Indium-mediated alkynylation of sugars: Synthesis of C-glycosyl compounds bearing a protected amino alcohol moiety

Article abstract of DOI:10.1016/j.carres.2010.07.033

The coupling of glycals with an alkynyl iodide bearing a protected amino alcohol moiety was achieved in the presence of metallic indium under Barbier conditions. It gave functionalized C-glycosyl compounds, precursors of C-glycosyl amino acids with α conf

Full text of DOI:10.1016/j.carres.2010.07.033

Carbohydrate Research 345 (2010) 2566–2570
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Carbohydrate Research
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Note
Indium-mediated alkynylation of sugars: synthesis of C-glycosyl
compounds bearing a protected amino alcohol moiety
*
*
Charfedinne Ayed, Sara Palmier, Nadège Lubin-Germain , Jacques Uziel, Jacques Augé
University of Cergy-Pontoise, Laboratoire de Synthèse Organique Sélective et Chimie bioOrganique, F-95000 Cergy-Pontoise, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 30 June 2010
Received in revised form 19 July 2010
Accepted 21 July 2010
Available online 25 July 2010
The coupling of glycals with an alkynyl iodide bearing a protected amino alcohol moiety was achieved in
the presence of metallic indium under Barbier conditions. It gave functionalized C-glycosyl compounds,
precursors of C-glycosyl amino acids with
a configuration.
Ó 2010 Elsevier Ltd. All rights reserved.
Keywords:
C-Glycosylation
Glycopeptides
Anomeric reactivity
Organometallic coupling
Indium
Alkynylation
Introduction of organometallic species into the anomeric posi-
tion of a glycal or a sugar derivative bearing a leaving group at
C-1 is a practical approach for the synthesis of C-glycosyl com-
pounds.1–4 Among them, alkynylation with organomagnesium,5
organoaluminum,6 organotin7 or organoindium8 nucleophiles has
already been reported. We have recently described an indium-
mediated alkynylation reaction under Barbier conditions either
on a glucal derivative following a Ferrier-type reaction9 or by a
direct substitution of an acetyl group10 leading to various C-glyco-
syl compounds, based on our previous work concerning the alky-
nylation of carbonyl derivatives.11 Since this reaction is very
efficient with simple alkynyl iodides leading to the corresponding
coupling compounds in a highly stereoselective manner, we were
driven to apply this methodology to more functionalized deriva-
tives. The use of alkynyl iodides bearing a protected amino alcohol
moiety allowed easy access to C-glycosyl amino acids precursors.
These latter compounds are particularly interesting targets as the
C–C link between the amino acid and the sugar part provides them
with a chemical and metabolic stability.
(tri-O-acetyl-D-glucal) under the standard conditions developed in
our laboratory that is in the presence of metallic indium in reflux-
ing dichloromethane for 24 h. No coupling product was detected.
Instead, we observed the formation of 4 as a pure isomer in an
excellent yield. There is an uncertainty concerning the Z or E con-
figuration of that product. Such a cyclic compound could result
from the reduction of the carbamate function with indium(0)
followed by cyclization at the level on the triple bond activated
by indium(I). Indium(0) as a radical initiator has been largely used
in cyclization approaches, but to the best of our knowledge such
reduction of a carbamate has never been reported14 (Scheme 2).
It thus appears that the use of indium is incompatible with a
Boc protection of the amino group. In order to avoid this reactivity,
we chose to prepare another amino alcohol synthon such as com-
pound 10 bearing a o-diphenyl amido group. This particular pro-
tecting group was chosen, leading to crystalline and quite stable
synthetic intermediates. Compound 5 (Scheme 3) could be pre-
pared according to a reported procedure using iodomethane in
the esterification step following the carbamoylation.15 In order to
avoid this carcinogenic compound, we have decided to esterify
We first considered alkynyl iodide 3 obtained starting from
Garner’s aldehyde 112 after a Seyferth–Gilbert homologation with
the Ohira–Bestmann’s reagent (according to Meffre’s et al. proce-
dure13) followed by the iodination of the terminal alkyne 2 with
iodine in benzene in the presence of morpholine (Scheme 1).
The alkynyl iodide 3 was then used in the reaction with
L-serine with methanol under acidic conditions. This modification
allowed us to greatly improve the yield in 5. Preparation of 6
was carried out according to a literature procedure.15 The follow-
ing steps (Scheme 3) include the reduction of the ester into an alco-
hol, oxidation into an aldehyde, Seyferth–Gilbert homologation,
and iodination to afford 10 in 37% overall yield for seven steps
1,5-anhydro-3,4,6-tri-O-acetyl-2-deoxy-D-arabino-hex-1-enitol
starting from L-serine.
As described earlier,10 the indium-mediated alkynylation at
the anomeric position can only proceed in the absence of a
* Corresponding authors. Tel.: +33 134257051; fax: +33 134257071 (J.A.).
E-mail address: jacques.auge@u-cergy.fr (J. Augé).
0008-6215/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2010.07.033

C. Ayed et al. / Carbohydrate Research 345 (2010) 2566–2570
2567
I
CH=O
a
b
O
O
O
NBoc
CH3
NBoc
CH3
NBoc
CH3
H3C
H3C
H3C
1
2
3
Scheme 1. Reagents and conditions: (a) MeCOC(@N2)P(O)(OMe)2, K2CO3, MeOH, 0 °C, 24 h, 67%; (b) I2, morpholine, benzene, 45 °C, 24 h, 90%.
I
OAc
OAc
In
O
O
AcO
AcO
+
AcO
O
NBoc
CH3
CH2Cl2, reflux
(0%)
H3C
3
NBoc
CH3
In
In
I
O
In
I
I
H3C
O
O
O
O
O
N
N
N
CH3
O
(91%)
H3C
H3C
H3C
CH3
O
O
CH3
O
4
.
C(CH3)3
+
Scheme 2. Proposed mechanism for the formation of 4.
O
O
OH
O
OMe
O
OMe
O
d
a-b
HO
c
O
N
L-Serine
O
N
HN
H3C
CH3
H3C
CH3
7
5
6
H
I
O
H
O
O
O
f
e
g
O
O
N
N
O
N
H3C
H3C
CH3
H3C
CH3
CH3
8
9
10
Scheme 3. Reagents and conditions: (a) CH3COCl, MeOH, 99%; (b) o-phenylbenzoyl chloride, Na2CO3, THF, 85%; (c) DMP, TsOH, benzene, CHCl3, 88%; (d) NaBH4, CaCl2, THF,
EtOH, 93%; (e) Me2SO, (COCl)2, ꢀ60 °C then Et3N, 76%; (f) MeCOC(@N2)P(O)(OMe)2, K2CO3, MeOH, 0 °C, 24 h, 97%; (g) I2, morpholine, benzene, 45 °C, 24 h, 73%.
participating group at C-2. Thus, we first investigated the coupling
reaction with 1,3,4,6-tetra-O-acetyl-2-deoxy- -lyxo-hexopyranose
anomeric mixture in the presence of 2 equiv of iodide 10 and
2.4 equiv of metallic indium in refluxing dichloromethane. Only
poor yield of the corresponding C-glycosylated derivative 11 show-
a
-selectivity when performing the reaction with either 1,5-anhy-
dro-3,4,6-tri-O-acetyl-2-deoxy- -lyxo-hex-1-enitol or -arabino-
hex-1-enitol (3,4,6-tri-O-acetyl- -galactal or -glucal, respectively)
under the same experimental conditions (Table 1). Determination of
D
D
D
D
D
the
a-selectivity was based on the NMR observations of H-5 and
ing an
a
configuration was obtained. However, 80% of 9 could be
C-5. In fact, Isobe et al.16 and Tanaka and Isobe17 established an
empirical rule fixing the chemical shift for H-5 around 4.1 ppm for
recovered, which is evidence that an organoindium species was
formed from 10. This species is not sufficiently reactive for the
direct C-glycosylation step. Starting from this observation we
decided to perform a Ferrier rearrangement with the same organo-
indium species. We were delighted to observe that the indium-
mediated Ferrier rearrangement with 10 led to the corresponding
products 12 and 13 in very good yields and with an exclusive
the
a
a-anomer and 3.75 ppm for the b-anomer. Moreover, the
-anomer exhibits a chemical shift8 for C-5 lower than 75 ppm.
We have shown that indium-mediated coupling reactions could
open the way to C-glycosyl amino acids with an
the anomeric position. Compounds 12 and 13 are useful precursors
of C-glycosyl amino acids. The functionalization of the carbohy-
a configuration at

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C. Ayed et al. / Carbohydrate Research 345 (2010) 2566–2570
Table 1
Indium mediated coupling reaction
Entry
Starting material
Coupling product
Yield (%)
OAc
OAc
O
AcO
11
1
1,3,4,6-Tetra-O-acetyl-2-deoxy-
D-lyxo-hexopyranose
10
N
O
O
CH3
H3C
OAc
OAc
O
12
2
3,4,6-Tri-O-acetyl-D-galactal
69
N
O
O
CH3
H3C
OAc
O
AcO
13
3
3,4,6-Tri-O-acetyl-D-glucal
83
N
O
O
CH3
H3C
drate part and the deprotection/oxidation of the amino alcohol
moiety should allow access to useful building blocks for peptide
synthesis.
ic phases were washed successively with satd aq NH4Cl (15 mL), a
satd aq NaHCO3 (15 mL), with water (15 mL), and then dried over
MgSO4. The obtained product was purified by flash chromatogra-
phy on silica gel (9:1 petroleum ether–EtOAc), yielding 3 (1.85 g,
90%), Rf 0.6 (9:1 cyclohexane–EtOAc); mp 61 °C. [
a
]
ꢀ104 (c 3.4,
D
1. Experimental
1.1. General
CHCl3). 1H NMR (250 MHz, CDCl3): d 4.62 (m, 1H, CH), 4.01 (m,
2H, CH2), 1.62 (s, 3H, CH3), 1.49 (s, 12H, 4 ꢁ CH3). 13C NMR
(62.9 MHz, CDCl3): d 151.4 (C@O), 94.3 (Cquat isopropyl), 92.9 (Cquat
C„C), 80.4 (Cquat Boc), 68.5 (CH2), 50.0 (CH), 28.3, 26.8, 25.7, 24.9,
Infrared spectra have been recorded on a Bruker Tensor 27
spectrophotometer. 1H and 13C NMR spectra have been recorded
on Brucker Avance 250 DPX and a JEOL ECX-400 spectrometer. Ele-
mental analyses have been performed at the Central Service of
Analysis (CNRS, Vernaison, France). High resolution mass spectra
have been obtained with a JEOL GC Mate II apparatus. Rotation val-
ues have been recorded on a JASPO DIP 370 instrument. Melting
points (uncorrected) have been determined on a Büchi B-545
apparatus.
24.4 (5 ꢁ CH3), ꢀ1.3 („C–I). IR:
12H18INO3: C, 41.04; H, 5.17; N, 3.99. Found: C, 41.10; H, 5.27; N,
3.84.
m
1677, 2980 cmꢀ1. Anal. Calcd for
C
1.3. 1-(Iodomethylene)-5,5-dimethyldihydro-1H-oxazolo[3,4-
c]oxazol-3(5H)-one (4)
Indium (0.2 g, 1.75 mmol) was stirred for 30 min under dimin-
ished pressure/argon in a sealed tube. Then, a soln of tert-butyl (R)-
4-iodoethynyl-2,2-dimethyloxazolidine-3-carboxylate
The preparation of the starting material 213 and the protection
of compound 5 leading to compound 615 have been performed
3 (0.51 g,
1.46 mmol) and tri-O-acetyl- -glucal (0.2 g, 0.73 mmol) in anhyd
D
according to literature procedures. L-Serine methyl ester hydro-
chloride12 has been prepared in 99% yield and the crude product
was involved in the following step without purification.
CH2Cl2 (15 mL) was added to the reaction mixture which was then
heated to reflux for 1 d. The mixture was filtered over Celite and
the crude mixture was purified by flash chromatography on silica
gel (7:3 cyclohexane–EtOAc), yielding
4 as the sole isomer
1.2. tert-Butyl (R)-4-iodoethynyl-2,2-dimethyloxazolidine-
3-carboxylate (3)
(0.39 g, 91%). [
a
]
D
ꢀ1 (c 0.6, CHCl3). 1H NMR (400 MHz, CDCl3): d
5.24 (d, 1H, J 0.6 Hz, C@CH), 4.76 (td, 1H, J 2.8, 0.6 Hz, CH), 4.12
(dd, 1H, J 3.3, 2.8 Hz, CH2), 3.63 (t, 1H, J 3.3 Hz, CH2), 1.66 (s, 1H,
CH3), 1.40 (s, 1H, CH3). 13C NMR (100 MHz, CDCl3): d 153.1
(C@O), 151.3 (C@C), 95.7 (Cquat isopropyl), 67.6 (CH2), 61.8 (CH),
In a mixture obtained by stirring iodine (1.64 g, 6.46 mmol) and
morpholine (1.53 mL, 17.57 mmol) for 30 min in benzene (7 mL)
was added a soln of the alkyne 2 (1.318 g, 5.85 mmol) in benzene
(10 mL). The reaction mixture was stirred for 24 h at 45 °C, then fil-
tered and washed with diethyl ether (30 mL). The combined organ-
47 (C–I), 27.5 (CH3), 23.0 (CH3). IR:
HRMS: Calcd for C8H10NO3I: 294.9706. Found: 294.9698.
m .
1742, 2361, 2921 cmꢀ1

C. Ayed et al. / Carbohydrate Research 345 (2010) 2566–2570
2569
1.4. (S)-2-(o-Phenylbenzoyl)amino-3-hydroxypropionic acid
methyl ester (5)
3.65 (dl, 1H, J 6.8 Hz, CH), 3.28 (dd, 1H, J 7.5, 6.8 Hz, CH2), 1.71
(s, 3H), 1.30 (s, 3H). 13C NMR (100 MHz, CDCl3): d 196.9 (CH@O),
168.2 (C@O), 139.3, 137.6, 136.2, 130.1, 129.6, 129.0, 128.3,
128.0 (aromatics), 96.8 (Cquat isopropyl), 65.8 (CH), 63.9 (CH2),
To a L-serine methyl ester hydrochloride (511 mg, 3.28 mmol)
soln in a saturated aq soln of sodium carbonate (13 mL) was added
THF (15 mL). The soln was cooled to 0 °C and o-phenylbenzoyl
chloride (1.07 g, 4.93 mmol) was added dropwise. The soln was
maintained at pH 8–9 by further addition of carbonate. After stir-
ring at room temperature for 12 h, THF was evaporated under
diminished pressure. The soln was then extracted with EtOAc
(3 ꢁ 35 mL) and the combined organic layers were washed with
saturated NaHCO3 (3 ꢁ 10 mL), saturated KHSO4 (3 ꢁ 10 mL), and
saturated NaCl (3 ꢁ 10 mL). The organic layer was dried over
MgSO4, filtered, and evaporated. Purification by flash chromatogra-
phy on silica gel (1:1 cyclohexane–EtOAc) yielded (S)-2-(o-phen-
ylbenzoyl)amino-3-hydroxypropionic acid methyl ester (839 mg,
85%). Spectroscopic data (1H NMR, 13C NMR, and HRMS) were sim-
ilar to literature data.15
25.8, 22.4 (2 ꢁ CH3). IR:
m
1641, 1735, 2984, 3061 cmꢀ1. HRMS:
Calcd for C19H19NO3: 309.1379. Found: 309.1365.
1.7. (R)-3-(o-Phenylbenzoyl)-4-ethynyl-2,2-dimethyloxazoli-
dine (9)
Into a vigorously stirred soln of aldehyde 8 (5.26 g, 17 mmol) in
MeOH (360 mL) were added at 0 °C potassium carbonate (4.4 g,
31.8 mmol) and a soln of dimethyl 1-diazo-2-oxopropylphospho-
nate (5.53 g, 28.8 mmol) in MeOH (5 mL). After 16 h of stirring at
room temperature, the reaction mixture was diluted with diethyl
ether (400 mL), washed with a 5% solution of NaHCO3 (50 mL),
and dried over MgSO4. The crude mixture was purified by flash
chromatography on silica gel (9:1 cyclohexane–EtOAc) yielding
compound 9 (5.05 g, 97%), Rf 0.9 (9:1 cyclohexane–EtOAc). [a]
D
1.5. (R)-3-(o-Phenylbenzoyl)-2,2-dimethyloxazolidine-4-
methanol (7)
ꢀ6 (c 1.4, CHCl3). 1H NMR (400 MHz, CDCl3): d 7.42 (m, 9H, aro-
matics), 3.81 (sl, 1H, CH), 3.70 (d, 1H, J 7.8 Hz, CH2), 3.16 (sl, 1H,
CH2), 2.10 (d, 1H, J 1.8 Hz, C„CH), 1.74 (s, 3H), 1.28 (s, 3H). 13C
NMR (100 MHz, CDCl3): d 167.7 (C@O), 139.5, 136.5, 129.7,
129.3, 128.9, 128.7, 128.1, 128.0, 127.7 (aromatics), 96.1 (Cquat iso-
propyl), 81.4 (Cquat C„C), 71.7 (C„CH), 68.9 (CH2), 49.6 (CH), 26.2,
In a suspension of calcium chloride (3.44 g, 31 mmol) in THF
(18 mL) was added a soln of (S)-3-(o-phenylbenzoyl)-2,2-dimethyl-
oxazolidine-4-carboxylic acid methyl ester (6) (1.38 g, 4.1 mmol) in
freshly distilled EtOH (30 mL). The mixture was cooled down to
ꢀ20 °C and sodium borohydride (2 g, 53 mmol) was added in small
portions. After overnight stirring at room temperature, the reaction
mixture was diluted with diethyl ether (60 mL) and treated with
satd aq Na2SO4 (50 mL). The white suspension was separated from
the liquid phase by decantation and the supernatant was reduced
to 10 mL by evaporation under diminished pressure. Diethyl ether
(50 mL) was added and the soln was washed with brine (2 ꢁ
10 mL) and then dried over MgSO4. The crude mixture was purified
by flash chromatography on silica gel (2:3 cyclohexane–EtOAc),
yielding (R)-3-(o-phenylbenzoyl)-2,2-dimethyloxazolidine-4-meth-
22.7 (2 ꢁ CH3). IR:
m .
1613, 1739, 2176, 2983, 3058, 3287 cmꢀ1
HRMS: Calcd for C20H19NO2: 305.1416. Found: 305.1414.
1.8. (R)-3-(o-Phenylbenzoyl)-4-iodoethynyl-2,2-
dimethyloxazolidine (10)
In a mixture obtained after stirring for 45 min iodine (6.28 g,
24.7 mmol) and morpholine (4.4 mL, 0.5 mmol) in benzene
(60 mL) was added a soln of 9 in benzene (15 mL). The mixture
was stirred for 48 h at 45 °C, then filtered and washed with diethyl
ether (100 mL). After filtration and concentration up to 30 mL,
washing successively with satd aq NH4Cl (2 ꢁ 20 mL), satd aq NaH-
CO3 (20 mL), water (20 mL), and then drying over MgSO4, the
resulting product was purified by flash chromatography on silica
gel (9:1 cyclohexane–EtOAc) yielding compound 10 (5.2 g, 73%),
anol (7) (1.27 g, 93%), Rf 0.1 (2:3 cyclohexane–EtOAc). [
a
]
ꢀ185
D
(c 1.1, CHCl3). 1H NMR (400 MHz, CDCl3): d 7.44 (m, 9H, aromatics),
3.69 (d, 1H, J 8.7 Hz, CH2), 3.29 (dd, 1H, J 8.7, 8.2 Hz, CH2OH), 3.21
(m, 1H, CH), 3.16 (m, 1H, CH2OH), 3.01 (dd, 1H, J 8.7, 5.0 Hz, CH2),
1.66 (s, 3H), 1.49 (br s, 1H, OH), 1.23 (s, 3H). 13C NMR (100 MHz,
CDCl3): d 168.1 (C@O), 139.5, 137.8, 136.6, 129.7, 129.1, 128.8,
128.1, 127.9, 127.7 (aromatics), 95.5 (Cquat isopropyl), 65.0 (CH2),
Rf 0.9 (9:1 cyclohexane–EtOAc). [
a
]
ꢀ5 (c 1.4, CHCl3). 1H NMR
D
(400 MHz, CDCl3): d 7.42 (m, 9H, aromatics), 3.87 (sl, 1H, CH),
3.70 (d, 1H, J 6.9 Hz, CH2), 3.23 (sl, 1H, CH2), 1.73 (s, 3H), 1.28 (s,
3H). 13C NMR (100 MHz, CDCl3): d 167.9 (C@O), 139.6, 137.6,
136.6, 129.8, 129.4, 128.9, 128.7, 128.3, 128.1, 127.7 (aromatics),
96.2 (Cquat isopropyl), 91.7 (Cquat C„C), 68.8 (CH2), 51.2 (CH),
62.1 (CH2OH), 58.9 (CH), 27.0, 21.9 (2 ꢁ CH3). IR:
m 1610, 2982,
3409 cmꢀ1. HRMS: Calcd for C19H21NO3: 311.1521. Found: 311.1534.
1.6. (S)-3-(o-Phenylbenzoyl)-2,2-dimethyloxazolidine-4-
formaldehyde (8)
26.1, 22.9 (2 ꢁ CH3), 1.3 („C–I). IR:
m .
1613, 2177, 2982 cmꢀ1
HRMS: Calcd for C20H18INO2: 431.0383; Found: 431.0379.
To a soln of oxalyl chloride (0.5 mL, 6.1 mmol) in CH2Cl2 (12 mL)
cooled down to ꢀ78 °C was added dropwise a soln of Me2O
(0.9 mL, 12 mmol) in CH2Cl2 (2 mL). After 10 min, a soln of the
above (R)-3-(o-phenylbenzoyl)-2,2-dimethyloxazolidine-4-metha-
nol in CH2Cl2 (6 mL) was added dropwise and the reaction mixture
was maintained at ꢀ60 °C for 30 min. Then a soln of Et3N (2.8 mL,
20.4 mmol) in CH2Cl2 (2 mL) was added dropwise; the reaction
mixture was warmed up to room temperature and water (6 mL)
was added. After the separation of the layers, the aq one was ex-
tracted with CH2Cl2 (3 ꢁ 3 mL). The combined organic layers were
washed with water (3 ꢁ 20 mL) and brine (20 mL). After drying
over MgSO4, the crude aldehyde 8 was obtained in quantitative
yield and could be used in the next step without any purification.
However, it was purified by flash chromatography on silica gel (7:3
cyclohexane–EtOAc) (0.96 g, 76%), Rf 0.1 (7:3 cyclohexane–EtOAc).
1.9. 2-[(R)-3-(o-Phenylbenzoyl)-2,2-dimethyloxazolidin-4-
yl]ethyne 3,4,6-tri-O-acetyl-2-deoxy-D-lyxo-hexopyranosyl (11)
Indium (0.40 g, 3.41 mmol) was stirred for 30 min under dimin-
ished pressure/argon in a sealed tube. Then, a soln of (R)-3-(o-phen-
ylbenzoyl)-4-iodoethynyl-2,2-dimethyloxazolidine 10 (0.61 g,
1.41 mmol) and tri-O-acetyl-D-galactal (0.24 g, 0.70 mmol) in anhyd
CH2Cl2 (25 mL) was introduced into the reaction mixture which was
refluxed for 3 d. The reaction mixture was filtered over Celite and the
crude product was purified by flash chromatography on silica gel
(2:1 cyclohexane–EtOAc), leading to the precursor compound 9
(0.34 g, 80%), Rf 0.9 (9:1 cyclohexane–EtOAc), and to the coupling
compound 11 (0.04 g, 10%), Rf 0.3 (2:1 cyclohexane–EtOAc).
[
a
]
ꢀ35 (c 7, CHCl3). 1H NMR (400 MHz, CDCl3): d 7.43 (m, 9H,
D
aromatics), 5.25 (m, 1H, H-4), 4.99 (m, 1H, H-3), 4.67 (sl, 1H, H-1),
4.28 (m, 1H, H-5), 4.14 (m, 2H, H-6,60), 3.85 (sl, 1H, CH2), 3.68 (sl,
1H, CH2), 3.18 (s, 1H, CH), 2.45 (m, 1H, H-2), 2.10 (s, 3H, Ac), 2.06
[
a]
D
ꢀ84 (c 10.2, CHCl3). 1H NMR (400 MHz, CDCl3): d 9.23 (s, 1H,
CH@O), 7.44 (m, 9H, aromatics), 3.88 (dd, 1H, J 7.5, 1.8 Hz, CH2),

2570
C. Ayed et al. / Carbohydrate Research 345 (2010) 2566–2570
(s, 3H, Ac), 2.04 (s, 3H, Ac), 1.93 (m, 1H, H-2), 1.73 (s, 3H isopropyl),
1.27 (s, 3H isopropyl). 13C NMR (100 MHz, CDCl3): d 170.6 (C@O),
170.5 (C@O, Ac), 170.0 (C@O, Ac), 167.6 (C@O), 128.8–128.0 (aro-
matics), 95.9 (Cquat isopropyl), 83.3 (C„C), 81.3 (C„C), 74.7, 73.8,
70.2, 68.7 (C-1, C-3, C-4, C-5), 67.8 (CH2), 62.7 (C-6), 49.7 (CHN),
38.5 (C-2), 26.9, 22.7 (2 ꢁ CH3, isopropyl), 20.9, 20.8, 20.7
0.55 mmol) and tri-O-acetyl-D-glucal (0.08 g, 0.27 mmol) in anhyd
CH2Cl2 (5 mL) was introduced into the reaction mixture which was
refluxed for 24 h. The reaction mixture was filtered over Celite and
the crude product was purified by flash chromatography on silica
gel (2:1 cyclohexane–EtOAc), yielding 13 (0.12 g, 83%), Rf 0.8 (3:1
cyclohexane–EtOAc). [
a]
ꢀ3 (c 2.9, CHCl3). 1H NMR (400 MHz,
D
(3 ꢁ CH3, Ac). IR:
m
1643, 1745, 2160, 2919 cmꢀ1. HRMS: Calcd for
CDCl3): d 7.41 (m, 9H, aromatics), 5.74 (d,1 H, J 10.5 Hz, H-3), 5.66
(d, 1H, J 10.5 Hz, H-2), 5.24 (m, 1H, H-4), 4.77 (sl, 1H, H-1), 4.14
(m, 2H, H-6,60), 3.89 (m, 1H, H-5), 3.83 (sl, 1H, CH), 3.67 (d, 1H, J
7.8 Hz, CH2), 3.16 (m, 1H, CH2), 2.10 (s, 3H, Ac), 2.07 (s, 3H, Ac),
1.72 (s, 3H isopropyl), 1.26 (s, 3H isopropyl). 13C NMR (100 MHz,
CDCl3): d 170.9 (C@O, Ac), 170.3 (C@O, Ac), 167.7 (C@O), 139.4,
137.7, 136.6, 129.7, 129.5, 128.9, 128.7, 128.1, 127.5 (aromatics),
125.6 (C-3), 96.0 (Cquat isopropyl), 84.8 (C„C), 79.0 (C„C), 70.0
(C-5), 68.8 (CH2), 64.6 (C-4), 63.7 (C-1), 63.1 (C-6), 49.8 (CHN),
C32H35NO9: 577.2311. Found: 577.2339.
1.10. 2-[(R)-3-(o-Phenylbenzoyl)-2,2-dimethyloxazolidin-4-
yl]ethyne 4,6-di-O-acetyl-2,3-dideoxy-D-threo-hex-2-
enopyranosyl (12)
Indium (0.5 g, 4.4 mmol) was stirred for 30 min under dimin-
ished pressure/argon in a sealed tube. Then, a soln of (R)-3-(o-phen-
ylbenzoyl)-4-iodoethynyl-2,2-dimethyloxazolidine 10 (1.58 g,
26.4, 22.6 (2 ꢁ CH3, isopropyl), 21.1, 20.9 (2 ꢁ CH3, Ac). IR:
m 1640,
1741, 2939, 3019 cmꢀ1. HRMS: Calcd for C30H31NO7: 517.2100.
Found: 517.2106.
3.67 mmol) and tri-O-acetyl-D-galactal (0.5 g, 1.84 mmol) in anhyd
CH2Cl2 (30 mL) was introduced into the reaction mixture which
was refluxed for 3 d. The reaction mixture was filtered over Celite
and the crude product was purified by flash chromatography on sil-
ica gel (2:1 cyclohexane–EtOAc), yielding 12 (0.66 g, 69%), Rf 0.8 (3:1
References
cyclohexane–EtOAc). [
a
]
D
ꢀ4 (c 5.3, CHCl3). 1H NMR (400 MHz,
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CDCl3): d 7.41 (m, 9H, aromatics), 5.96 (dd, 1H, J 8.5, 4.1 Hz, H-3),
5.85 (d, 1H, J 8.5 Hz, H-2), 5.01 (m, 1H, H-4), 4.84 (sl, 1H, H-1), 4.20
(m, 2H, H-6,60), 4.11 (m, 1H, H-5), 3.82 (sl, 1H, CH), 3.66 (d, 1H, J
7.8 Hz, CH2), 3.19 (m, 1H, CH2), 2.07 (s, 3H, Ac), 2.05 (s, 3H, Ac),
1.71 (s, 3H isopropyl), 1.26 (s, 3H isopropyl). 13C NMR (100 MHz,
CDCl3): d 170.7 (C@O, Ac), 170.4 (C@O, Ac), 167.7 (C@O), 139.5,
137.7, 136.6, 131.5, 129.8, 129.7, 129.5, 128.9, 128.7, 128.1, 127.5
(aromatics), 122.6 (C-3), 96.1 (Cquat isopropyl), 84.9 (C„C), 78.6
(C„C), 69.8 (C-5), 68.9 (CH2), 63.6 (C-1), 63.1 (C-4), 62.9 (C-6),
49.8 (CHN), 26.4, 22.7 (2 ꢁ CH3, isopropyl), 20.9 (2 ꢁ CH3, Ac). IR:
m
1641, 1740, 2986, 3058 cmꢀ1
517.2100. Found: 517.2106.
. HRMS: Calcd for C30H31NO7:
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1.11. 2-[(R)-3-(o-Phenylbenzoyl)-2,2-dimethyloxazolidin-4-
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Indium (0.08 g, 0.66 mmol) was stirred for 30 min under dimin-
ished pressure/argon in a sealed tube. Then, a soln of (R)-3-(o-phen-
ylbenzoyl)-4-iodoethynyl-2,2-dimethyloxazolidine 10 (0.23 g,
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