Practical Gram-Scale Synthesis of Either α- Or β-Anomer of C -Vinyl Glycosides

Article abstract of DOI:10.1055/s-0037-1611800

The synthesis C -vinyl glycosides, useful intermediates for the synthesis of C -glycoconjugates, was carried out on gram-scale by controlled reduction of the corresponding ethynyl derivatives in good to excellent yields in different carbohydrate series.

Full text of DOI:10.1055/s-0037-1611800

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–E
psp
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F. Rouzier et al.
PSP
Synthesis
Practical Gram-Scale Synthesis of Either - or -Anomer of C-Vinyl
Glycosides
Florian Rouziera
Rosanne Silléa
Arnaud Nourrya
Arnaud Tessierb
Muriel Pipelierb
Stéphane Guillarme*a
a IMMM - UMR 6283 CNRS, Le Mans Université, Avenue Olivier
Messiaen, 72085 Le Mans, Cedex 9, France
stephane.guillarme@univ-lemans.fr
b CEISAM, UMR 6220 CNRS, Université de Nantes, Faculté des
Sciences et des Techniques, 2, rue de la Houssinière, 44322
Nantes cedex 3, France
Received: 15.02.2019
Accepted after revision: 22.03.2019
Published online: 15.04.2019
79% yield on a gram-scale (Scheme 1A, path b).2b A two-
step strategy from 2,3,4,6-tetra-O-benzylglyconolactone
has also been described by addition of vinylmagnesium
bromide followed by reduction of the hemiketal intermedi-
ate (Scheme 1B).2c,4 By this approach, only -anomer was
formed in moderate yield whatever the series. Synthesis of
C-vinyl glycoside has also been described from glycal
DOI: 10.1055/s-0037-1611800; Art ID: ss-2019-z0104-psp
Abstract The synthesis C-vinyl glycosides, useful intermediates for the
synthesis of C-glycoconjugates, was carried out on gram-scale by con-
trolled reduction of the corresponding ethynyl derivatives in good to ex-
cellent yields in different carbohydrate series.
Key words C-glycosides, controlled reduction, alkynes, gram-scale
A) SN2-like substitution of α glycosyl bromide/iodide
OP
OP
path a : X = Br, P = Ac
C-Glycosidic analogues of natural products have attract-
ed much attention because they can act as stable mimics of
their O-glycosidic congeners since they are inert towards in
vivo enzymatic hydrolysis. Moreover, in some cases, biolog-
ical activities of C-glycosidic analogues can even be im-
proved.1 In this context, numerous research groups have ex-
tensively investigated efficient diastereoselective syntheses
of C-glycoside building blocks.
One of the most convergent and powerful synthetic
strategies to prepare the targeted C-glycoconjugates implies
metathesis reaction of fully protected C-vinyl glycosides as
key intermediates.2 Synthesis of the latter have been imple-
mented through different methods. The first reported one
consisting in addition of vinylmagnesium bromide to per-
acetylated--D-glucopyranosyl bromide afforded the ex-
pected C-vinyl glucoside in only poor yield3 and often as an
inseparable mixture of both anomers3d (Scheme 1A, path
a). Moreover, following this strategy, a subsequent acetyla-
tion step with acetic anhydride was required to offset
deprotection due to the excess of Grignard reagent. Later, in
the course of the synthesis of C-glycoside analogue of Bb-
GL2, Gervay-Hague et al. have described the stereoselective
preparation of -C-vinyl galactoside by treatment of -ga-
lactosyl iodide (obtained by in situ anomerization of the
corresponding -iodide) with vinylmagnesium bromide in
O
O
then Ac2O
BrMg
PO
PO
path b: X = I, P = Bn
X
path a: α/β: 0.2:1 to 0:1
path b: α/β: 12:1
BrMg
TBAI
then
B) Addition to glyconolactones/Hemiketal reduction
OBn
OBn
O
THF
1)
BrMg
O
BnO
BnO
2) Et3SiH, BF3·OEt2
CH3CN
O
Only β-anomer
C) Epoxidation/Ring opening of 1,2-anhydroglycals
R1
R1
OBn
OBn
HO
1) DMDO
O
R2
O
R2
BnO
BnO
2)
BrMg
Al
or
(vinyl)MgBr, β-anomer
(vinyl)3Al, α-anomer
3
D) Isomerization/ Ethylene Cross-Metathesis sequence
OP
OP
1) Pd or Ir
O
O
catalyst
PO
PO
2) Grubbs
ethylene
P = Ac or Bn
Scheme 1 Main strategies to access C-vinyl glycosides
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–E

B
F. Rouzier et al.
PSP
Synthesis
through epoxidation followed by ring opening of 1,2-anhy-
dro intermediate with vinylaluminum or -magnesium re-
agents (Scheme 1C).
R1
R1
OBn
OBn
H2
PdLindlar
R4
O
R4
O
R2
BnO
R2
BnO
EtOAc or
THF/MeOH
R3
R3
The nature of the organometallic species allowed to iso-
late selectively either the -anomer5 or the  one.6 Isomeri-
zation/ethylene cross-metathesis sequence has been re-
ported from C-allyl glycosides to access the corresponding
vinylic derivatives (Scheme 1D).2a,7 Main advantage of the
latter methodology is that either the isomerization step8 or
the two-step sequence7 could be performed on carbohy-
drates with a great variety of protecting groups. In addition
to these main strategies (Scheme 1), the stereoselective pal-
ladium-catalyzed -allyl cycloetherification9 leading to ei-
ther - or -anomer or the controlled reduction of the -C-
alkynyl galactoside2a could also be mentioned.
As part of our ongoing program on the preparation of
new C-galactoside analogues with biological interest, our
strategy required the preparation on large scale of either -
or -anomer of C-vinyl galactosides as key intermediates.
Herein, we describe a practical gram-scale general synthe-
sis of either - or -anomer of C-vinyl glycosides in differ-
ent series.
R1, R2 = H or OBn
2a–h
1a–h
α or β
α or β
R3, R4 = H or OBn or NHAc
OBn
OBn
O
BnO
BnO
BnO
BnO
BnO
OBn
O
O
BnO
BnO
OBn
OBn
2a, 81%
2b, 81%
2c, 84%
OBn
O
OBn
O
BnO
BnO
BnO
OBn
O
BnO
BnO
BnO
BnO
BnO
BnO
2d, 87%
2e, 76%
2f, 87%
OBn
O
BnO
BnO
OBn
O
BnO
BnO
AcNH
NHAc
2g, 62%
2h, 88%
Scheme 2 Controlled reduction of C-ethynyl glycoside 1
Initially, we attempted to prepare selectively - or -C-
vinyl glycosides in two steps from glycal as described in
Scheme 1C. In our hands, whatever the series, ring opening
of 1,2-anhydro sugar intermediates with vinyl organomag-
nesium reagent afforded only -anomers in poor yields
(23% and 21% in galactose and glucose series, respectively).
When the reaction was performed with the vinyl organoa-
lane reagent, -anomer was also isolated in galactose series
in only 40% yield. We then focused our attention on the
isomerization/ethylene cross-metathesis sequence in galac-
tose series (Scheme 1D), but the isomerization step re-
mained incomplete whatever the nature of catalyst used re-
sulting in an inseparable mixture of the expected com-
pound and starting material.
The controlled reduction of C-glycopyranosyl alkyne ap-
peared to be an interesting pathway since Dondoni have re-
ported the synthesis of either - or -anomer of alkynyl de-
rivatives on a large scale.10 Using Franck’s procedure2a for
the reduction of -C-ethynyl galactoside 1a in the presence
of 66% wt/wt Lindlar palladium charge (Scheme 2), the re-
action was complete in 30 minutes but a 1:1 mixture of the
expected compound and the over-reduced one was ob-
tained.
By reducing the catalyst charge to 20% wt/wt and after
45 minutes of reaction, the -C-vinyl galactoside 2a4b was
formed as the sole product of the reaction and was isolated
in 81% yield. These conditions appeared reproducible in
yield up to one gram (Scheme 2). Similarly, our optimized
conditions were successfully applied for the controlled re-
duction of -C-alkynyl derivatives 1b and 1c to yield, after
purification, the corresponding C-vinyl glycoside 2b2c and
2c in excellent 81 and 84% yield, respectively (Scheme 2).
The reduction of the alkynes in -series was achieved in 1
hour reaction time giving rise to the corresponding C-vinyl
glycoside 2d2a,b to 2f in a range of 76–87% yield (Scheme 2).
It is noteworthy that, with these -anomers, the TLC moni-
toring of the reaction remained difficult as the products
and the starting materials display the same Rf-value. How-
ever, this rugged reaction was successfully implemented on
a 4 grams scale on alkyne 1d.
In view of extending the scope of this reaction, the opti-
mized conditions were applied to N-acetylglycosylamine
series. The - or -anomers of vinyl 2-acetamido-2-deoxy-
C-galactosides 2g and 2h were obtained from the corre-
sponding alkyne, which were prepared in four steps from
3,4,6-tri-O-benzyl-2-nitro-D-galactal (3) (Scheme 3).
OBn
O
BnO
BnO
OBn
O
OBn
O
BnO
BnO
BnO
BnO
a
TMS
+
O2N
O2N
4a, 40%
O2N
3
4b, 30%
TMS
b–d
b–d
OBn
O
OBn
BnO
BnO
BnO
BnO
O
NHAc
1g, 75%
AcNH
1h, 72%
Scheme 3 Preparation of galactosylamine-derived alkynes 1g and 1h.
Reagents and conditions: (a) Lithium TMS-acetylide, THF, –78 °C, 1 h;
(b) Zn, concd HCl, AcOH, THF, H2O, 0 °C, 2 h; (c) Ac2O, Et3N, DMAP
(5 mol%), CH2Cl2, r.t., 1.5 h; (d) aq 1 N NaOH, CH2Cl2, MeOH, r.t., 2 h.
In a first attempt, the addition of vinylmagnesium bro-
mide to nitrogalactal 3 was performed leading to an insepa-
rable mixture of the two expected C-vinyl-2-nitrogalacto-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–E

C
F. Rouzier et al.
PSP
Synthesis
sides along with a third product.11 Then, following a report-
ed procedure in glucose series,12 the nitrogalactal 3 was
treated with lithium trimethylsilylacetylide at –78°C in THF
leading to a separable mixture of -anomer 4a in 40% yield
and -anomer 4b in 30% yield. The two anomers were
13C, COSY and HSQC NMR experiments. High-resolution mass spec-
troscopy was performed with a Bruker microTOF QIII mass spectrom-
eter using ESI techniques.
C-Vinyl Glycosides 2; General Procedure
To a solution of alkyne 1 in EtOAc (0.03 M, 1a–f)) or THF/MeOH (1:1,
0.1 M, 1g, h)) was added the Lindlar catalyst (20% wt/wt). The reac-
tion mixture was degassed with argon, saturated with H2, and stirred
at r.t. under a H2 atmosphere (1 atm). Reaction time was determined
by a follow-up performed on TLC indicating the clean reduction of
carbohydrate-derived acetylene to a slightly less polar product (only
for 1a–c). Reaction time was also 1 h for derivatives 1d–f or 3 h for 1g
and 1h. (CAUTION: Reaction time could depend on the quality of the
commercial Lindlar catalyst batch). The reaction mixture was filtered
through a short pad of Celite and concentrated. The residue was then
purified by column chromatography on silica gel to furnish the pure
compound.
1
clearly identified from the H NMR spectrum of 4a, which
presented a doublet at 4.45 ppm (anomeric proton) with a
coupling constant of 10.0 Hz, characteristic of -anomer
configuration. For the compound 4b, the presence of a dou-
blet at 5.22 ppm with a coupling constant of 5.8 Hz was
representative of the anomeric proton of -anomer. Then,
the same three-step sequence (reduction of nitro function,
acetylation, and cleavage of silicon–carbon bond) was ap-
plied on both anomers leading to the galactosylamine-de-
rived alkynes 1g and 1h in 75 and 72% yield, respectively
(Scheme 3). Although these two anomers have already been
isolated following another strategy,10 the preparation of
these two alkynes 1g and 1h from one single starting mate-
rial, that is, 3,4,6-tri-O-benzyl-2-nitro-D-galactal 3, was
highly relevant.
2,3,4,6-Tetra-O-benzyl-1-deoxy--D-galactopyranosylethene (2a)4b
Yield: 628 mg (81%); white solid; mp 50.9–53.8 °C; Rf = 0.30 (cyclo-
hexane/EtOAc 9:1); []D25 +11.4 (c 1.0, CHCl3) [Lit.4b +19.2 (c 1.3, CH-
Cl3)].
1H NMR (400 MHz, CDCl3):  = 7.37–7.23 (m, 20 H, H-Bn), 6.01–5.93
(m, 1 H, H-1), 5.42 (dd, J = 17.2, 1.2 Hz, 1 H, H-2a), 5.26 (dd, J = 10.5,
1.5 Hz, 1 H, H-2b), 4.96 and 4.62 (AB syst., J = 11.6 Hz, 2 H, CH2Ph),
4.83 and 4.64 (AB syst., J = 10.5 Hz, 2 H, CH2Ph), 4.75 and 4.71 (AB
syst., J = 11.8 Hz, 2 H, CH2Ph), 4.47 and 4.42 (AB syst., J = 11.9 Hz, 2 H,
CH2Ph), 3.98 (d, J = 2.7 Hz, 1 H, H-4′), 3.74–3.73 (m, 2 H, H-1′, H-3′),
3.62–3.65 (m, 4 H, H-2′, H-5′, H-6′).
13C NMR (100 MHz, CDCl3):  = 138.8 (quat-C), 138.4 (quat-C), 138.3
(quat-C), 137.9 (quat-C), 135.4 (C-1), 128.4 (CH), 128.3 (2 × CH), 128.2
(CH), 127.9 (CH), 127.8 (CH), 127.7 (2 × CH), 127.6 (2 × CH), 127.5 (2 ×
CH), 118.2 (C-2), 84.4 (C-2′), 80.7 (C-3′), 79.0 (C-1′), 76.9 (C-5′), 75.3
(CH2), 74.6 (CH2), 74.0 (C-4′), 73.6 (CH2), 72.6 (CH2), 68.9 (C-6′).
Controlled reduction was then performed on alkyne 1g
under optimized conditions, but the reaction was incom-
plete even after 6 hours resulting in an inseparable mixture
of starting material and expected compound in a 3:7 ratio
estimated by 1H NMR analysis. This outcome seemed to be
due to the low solubility of alkynes 1g and 1h in ethyl ace-
tate. This solvent was then replaced by a methanol/tetrahy-
drofuran (1:1) mixture allowing a complete reaction after 3
hours. In these conditions, the C-vinyl glycosides 2g and 2h
were isolated in 62 and 88% yield, respectively.
In summary, we have explored the controlled reduction
of C-ethynyl glycosides to access the corresponding C-vinyl
glycosides, which are highly valuable building blocks for the
synthesis of C-glycoconjugates. The C-vinyl glycosides were
isolated in different series in good to excellent yields on a
scale up to 4 grams. In addition, the reaction was also im-
plemented to prepare C-vinyl-N-acetylgalactosamine deriv-
atives.
2,3,4,6-Tetra-O-benzyl-1-deoxy--D-glucopyranosylethene (2b)2c
Yield: 624 mg (81%); white solid; mp 74.0–77.1 °C; Rf = 0.34 (cyclo-
20
hexane/EtOAc 9:1); []D +21.9 (c 0.24, CHCl3) {Lit.2c mp 68–69 °C,
[]D20 +28.0 (c 0.2, CHCl3), Lit.4b mp 72–73 °C}. Analytical data were in
accordance with those reported.
2,3,4,6-Tetra-O-benzyl-1-deoxy--D-mannopyranosylethene (2c)
Yield: 588 mg (84%); white solid; mp 54.2–55.8 °C; Rf = 0.27 (cyclo-
hexane/EtOAc 9:1); []D25 –12.3 (c 0.99, CHCl3).
All experiments were carried out under argon with anhydrous sol-
vents in dried glassware. THF was dried over activated alumina on a
dry station purchased from Innovative Technologies. Commercially
available materials were used without further purification. Alkynes
1a–f were prepared according to reported procedures.10 The prepara-
tion of compounds 1g,h is described in the Supporting Information.
Lindlar catalyst was purchased from Sigma-Aldrich. Flash chromatog-
raphy was performed on silica gel (40–63 m from Macherey-Nagel)
using Reveleris X² Grace apparatus. Analytical TLCs were carried out
on pre-coated silica gel 60 F254 from Macherey-Nagel. Optical rota-
tions were measured using a Jasco P2000 at the sodium D line ( =
589 nm) with a 1 dm path length cell at 25 °C. Melting points were
measured using Büchi B-545 apparatus. NMR spectra were recorded
on a Bruker Avance 400 spectrometer. Chemical shifts are reported in
ppm from TMS as the internal standard for the 1H NMR spectrum and
from the residual peaks of the solvent (CDCl3) for 13C NMR spectrum.
Structural assignments of the isolated compounds were based on 1H,
1H NMR (400 MHz, CDCl3):  = 7.38–7.22 (m, 18 H, H-Bn), 7.19–7.17
(m, 2 H, H-Bn), 5.97–5.88 (m, 1 H, H-1), 5.35–5.31 (m, 1 H, H-2a),
5.19–5.16 (m, 1 H, H-2b), 4.92–4.87 (m, 2 H, CH2Ph), 4.74–4.64 (m, 4
H, CH2Ph), 4.59–4.54 (m, 2 H, CH2Ph), 3.95 (t, J = 9.5 Hz, 1 H, H-4′),
3.85–3.83 (m, 1 H, H-1′), 3.82–3.79 (m, 1 H, H-2′), 3.78–3.75 (m, 2 H,
H-6′), 3.64 (dd, J = 9.4, 2.8 Hz, 1 H, H-3′), 3.52–3.48 (m, 1 H, H-5′).
13C NMR (100 MHz, CDCl3):  = 138.6 (quat-C), 138.5 (quat-C), 138.4
(2 quat-C), 135.6 (C-1), 128.4 (CH), 128.3 (CH), 128.2 (CH), 128.1 (CH),
128.0 (CH), 128.0 (CH), 127.9 (CH), 127.6 (CH), 127.6 (CH), 127.5 (CH),
127.4 (2 × CH), 116.7 (C-2), 84.7 (C-3′), 79.6 (C-5′), 79.4 (C-1′), 76.7 (C-
2′), 75.2 (CH2), 75.1 (C-4′), 74.4 (CH2), 73.5 (CH2), 72.2 (CH2), 69.7 (C-
6′).
HRMS (ESI): m/z [M
+
H]+ calcd for C36H39O5: 551.2792;
found: 551.2799.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–E

D
F. Rouzier et al.
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Synthesis
2,3,4,6-Tetra-O-benzyl-1-deoxy--D-galactopyranosylethene
1H NMR (400 MHz, CDCl3):  =7.36–7.24 (m, 15 H, H-Bn), 5.88–5.79
(m, 1 H, H-1), 5.31–5.16 (m, 3 H, H-2 and NH), 4.90 and 4.61 (AB syst.,
J = 11.6 Hz, 2 H, CH2Ph), 4.68 and 4.44 (AB syst., J = 11.9 Hz, 2 H,
CH2Ph), 4.47 and 4.43 (AB syst., J = 11.8 Hz, 2 H, CH2Ph), 4.02–3.97 (m,
2 H, H-3′, H-4′), 3.93–3.82 (m, 2 H, H-1′, H-2′), 3.65–3.62 (m, 1 H, H-
5′), 3.59–3.58 (m, 2 H, H-6′), 1.85 (s, 3 H, CH3).
13C NMR (100 MHz, CDCl3):  =170.2 (C=O), 138.6 (quat-C), 138.1
(quat-C), 137.9 (quat-C), 135.2 (C-1), 128.5 (CH), 128.4 (CH), 128.2
(2 × CH), 128.0 (2 × CH), 127.9 (CH), 127.8 (CH), 127.5 (CH), 118.7
(C-2), 79.9 (C-4′), 79.4, (C-1′), 76.8 (C-5′), 74.5 (CH2), 73.5 (CH2), 72.6
(C-3′), 71.5 (CH2), 68.7 (C-6′), 52.8 (C-2′), 23.6 (CH3).
(2d)2a,b
Yield: 3.4 g (85%); colorless oil; Rf = 0.36 (cyclohexane/EtOAc 9:1);
[]D25 + 60.1 (c 1.2, CHCl3).
1H NMR (400 MHz, CDCl3):  = 7.33–7.24 (m, 20 H, H-Bn), 6.11–6.03
(m, 1 H, H-1), 5.42 (dt, J = 17.5, 1.8 Hz, 1 H, H-2a), 5.32 (dt, J = 10.8, 1.9
Hz, 1 H, H-2b), 4.84 and 4.58 (AB syst., J = 11.6 Hz, 2 H, CH2Ph), 4.71–
4.55 (m, 5 H, H-1′, CH2Ph), 4.50 and 4.43 (AB syst., J = 11.9 Hz, 2 H,
CH2Ph), 4.08–4.04 (m, 1 H, H-2′), 4.03–3.99 (m, 1 H, H-5′), 3.95 (t, J =
2.6 Hz, 1 H, H-4′), 3.70–3.56 (m, 3 H, H-3′, H-6′).
13C NMR (100 MHz, CDCl3):  = 138.7 (quat C), 138.6 (quat C), 138.4
(quat C), 138.2 (quat C), 132.5 (C-1), 128.3 (3 × CH), 128.2 (CH), 128.1
(CH), 127.8 (CH), 127.7 (CH), 127.6 (CH), 127.6 (CH), 127.5 (CH), 127.5
(CH), 127.4 (CH), 118.1 (C-2), 78.9 (C-3′), 76.8 (C-2′), 75.0 (C-4′), 74.0
(CH2), 73.3 (C-1′ or CH2), 73.2 (C-1′ or CH2), 72.9 (CH2), 71.8 (C-5′),
68.5 (C-6′).
HRMS ESI): m/z [M + H]+ Calcd for C31H36NO5: 502.2588 ; found:
502.2589.
2-Acetamido-3,4,6-tri-O-benzyl-1,2-dideoxy--D-galactopyrano-
sylethene (2h)
+
H]+ calcd for C36H39O5: 551.2792;
Yield: 772 mg (88%); white solid; mp 137.5–139.2 °C; Rf = 0.25 (cyclo-
hexane/EtOAc 1:1); []D25 +54.1 (c 1.0, CHCl3).
HRMS (ESI): m/z [M
found: 551.2792 .
1H NMR (400 MHz, CDCl3):  = 7.32–7.27 (m, 15 H, H-Bn), 5.68 (ddd,
J = 17.3, 10.8, 4.2 Hz, 1 H, H-1), 5.45 (d, J = 7.0 Hz, 1 H, NH), 5.35 (ddd,
3J = 17.3, 2J = 1.8, 4J = 1.8 Hz, 1 H, H-2), 5.23 (ddd, 3J = 10.8, 2J = 1.8,
4J = 1.8 Hz, 1 H, H-2), 4.73 and 4.60 (AB syst., J = 11.9 Hz, 2 H, CH2Ph),
4.65–4.61 (m, 1 H, H-1′), 4.58–4.48 (AB syst., J = 11.9 Hz, 2 H, CH2Ph),
4.57 and 4.53 (AB syst., J = 12.3 Hz, 2 H, CH2Ph), 4.29–4.25 (m, 1 H, H-
5′), 4.21–4.18 (m, 1 H, H-2′), 4.08–4.04 (m, 1 H, H-6′), 3.90–3.86 (m, 1
H, H-3′), 3.88–3.87 (m, 2 H, H-4′, H-6′), 1.91 (s, 3 H, CH3).
13C NMR (100 MHz, CDCl3):  =169.9 (C=O), 138.4 (quat-C), 138.2
(quat-C), 137.9 (quat-C), 133.6 (C-1), 128.3 (4 × CH), 127.7 (CH), 127.6
(3 × CH), 127.5 (CH), 117.4 (C-2), 74.7 (C-5′), 74.5 (C-3′), 73.1 (CH2),
72.5 (CH2), 71.5 (C-4′), 67.6 (C-1′), 65,9 (C-6′), 50.6 (C-2′), 23.2 (CH3).
2,3,4,6-Tetra-O-benzyl-1-deoxy--D-glucopyranosylethene (2e)
Yield: 389 mg (84%); colorless oil; Rf = 0.36 (cyclohexane/EtOAc 9:1);
[]D25 + 58.9 (c 0.97, CHCl3).
1H NMR (400 MHz, CDCl3):  = 7.34–7.24 (m, 18 H, H-Bn), 7.13–7.11
(m, 2 H, H-Bn), 6.19–6.11 (m, 1 H, H-1), 5.49–5.41 (m, 2 H, H-2), 4.94
and 4.78 (AB syst., J = 10.9 Hz, 2 H, CH2Ph), 4.81 and 4.61 (AB syst., J =
11.5 Hz, 2 H, CH2Ph), 4.69 and 4.64 (AB syst., J = 11.6 Hz, 2 H, CH2Ph),
4.63–4.56 (m, 1 H, H-1′), 4.51–4.45 (m, 2 H, CH2Ph), 3.80–3.60 (m, 6
H, H-2′, H-3′, H-4′, H-5′, H-6′).
13C NMR (100 MHz, CDCl3):  = 138.7 (quat-C), 138.2 (quat-C), 138.1
(quat-C), 138.0 (quat-C), 131.9 (C-1), 128.4 (CH), 128.3 (3 × CH), 127.9
(3 × CH), 127.8 (2 × CH), 127.7 (CH), 127.6 (2 × CH), 119.8 (C-2), 82.8
(C-2′ or C-3′ or C-4′), 80.0 (C-2′ or C-3′ or C-4′), 78.3 (C-2′ or C-3′ or C-
4′), 75.5 (CH2), 75.1 (CH2), 74.1 (C-1′), 73.5 (CH2), 72.9 (CH2), 72.0 (C-
5′), 69.0 (C-6′).
HRMS (ESI): m/z [M + H]+ Calcd for C31H36NO5: 502.2588 ; found:
502.2594.
Funding Information
HRMS (ESI): m/z [M
+
H]+ calcd for C36H39O5: 551.2792;
found: 551.2790.
This work was supported by the Région des Pays de la Loire through
the GlycoOuest program and the Ministère de l’Enseignement
Supérieur et de la Recherche of France [Ph.D. fellowship (F.R.)].()
2,3,4,6-Tetra-O-benzyl-1-deoxy--D-mannopyranosylethene (2f)
Yield: 728 mg (87%); colorless oil; Rf = 0.27 (cyclohexane/EtOAc 9:1);
[]D25 + 26.5 (c 1.0, CHCl3).
1H NMR (400 MHz, CDCl3):  = 7.39–7.16 (m, 20 H, H-Bn), 5.84–5.76
(m, 1 H, H-1), 5.28–5.18 (m, 2 H, H-2), 4.77 and 4.50 (AB syst., J = 11.0
Hz, 2 H, CH2Ph), 4.71 and 4.64 (AB syst., J = 12.4 Hz, 2 H, CH2Ph), 4.61–
4.53 (m, 5 H, 2 × CH2Ph, H-1′), 3.93 (t, J = 7.9 Hz, 1 H, H-4′), 3.85–3.81
(m, 1 H, H-5′), 3.75–3.70 (m, 4 H, H-2′, H-3′, H-6′).
Acknowledgment
We thank Frédéric Legros for technical support, Sullivan Bricaud and
Corentin Jacquemoz for the NMR analyses, Patricia Gangnery and
Emmanuelle Mebold for the HRMS analyses.
13C NMR (100 MHz, CDCl3):  = 138.4 (quat-C), 138.3 (quat-C), 138.2
(2 quat-C), 134.3 (C-1), 128.3 (3 × CH), 128.2 (CH), 127.9 (CH), 127.8
(2 × CH), 127.7 (CH), 127.6 (2 × CH), 127.5 (CH), 127.4 (CH), 117.8 (C-
2), 78.5 (C-3′), 76.1 (C-2′), 75.1 (C-4′), 74.4 (CH2), 74.0 (CH2), 73.9 (C-
5′), 73.3 (CH2), 72.1 (C-1′), 71.7 (CH2), 69.4 (C-6′).
Supporting Information
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1611800.
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HRMS (ESI): m/z [M
+
Na]+ calcd for C36H38O5Na: 573.2611;
found: 573.2628.
References
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–E