3-diyl phos-
phate as an anomeric leaving group.
D
The requisite O-acetyl and O-benzyl protected glycosyl
donors were readily prepared by means of phosphoryla-
tion of the anomeric hydroxyl group with propane-1,3-
diyldioxyphosphoryl chloride 5 in the presence of
N-methyl imidazole in excellent yields.15,16 Similarly
1
ion by cyanide ion. The H and 13C NMR spectral data
of the a-cyanoacetals were consistent with the struc-
tures. The 13C NMR data were most informative for
assignment of the exo/endo isomers and exhibit the
ꢀCꢁN resonance in the region between 116 to 117
ppm.19 These a-cyanoacetals were stereoselectively con-
verted to the corresponding per-O-acetyl glycopyran-
osyl cyanides (Schemes 2 and 3) by treatment with 1
equiv. of TMSOTf at room temperature for 24 h. Both
acetylation of
dride and pyridine solvent gave 1,2,3,4-tetra-O-acetyl-
-rhamnopyranose 2, which was converted to the
L
-rhamnopyranose 1 with acetic anhy-
a,b-
L
a-rhamnopyranosyl bromide 3 by treatment with 33%
HBr–AcOH. Oxidation of 3 with Ag2CO3 gave 2,3,4-
the
L-fuco-, and D-galactopyranosyl 1,2-O-(1-cyano-
tri-O-acetyl-a,b- -rhamnopyranose 4 in 86% overall
L
ethylidene) derivatives 15a/15b and 21a/21b were
readily rearranged to the corresponding C-cyano gly-
cosides in good yields (Table 1). Thus, the propane-1,3-
yield. Reaction of 4 with propane-1,3-diyldioxyphos-
phoryl chloride 5 gave phosphates 6a and 6b as a
hygroscopic mixture in a 5:1 ratio (Scheme 1).
diyl 2,3,4-tri-O-acetyl-a,b-L-fucopyranosyl phosphate
10 with TMSCN in the presence of 1 equiv. of
TMSOTf gave a mixture of compounds 11 and 125c,19
in 63 and 15% yields, respectively, with the a-isomer
predominant (ratio=4:1). In the case of glycosyl donor
In all of the cases examined it was found that the
a-anomer was the major product based on the 1H
NMR spectral data. The 1H NMR spectrum of 6a
showed a quartet (J 1.3 Hz) for C(1)H at l 5.64 and a
multiplet (JP-H 15.2 Hz) for the C(5ax) and C(5eq)
protons at l 1.86–1.93 and l 2.32–2.38 respectively. In
16 we obtained 2,3,4,6-tetra-O-acetyl-b-D-galactopy-
ranosyl cyanide 18 as the major product in 45%
Scheme 1. (i) Ac2O, Py, rt, 12 h; (ii) 33% HBr–AcOH, rt, 15 min; (iii) Ag2CO3, acetone, 0.5 h.

G. Singh, H. Vankayalapati / Tetrahedron: Asymmetry 12 (2001) 1727–1735
1729
Table 1. Reactions of O-acetyl and O-benzyl protected glycosyl donors with TMSCN and allyltrimethylsilane in presence of
with TMSOTf
yield.7b,7c,19 The
L
-rhamanose analogue 9a/9b was more
ration of C-cyano glycosides. In the case of glycosyl
donor 22 on treatment with TMSCN in presence of
resistant to conversion using these conditions in that
only 37% of 7a was obtained after 24 hours along with
recovered a-cyanoacetal 9a in 46% yield, reflecting the
increased stability of the cis-fused 6,5-ring system
towards Lewis acids. The 13C NMR spectral data of
these a,b-C-glycosyl cyanides exhibit a resonance
between 113 and 114 ppm and consistent with the data
of reported compounds.7b,19
TMSOTf at −78°C afforded a mixture of a,b-D-
mannopyranosyl cyanides 23 and 24 (Scheme 3) in 49
and 32% and the a:b ratio is 3:2. The stereochemistry at
1
the anomeric centre was assigned on the basis of H
and 13C NMR spectral data. In particular the reso-
nance for the cyanide carbon at l 116.02 (a-anomer)
and 115.36 (b-anomer) was particularly informative and
this was in agreement with the data reported by
Ichikawa,20 however, this was not consistent with the
Similarly, the O-benzylated
ranosyl donors 22 and 27 were employed in the prepa-
D-manno- and D-glucopy-
data reported by Gervay.20b,21 In the case of the
D-

1730
G. Singh, H. Vankayalapati / Tetrahedron: Asymmetry 12 (2001) 1727–1735
Scheme 2. (i) 1 equiv. of TMSCN, cat. TMSOTf, −78 to 0°C, CH2Cl2, 0.5 h; (ii) 1 equiv. of allyltrimethylsilane, TMSCN, cat.
to 1 equiv. of TMSOTf, −78 to 0°C, CH2Cl2, 0.5–24 h.
glucopyranosyl donor 27 under similar reaction condi-
ophilicity of the allyltrimethyl silane function in com-
parison to trimethylsilyl cyanide.
tions we obtained a,b- -glucopyranosyl cyanides 28
D
and 29 with selectivity in favour of the a-isomer (a:b
ratio, 3:2).
We have performed further allylation experiments with
allyltrimethylsilane on O-benzyl protected glycosyl
Under similar conditions, treatment of O-acetyl pro-
tected glycosyl donors 6 and 10 (Table 1) with
allyltrimethyl silane in presence of TMSOTf at −78°C
resulted in the formation of the C-allyl glycosides
donors 22 and 27. Thus, C-glycosidation of
D-
mannopyranosyl phosphate 22 with TMSOTf at −78°C
afforded the a,b-C-allyl mannopyranosides9a,b,13b 25
and 26 (Scheme 3) in good yield (a:b anomers 1:1)
(Scheme 3). When glycosyl donor 27 was reacted with
allyltrimethylsilane in presence of TMSOTf under simi-
lar conditions we obtained higher stereoselectivity in
(Scheme 2). Initially 3-(tri-O-acetyl-a-L-rhamnopyran-
osyl)-1-propene 8a9b was obtained in 76% yield and its
b-isomer was identified in TLC, but we were unable to
isolate the compound 8b (ratio a,b=4:1). Reaction of
glycosyl donor 10 with allyltrimethylsilane gave mixture
that b-C-allyl- -glucoside 30b (Scheme 3) was the
D
major isomer, (ratio a:b 1:12) in 79% yield. We were
unable to isolate the a-isomer by silica gel column
chromatography.
of 3-(tri-O-acetyl-a,b- -fucopyranosyl)-1-propene 13
L
and 1422 in yields of 49 and 31%, respectively. Allyla-
tion of glycosyl donor 16 with allyltrimethylsilane, the
a,b-
-galactoyranosyl-1-propene 1912c and 2014,22 was
D
obtained (Scheme 3) in 12 and 61% yield with high
b-selectivity (a,b=1:5). In the examples wherein 6, 10
and 16 were the glycosyl donors we did not observe the
analogous orthoesters, reflecting the increased nucle-
3. Conclusion
We have demonstrated that the treatment of a range of
O-acetyl and O-benzyl protected glycosyl donors with
Scheme 3. (i) 1 equiv. of TMSCN, cat. TMSOTf, −78 to 0°C, CH2Cl2, 0.5 h; (ii) 1 equiv. of allyltrimethylsilane, TMSCN, cat.
to 1 equiv. of TMSOTf, −78 to 0°C, CH2Cl2, 0.5–4 h.

G. Singh, H. Vankayalapati / Tetrahedron: Asymmetry 12 (2001) 1727–1735
1731
TMSCN and allyltrimethylsilane in the presence of
TMSOTf as an anomeric activator proceeds in good
yields, high stereoselectivity and provides ready access
to C-glycosides.
JP-H=15.2 Hz, H-5ax), 2.01 (3H, s), 2.08 (3H, s), 2.17
(3H, s), 2.32–2.38 (1H, m, JP-H=15.2 Hz, H-5eq), 4.03–
4.16 (1H, m), 4.38–4.59 (4H, m), 5.13 (1H, d, J=9.2
Hz), 5.29–5.36 (2H, m), 5.64 (1H, q, J=1.3 Hz); 13C
NMR (67.8 MHz, CDCl3) l 17.17, 20.37, 20.49 (2C),
25.67, 68.31, 68.59, 68.91, 69.05, 69.09, 70.03, 94.81
(JC-H=183.8 Hz), 169.63, 169.97 (2C); 31P NMR
(109.25 MHz, CDCl3) l −11.63; m/z (CI, NH3) calcd
for C15H27NO11P: 428.1322. Found: 428.1322 [M+
NH4]+; anal. calcd for C15H27NO11P: C, 43.91; H, 5.65;
P, 7.55. Found: C, 43.34; H, 5.31; P, 7.68. For isomer
4. Experimental
Melting points were determined on a GallenKamp cap-
illary melting-point apparatus and are uncorrected.
Optical rotations were determined on a Bellingham &
Stanley ADP 220 polarimeter. [h]D values are in units
of 10−1 deg cm2 g−1. All reactions were monitored by
TLC on Silica Gel 60 F-254 plated (Merck) with detec-
tion by UV, phosphomolybdic acid or basic aq. potas-
sium permanganate solutions. Flash chromatography
was performed on a Silica Gel 60 (230–400 mesh,
Merck). All reactions were carried out under argon or
nitrogen atmosphere in oven-dried glassware unless
otherwise stated. CH2Cl2 was distilled from calcium
1
6b (minor): H NMR (270 MHz, CDCl3) l 5.49 (d,
J=8.6 Hz), 13C NMR (67.8 MHz, CDCl3) l 93.46 (d,
J=3.9, JC-H=162.3 Hz); 31P NMR (109.25 MHz,
CDCl3) l −10.90.
4.2. 2,3,4-Tri-O-acetyl-a-L-rhamnopyranosyl cyanide 7a
To a stirred solution of propane-1,3-diyl 2,3,4-tri-O-
acetyl-a,b- -rhamnopyranosyl phosphate 6 (1 g, 2.44
L
,
hydride and stored over 4 A molecular sieves. Organic
mmol) and TMSOTf (540 mg, 2.44 mmol) in dry
CH2Cl2 (10 mL) at 0°C was added trimethylsilyl cya-
nide (240 mg, 2.42 mmol) over 5 min and the reaction
mixture stirred for 24 h at rt. After quenching with aq.
NaHCO3 (10 mL), the mixture was diluted with CH2Cl2
(10 mL) and washed with water (15 mL). The organic
phase was dried over Na2SO4. The solvent was removed
in vacuo and the residue was purified by silica gel
column chromatography (EtOAc–‘petrol’ 7:3) to give
7a as a white solid (0.270 g, 37%): mp 117–119°C;
[h]2D2=+19.7 (c 1.5, CHCl3); wmax (KBr) 3023, 2980,
1754, 1430, 1373, 1216 cm−1;1H NMR (270 MHz,
CDCl3) l 1.29 (3H, d, J=5.9 Hz), 2.00 (3H, s), 2.06
(3H, s), 2.25 (3H, s), 3.51 (1H, dq, J=5.9, 3.3 Hz), 4.58
(1H, d, J=1.3 Hz), 4.97 (1H, dd, J=3.3, 2.6 Hz), 5.04
(1H, d, J=9.2 Hz), 5.59 (1H, dd, J=3.3, 1.3 Hz); 13C
NMR (67.8 MHz, CDCl3) l 17.33, 20.38, 20.41, 20.55,
66.43, 67.80, 69.35, 70.47, 75.52, 113.90, 169.53, 169.66,
169.94; m/z (CI, NH3) calcd for C13H21N2O7: 317.3196.
Found: 317.2361 [M+NH4]+.
solutions were dried over Na2SO4 and evaporations
were carried out under reduced pressure at 40°C.
‘Petrol’ refers to petroleum spirit (distillation range
40–60°C), which was distilled prior to use, and ‘ether’
refers to diethyl ether.
The 1H NMR and 13C NMR spectra were recorded
with JEOL GSX 270 NMR spectrometer, for solutions
in CDCl3 (unless stated otherwise) [residual CHCl3 (lH
7.26 ppm) or CDCl3 (lC 77.0 ppm) as internal stan-
dard] at 300 K. 31P NMR spectra were recorded in
CDCl3, at 109.25 MHz on a JEOL GSX 270 NMR
spectrometer, using trimethyl phosphate as the external
reference. IR spectra were recorded on a UNICAM
series FTIR spectrometer. Mass spectra were obtained
on an AEI MS 902 or VG ZAB-E spectrometer. Micro-
analysis were performed by MEDAC Ltd, Surrey, UK.
4.1. 2%,3%,4%-Tri-O-acetyl-a,b-
L-rhamnopyranosyl-[1,3,2]-
dioxaphosphinane 2-oxide 6a and 6b
2,3,4-Tri-O-acetyl-a,b-
L
-rhamnopyranose 4 (3 g, 10.34
4.3. 3-(2,3,4-Tri-O-acetyl-a-
L-rhamnopyranosyl)-1-
mmol) was dissolved in CH2Cl2 (30 mL) and the solu-
tion was cooled to 0°C. To this solution was added
2-chloro-[1,3,2]-dioxaphosphinane-2-oxide 5 (4.84 g,
31.03 mmol) and 1-methylimidazole (2.5 g, 30.44 mmol)
dropwise over 5 min. Stirring was continued for 16 h,
with gradual warming to room temperature. The sol-
vent was removed, the residue was re-dissolved in
CH2Cl2 (30 mL) and the resulting solution was evapo-
rated to remove traces of 1-methylimidazole. The
resulting residue was dissolved in CH2Cl2 (30 mL) and
washed successively with ice-water (30 mL), aq.
NaHCO3 (2×30 mL) and water (30 mL). The organic
layer was dried over Na2SO4 and the solvent was
removed in vacuo. The oily residue was purified by
silica gel column chromatography (EtOAc–‘petrol’ 7:3)
to afford the phosphates 6a and 6b (ratio 5:1) as an
inseparable hygroscopic mixture (2.70 g, 63%). For
isomer 6a (major): [h]1D9mix=−35.7 (c 2.9, CHCl3); IR
propene 8a
A solution of 6 (1 g, 2.44 mmol) in CH2Cl2 (10 mL) was
cooled to −78°C under an N2 gas atmosphere was
added TMSOTf (catalytic). After 2 min allyltrimethylsi-
lane (280 mg, 2.45 mmol) in CH2Cl2 (2 mL) was added,
and the reaction mixture was stirred for 30 min at
−78°C and then allowed to warm to 0°C. The reaction
mixture was diluted with CH2Cl2 (10 mL) and washed
successively with aq. NaHCO3 (15 mL) and water (15
mL) followed by drying over Na2SO4. The solvent was
removed in vacuo and the residue was purified by silica
gel column chromatography (EtOAc–‘petrol’ 2:8) to
yield the title compound 8a as a colourless oil (580 mg,
76%): [h]2D2=−1.8 (c 2.2, CHCl3); wmax (film) 1745, 1643,
1
1228 cm−1; H NMR (270 MHz, CDCl3) l 1.23 (3H, d,
J=5.9 Hz), 2.01 (3H, s), 2.07 (3H, s), 2.13 (3H, s),
2.55–2.61 (2H, m), 3.73 (1H, dq, J=6.6, 2.0 Hz), 4.00
(1H, dt, J=9.2, 2.6 Hz), 5.00 (1H, dd, J=9.9, 2.0 Hz),
5.07 (1H, dd, J=9.2, 5.3 Hz), 5.20–5.33 (3H, m), 5.71
(1H, ddt, J=9.9, 6.6, 3.3 Hz); 13C NMR (67.8 MHz,
(film) wmax 1749, 1373, 1216 cm−1; H NMR (270 MHz,
CDCl3) l 1.27 (3H, d, J=6.6 Hz), 1.86–1.93 (1H, m,
1

1732
G. Singh, H. Vankayalapati / Tetrahedron: Asymmetry 12 (2001) 1727–1735
CDCl3) l 17.46, 20.56, 20.66, 20.82, 33.50, 68.01, 68.92,
70.21, 71.35, 74.29, 118.05, 132.76, 169.74, 169.98,
170.16; m/z (CI, NH3) calcd for C15H26NO7: 332.1709.
Found: 332.1710 [M+NH4]+.
(1H, t, J=9.9 Hz); 13C NMR (67.8 MHz, CDCl3) l
15.89, 20.35, 20.42 (2C), 66.01, 66.55, 69.65, 71.08,
74.21, 114.70, 168.81, 169.79, 170.28; m/z (CI, NH3)
calcd for C13H21N2O7: 317.3196. Found: 317.2349 [M+
NH4]+.
4.4. 3,4-Di-O-acetyl-1,2-O-[1-(exo-,endo-cyano)-ethyli-
dene]-a-L
-rhamnopyranose 9a and 9b18a
4.6. 3-(2%,3%,4%-Tri-O-acetyl-a,b-L-fucopyranosyl)-1-
propene 13 and 1422
The title compounds were prepared using a similar
procedure to that employed for compound 7a, by treat-
ing compound 6 (1 g, 2.44 mmol) with TMSOTf (67 mg,
0.30 mmol) and trimethylsilyl cyanide (240 mg, 2.44
mmol) in CH2Cl2 (10 mL) at −78°C over 0.5 h. Chro-
matographic purification of the resulting residue
(EtOAc–‘petrol’ 3:7) gave a mixture of exo-9a (331 mg,
46%) and endo-9b (245 mg, 33%) isomers (ratio exo/
endo 3.8:2.2). For exo isomer 9a: mp 143–145°C; [h]2D2=
−2.4 (c 5.0, CHCl3); wmax (KBr) 3019, 1754, 1373, 1216
cm−1; 1H NMR (270 MHz, CDCl3) l 1.21 (3H, d, J=5.9
Hz), 1.93 (3H, s), 2.07 (3H, s), 2.13 (3H, s), 3.51 (1H,
dddd, J=9.9, 6.6, 5.9, 2.6 Hz), 4.57 (1H, dd, J=4.6, 2.0
Hz), 5.02 (1H, dd, J=10.6, 9.9 Hz), 5.21 (1H, dd,
J=9.9, 4.0 Hz), 5.41 (1H, d, J=2.0 Hz); 13C NMR (67.8
MHz, CDCl3) l 17.28, 20.60, 20.63, 26.44, 69.31, 69.71,
69.74, 78.27, 96.54, 101.57, 116.61, 169.71, 170.08. For
To a solution of propane-1,3-diyl 2,3,4-tri-O-acetyl-a,b-
-fucopyranosyl phosphate 10 (1 g, 2.44 mmol) in
L
CH2Cl2 (10 mL) at −78°C was reacted with TMSOTf (33
mg, 0.15 mmol) and allyltrimethylsilane (0.278 g, 2.39
mmol) similar to that detailed in the preparation of
compound 8a. Flash chromatographic purification of
the resulting residue (EtOAc–‘petrol’ 3:7) gave a mixture
of anomers 13 (370 mg, 49%) and 14 (240 mg, 31%) in
the ratio 3:2. For isomer 13: wmax (film) 1749, 1640, 1216
cm−1; 1H NMR (270 MHz, CDCl3) l 1.06 (3H, d, J=6.0
Hz), 1.94 (3H, s), 1.98 (3H, s), 2.09 (3H, s), 2.17 (1H,
ddd, J=15.2, 6.6, 5.3 Hz), 2.39 (1H, ddd, J=15.2, 7.3,
3.3 Hz), 3.87 (1H, dq, J=6.6, 2.0 Hz), 4.17 (1H, dt,
J=10.6, 5.3 Hz), 5.01 (1H, dd, J=9.9, 2.6 Hz), 5.03 (1H,
dd, J=15.2, 1.3 Hz), 5.12 (1H, dd, J=9.9, 3.3 Hz), 5.19
(1H, dd, J=4.0, 2.0 Hz), 5.24 (1H, dd, J=9.9, 5.3 Hz),
5.63 (1H, ddt, J=16.4, 9.9, 6.6 Hz); 13C NMR (67.8
MHz, CDCl3) l 15.84, 20.60, 20.64, 20.71, 30.53, 65.53,
68.12, 68.43, 70.66, 71.93, 117.30, 133.78, 169.88, 170.13,
1
endo isomer 9b: [h]D22=+61.06 (c 2.2, CHCl3); H NMR
(270 MHz, CDCl3) l 1.21 (3H, d, J=6.6 Hz), 1.92 (3H,
s), 2.07 (3H, s), 2.13 (3H, s), 3.49 (1H, dddd, J=9.2, 6.6,
5.9, 2.6 Hz), 4.57 (1H, dd, J=4.0, 2.6 Hz), 4.83 (1H, d,
J=2.0 Hz), 5.21 (1H, dd, J=9.9, 4.0 Hz), 5.41 (1H, dd,
J=3.3, 2.6 Hz); 13C NMR (67.8 MHz, CDCl3) l 17.23,
20.43, 20.59, 26.44, 65.45, 68.93, 69.80, 72.36, 96.62,
101.57, 116.61, 169.64, 169.70.
1
170.54. For isomer 14: H NMR (270 MHz, CDCl3), l
1.08 (3H, d, J=6.6 Hz), 1.94 (3H, s), 1.95 (3H, s), 2.08
(3H, s), 2.18 (1H, ddd, J=15.2, 7.9, 3.3 Hz), 2.39 (1H,
ddd, J=15.2, 6.0, 2.6 Hz), 3.48–3.66 (1H, m), 3.86 (1H,
dq, J=6.6, 1.3 Hz), 4.19 (1H, dt, J=6.6, 5.3 Hz), 4.98
(1H, dd, J=10.6, 3.3 Hz), 5.05–5.17 (1H, m), 5.12 (1H,
dd, J=9.9, 3.3 Hz), 5.23–5.26 (1H, m), 5.60 (1H, ddt,
J=16.5, 8.6, 6.6 Hz); 13C NMR (67.8 MHz, CDCl3) l
15.93, 20.57, 20.60, 20.65, 29.65, 65.52, 66.44, 67.79,
68.20, 70.60, 117.37, 133.82, 169.94, 170.19, 170.54.
4.5. 2,3,4-Tri-O-acetyl-a,b-L-fucopyranosyl cyanide 11
and 1219
The title compounds were prepared using similar proce-
dure to that detailed for 7a. Thus, to the propane-1,3-
diyl 2,3,4-tri-O-acetyl-a,b-L-fucopyranosyl phosphate
4.7. 3,4-Di-O-acetyl-1,2-O-[1-(exo,endo-cyano)-ethyli-
dene]-a-L
-fucopyranose 15a and 15b18c
10 (1 g, 2.44 mmol) in CH2Cl2 (10 mL) was added
TMSOTf (540 mg, 2.44 mmol) and trimethylsilyl cya-
nide (240 mg, 2.44 mmol) at 0°C and the reaction
mixture was stirred at rt for 24 h. Chromatographic
purification of the obtained residue (Et2O–‘petrol’ 7:3)
gave 11 (460 mg, 63%) and 12 (115 mg, 15%) as a
mixture (ratio a:b, 4:1). For isomer 11: mp 98°C (lit.:19
97–98°C); [h]2D2=−112.3 (c 3.3, CHCl3); wmax (KBr) 3023,
1752, 1430, 1373, 1216 cm−1; 1H NMR (270 MHz,
CDCl3) l 1.21 (3H, d, J=6.59 Hz), 2.02 (3H, s), 2.14
(3H, s), 2.17 (3H, s), 4.20 (1H, dq, J=7.28, 5.28 Hz),
5.12 (1H, d, J=5.27 Hz), 5.19 (1H, dd, J=10.56, 5.28
Hz), 5.27 (1H, dd, J=2.64, 1.97 Hz), 5.36 (1H, q,
J=1.32 Hz); 13C NMR (67.8 MHz, CDCl3) l 15.91,
20.39, 20.49, 20.55, 64.96, 65.55, 68.77, 69.77, 70. 85,
114.40, 169.56, 169.88, 170.15; m/z (CI, NH3) calcd for
C13H21N2O7: 317.3196. Found: 317.2349 [M+NH4]+.
For isomer 12: mp 124–126°C (lit.:19 123–125°C); [h]D22=
−39.7 (c 3.5, CHCl3); wmax (KBr) 3023, 1752, 1430, 1371,
The title compounds were prepared using a similar
procedure to that employed for compound 7a, by treat-
ing compound 10 (1 g, 2.44 mmol) with TMSOTf (0.068
g, 0.30 mmol) and trimethylsilyl cyanide (240 mg, 2.44
mmol) in CH2Cl2 (10 mL) at −78°C over 0.5 h. Flash
chromatographic purification of the resulting residue
(Et2O–‘petrol’ 3:7) gave mixture of exo 15a (522 mg,
72%) and endo 15b (8 mg, 1%) isomers. For isomer 15a:
[h]2D2=+1.3 (c, 1.0, CHCl3); wmax (film) 3021, 1752, 1430,
1
1371, 1216 cm−1; H NMR (270 MHz, CDCl3) l 1.21
(3H, d, J=6.6 Hz), 1.85 (3H, s), 2.07 (3H, s), 2.15 (3H,
s), 4.23 (1H, dd, J=4.6, 3.3 Hz), 4.91 (1H, dd, J=7.3,
3.3 Hz), 5.21 (1H, dd, J=3.3, 1.3 Hz), 5.30–5.37 (1H,
m), 5.84 (1H, d, J=5.3 Hz); 13C NMR (67.8 MHz,
CDCl3) l 16.06, 20.46, 20.61, 25.94, 68.18, 68.29, 71.55,
72,14, 96.60, 99.62, 116.95, 169.97, 170.10. For isomer
15b: mp 100–102°C (lit.:18c 103–105°C); [h]2D2=+134.6 (c,
1
0.3, CHCl3); H NMR (270 MHz, CDCl3) l 1.22 (3H,
1
1216 cm−1; H NMR (270 MHz, CDCl3) l 1.21 (3H, d,
d, J=6.6 Hz), 1.78 (3H, s), 2.02 (3H, s), 2.17 (3H, s),
4.27 (1H, dd, J=4.2, 2.6 Hz), 5.02–5.13 (1H, m), 5.25
(1H, dd, J=2.6, 2.0 Hz), 5.43 (1H, dd, J=7.9, 3.3 Hz),
5.69 1H, d, J=5.3 Hz).
J=6.6 Hz), 2.00 (3H, s), 2.12 (3H, s), 2.21 (3H, s), 3.82
(1H, dq, J=6.6, 6.0 Hz), 4.28 (1H, d, J=9.9 Hz), 4.99
(1H, q, J=3.3 Hz), 5.27 (1H, dd, J=3.3, 3.3 Hz), 5.46

G. Singh, H. Vankayalapati / Tetrahedron: Asymmetry 12 (2001) 1727–1735
1733
4.8. 2,3,4,6-Tetra-O-acetyl-a,b-
D
-galactopyranosyl cya-
1.3, 1.3 Hz), 2.34 (1H, ddddd, J=15.2, 7.3, 2.6, 1.3, 1.3
Hz), 3.36 (1H, ddd, J=9.2, 5.9, 2.6 Hz), 3.76 (1H, dd,
J=6.6, 1.3, Hz), 3.95–4.05 (3H, m), 4.07 (1H, dt,
J=9.2, 3.3 Hz), 5.01–5.22 (1H, m), 5.11–5.22 (1H, m),
5.33 (1H, dd, J=3.3, 2.6 Hz), 5.61 (1H, dddd, J=17.2,
10.6, 7.3, 3.3 Hz); 13C NMR (67.8 MHz, CDCl3) l
20.44, 20.51 (2C), 20.56, 30.80, 61.28, 67.49, 67.82,
68.20 (2C), 71.31, 117.45, 133.29, 169.62, 169.72,
169.91, 170.35; HRMS (EI) calcd for C17H25O9:
373.1498. Found: 373.1504 [M+H].
nide 17 and 1819
The title compounds were prepared using a similar
procedure to that employed for compound 7a, by treat-
ing
propane-1,3-diyl
2,3,4,6-tetra-O-acetyl-a-b-D-
galactopyranosyl phosphate 16 (1 g, 2.14 mmol) with
TMSOTf (475 mg, 2.14 mmol) and trimethylsilyl cya-
nide (220 mg, 2.14 mmol) in CH2Cl2 (10 mL) at 0°C.
The reaction mixture was stirred at rt for 24 h. Flash
chromatographic purification of the obtained residue
(EtOAc–‘petrol’ 3:7) gave a mixture of isomers 17 (230
mg, 31%) and 18 (340 mg, 45%) (ratio 2:3). For isomer
17: mp 94–96°C (lit.:19,22 93–94°C); [h]2D2=+122.0 (c 2.0,
CHCl3); wma1x (KBr) 3023, 2980, 2930, 1754, 1430, 1371,
1216 cm−1; H NMR (270 MHz, CDCl3) l 2.02 (3H, s),
2.07 (3H, s), 2.15 (6H, s), 4.10–4.16 (2H, m), 4.30 (1H,
dt, J=6.6, 4.6 Hz), 5.18 (1H, appt, J=5.9, 4.0 Hz),
5.25 (1H, d, J=5.3 Hz), 5.28 (1H, dd, J=2.0, 1.3 Hz),
5.52 (1H, q, J=1.3, Hz); 13C NMR (67.8 MHz, CDCl3)
l 20.35 (2C), 20.45 (2C), 60.99, 64.93, 65.61, 66.78,
68.30, 72.33, 113.89, 169.43, 169.72, 169.76, 170.14; m/z
(CI, NH3) calcd for C15H23N2O9: 375.3562. Found:
375.3606 [M+NH4]+. For isomer 18: mp 166–168°C
(lit.:22 168–169°C); [h]D28=+67.7 (c 1.6, CHCl3); wmax
(KBr) 3025, 2981, 2927, 1754, 1430, 1371, 1216 cm−1;
1H NMR (270 MHz, CDCl3) l 2.01 (3H, s), 2.03 (3H,
s), 2.05 (3H, s), 2.07 (3H, s), 3.95 (1H, dt, J=6.6, 1.3
Hz), 4.07–4.30 (2H, m), 4.31 (1H, d, J=10.6 Hz), 5.00
(1H, q, J=3.3, Hz), 5.32 (1H, q, J=1.3, Hz), 5.49 (1H,
t, J=10.6 Hz); 13C NMR (67.8 MHz, CDCl3) l 20.32,
20.41, 20.44, 20.47, 61.14, 65.97, 66.67, 66.69, 70.71,
75.31, 114.31, 169.87, 170.00, 170.03, 170.19; m/z (CI,
NH3) calcd for C15H23N2O9: 375.3562. Found: 375.3606
[M+NH4]+.
4.10. 3,4,6-Tri-O-acetyl-1,2-O-[1(-exo,endo-cyano)-eth-
ylidene]-a-D-galactopyranose 21a and 21b
The title compounds were prepared using a similar
procedure to that employed for compound 7a, by treat-
ing compound 16 (500 mg, 1.06 mmol) with TMSOTf
(46 mg, 0.20 mmol) and trimethylsilyl cyanide (105 mg,
1.06) in CH2Cl2 (5 mL) at −78°C over 0.5 h. Chromato-
graphic purification of the resulting residue (Et2O–
‘petrol’ 3:7) gave exo-21a (203 mg, 53%) and endo-21b
(87 mg, 23%) isomers (ratio exo/endo 7:3). For exo
isomer 21a: [h]D20=+74.3 (c 1.8, CHCl3); wmax (film)
1
3025, 2962, 1754, 1430, 1371, 1226 cm−1; H NMR (270
MHz, CDCl3) l 1.76 (3H, s), 1.95 (3H, s), 1.96 (3H, s),
2.01 (3H, s), 4.02 (1H, d, J=1.3 Hz), 4.05 (1H, d,
J=1.3 Hz), 4.20 (1H, d, J=5.3 Hz), 4.23 (1H, d, J=4.6
Hz), 4.86 (1H, dd, J=6.6, 4.0 Hz), 5.27 (1H, dd,
J=3.3, 2.0 Hz), 5.76 (1H, d, J=4.6 Hz); 13C NMR
(67.8 MHz, CDCl3) l 20.13, 20.20, 20.29, 25.57, 61.12,
65.17, 69.60, 70.87, 72.53, 97.06, 98.74, 116.58, 169.41,
169.53, 170.04. For endo isomer 21b: [h]2D0=+13.2 (c,
2.4, CHCl3); wmax (film) 3019, 1752, 1371, 1214 cm−1; 1H
NMR (270 MHz, CDCl3), l 1.87 (3H, s), 2.04 (3H, s),
2.07 (6H, s), 4.08–4.21 (2H, m), 4.24–4.46 (2H, m), 4.96
(1H, dd, J=6.6, 3.3 Hz), 5.42 (1H, dd, J=7.3, 2.6 Hz),
5.86 (1H, d, J=5.3 Hz); 13C NMR (67.8 MHz, CDCl3)
l 20.38, 20.43, 20.54, 25.80, 61.20, 65.34, 69.82, 71.11,
72.70, 98.54, 98.93, 117.48, 169.43, 169.48, 170.31.
4.9. 3-(2%,3%,4%,6%-Tetra-O-acetyl-a,b-D-galactopyran-
osyl)-1-propene 19 and 2012c,14,22
To a solution of propane-1,3-diyl 2,3,4,6-tetra-O-ace-
tyl-a,b- -galactopyranosyl phosphate 16 (500 mg, 1.06
D
4.11. 2,3,4,6-Tetra-O-benzyl-a,b-D-mannopyranosyl cya-
mmol) in CH2Cl2 (5 mL) at −78°C was added TMSOTf
(59 mg, 0.26 mmol) and allyltrimethylsilane (130 mg,
1.06 mmol) as detailed in the preparation of compound
8a. Flash chromatographic purification of the resulting
residue (EtOAc–‘petrol’ 2:8) gave a mixture of anomers
19 (46 mg, 12%) and 20 (238 mg, 61%) in the ratio 1:5.
For isomer 19: [h]D27=+20.8 (c 1.8, CHCl3); wmax (film)
nide 23 and 2420
The title compounds were prepared using a similar
procedure to that employed for compound 7a, by treat-
ing
propane-1,3-diyl
2,3,4,6-tetra-O-benzyl-a-b-D-
mannopyranosyl phosphate 22 (500 mg, 0.75 mmol)
with TMSOTf (21 mg, 0.094 mmol) and trimethylsilyl
cyanide (75 mg, 0.75 mmol) in CH2Cl2 (10 mL) at
−78°C. Flash chromatographic purification of the
obtained residue (Et2O–‘petrol’ 4:6) gave a mixture of
23 (204 mg, 49%) and 24 (136 mg, 32%) isomers (ratio
1
1752, 1642, 1218 cm−1; H NMR (270 MHz, CDCl3) l
2.03 (3H, s), 2.04 (3H, s), 2.08 (3H, s), 2.12 (3H, s), 2.28
(1H, dddt, J=9.9, 6.0, 2.6, 1.3 Hz), 2.45 (1H, dddt,
J=9.9, 8.6, 2.6, 1.3 Hz), 4.06–4.13 (2H, m), 4.18 (1H,
dd, J=8.6, 3.3 Hz), 4.25 (1H, ddd, J=5.3, 4.6, 4.0 Hz),
5.09 (2H, m), 5.18 (2H, m), 5.41 (1H, dt, J=3.3, 2.6
Hz), 5.69 (1H, dddd, J=17.2, 9.2, 6.6, 3.2 Hz); 13C
NMR (67.8 MHz, CDCl3), l 20.50, 20.57 (2C), 20.62,
30.84, 61.33, 67.51, 67.85, 68.21 (2C), 71.34, 117.27,
133.30, 169.70, 169.80, 169.97, 170.43; HRMS (EI)
calcd for C17H25O9: 373.1498. Found: 373.1501[M+H].
For isomer 20: mp 103–105°C. [h]2D3=+15.3 (c 3.7,
1
3:2). For isomer 23: [h]D=+30.6 (c, 6.7, CHCl3); H
NMR (270 MHz, CDCl3) l 3.67–3.86 (4H, m), 3.89
(1H, dd, J=9.2, 3.3 Hz), 3.98 (1H, t, J=8.6 Hz), 4.46
(1H, d, J=11.9 Hz), 4.50 (1H, d, J=10.6 Hz), 4.54
(1H, d, J=11.2 Hz), 4.59 (1H, d, J=9.2 Hz), 4.62 (1H,
d, J=11.2 Hz), 4.64 (2H, m), 4.76 (1H, d, J=2.6 Hz),
4.82 (1H, d, J=10.6 Hz), 7.14–7.35 (20H, m); 13C
NMR (67.8 MHz, CDCl3) l 65.19, 68.36, 72.54, 72.66,
73.31, 73.73, 74.71, 74.98, 77.00, 79.71, 115.36, 127.52,
127.62, 127.70, 127.75, 127.78, 127.81, 128.00, 128.25,
128.40, 128.46, 136.99, 137.66, 137.88, 137.99. For iso-
1
CHCl3); wmax (KBr) 1752, 1643, 1226 cm−1; H NMR
(270 MHz, CDCl3) l 1.95 (3H, s), 1.96 (3H, s), 1.99
(3H, s), 2.04 (3H, s), 2.15 (1H, ddddd, J=15.2, 8.6, 6.6,

1734
G. Singh, H. Vankayalapati / Tetrahedron: Asymmetry 12 (2001) 1727–1735
mer 24: [h]D=−12.5 (c, 3.7, CHCl3); 1H NMR (270
MHz, CDCl3) l 3.36 (1H, ddd, J=9.9, 4.0, 3.3 Hz),
3.46 (1H, dd, J=9.2, 2.6 Hz), 3.69–3.70 (2H, m), 3.86
(1H, d, J=9.2 Hz), 3.94 (1H, s), 4.10 (1H, s), 4.48 (1H,
d, J=11.9 Hz), 4.49 (1H, d, J=9.2 Hz), 4.52 (1H, m),
4.61 (2H, m), 4.79 (1H, d, J=10.6 Hz), 4.86 (1H, d,
J=11.9 Hz), 4.93 (1H, d, J=11.9 Hz), 7.13–7.46 (20H,
m); 13C NMR (67.8 MHz, CDCl3) l 67.28, 68.80, 72.42,
73.45, 73.93, 74.14, 74.54, 75.15, 80.32, 82.25, 116.02,
127.48, 127.69, 127.77, 127.80, 127.92, 128.17, 128.23
(2C), 128.26, 128.42, 137.45, 137.62, 137.85, 137.95.
ranosyl phosphate 27 (500 mg, 0.75 mmol) with
TMSOTf (21 mg, 0.094 mmol) and trimethylsilyl cya-
nide (75 mg, 0.75 mmol) in CH2Cl2 (10 mL) at −78°C
and the reaction mixture was stirred for 0.5 h. Flash
chromatographic purification of the obtained residue
(Et2O–‘petrol’ 3:7) gave a mixture of isomers 28 (198
mg, 48%) and 29 (132 mg, 32%) (ratio 3:2). For isomer
1
28: [h]2D8=+37.3 (c, 1.6, CHCl3); H NMR (270 MHz,
CDCl3) l 3.62–3.68 (2H, m), 3.71 (1H, dd, J=3.3, 2.6
Hz), 3.79 (1H, dd, J=3.3, 2.0 Hz), 3.83 (1H, dd,
J=3.3, 2.6 Hz), 3.89 (1H, d, J=9.2 Hz), 4.41 (1H, d,
J=12.5 Hz), 4.48 (1H, d, J=10.6 Hz), 4.53 (1H, d,
J=11.9 Hz), 4.59 (1H, d, J=11.9 Hz), 4.60 (1H, d,
J=6.6 Hz), 4.77 (1H, d, J=11.9 Hz), 4.80 (1H, d,
J=10.6 Hz), 4.82 (1H, d, J=10.6 Hz), 4.93 (1H, d,
J=10.6 Hz), 7.11–7.38 (20H, m); 13C NMR (67.8 MHz,
CDCl3) l 66.87, 67.81, 73.48, 73.83, 75.10, 75.89, 76.14,
76.28, 77.47, 83.08, 115.33, 127.60, 127.71, 127.74,
127.80, 128.03, 128.23, 128.25, 128.36 (2C), 128.29 (2C),
128.68, 137.15, 137.49, 137.89, 138.22; m/z (CI, NH3)
calcd for C35H39N2O5: 567.7073. Found: 567.3861 [M+
4.12. 3-(2%,3%,4%,6%-Tetra-O-benzyl-a,b-D-mannopyran-
osyl)-1-propene 25 and 269
To a solution of propane-1,3-diyl 2,3,4,6-tetra-O-ben-
zyl-a,b- -mannopyranosyl phosphate 22 (796 mg, 1.19
D
mmol) in CH2Cl2 (10 mL) at −78°C was reacted with
TMSOTf (33 mg, 0.15 mmol) and allyltrimethylsilane
(136 mg, 1.20 mmol) similar to that detailed in the
preparation of compound 8a. Flash chromatographic
purification of the resulting residue (Et2O–‘petrol’ 2:8)
gave a mixture of anomers 2520a (265 mg, 39%) and
2620a (265 mg, 39%) in the ratio 1:1. For isomer 25:
[h]2D5=+10.9 (c, 2.2, CHC3); 1H NMR (270 MHz,
CDCl3) l 2.25–2.32 (2H, m), 3.38 (1H, q, J=6.60, Hz),
3.56 (1H, dd, J=4.6, 2.6 Hz), 3.66 (1H, d, J=3.3 Hz),
3.69–3.75 (2H, m), 3.77 (1H, dd, J=7.3, 4.6 Hz),
3.96–4.02 (1H, m), 4.45 (1H, d, J=11.2 Hz), 4.48 (1H,
d, J=12.5 Hz +1H, unresolved), 4.49 (1H, d, J=11.9
Hz+1H, d, J=11.9 Hz), 4.51 (1H, d, J=12.5 Hz), 4.53
(1H, m), 4.63 (1H, d, J=11.2 Hz), 4.93 (1H, dd,
J=14.5, 1.3 Hz), 4.94 (1H, dd, J=13.2, 1.3 Hz), 5.62–
5.78 (1H, m), 7.10–7.35 (20H, m); 13C NMR (67.8
MHz, CDCl3) l 34.65, 65.77, 69.17, 71.53, 72.07, 72.30,
73.25, 73.73 (2C), 74.93, 75.28, 76.88, 117.10, 127.42,
127.58, 127.65, 127.67, 127.84, 127.93, 127.95, 128.19,
128.28, 128.33 (2C), 134.34, 138.20, 138.30, 138.31,
138.47; m/z (CI, NH3) calcd for C37H44NO5: 582.3219.
Found: 582.3224 [M+NH4]+. For isomer 26: [h]D25=
1
NH4]+ For isomer 29: [h]D28=+16.7 (c, 1.3, CHCl3); H
NMR (270 MHz, CDCl3) l 3.32–3.38 (1H, m), 3.42
(1H, dd, J=9.2, 2.6 Hz), 3.54–3.63 (2H, m), 3.80 (1H,
d, J=8.6 Hz), 3.91 (1H, d, J=1.3 Hz), 4.10 (1H, bs),
4.33 (1H, d, J=12.5 Hz), 4.43 (1H, d, J=11.2 Hz), 4.47
(1H, d, J=11.2 Hz+1H, unresolved), 4.51 (1H, d, J=
12.5 Hz), 4.73 (1H, d, J=11.9 Hz), 4.85 (1H, 1H, d,
J=11.2 Hz), 4.88 (1H, m), 7.12–7.39 (20H, m); 13C
NMR (67.8 MHz, CDCl3) l 67.39, 68.81, 72.56, 73.56,
73.96, 74.61, 75.27, 80.45, 82.33, 83.07, 116.00, 127.59,
127.72, 127.76, 127.79, 127.90, 128.00, 128.04, 128.31,
128.36, 128.40, 128.51, 128.68, 137.43, 137.62, 137.83,
138.20; m/z (CI, NH3) calcd for C35H39N2O5: 567.7073
Found: 567.3861 [M+NH4]+.
4.14. 3-(2%,3%,4%,6%-Tetra-O-benzyl-b-
D-glucopyranosyl)-1-
propene 30b
1
−4.62 (c, 0.43, CHCl3); H NMR (270 MHz, CDCl3) l
To a solution of propane-1,3-diyl 2,3,4,6-tetra-O-ben-
zyl-a,b- -glucopyranosyl phosphate 27 (792 mg, 1.20
2.21–2.32 (1H, m), 2.40–2.51 (1H, m), 3.25 (1H, dd,
J=7.3, 6.6 Hz), 3.37 (1H, q, J=6.6 Hz), 3.53–3.61 (2H,
m), 3.63 (1H, d, J=6.0 Hz), 3.69 (1H, dd, J=2.6, 1.3
Hz), 3.81 (1H, appt, J=9.9 Hz), 4.45 (1H, d, J=11.9
Hz) 4.47 (1H, d, J=10.6 Hz+1H, unresolved), 4.49
(1H, d, J=11.9 Hz), 4.55 (1H, d, J=11.9 Hz), 4.63
(1H, d, J=12.5 Hz), 4.71 (1H, d, J=11.9 Hz), 4.79
(1H, d, J=10.6 Hz), 4.93–5.00 (2H, m), 5.56–5.72 (1H,
m), 7.10–7.34 20H, m); 13C NMR (67.8 MHz, CDCl3) l
35.69, 65.82, 69.77, 72.47, 73.45, 74.34, 74.83, 75.18,
75.49, 78.26, 79.92, 85.49, 117.21, 127.40, 127.46,
127.51, 127.61, 127.64, 127.67, 127.89, 128.01, 128.08,
128.22, 128.26, 128.3228.37, 134.72, 138.42, 138.45,
138.59, 138.90; m/z (CI, NH3) calcd for C37H44NO5:
582.3219. Found: 582.3227 [M+NH4]+.
D
mmol) in CH2Cl2 (10 mL) at −78°C was reacted with
TMSOTf (33 mg, 0.15 mmol) and allyltrimethylsilane
(137 mg, 1.20 mmol) similar to that detailed in the
preparation of compound 8a. Flash chromatographic
purification of the resulting residue (Et2O–‘petrol’ 3:7)
gave 30b (530 mg, 79%) as the major isomer: [h]2D6=
1
+20.7 (c 0.9, CHCl3); H NMR (270 MHz, CDCl3) l
1.67–1.77 (1H, m), 2.46–2.52 (1H, m), 3.60–3.63 (2H,
m), 3.68 (1H, dd, J=7.3, 3.3 Hz), 3.75–3.79 (2H, m),
4.09–4.16 (1H, m), 4.28 (1H, appt, 6.6 Hz), 4.44 (1H, d,
J=12.5 Hz), 4.46 (1H, d, J=10.6 Hz), 4.59 (1H, d,
J=11.9 Hz), 4.64 (1H, m), 4.67 (1H, d, J=11.9 Hz),
4.78 (1H, d, J=10.6 Hz), 4.79 (1H, d, J=10.6 Hz), 4.91
(1H, d, J=10.6 Hz), 5.04 (1H, dd, J=9.2, 2.0 Hz), 5.08
(1H, dd, J=14.5, 2.0 Hz), 5.74–5.89 (1H, m), 7.11–7.73
(20H, m); 13C NMR (67.8 MHz, CDCl3) l 29.66, 69.05,
71.22, 73.08, 73.48 (2C), 73.73, 75.02, 75.38, 78.18,
80.11, 82.41, 116.82, 127.55, 127.58, 127.68, 127.76,
127.81, 127.86, 127.89, 127.94, 128.31, 128.37, 128.42,
134.28, 138.29 (2C), 138.82 (2C); m/z (CI, NH3) calcd
for C37H44NO5: 582.3219. Found: 582.3216. [M+NH4].
4.13. 2,3,4,6-Tetra-O-benzyl-a,b-D-glucopyranosyl cya-
nide 28 and 2920a
The title compounds were prepared using similar proce-
dure to that employed for compound 7a, by treating
propane-1,3-diyl 2,3,4,6-tetra-O-benzyl-a-b-D-glucopy-

G. Singh, H. Vankayalapati / Tetrahedron: Asymmetry 12 (2001) 1727–1735
1735
Acknowledgements
(e) Curran, D. P.; Yoo, B. Tetrahedron Lett. 1992, 33,
6931–6934.
10. (a) Xu, J.; Egger, A.; Bernet, B.; Vasella, A. Helv. Chim.
Acta 1996, 79, 2004–2022; (b) Jobron, L.; Leteux, C.;
Veyrie`res, A.; Beau, J.-M. Carbohydr. Chem. 1994, 13,
507–512; (c) Khorlin, A. Y.; Shiyan, S. D.; Shulman, M.
L. Carbohydr. Res. 1974, 33, 229–235.
11. Lewis, M. D.; Cha, J. K.; Kishi, Y. J. Am. Chem. Soc.
1982, 104, 4976–4978.
12. (a) Keck, G. E.; Enholm, E. J.; Yates, Y. B. Tetrahedron
1985, 41, 4079–4094; (b) Keck, G. E.; Byers, J. H. J. Org.
Chem. 1985, 50, 5442–5444; (c) Ponte´n, F.; Magnusson,
G. J. Org. Chem. 1996, 61, 7463–7466.
13. (a) Hung, S.-C.; Lin, C.-C.; Wong, C. H. Tetrahedron
Lett. 1997, 38, 5419–5422; (b) Saleh, T.; Rousseau, G.
Synlett 1999, 617–619; (c) Allevi, P.; Anastasia, M.; Ciuf-
freda, P.; Fiecchi, A.; Scala, A. J. Chem. Soc., Chem.
Commun. 1987, 1245–1246; (d) Giannis, A.; Sandhoff, K.
Tetrahedron Lett. 1985, 26, 1479–1482.
We thank Professor C. H. Wong, (Scripps Research
Institute, La Jolla) for providing comparative spectral
data for the C-allyl glycosides. We also wish to express
our thanks to Professor J. Gervay (University of Ari-
zona) for providing copies of their data for the man-
nose derivative. We are indebted to the EPSRC for
access to the mass spectrometry service at the Univer-
sity of Wales, Swansea (Director, Professor D. Games).
References
1. (a) Varki, A. Glycobiology 1993, 3, 97–130; (b) Feizi, T.
Curr. Opin. Struct. Biol. 1994, 4, 296; (c) Varki, A. Proc.
Natl. Acad. Sci. USA 1994, 91, 7390–7397.
2. (a) Gyler, M.; Rose, D.; Bundle, D. Science 1991, 253,
442–445; (b) Boren, T.; Falk, P.; Roth, K. A.; Larson,
G.; Normark, S. Science 1993, 262, 1892–1895.
3. Paulson, J. C. The Receptors; Academic Press: New
York, 1985; Vol. 2.
4. Walz, G.; Aruffo, A.; Kolanus, W.; Polley, M. J.; Wag-
ner, E.; Nudelman, E.; Sinhal, A. K.; Hakomori, S.;
Paulson, J. C. Proc. Natl. Acad. Sci. USA 1991, 88,
6224–6228.
14. Praly, J.-P.; Chen, G.-R.; Gola, J.; Hetzer, G.; Raphoz,
C. Tetrahedron Lett. 1997, 38, 8185–8188.
15. (a) Hariprasad, V.; Singh, G.; Tranoy, I. J. Chem. Soc.,
Chem. Commun. 1998, 2129–2130; (b) Singh, G.; Vankay-
alapati, H. Tetrahedron: Asymmetry 2000, 11, 125–138.
16. (a) Vankayalapati, H.; Singh, G. Tetrahedron Lett. 1999,
40, 3925–3928; (b) Vankayalapati, H.; Singh, G. J. Chem.
Soc., Perkin Trans. 1 2000, 2187–2193.
5. (a) Postema, M. H. D. C-Glycosides Synthesis; CRC
Press: Boca Raton, 1995; (b) Levey, D. E.; Tang, C. The
Chemistry of C-Glycosides; Pergamon, Elsevier Science:
Oxford, 1995; (c) Meyers, R. W.; Lee, Y. C. Carbohydr.
Res. 1986, 154, 145–163; (d) Albrecht, H. P.; Repke, D.
B.; Moffat, J. G. J. Org. Chem. 1973, 38, 1836–1840.
6. (a) Coxon, B.; Fletcher, H. G. J. Am. Chem. Soc. 1963,
85, 2637–2642; (b) Lemieux, R. U.; Abbas, S. Z.; Chung,
B. Y. Can. J. Chem. 1982, 60, 58–62; (c) Martin, J.;
Jaramillo, G. L. M.; Wang, P. G. Tetrahedron Lett. 1998,
39, 5927–5930.
7. (a) Drew, K. N.; Gross, P. H. J. Org. Chem. 1991, 56,
509–513; (b) Koll, P.; Fortsch, A. Carbohydr. Res. 1987,
171, 441–449; (c) Somsak, L.; Batta, G.; Farkas, I. Tetra-
hedron Lett. 1986, 27, 5877–5880; (d) Buchanan, J. G.;
Clelland, P. W.; Johnson, T.; Rennie, R. A. C.; Wight-
man, R. H. J. Chem. Soc., Perkin Trans. 1 1992, 2593–
2601.
17. Kobertz, W. R.; Betozzi, C. R.; Bednarski, M. D. Tetra-
hedron Lett. 1992, 33, 737.
18. (a) Kochetkov, N. K.; Malysheva, N. N. Tetrahedron
Lett. 1980, 21, 3093–3096; (b) Vogel, C.; Bergemann, C.;
Boye, H. J. Carbohydr. Chem. 1994, 13 (1), 47–62; (c)
Betaneli, V. I.; Ovchinnikov, V. M.; Backinowsky, L. V.;
Kochetkov, N. K. Bull. Acad. Sci. USSR, Div. Chem. Sci.
1979, 28, 2561–2567.
19. Meyers, R. W.; Lee, Y. C. Carbohydr. Res. 1984, 132,
61–82 and references cited therein.
20. (a) Igarashi, Y.; Shiozawa, T.; Ichikawa, Y. Bioorg. Med.
Chem. Lett. 1999, 7, 613–616; (b) Gervay, J.; Hadd, M. J.
J. Org. Chem. 1997, 62, 6961–6967.
21. Closer examination of Gervay’s data suggested that the
resonance for the nitrile carbon of compound 24 was
absent as were the resonances for the some of the aro-
matic carbons. In addition the [h]D [−12.5 (c, 3.7); lit.:20a
−14.9 (c, 1.0); lit.:20b −51.2 (c, 6.6)] was found to be at
variance with our findings and with those of Ichikawa, at
higher concentrations we found little variance.
8. (a) Legler, G. Adv. Carbohydr. Chem. Biochem. 1990, 48,
319–384; (b) Evans, D. A.; Trotter, B. W.; Cote, B.
Tetrahedron Lett. 1998, 39, 1709–1712.
22. (a) Uchiyama, T.; Woltering, T. J.; Wong, W.; Lin, C.-C.;
Kajimoto, T.; Takebayashi, M.; Weitz-Schmidt, G.;
Asakura, T.; Noda, M.; Wong, C.-H. Bioorg. Med.
Chem. 1996, 4, 1149–1165; (b) Luengo, J. I.; Gleason, J.
G. Tetrahedron Lett. 1992, 33, 6911–6914; (c) Horton, D.;
Miyaki, T. Carbohydr. Res. 1998, 184, 221–229; (d)
BeMiller, J. N.; Yadav, M. P.; Kalabokis, V. N.; Mayers,
R. W. Carbohydr. Res. 1990, 200, 111–126.
9. (a) Nicolaou, K. C.; Hwang, C.-K.; Duggan, M. E. J.
Am. Chem. Soc. 1989, 111, 6682–6690; (b) Richter, P. K.;
Tomaszewski, M. J.; Miller, R. A.; Patron, A. P.; Nico-
laou, K. C. J. Chem. Soc., Chem. Commun. 1994, 1151–
1152; (c) Armstrong, R. W.; Hughes, R.; Stark, T. M.;
Sutherlin, D. P. J. Org. Chem. 1996, 61, 8350–8354; (d)
Huwe, C. M.; Woltering, T. J.; Jiricek, J.; Weitz-Schmidt,
G.; Wong, C.-H. Bioorg. Med. Chem. 1999, 7, 773–788;
.