Synthesis of Oxaphosphinane-Based Pseudodisaccharides

Article abstract of DOI:10.1002/ejoc.201700878

The synthesis of pseudodisaccharides based on an oxaphosphinane heterocycle is described. Disaccharide mimetics 5 and 6 were readily obtained through glycosylation of a hydroxy group with appropriately protected furanosyl or pyranosyl carbohydrates using

Full text of DOI:10.1002/ejoc.201700878

DOI: 10.1002/ejoc.201700878
Full Paper
Oxaphosphinane Pseudodisaccharides
Synthesis of Oxaphosphinane-Based Pseudodisaccharides
[
a,b]
[a]
[c]
[c]
Rachida Babouri,[
Ludovic Clarion, Marc Rolland, Arie Van der Lee,
b]
[a]
[a]
[a]
Zahia Kabouche, Jean-Noël Volle,* David Virieux,* and Jean-Luc Pirat
Abstract: The synthesis of pseudodisaccharides based on an anosyl carbohydrates using a trichloroacetamidate coupling
oxaphosphinane heterocycle is described. Disaccharide mimet- strategy. Selective or complete deprotection then produced the
ics 5 and 6 were readily obtained through glycosylation of a chiral pseudodisaccharides in good yields.
hydroxy group with appropriately protected furanosyl or pyr-
Introduction
events. As a consequence, they have been found to have a
profound influence on normal cell functions, and on cell adhe-
Glycans are essential components of life, and are some of the sion or migration and receptor activation in many pathologies.
[
1]
most complex natural oligomeric structures. Monosaccharides These properties are manifested by potent effects related to
[
2]
are the principal source of energy for cellular metabolism, while inflammation, cancer, and infection. In the modern therapeu-
polysaccharides or glycoconjugates are involved in many other tic arsenal, glycosidic or pseudoglycosidic molecules are of
important biological processes. It is now well established that great interest for the treatment of diverse pathologies. For
carbohydrates play critical and central roles in key recognition example, acarbose,
a specific glycosidase inhibitor, and
Figure 1. Acarbose, Dapagliflozin, and heteroatom-based pseudodisaccharides 1–3.
dapagliflozin,
a sodium-glucose cotransporter 2 inhibitor
[
a] Institut Charles Gerhardt – UMR 5253, CNRS 5253, AM2N, ENSCM,
rue de l'Ecole Normale, 34296 Montpellier CEDEX 5, France
(SGLT2), are both used for the treatment of diabetes. In addition
to this approach, Bertozzi et al. have highlighted the potential
of more complex saccharidic oligomers to be used in glycan-
8
E-mail: jean-noel.volle@enscm.fr
david.virieux@enscm.fr
[
3]
based therapies.
[
[
b] Université Mentouri-Constantine, Département de Chimie,
Laboratoire d'Obtention de Substances Thérapeutiques (LOST),
Campus Chaabet Ersas, 25000 Constantine, Algeria
c] Institut Européen des Membranes – UMR CNRS 5635,
Université de Montpellier, cc407, 34095 Montpellier, France
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.201700878.
The spectacular development of carbohydrate chemistry has
led to a wide variety of more stable heteroatom-based bio-
isosteres such as imino- or carbasugars, which may act as
[
4,5]
“
ideal” sugar mimics.
In this context, the 6′-thiodisaccharide
1 was found to inhibit ꢀ-(1→4)-galactosyltransferase with an
Eur. J. Org. Chem. 2017, 5357–5369
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inhibition constant (K ) in the millimolar range. The search for pyranosyl sugar unit onto oxaphosphinanes 4a and 4b as glyc-
i
new therapeutic opportunities has also led to the preparation osyl acceptors, and we were particularly interested in the forma-
of glycomimetics such as the protected dimeric hydroxylamine- tion of glycosidic bonds at the free hydroxy group at the 2-
[
6]
[7]
based glucan 2 or phostone pseudodisaccharide 3 (Fig- position (Figure 2). The main purpose of this work was to inves-
ure 1). Compared to monosaccharides, disaccharides or their tigate the behaviour of phostines as glycosyl acceptors at this
analogues may show enhanced binding affinity, and conse- stereochemically demanding position. With a pK close to 13.6,
a
[
8]
quently greater potency or selectivity.
an alcohol group adjacent to a phosphoryl group is slightly
Glycosyltransferases are enzymes that catalyse the formation more acidic than a typical sugar alcohol.
of a glycosidic linkage. The synthesis of inhibitors of these en-
zymes may lead to the development of potential therapeutic
agents.
Results and Discussion
[
9,10]
The selective formation of glycosidic linkages is the cornerstone
of glycan synthesis. Due to the strategic importance of this
process, several methods for the formation of glycosidic bonds
In this paper, we present the synthesis of pseudodisac-
charides based on an oxaphosphinane core. The main goal was
to develop heteroatom analogues of carbohydrates to provide
the closest analogy with the anomeric carbon without its draw-
backs. Replacement of the anomeric carbon by a phospha-
lactone, i.e., a phosphono- or phosphinolactone functional
group, may lead to more stable pseudoglycans. Glycoside ana-
logues 3 based on phostones (formerly phosphonates) were
[
14]
have been described.
A general approach involves the cou-
pling of a fully protected glycosyl donor with an acceptor. In
such reactions, the nature of the leaving group at the anomeric
carbon has a decisive influence. The Koenigs–Knorr method
[
15]
uses glycosyl halides as donors,
with Lewis acid activa-
[
16–18]
[
11]
tion to promote the glycosylation step. α-Thioglycosides
are also efficient donors when activated appropriately.
originally developed by Hanessian et al.
and then by other
[
19–23]
[
12]
[7a]
The
groups
as potential glycomimetics. Hanessian
and
[
7b]
most popular strategy developed to date is based on the reac-
Crich
later proposed their use as glycosyl donors. In such
tion of O-glycosyl imidates, and was introduced by Schmidt and
derivatives, the glycosidic linkage (C–O) is replaced by a phos-
phorus oxygen bond.
[
24]
Michel in 1980.
Acetimidates are activated by various pro-
moters, and glycosylation reactions involving these donors gen-
We were interested in oxaphosphinanes 4a and 4b, cyclic
phosphinates that may be considered to be analogues of C-aryl
hexopyranoses, of glucose and mannose, respectively. These
compounds were found to show potent antiproliferative, anti-
[
24–26]
erally give excellent yields.
The synthesis of pseudodisaccharides was accomplished us-
ing trichloroacetimidate glycosyl donors 7a–7d. These com-
pounds were prepared by mixing trichloroacetonitrile and the
corresponding protected sugars according to the literature pro-
cedure. α-Mannofuranosyl trichloroacetimidate α-7a was iso-
lated in 73 % yield from the reaction of di-O-isopropylidene-
[
13]
migration, and anti-invasion activities.
After extensive syn-
thetic work, we noticed that P-aryl-substituted derivatives
showed the best activities. A cell-based assay demonstrated
that oxaphosphinane 4a altered the ꢀ-(1→6)-GlcNAc-based N-
glycans of Glioblastoma-multiforme-initiating cells (GIC)
through inhibition of the activity of the enzyme N-acetylglucos-
amine glycosyltransferase 5 (MGAT5). This enzyme is known to
regulate tumoral development, and so cascade modifications
such as a drastic reduction of invasive and proliferative capacity
[
27]
D
-mannofuranose with sodium hydride.
2,3,5-Tri-O-benzyl-D-
ribofuranose was treated with potassium hydride to give tri-
[
28]
chloroacetimidate α/ꢀ-7b quantitatively, as a mixture of two
anomers in a 90:10 ratio. In pyranose series, tetra-O-benzyl-
D
-
[
29]
glucopyranosyl trichloroacetimidate (α/ꢀ-7c)
quantitatively, with an α/ꢀ anomeric ratio of 91:9. Tetra-O-
acetyl-α- -glucopyranosyl acetimidate α-7d was synthesised in
4 % yield using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) as a
was isolated
[
13d]
were seen in vivo.
In order to extend the scope of this new
D
pharmacophore, we set out to explore the formation of pseudo-
disaccharides starting from oxaphosphinanes 4a and 4b, which
show potent activities. We envisaged that pseudodisaccharides
8
[
30]
base (Scheme 1).
Oxaphosphinanes 4a and 4b were prepared according to
5
and 6 could be synthesised by introducing a furanosyl or
[
31]
previously published procedures.
The first coupling reaction
was carried out using an excess of the glycosyl donor α-
mannosyl trichloroacetimidate α-7a and the glucose-like oxa-
phosphinane 4a in the presence of a dichloromethane solution
of boron trifluoride diethyl etherate at 0 °C. After a reaction
time of 1 h, 4a was completely consumed, and after chromatog-
raphy on silica gel two pseudodisaccharides α-5a (22 % yield)
and α-8 (57 % yield) were isolated, each as a single α-furanosyl
anomer. A similar result was observed with the epimer 4b,
which led to α-5b (31 % yield) and α-9 (11 % yield) in 42 %
overall yield. Thus, partial deprotection leading to α-8 and α-9
was observed during the glycosylation reaction. Such a side
reaction has already been reported by Saxena et al. with
[
32]
phenolic derivatives under similar conditions. The partial de-
ketalisation observed during the coupling of α-7a with 4a or
4b was not surprising (Scheme 2).
Figure 2. Target pseudosaccharides 5 and 6 derived from oxaphosphinanes
a and 4b.
4
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Scheme 1. Preparation of glycosyl trichloroacetimidate donors 7a–7d.
mers, in 91 and 77 % yields, respectively, as the result of a nu-
cleophilic attack at the less hindered face of the glycosyl donor.
The glycosylations of mannose-like diastereoisomer 4b were
more difficult than those of glucose-like derivative 4a
(Scheme 3). Two phenomena can explain this difference. Be-
cause oxaphosphinanes 4a and 4b occupy a stable chair con-
formation, the free hydroxy group at the 2-position lies in an
equatorial position for 4a and in an axial position for 4b. Axial
approaches are generally more difficult due to unfavourable
1
,3-diaxial interactions. Also, the possibility of hydrogen bond-
ing between the hydroxy and phosphoryl groups in oxaphos-
phinane 4a probably increases the nucleophilicity of this com-
pound compared to its axial stereoisomer 4b.
Scheme 2. Glycosylation of 4a and 4b with mannofuranosyl trichloroacet-
imidate α-7a.
No reaction was observed between arabinofuranosyl donor
α/ꢀ-7b and oxaphosphinanes 4a or 4b under these reaction
conditions, even at higher temperature. This lack of reactivity
was circumvented by using a palladium/silver catalytic system
[
33]
in the presence of 2 equiv. of glycosyl donor α/ꢀ-7b.
In this
approach, a cationic palladium catalyst Pd(PhCN) (OTf) is gen-
2
2
erated in situ. This species is known to generally direct ꢀ select-
ivity. Under these conditions, the expected pseudodisac-
charides α/ꢀ-5c and α/ꢀ-5d were obtained in 62 and 36 %
yields, respectively, as mixtures of two anomers (36:62 for 5c).
This method was then used for the reaction of the previous
protected donor α-7a with 4a and 4b. These reactions gave
pseudodisaccharides α-5a and α-5b exclusively as the α ano-
Scheme 3. Palladium-catalysed coupling of 4a and 4b with furanosyl tri-
chloroacetimidates α-7a and α/ꢀ-7b.
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Coupling of 4a with glucopyranosyl acetimidate α/ꢀ-7c us-
According to these results, the ꢀ selectivity generally ob-
ing the previous conditions led to an almost quantitative yield served with the Pd(PhCN) (OTf) catalyst appears to be strongly
2
2
of α/ꢀ-6a with an α/ꢀ anomeric ratio of 92:8. The major α ano- affected by the oxaphosphinane acceptor when the reaction is
mer was isolated in 83 % yield after purification by chromatog- run at room temperature. At this temperature, pseudodisac-
raphy on silica gel, whereas the minor ꢀ anomer was obtained charides 6a and 6b obtained from the reaction of tetrabenzyl-
only in a trace amount. Under the same conditions, the reaction
D
-glucopyranose 7c were formed mainly as the opposite α ano-
of diastereoisomer 4b with glucopyranosyl acetimidate α/ꢀ-7c mers. The postulated cyclic cationic palladium complex with
gave 6b as a mixture of major α and minor ꢀ diastereoisomers. the glycosyl donor may have been partially disrupted. Conse-
Separation by chromatography gave diastereomerically pure quently, the α selectivity could be the result of an S 1-like sub-
N
α-6b in 21 % yield. In another reaction, coupling of oxaphos- stitution, or this change of selectivity could result from the for-
[
34]
phinane 4a with glucosyl donor α-7d gave pseudodisaccharide mation of a palladium complex with the phosphoryl group.
ꢀ
-6c exclusively in 57 % yield as a result of acetyl neighbouring-
The structures of the α and ꢀ anomers of pyranosyl pseudo-
disaccharides 6a–6c were supported by NMR correlation spec-
tra (COSY, HMBC, and HMQC) and assignment of the complete
group participation. In constrast, an attempted reaction be-
tween mannose-like oxaphosphinane 4b and glucosyl donor α-
7
d failed (Scheme 4).
1
spin systems in the H NMR spectra. Indeed, each anomer can
be clearly identified by determination of the coupling constants
3
JH,H between the anomeric proton and the proton at the 2-
position of the sugar unit derived from the glycosyl donor. The
α anomer is characterised by an equatorial–axial coupling con-
3
stant J
of about 3.7 Hz, whereas for the ꢀ anomer, the
Heq,Hax
3
coupling constant J
is close to 7.9 Hz, based on the val-
Hax,Hax
[
34]
ues described in the literature for α- and ꢀ-pyranoses.
configuration of the glycosidic linkage in pseudodisaccharide
-6c was also determined by an X-ray diffraction experiment,
The
ꢀ
along with its solid-state conformation. Thus, the ꢀ-(1→2) link-
age was unambiguously confirmed, and chair conformations
were found to be preferred for both of the six-membered rings
(Figure 3).
For furanosyl pseudodisaccharides 5, the stereochemistry of
the anomeric carbon could not be assigned as easily. The ano-
meric configuration of mannofuranose derivatives 5a and 5b
was assigned according to literature data, assuming that the
bicyclic nature of the structure drastically limits the number of
[
35]
conformations that it can adopt.
The vicinal coupling con-
3
stant J depends on the geometry of the anomeric carbon.
H,H
The proton linked to the anomeric carbon and the adjacent
proton are positioned with a torsion angle close to 90° for the
α anomer. Based on the Karplus relationship, the corresponding
coupling constant is expected to be minimal, and generally
<0.4 Hz for this configuration. All isolated derivatives 5a, 5b, 8,
and 9 showed no coupling between these protons, thus unam-
biguously confirming the α-(1→2) linkage. In contrast, the situ-
Scheme 4. Palladium-catalysed coupling of 4a and 4b with pyranosyl tri-
chloroacetimidates α/ꢀ-7c and α-7d.
Figure 3. Configuration of glycosidic linkage and conformation of ꢀ-6c, as confirmed by X-ray diffraction analysis.
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ation for 5c and 5d was more complex. The flexibility of the ose-like oxaphosphinane 4a was selectively removed. Cleavage
arabinofuranose ring induces different conformational behav- of this benzyl group was accomplished by reaction with zinc
iour, and large variations in coupling constants can be observed chloride in the presence of acetic anhydride in acetic acid
[
36]
resulting from the variation in the ring torsion angles.
As a (Scheme 6). The reaction gave diacetyloxaphosphinane 14 in
consequence, it was not possible to assign the stereochemistry 89 % yield, similarly to results reported in the literature for glyc-
[
37]
at this position with absolute certainty.
osides.
Both acetyl groups were removed by transesterifica-
Representative pseudodisaccharides were selected to be par- tion to give dihydroxyoxaphosphinane 15 in 85 % isolated
tially or fully deprotected. The first one to be subjected to a yield. The structures of glycosyl analogues 14 and 15 were de-
deprotection reaction was 5c. Palladium-catalysed hydrogenol- termined by X-ray analysis, which confirmed the selectivity of
ysis of the benzyl groups gave the fully deprotected pseudo- the deprotection reaction. Glycosylation was attempted using
disaccharide 10 in 94 % yield. No epimerisation was observed boron trifluoride etherate as activating agent because we had
at this stage. A similar reaction with α-5a produced the ex- previously found that no reaction occurred at the 2-position
pected deprotected oxaphosphinane α-11 in 43 % isolated under these conditions. The reaction mainly gave the arabinosyl
yield. A small quantity of monodeprotected derivative α-12 was oxaphosphinane by reaction of the less hindered primary alco-
formed concomitantly, and was isolated in 8 % yield. Cleavage hol. The resulting product 16 was however isolated in 11 %
of the isopropylidene protection of pseudodisaccharide α-5a yield as a single anomer after chromatography.
using acidic amberlyst 15 resin in a mixture of methanol/ethyl
acetate at room temperature was also tested. Surprisingly, only
the isopropylidene group at the 5,6-position was removed to
give α-8 in 15 % yield. Increasing the reaction temperature re-
sulted in the cleavage of the glycosidic linkage. Complete
deacetylation of ꢀ-6c by treatment with sodium methoxide in
methanol at room temperature gave glucosyl oxaphosphinane
ꢀ-13 in 75 % yield (Scheme 5).
Scheme 6. Formation of (1→6)-linked pseudodisaccharide 16.
Conclusions
The glycosylation of glucose- and mannose-like oxaphos-
phinanes 4a and 4b with protected furanoses 7a and 7b or
pyranoses 7c and 7d using a trichloroacetamidate coupling
strategy gave two series of original protected (1→2)-linked
pseudodisaccharides. The formation of the expected com-
pounds appears to be reliable and in accordance with the litera-
ture for glycosides, although the reactions take place at a more
sterically hindered position. The stereocontrol observed for the
formation of the glycosidic linkage with the different donors
appears to depend mainly on the nature of the donor itself. It
is known that palladium-catalysed glycosylation generally fa-
vours the formation of ꢀ-glycosidic linkages, but here mainly or
exclusively α anomers were formed. We also noticed a slight
difference between the glucosyl 4a and mannosyl 4b oxa-
phosphinanes, with the latter giving generally lower yields. Se-
lective or complete deprotection of the resulting intermediates
Scheme 5. Deprotection reactions of pseudosaccharides α-5a, 5c, and ꢀ-6c.
We then turned our attention to the formation of a (1→6)- gave disaccharide mimetics in good yields. The synthesis of
linked pseudodisaccharide keeping the hydroxy group at the pseudodisaccharides based on an oxaphosphinane core has
2-position of the oxaphosphinane free of protection. For this been clearly demonstrated, which opens up the possibility of
purpose, the protecting group on the primary alcohol of gluc- obtaining more complex glycans.
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Experimental Section
12 mmol) and potassium hydride (57 mg, 1.42 mmol) were added.
The resulting mixture was stirred for 30 min at room temperature.
The mixture was then filtered through Celite, and concentrated un-
der reduced pressure to give α/ꢀ-7b (677 mg, quantitative) as a
General Remarks: All reactions were carried out under dry nitro-
gen in flame-dried glassware. Before use, solvents were dried, and
reagents were freshly distilled when possible. Purification by chro-
matography was carried out using silica gel (60 Å, 35–70 μm) or
1
yellowish oil, as a mixture of anomers (α/ꢀ = 10:90). H NMR
3
2
(
5
4
400.13 MHz, CDCl ): δ = 3.66 (dd, J = 5.2, J = 11.0 Hz, 1 H,
3 H,H H,H
prepacked column (15–70 μm). NMR spectra were recorded with a
3
2
3
a-H), 3.75 (dd, J = 3.7, J = 11.0 Hz, 1 H, 5b-H), 4.11 (d, J
.6 Hz, 1 H, 2-H), 4.18 (dd, J = 4.6, J = 7.5 Hz, 1 H, 3-H), 4.49
d, JH,H = 11.7 Hz, 1 H, PhCH ), 4.50–4.56 (m, 1 H, 4-H), 4.59 (d,
JH,H = 11.7 Hz, 1 H, PhCH ), 4.60 (d, J
=
H,H
H,H
H,H
1
4
00 MHz instrument operating at 400.13 MHz ( H), 100.61 MHz
3
3
H,H
H,H
13
31
(
C), and 161.97 MHz ( P). Chemical shifts (δ) are given in ppm,
and were calibrated from the residual signals of CDCl3 (δ =
.26 ppm), [D ]DMSO (δ = 2.50 ppm), D O (δ = 4.79 ppm), or
2
(
2
2
2
= 5.1 Hz, 2 H, PhCH ),
2
H,H
2
7
2
2
6
2
4
.71 (d, J
= 12.1 Hz, 1 H, PhCH ), 4.84 (d, J
= 12.1 Hz, 1 H,
H,H
2
H,H
1
[
[
[
D ]methanol for H NMR spectra, and CDCl3 (δ = 77.16 ppm),
D ]DMSO (δ = 39.52 ppm), [D ]acetone (δ = 29.84 ppm), or
D ]methanol (δ = 49.00 ppm) for C NMR spectra. Signals were
4
PhCH ), 6.37 (s, 1 H, 1-H), 7.27–7.45 (m, 15 H, CH ), 8.51 (s, 1 H, NH)
2
ar
6
6
13
ppm. C NMR (100.61 MHz, CDCl ): δ = 70.2 (s, 1 C, CH -5), 72.2 (s,
3
2
1
3
4
1
C, PhCH ), 72.5 (s, 1 C, PhCH ), 73.2 (s, 1 C, PhCH ), 77.2 (s, 1 C,
2 2 2
assigned using 1D and 2D NMR spectra (HMQC, HMBC, HSQC,
COSY). Low- and high-resolution mass spectra were measured using
electrospray ionisation in ESI, positive-ion mode, and QTOF-ESI, re-
spectively. The following numbering scheme is used to describe the
NMR spectra of the pseudodisaccharides. CCDC 1541977 (for ꢀ-6c),
CH), 78.5 (s, 1 C, CH), 82.1 (s, 1 C, CH), 103.4 (s, 1 C, CH-1), 127.5,
27.6, 127.9, 128.0, 128.0, 128.1, 128.3, 128.4, 128.5, 137.5 (s, 2 C,
CqBn), 138.2 (s, 1 C, CqBn), 160.7 (s, 1 C, CqNH) ppm.
1
2,3,4,6-Tetra-O-benzyl-
D
-glucopyranosyl Trichloroacetimidate
2,3,4,6-Tetra-O-benzyl- -glucopyranose (0.54 g,
1 mmol) was dissolved in CH Cl (15 mL), and trichloroacetonitrile
[
29]
1
542091 (14), and 1542090 (for 15) contain the supplementary crys- (α/ꢀ-7c):
D
tallographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre.
2
2
(1.0 mL, 10 mmol) and potassium hydride (48 mg, 1.2 mmol) were
added. The resulting mixture was stirred for 1 h at room tempera-
ture. The mixture was then filtered through Celite, and concentrated
under reduced pressure to give α/ꢀ-7c (685 mg, quantitative) as a
1
yellowish oil, as a mixture of anomers (α/ꢀ = 91:9). H NMR
3
3
(
400.13 MHz, CDCl ): δ = 3.59 (d, J
= 2.0, J
= 11.0 Hz, 1 H,
3
H,H
H,H
3
3
3
6
3
1
5
a-H), 3.69 (dd, J = 3.5, J = 9.7 Hz, 1 H, 2-H), 3.70 (d, J
.3, J = 11.0 Hz, 1 H, 6b-H), 3.71 (dd, J = 9.7, J = 10.2 Hz,
=
H,H
H,H
H,H
3
3
3
H,H
H,H
H,H
3
3
3
H, 4-H), 3.91 (ddd, J = 2.0, J = 3.3 Hz, J = 10.2 Hz, 1 H,
H,H
H,H
H,H
2
,3:5,6-Di-O-isopropylidene-α-
D
-mannofuranosyl Trichloroacet-
3
3
2
-H), 3.97 (dd, J = 9.4, J = 9.4 Hz, 1 H, 3-H), 4.39 (d, J
=
H,H
H,H
2
H,H
[27]
amidate (7a):
2,3:5,6-Di-O-isopropylidene-α- -mannofuranose
D
1
2.0 Hz, 1 H, PhCH ), 4.45 (d, J = 10.6 Hz, 1 H, PhCH ), 4.52 (d,
2
H,H
2
(1.00 g, 3.84 mmol), trichloroacetonitrile (3.85 mL, 38.4 mmol), and
2
2
JH,H = 12.0 Hz, 1 H, PhCH ), 4.60 (d, J
= 11.8 Hz, 1 H, PhCH ),
2
H,H
2
sodium hydride (0.11 g, 4.6 mmol) were successively added to
CH Cl (30 mL). The resulting mixture was stirred for 1 h at room
2
2
4
.67 (d, J
= 11.8 Hz, 1 H, PhCH ), 4.75 (d, J
= 11.0 Hz, 1 H,
H,H
2
H,H
2
2
2
2
PhCH ), 4.78 (d, J = 10.6 Hz, 1 H, PhCH ), 4.88 (d, J = 11.0 Hz,
= 3.5 Hz, 1 H, 1-H), 7.05–7.09 (m, 2 H,
CH ), 7.17–7.24 (m, 18 H, CH ), 8.50 (s, 1 H, NH) ppm. C NMR
2
H,H
2
H,H
temperature. After this time, the mixture was filtered through Celite,
and the filtrate was evaporated under reduced pressure to give a
lightly coloured oil. This oil was triturated with hexane to give a
white solid precipitate. The precipitate was removed by filtration,
and the solvent was removed from the filtrate. The resulting oil
3
1
H, PhCH ), 6.44 (d, J
2
H,H
13
ar
ar
(
100.61 MHz, CDCl ): δ = 68.0 (s, 1 C, CH -6), 72.9 (s, 1 C, PhCH ),
3 2 2
7
1
3
1
1
3.3 (s, 1 C, CH-5), 73.5 (s, 1 C, PhCH ), 75.4 (s, 1 C, PhCH ), 75.7 (s,
2 2
C, PhCH ), 76.8 (s, 1 C, CH-4), 79.4 (s, 1 C, CH-2), 81.4 (s, 1 C, CH-
2
crystallised spontaneously to give pure trichloroacetamidate 7a
3
), 94.4 (d, J = 8.4 Hz, 1 C, CH-1), 127.6 (s), 127.7 (s), 127.7 (s),
C,P
1
(1.13 g, 73 %) as a white solid. H NMR (400.13 MHz, CDCl ): δ =
3
27.8 (s), 127.9 (s), 128.0 (s), 128.0 (s), 128.1 (s), 128.4 (s), 128.4 (s),
28.4 (s), 128.4 (s), 137.8 (s, 1 C, CqBn), 138.0 (s, 1 C, CqBn), 138.1
1
.39 (s, 3 H, CH ), 1.40 (s, 3 H, CH ), 1.47 (s, 3 H, CH ), 1.52 (s, 3 H,
3
3
3
3
2
CH ), 4.05 (dd, J = 4.2, J = 8.9 Hz, 1 H, 6a-H), 4.11–4.16 (m,
2
3
H,H
H,H
(s, 1 C, CqBn), 138.6 (s, 1 C, CqBn), 161.4 (s, 1 C, CqNH) ppm.
3
3
3
H, 4-H, 6b-H), 4.45 (ddd, J = 4.2, J = 6.2 Hz, J = 8.2 Hz,
H,H H,H H,H
1
H, 5-H), 4.88 (d, 3JH,H = 5.9 Hz, 1 H, 2-H), 4.94 (dd, 3JH,H = 3.4,
2,3,4,6-Tetra-O-acetyl-α-
D
-glucopyranosyl Trichloroacetimidate
(α-7d): A suspension of 2,3,4,6-tetra-O-acetyl-α- -glucopyranose
(0.9 g, 2.6 mmol) and activated molecular sieves in CH Cl (15 mL)
3
J
= 5.9 Hz, 1 H, 3-H), 6.28 (s, 1 H, 1-H), 8.61 (s, 1 H, NH) ppm.
[30]
H,H
D
13
C NMR (100.61 MHz, CDCl ): δ = 24.8 (s, 1 C, CH ), 25.1 (s, 1 C,
3
3
2
2
CH ), 26.0 (s, 1 C, CH ), 26.9 (s, 1 C, CH ), 67.1 (s, 1 C, CH -6), 72.7
3
3
3
2
was cooled to 0 °C, and trichloroacetonitrile (2.6 mL, 26 mmol) was
added. The solution was stirred for 1 h. Then, 1,8-diazabicyclo-
(s, 1 C, CH-5), 79.3 (s, 1 C, CH-3), 82.9 (s, 1 C, CH-4), 84.8 (s, 1 C, CH-
2
1
), 104.8 (s, 1 C, CH-1), 109.4 (s, 1 C, Cq), 113.4 (s, 1 C, Cq), 160.7 (s,
C, CqNH) ppm.
[5.4.0]undec-7-ene (DBU; 80 μL, 0.53 mmol) was added, and the
reaction mixture was stirred at room temperature for 4.5 h. After
this time, the mixture was filtered through Celite, and the solvent
was removed under vacuum. Purification by chromatography on
2
7
,3,5-Tri-O-benzyl-
D
-ribofuranosyl Trichloroacetimidate (α/ꢀ-
b)[
28]
silica gel (hexane/ethyl acetate, 2:1) gave α-7d (1.08 g, 84 %) as a
Protocol 1: 2,3,5-Tri-O-benzyl-D-ribofuranose (1.00 g, 2.38 mmol)
white foam. 1H NMR (400.13 MHz, CDCl ): δ = 1.93 (s, 3 H, CH ),
3
3
was dissolved in CH Cl (20 mL), and trichloroacetonitrile (4 mL,
2
2
1
.94 (s, 3 H, CH ), 1.96 (s, 3 H, CH ), 1.98 (s, 3 H, CH ), 4.03 (dd,
3 3 3
4
0 mmol) and potassium carbonate (396 mg, 2.87 mmol) were
3
2
3
3
JH,H = 2.1, J = 12.3 Hz, 1 H, 6a-H), 4.13 (ddd, J = 2.1, J
4
=
H,H
H,H
2
H,H
added. The resulting mixture was stirred overnight at room temper-
ature. The mixture was then filtered through Celite, and concen-
trated under reduced pressure to give α/ꢀ-7b (1.34 g, quantitative)
as a yellowish oil, as a mixture of anomers (α/ꢀ = 14:86).
.2 Hz, 3J = 10.3 Hz, 1 H, 5-H), 4.19 (dd, J = 4.2, J = 12.3 Hz,
3
H,H
H,H
H,H
3
3
1
H, 6b-H), 5.04 (dd, J = 3.7, J = 10.2 Hz, 1 H, 2-H), 5.09 (dd,
H,H H,H
3
3
3
3
JH,H = 9.5, J
= 10.3 Hz, 1 H, 4-H), 5.47 (dd, J
= 9.5, J
=
H,H
H,H
H,H
3
1
0.2 Hz, 1 H, 3-H), 6.46 (d, J = 3.7 Hz, 1 H, 1-H), 8.69 (s, 1 H, NH)
H,H
13
Protocol 2: 2,3,5-Tri-O-benzyl-
D
-ribofuranose (0.5 g, 1.2 mmol) was
ppm. C NMR (100.61 MHz, CDCl ): δ = 20.3 (s, CH ), 20.5 (s, CH ),
3 3 3
dissolved in CH Cl2 (15 mL), and trichloroacetonitrile (1.19 mL,
20.5 (s, CH ), 61.3 (s, CH -6), 67.6 (s, CH), 69.6 (s, CH), 69.7 (s, CH),
2
3
2
Eur. J. Org. Chem. 2017, 5357–5369
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5362
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
2
6
9.9 (s, CH), 92.8 (s, CH-1), 160.5 (s, CqNH), 169.3 (s, Cq), 169.7 (s, 4.53 (d, 3JH,H = 5.9 Hz, 1 H, 2′-H), 4.55 (m, 1 H, 4-H), 4.55 (d, J
=
H,H
2
Cq), 169.8 (s, Cq), 170.3 (s, Cq) ppm.
12.1 Hz, 1 H, PhCH ), 4.59 (s, 1 H, 1′-H), 4.65 (d, J
= 12.1 Hz, 1
2
H,H
2
2
H, PhCH ), 4.73 (d, JH,H = 10.7 Hz, 1 H, PhCH ), 4.75 (d, JH,H
=
2
2
(
(
2S ,3S,4S,5S,6R)-4,5-Bis(benzyloxy)-6-benzyloxymethyl-3-O-
P
2,3:5,6-di-O-isopropylidene-α-D-mannofuranosyl)-2-phenyl-2-
2
1
1.2 Hz, 1 H, PhCH ), 4.95 (d, J = 10.7 Hz, 1 H, PhCH ), 4.97 (d,
JH,H = 11.2 Hz, 1 H, PhCH ), 7.19–7.21 (m, 2 H, CH ), 7.29–7.39 (m,
3 H, CH ), 7.54–7.59 (m, 2 H, CH ), 7.64–7.68 (m, 1 H, CH ), 7.89–
2 H,H 2
2
5
2
ar
oxo-2λ -[1,2]-oxaphosphinane (α-5a) and (2S ,3S,4S,5S,6R)-4,5-
Bis(benzyloxy)-6-benzyloxymethyl-3-O-(2,3-O-isopropylidene-
α-D-mannofuranosyl)-2-phenyl-2-oxo-2λ5-[1,2]-oxaphos-
phinane (α-8)
P
1
7
1
9
ar ar ar
13
.95 (m, 2 H, CH ) ppm. C NMR (100.61 MHz, CDCl ): δ = 24.4 (s,
ar
3
3
C, CH ), 25.7 (s, 1 C, CH ), 64.1 (s, 1 C, CH -6′), 68.4 (d, JC,P
=
3
3
2
1
.3 Hz, 1 C, CH -5), 69.9 (s, 1 C, CH-5′), 73.2 (d, J = 98.4 Hz, 1 C,
2
C,P
2
Protocol 1: BF ·OEt (46 μL, 0.37 mmol) was added to a stirred
solution of 4a (125 mg, 0.23 mmol) and 2,3:5,6-di-O-isopropylidene-
CH-1), 73.6 (s, 1 C, PhCH
1 C, PhCH ), 76.6 (s, 1 C, PhCH
-mannofuranosyl trichloroacetimidate (7a; 149 mg, 0.37 mmol) in 4′), 79.5 (s, 1 C, CH-3′), 82.4 (d, JC,P = 6.0 Hz, 1 C, CH-2), 84.7 (s, 1
2
), 74.9 (d, JC,P = 5.2 Hz, 1 C, CH-4), 75.5 (s,
3
2
), 78.5 (s, 1 C, CH-3), 79.1 (s, 1 C, CH-
2
2
2
D
CH Cl (5 mL) at 0 °C. The mixture was stirred for 1 h at 0 °C, and
then a saturated aqueous solution of sodium hydrogen carbonate
was added. The resulting mixture was extracted with diethyl ether.
C, CH-2′), 104.2 (s, 1 C, CH-1′), 112.6 [s, 1 C, Cq(CH ) ], 127.7, 127.8,
127.8, 127.8, 127.9, 128.0, 128.5, 128.5, 128.6 (d, JC,P = 133.1 Hz, 1
3 2
2
2
1
3
2
C, Cqar), 129.1 (d, JC,P = 13.2 Hz, 1 C, CH
), 131.9 (d, JC,P = 10.7 Hz,
), 137.7 (s, 1 C, CqBn),
m
4
The organic phase was dried with MgSO , filtered, and concentrated 1 C, CH
), 133.6 (d, JC,P = 2.7 Hz, 1 C, CH
137.8 (s, 1 C, CqBn), 138.0 (s, 1 C, CqBn) ppm. MS (ES ): m/z = 747.29
[M + H] . HRMS (ESI-QTOF): calcd. for C41
4
o
p
+
under vacuum. Chromatography on silica gel (n-heptane/ethyl acet-
ate, 60:40 to 0:100) gave α-5a (40 mg, 22 %) and α-8 (99 mg, 57 %).
+
+
H
O
11P [M + H] 747.2934;
48
found 747.2933.
Protocol 2: A powder mixture of Pd(PhCN) Cl (10.2 mg,
2
2
(
(
2S ,3R,4S,5S,6R)-4,5-Bis(benzyloxy)-6-benzyloxymethyl-3-O-
0
.027 mmol) and AgOTf (13.6 mg, 0.053 mmol) was added to a
stirred solution of 4a (289 mg, 0.53 mmol) and 2,3:5,6-di-O-isoprop-
ylidene-α- -mannofuranosyl trichloroacetimidate (α-7a; 428 mg,
.06 mmol) in freshly distilled CH Cl (9 mL). The resulting mixture
P
2,3:5,6-di-O-isopropylidene-α-
D
-mannofuranosyl)-2-phenyl-2-
5
oxo-2λ -[1,2]-oxaphosphinane (α-5b) and (2S ,3R,4S,5S,6R)-4,5-
D
P
Bis(benzyloxy)-6-benzyloxymethyl-3-O-(2,3-O-isopropylidene-
1
2
2
5
α-
D
-mannofuranosyl)-2-phenyl-2-oxo-2λ -[1,2]-oxaphos-
was stirred at room temperature for 40 min. The mixture was then
filtered through Celite, and concentrated under vacuum. The resi-
due was purified by chromatography on silica gel (n-heptane/ethyl
acetate, 60:40) to give disaccharide α-5a (378 mg, 91 %).
phinane (α-9)
Protocol 1: BF ·OEt2 (147 μL, 1.19 mmol) was added to a stirred
3
solution of 4b (400 mg, 0.73 mmol) and 2,3:5,6-di-O-isopropylidene-
Data for α-5a: 31P NMR (161.97 MHz, CDCl ): δ = 32.76 (s) ppm. 1H
α-
D
-mannofuranosyl trichloroacetimidate (α-7a; 474 mg,
3
1.17 mmol) in CH Cl2 (22 mL) at 0 °C. The reaction mixture was
NMR (400.13 MHz, CDCl ): δ = 1.22 (s, 3 H, CH ), 1.29 (s, 3 H, CH ),
2
3
3
3
3
2
stirred at 0 °C for 1 h, and then a saturated aqueous solution of
NaHCO was added. The resulting mixture was extracted with Et O
(3 ×). The combined organic phases were dried with MgSO , fil-
tered, and concentrated under vacuum. The residue was purified
by chromatography on silica gel (n-heptane/ethyl acetate, 60:40 to
0:100) to give α-5b (180 mg, 31 %), and α-9 (204 mg, 37 %) with a
purity of 93 %. A second purification of α-9 by chromatography on
silica gel (CH Cl /MeOH, 12:1) gave pure α-9 (66 mg, 11 %).
1
1
.30 (s, 3 H, CH ), 1.35 (s, 3 H, CH ), 3.75 (dd, JH,H = 2.0, J
1.2 Hz, 1 H, 5a-H), 3.79 (dd, J = 5.3, J = 8.6 Hz, 1 H, 6′a-H),
=
3
3
H,H
3
2
3
2
H,H
H,H
3
3
3
3
.89 (dd, J = 3.3, J = 7.7 Hz, 1 H, 4′-H), 3.97 (dd, J = 6.4,
4
H,H
H,H
H,H
2
2
3
4
JH,H = 8.6 Hz, 1 H, 6′b-H), 3.98 (dt, J = 2.5, J = 2.5 Hz, J =
1.2 Hz, 1 H, 5b-H), 4.03 (dd, J = 9.0, J = 10.0 Hz, 1 H, 3-H),
.18 (m, 1 H, 5′-H), 4.19 (dd, J = 4.8, J = 10.1 Hz, 1 H, 1-H),
H,H
H,P
H,H
3
3
1
4
4
H,H H,H
2
3
H,P
H,H
3
3
3
.26 (ddd, J = 3.2, J = 9.0 Hz, J = 10.1 Hz, 1 H, 2-H), 4.44
H,P
H,H
H,H
3
3
3
(
d, J = 5.9 Hz, 1 H, 2′-H), 4.46 (dd, J = 3.3, J = 5.9 Hz, 1
H, 3′-H), 4.54 (m, 1 H, 4-H), 4.54 (d, J = 12.1 Hz, 1 H, PhCH ), 4.63
d, J = 12.1 Hz, 1 H, PhCH ), 4.67 (d, J = 10.8 Hz, 1 H, PhCH ),
.79 (s, 1 H, 1′-H), 4.85 (s, 2 H, PhCH ), 4.91 (d, J = 10.8 Hz, 1 H,
2
2
H,H
H,H
H,H
2
H,H
2
Protocol 2: Pd(PhCN) Cl2 (10.2 mg, 0.027 mmol) and AgOTf
(13.6 mg, 0.053 mmol) were added to a stirred solution of 4b
(289 mg, 0.53 mmol) and 2,3:5,6-di-O-isopropylidene-α-D-manno-
2
2
2
(
4
H,H
2
H,H
2
2
2
H,H
PhCH ), 7.15–7.18 (m, 2 H, CH ), 7.26–7.36 (m, 13 H, CH ), 7.52– furanosyl trichloroacetimidate (α-7a; 428 mg, 1.06 mmol) in freshly
2
ar
ar
7
.56 (m, 2 H, CH ), 7.62–7.66 (m, 1 H, CH ), 7.88–7.94 (m, 2 H, CH ) distilled CH Cl (9 mL). The resulting mixture was stirred at room
2 2
13
ar
ar
ar
ppm. C NMR (100.61 MHz, CDCl ): δ = 24.4 (s, 1 C, CH ), 25.3 (s, 1 temperature for 1 h, then it was filtered through Celite, and concen-
C, CH ), 25.6 (s, 1 C, CH ), 26.6 (s, 1 C, CH ), 67.0 (s, 1 C, CH -6′), 68.5
3
3
3
3
3
2
trated under vacuum. The residue was purified by chromatography
on silica gel (n-heptane/ethyl acetate, 60:40 to 40:60) to give α-5b
(323 mg, 77 %).
Data for α-5b: 31P NMR (161.97 MHz, CDCl ): δ = 36.63 (s) ppm. 1H
3
(d, J = 9.2 Hz, 1 C, CH -5), 72.8 (s, 1 C, CH-5′), 73.5 (s, 1 C, PhCH ),
C,P 2 2
1
2
7
4
3.5 (d, J = 96.3 Hz, 1 C, CH-1), 74.9 (d, J = 5.2 Hz, 1 C, CH-
C,P C,P
), 75.5 (s, 1 C, PhCH ), 76.5 (s, 1 C, PhCH ), 78.0 (s, 1 C, CH-3), 79.1
2
2
2
3
(s, 1 C, CH), 81.1 (s, 1 C, CH-4′), 82.6 (d, JC,P = 5.3 Hz, 1 C, CH-2),
NMR (400.13 MHz, CDCl ): δ = 1.32 (s, 9 H, 3 CH ), 1.41 (s, 3 H, CH ),
3
3
3
8
5.2 (s, 1 C, CH), 104.4 (s, 1 C, CH-1′), 109.2 [s, 1 C, Cq(CH ) ], 112.5
3 2
3
3
3
2
.30 (dd, J = 3.7, J = 8.1 Hz, 1 H, 4′-H), 3.49 (dd, J = 5.2,
H,H H,H H,H
[
s, 1 C, Cq(CH ) ], 127.7, 127.7, 127.8, 127.8, 127.8, 128.4, 128.4,
3 2
1
1
3
2
JH,H = 8.5 Hz, 1 H, 6′a-H), 3.80 (dd, J = 1.9, J = 11.3 Hz, 1 H,
3
H,H
H,H
1
1
1
28.4, 128.9 (d, J = 132.8 Hz, 1 C, Cq ), 128.9 (d, J = 13.2 Hz,
C,P ar C,P
3
= 6.4, 1JH,H = 8.5 Hz, 1 H, 6′b-H), 4.01 (ddd,
H,H
5
a-H), 3.97 (dd, J
2
4
C, CH ), 131.9 (d, J = 10.7 Hz, 1 C, CH ), 133.5 (d, J = 2.7 Hz,
m
C,P
o
C,P
3
JH,P = 2.6, JH,H = 3.1 Hz, 2JH,H = 11.3 Hz, 1 H, 5b-H), 4.11 (ddd,
4
C, CH ), 137.8 (s, 1 C, CqBn), 137.8 (s, 1 C, CqBn), 138.2 (s, 1 C,
p
3J
3
2
3
= 5.2, J = 6.4 Hz, J = 8.1 Hz, 1 H, 5′-H), 4.28 (dd, J =
+
+
H,H
H,H
H,H
H,H
CqBn) ppm. MS (ES ): m/z = 787.32 [M + H] . HRMS (ESI-QTOF):
calcd. for C H O P [M + H] 787.3247; found 787.3249.
3
3
3
3.7, J = 5.9 Hz, 1 H, 3′-H), 4.35 (dd, J = 8.8, J = 9.7 Hz, 1
+
H,H H,H H,H
44
52 11
3
3
H, 3-H), 4.39 (dd, J = 1.9, J = 8.8 Hz, 1 H, 2-H), 4.55 (m, 1 H,
4-H), 4.58 (d, J = 5.9 Hz, 1 H, 2′-H), 4.62 (d, J = 12.3 Hz, 1 H,
PhCH ), 4.63 (dd, J = 1.9, J = 9.1 Hz, 1 H, 1-H), 4.65 (d, J
H,H
H,H
Data for α-8: 31P NMR (161.97 MHz, CDCl ): δ = 32.53 (s) ppm. H
1
3
2
3
H,H
2
H,H
3
2
NMR (400.13 MHz, CDCl ): δ = 1.24 (s, 3 H, CH ), 1.29 (s, 3 H, CH ),
=
3
3
3
2
H,H
H,P
2
H,H
3
3
.45 (d, J = 4.2 Hz, 2 H, 6′-CH ), 3.70–3.78 (m, 3 H, 4′-H, 5′-H, 5a-
10.8 Hz, 1 H, PhCH ), 4.70 (d, J = 11.4 Hz, 1 H, PhCH ), 4.72 (d,
H,H
2
2
H,H
2
3
4
2
2
2
H), 3.99 (dt, J
= 2.5, J = 2.5 Hz, J
= 11.2 Hz, 1 H, 5b-H),
JH,H = 12.3 Hz, 1 H, PhCH ), 4.81 (d, J
= 11.4 Hz, 1 H, PhCH2),
H,H
H,P
H,H
2
H,H
3
3
2
2
4
.05 (dd, J = 9.0, J = 10.1 Hz, 1 H, 3-H), 4.20 (dd, J = 4.3, 4.96 (d, J
= 10.8 Hz, 1 H, PhCH ), 5.55 (s, 1 H, 1′-H), 7.21–7.24
H,H
H,H
H,P
3
H,H 2
3
3
3
JH,H = 10.4 Hz, 1 H, 1-H), 4.26 (ddd, J = 3.3, J = 9.0 Hz, J
0.4 Hz, 1 H, 2-H), 4.48 (dd, JH,H = 3.3, J
=
(m, 2 H, CH ), 7.28–7.42 (m, 13 H, CH ), 7.49–7.54 (m, 2 H, CH ),
7.60–7.65 (m, 1 H, CH ), 7.88–7.94 (m, 2 H, CH ) ppm. C NMR
ar ar
H,P
H,H
H,H
ar ar ar
3
3
13
1
= 5.9 Hz, 1 H, 3′-H),
H,H
Eur. J. Org. Chem. 2017, 5357–5369
www.eurjoc.org
5363
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
2
(
100.61 MHz, CDCl ): δ = 24.8 (s, 1 C, CH ), 25.1 (s, 1 C, CH ), 26.0
2JH,H = 11.8 Hz, 1 H, PhCH ), 4.21 (d, J
= 11.8 Hz, 1 H, PhCH ),
3
3
3
1
2
H,H
2
2
2
(s, 1 C, CH ), 26.8 (s, 1 C, CH ), 67.0 (s, 1 C, CH -6′), 67.8 (d, J
=
4.22 (d, J
= 12.2 Hz, 1 H, PhCH ), 4.23 (d, J
PhCH ), 4.21–4.28 (m, 2 H, 1-H, 2-H), 4.38 (d, J
PhCH ), 72.5 (s, CH-5′), 73.3 (s, 1 C, PhCH ), 74.2 (d, J = 1.7 Hz, 1 PhCH ), 4.41–4.45 (m, 1 H, 4-H), 4.43 (d, J = 12.1 Hz, 1 H, PhCH ),
= 11.9 Hz, 1 H,
= 11.9 Hz, 1 H,
3
3
2
C,P
H,H
2
H,H
3
2
1
04.0 Hz, 1 C, CH-1), 69.0 (d, JC,P = 8.9 Hz, 1 C, CH -5), 72.4 (s, 1 C,
2
3
2
H,H
2
2
2
C,P
2
H,H
2
2
2
2
C, CH-3), 75.7 (s, 1 C, PhCH ), 76.3 (d, J = 5.7 Hz, 1 C, CH-4), 79.4
(
8
4.53 (d, J
= 12.1 Hz, 1 H, PhCH ), 4.56 (d, J
PhCH ), 4.74 (d, J = 10.7 Hz, 1 H, PhCH ), 4.82 (d, J = 11.5 Hz,
= 10.7 Hz, 1 H,
2
C,P
H,H
2
H,H
2
2
2
s, 1 C, CH-3′), 81.2 (s, 1 C, CH-4′),82.0 (d, J = 5.8 Hz, 1 C, CH-2),
5.4 (s, 1 C, CH-2′), 107.0 (d, JC,P = 7.4 Hz, 1 C, CH-1′), 109.1 [s, 1 C,
C,P
2
H,H
2
H,H
3
2
3
1 H, PhCH ), 4.90 (d, J
= 11.5 Hz, 1 H, PhCH ), 5.43 (d, J
=
2
H,H
2
H,H
1
Cq(CH ) ], 112.7 [s, 1 C, Cq(CH ) ], 126.6 (d, J = 141.9 Hz, 1 C, 1.2 Hz, 1 H, 1′-H), 6.98–7.04 (m, 4 H, CH ), 7.10–7.30 (m, 28 H, CH ),
3
2
3 2
C,P
ar
ar
1
3
Cq ), 127.5, 127.6, 127.7, 127.8, 127.9, 128.3, 128.4, 128.4, 128.4, 7.42–7.46 (m, 1 H, CH ), 7.68–7.73 (m, 2 H, CH ) ppm. C NMR
ar
ar
ar
2
4
3
1
33.1 (d, J = 9.7 Hz, 1 C, CH ), 133.5 (d, J = 2.6 Hz, 1 C, CHp),
(100.61 MHz, CDCl ): δ = 68.4 (d, J = 9.4 Hz, 1 C, CH -5), 71.3 (s,
C,P
o
C,P
3 C,P 2
1
37.5 (s, 1 C, CqBn), 138.1 (s, 1 C, CqBn), 138.3 (s, 1 C, CqBn) ppm.
1 C, CH -5′), 71.9 (s, 1 C, PhCH ), 72.0 (s, 1 C, PhCH ), 72.6 (s, 1 C,
2 2 2
+
+
1
MS (ES ): m/z = 787.32 [M + H] . HRMS (ESI-QTOF): calcd. for
C H O P [M + H] 787.3247; found 787.3257.
PhCH ), 73.4 (s, 1 C, PhCH ), 73.8 (d, J = 106.0 Hz, 1 C, CH-1),
2 2 C,P
+
2
75.1 (d, J = 5.2 Hz, 1 C, CH-4), 75.6 (s, 1 C, PhCH ), 75.7 (s, 1 C,
C,P 2
44
52 11
PhCH ), 78.3 (s, 1 C, CH-3′), 78.3 (s, 1 C, CH-3), 79.5 (s, 1 C, CH-2′),
Data for α-9: 31P NMR (161.97 MHz, CDCl ): δ = 37.08 (s) ppm. H
1
2
3
2
3
8
5
1
1
0.1 (s, 1 C, CH-4′), 83.8 (d, J = 6.9 Hz, 1 C, CH-2), 106.2 (d, J
=
C,P
C,P
NMR (400.13 MHz, CDCl ): δ = 1.30 (s, 3 H, CH ), 1.40 (s, 3 H, CH ),
3
3
3
.9 Hz, 1 C, CH-1′), 126.5 (1 transition, 1 C, Cq ), 126.8, 127.5, 127.5,
3
3
3
ar
2
.19 (m, J = 3.7, J = 8.1 Hz, 1 H, 4′-H), 3.32 (dd, J = 6.2,
JH,H = 11.4 Hz, 1 H, 6′a-H), 3.55 (dd, J = 3.1, J = 11.4 Hz, 1
H,H H,H H,H
27.6, 127.6, 127.63, 127.7, 127.8, 127.8, 127.8, 127.9, 128.2, 128.3,
2
3
2
H,H
H,H
3
28.3, 128.4, 128.4, 128.5, 128.6 (d, J = 13.5 Hz, 1 C, CH ), 132.4
3
3
C,P
4
m
H, 6′b-H), 3.72 (m, J
= 3.1, J
= 6.2 Hz, 1 H, 5′-H), 3.80 (dd,
H,H
H,H
2
(
(
d, J = 10.2 Hz, 1 C, CH ), 133.3 (d, J = 2.7 Hz, 1 C, CH ), 137.6
s, 1 C, CqBn), 137.7 (s, 1 C, CqBn), 137.9 (s, 1 C, CqBn), 138.1 (s, 1
3
JH,H = 2.0, 2JH,H = 11.3 Hz, 1 H, 5a-H), 3.98 (dt, J = 2.9, 2JH,H
3
C,P
o
C,P
p
=
3
3
1
4
(
1.3 Hz, 1 H, 5b-H), 4.29 (dd, JH,H = 3.9, J = 5.9 Hz, 1 H, 3′-H),
.30–4.36 (m, 2 H, 2-H, 3-H), 4.54 (d, J = 5.9 Hz, 1 H, 2′-H), 4.54
H,H
+
+
C, CqBn), 138.3 (s, 1 C, CqBn) ppm. MS (ES ): m/z = 947.39 [M + H] .
HRMS (ESI-QTOF): calcd. for C H O P [M + H] 947.3924; found
3
H,H
+
2
2
58 60 10
m, 1 H, 4-H), 4.61 (d, J = 12.2 Hz, 1 H, PhCH ), 4.63 (dd, J
.0, J = 9.6 Hz, 1 H, 1-H), 4.63 (d, J
=
H,H
2
H,H
947.3928.
3
2
2
4
= 10.8 Hz, 1 H, PhCH ),
H,P
H,H
2
Data for anomer 2: 31P NMR (161.97 MHz, CDCl ): δ = 32.15 (s) ppm.
2
2
.68 (d, J
= 11.4 Hz, 1 H, PhCH ), 4.71 (d, J
= 12.2 Hz, 1 H,
3
H,H
2
H,H
1
3
2
2
2
H NMR (400.13 MHz, CDCl ): δ = 3.08 (dd, JH,H = 4.0, JH,H =
PhCH ), 4.78 (d, J = 11.4 Hz, 1 H, PhCH ), 4.93 (d, J = 10.8 Hz,
H, PhCH ), 5.48 (s, 1 H, 1′-H), 7.21–7.23 (m, 2 H, CH ), 7.28–7.42
3
2
H,H
2
H,H
3
2
1
0.9 Hz, 1 H, 5′a-H), 3.18 (dd, J = 3.6, J = 10.9 Hz, 1 H, 5′b-
1
H,H H,H
2
ar
3
3
3
H), 3.52 (dd, J = 4.2, J = 6.8 Hz, 1 H, 2′-H), 3.62 (dd, J =
4.2, J = 6.8 Hz, 1 H, 3′-H), 3.66 (dd, J = 2.0, J = –11.2 Hz,
(
m, 13 H, CH ), 7.48–7.53 (m, 2 H, CH ), 7.62–7.67 (m, 1 H, CH ),
H,H
H,H
H,H
ar
ar
ar
3
3
2
1
3
7
2
.86–7.91 (m, 2 H, CH ) ppm. C NMR (100.61 MHz, CDCl ): δ =
4.8 (s, 1 C, CH ), 26.0 (s, 1 C, CH ), 64.0 (s, 1 C, CH -6′), 67.8 (d,
JC,P = 104.4 Hz, 1 C, CH-1), 69.0 (d, JC,P = 9.0 Hz, 1 C, CH -5), 69.9
s, 1 C, CH-5′), 72.5 (s, 1 C, PhCH ), 73.3 (s, 1 C, PhCH ), 74.2 (d,
H,H
H,H
2
H,H
ar
3
3
4
1
H, 5a-H), 3.87 (dt, J = 2.5, J = 2.5, J = –11.2 Hz, 1 H, 5b-
H,H
H,P
H,H
3
3
2
3
3
3
1
3
H), 3.98 (dd, J
3
= 9.4, J
= 9.9 Hz, 1 H, 3-H), 4.04 (m, J
.6, J = 4.0 Hz, J = 4.2 Hz, 1 H, 4′-H), 4.16 (d, J = –12.1 Hz,
1 H, PhCH ), 4.22 (d, J = –12.1 Hz, 1 H, PhCH ), 4.27 (dd, J
=
H,H
H,H
H,H
2
3
3
2
(
H,H
H,H
2
H,H
2
2
3
3
2
=
JC,P = 1.5 Hz, 1 C, CH-3), 75.5 (s, 1 C, PhCH ), 76.3 (d, J = 5.8 Hz,
2
H,H
2
H,H
2
C,P
3
2
2
9.4, J = 9.9, Hz, 1 H, 2-H), 4.28 (d, J = –12.2 Hz, 1 H, PhCH ),
1
5
C, CH-4), 79.3 (s, 1 C, CH-4′), 79.9 (s, 1 C, CH-3′), 81.6 (d, J
=
H,H H,H 2
C,P
2
3
2
3
4.39 (dd, J = 5.4, J = 9.9 Hz, 1 H, 1-H), 4.41 (d, J = –12.0 Hz,
H,P H,H H,H
1 H, PhCH ), 4.43 (d, J = –12.0 Hz, 1 H, PhCH ), 4.48 (m, J
2.0, J = 2.5 Hz, J = 4.4 Hz, J = 9.9 Hz, 1 H, 4-H), 4.52 (d,
JH,H = –12.2 Hz, 1 H, PhCH ), 4.53 (d, J = –12.0 Hz, 1 H, PhCH ),
= –10.7 Hz, 1 H, PhCH ), 4.66 (d, J
1′-H), 4.70 (d, J = –11.5 Hz, 1 H, PhCH ), 4.78 (d, J = –12.0 Hz,
1 H, PhCH ), 4.82 (d, J = –10.7 Hz, 1 H, PhCH ), 5.16 (d, J =
.5 Hz, 1 C, CH-2), 84.9 (s, 1 C, CH-2′), 106.4 (d, J = 7.1 Hz, 1 C,
C,P
2
3
1
=
CH-1′), 112.7 [s, 1 C, Cq(CH ) ], 126.4 (d, J = 142.0 Hz, 1 C, Cq ),
2
H,H
2
H,H
3
2
C,P
ar
3
3
3
3
1
27.5, 127.7, 127.8, 127.88, 127.9, 127.9, 128.3 (d, J = 13.4 Hz, 1
C, CH ), 128.4, 128.4, 128.5, 133.3 (d, J = 9.9 Hz, 1 C, CH ), 133.5
d, J = 2.6 Hz, 1 C, CH ), 137.5 (s, 1 C, CqBn), 138.0 (s, 1 C, CqBn),
H,H
H,P
H,H
2
C,P
2
2
2
H,H
2
m
C,P
o
4.54 (d, 2J
3
= 4.2 Hz, 1 H,
4
(
1
H,H
2
H,H
2
C,P
p
2
+
+
38.2 (s, 1 C, CqBn) ppm. MS (ES ): m/z = 747.29 [M + H] . HRMS
H,H
2
H,H
2
2
(
ESI-QTOF): calcd. for C41H48O11P [M + H]+ 747.2934; found
2
H,H
2
H,H
–
11.5 Hz, 1 H, PhCH ), 7.00–7.54 (m, 33 H, CH ), 7.83–7.88 (m, 2 H,
7
47.2943.
2 ar
13
3
CH ) ppm. C NMR (100.61 MHz, CDCl ): δ = 68.7 (d, J = 9.2 Hz,
ar
3
C,P
(
(
2S ,3S,4S,5S,6R)-4,5-Bis(benzyloxy)-6-benzyloxymethyl-3-O-
-ribofuranosyl)-2-phenyl-2-oxo-2λ -[1,2]-
oxaphosphinane (α/ꢀ-5c): Pd(PhCN) Cl (8.1 mg, 0.021 mmol) and
AgOTf (10.9 mg, 0.042 mmol) were added to a stirred solution of
a (289 mg, 0.53 mmol) and 2,3,5-tri-O-benzyl- -ribofuranosyl tri-
chloroacetimidate (α/ꢀ-7b; 600 mg, 1.06 mmol) in freshly distilled
CH Cl (8 mL). The resulting mixture was stirred at room tempera-
ture for 1.5 h, then it was filtered through Celite, and the solvent
was removed under vacuum. The residue was purified by chroma-
tography on silica gel (n-heptane/ethyl acetate, 60:40) to give α/ꢀ-
P
1 C, CH -5), 69.3 (s, 1 C, CH -5′), 72.1 (s, 1 C, PhCH ), 72.5 (s, 1 C,
2 2 2
5
2,3,5-tri-O-benzyl-
D
2
PhCH ), 73.2 (s, 1 C, PhCH ), 73.4 (s, 1 C, PhCH ), 74.8 (d, JC,P
=
2
2
2
1
2
2
5.1 Hz, 1 C, CH-4), 75.3 (s, 1 C, CH-3′), 75.5 (d, J = 97.3 Hz, 1 C,
C,P
CH-1), 75.6 (s, 1 C, PhCH ), 75.7 (s, 1 C, PhCH ), 77.3 (s, 1 C, CH-2′),
2
2
4
D
2
7
7.8 (s, 1 C, CH-3), 81.7 (s, 1 C, CH-4′), 82.0 (d, J = 5.8 Hz, 1 C,
C,P
CH-2), 100.1 (s, 1 C, CH-1′), 127.0, 127.2, 127.4, 127.5, 127.5, 127.6,
127.7, 127.7, 127.9, 128.0, 128.0, 128.1, 128.2, 128.3, 128.3, 128.3,
2
2
3
1
1
1
1
28.4, 128.9 (d, J = 13.0 Hz, 1 C, CH ), 129.7 (d, J = 131.0 Hz,
C,P
2
m
C,P
4
C, Cq ), 132.0 (d, J = 10.6 Hz, 1 C, CH ), 133.3 (d, J = 2.5 Hz,
C, CH ), 137.9 (s, 1 C, CqBn), 138.0 (s, 1 C, CqBn), 138.1 (s, 1 C,
ar
C,P
o
C,P
p
5
c (312 mg, 62 %) as two anomers (α/ꢀ = 38:62). The two anomers
+
CqBn), 138.3 (s, 1 C, CqBn), 139.1 (s, 1 C, CqBn) ppm. MS (ES ): m/z =
were separated by chromatography on silica gel (CH Cl /Et O,
+
+
2
2
2
947.39 [M + H] . HRMS (ESI-QTOF): calcd. for C H O P [M + H]
58 60 10
1
00:00 to 85:15).
947.3924; found 947.3918.
Data for anomer 1: 31P NMR (161.97 MHz, CDCl ): δ = 34.94 (s) ppm.
(2S ,3R,4S,5S,6R)-4,5-Bis(benzyloxy)-6-benzyloxymethyl-3-O-
3
P
1
H NMR (400.13 MHz, CDCl ): δ = 2.11 (dd, JH,H = 7.0, 2JH,H
3
5
=
(2,3,5-tri-O-benzyl-
D
-ribofuranosyl)-2-phenyl-2-oxo-2λ -[1,2]-
3
3
2
1
0.4 Hz, 1 H, 5′a-H), 2.82 (dd, J = 4.4, J = 10.4 Hz, 1 H, 5′b-
oxaphosphinane (α/ꢀ-5d): Pd(PhCN) Cl (20.3 mg, 0.053 mmol)
H,H
H,H
2 2
3
3
3
H), 3.53 (dd, J = 4.5, J = 7.6 Hz, 1 H, 3′-H), 3.64 (dd, J
=
=
and AgOTf (27.2 mg, 0.106 mmol) were added to a stirred solution
of 4b (289 mg, 0.53 mmol) and 2,3,5-tri-O-benzyl- -ribofuranosyl
H,H
H,H
H,H
2
3
4
2
2
1
3
7
.0, J = 11.2 Hz, 1 H, 5a-H), 3.86 (dt, J = 2.5, J = 2.5, J
D
H,H
H,H
3
H,P
H,H
3
1.2 Hz, 1 H, 5b-H), 3.87 (dd, JH,H = 1.2, J = 4.5 Hz, 1 H, 2′-H),
trichloroacetimidate (α/ꢀ-7b; 600 mg, 1.06 mmol) in freshly distilled
H,H
3
3
3
.93–3.98 (m, 1 H, 3-H), 4.03 (ddd, J = 4.4, J = 7.0 Hz, J
.6 Hz, 1 H, 4′-H), 4.11 (d, JH,H = 12.2 Hz, 1 H, PhCH ), 4.14 (d,
=
CH Cl (9 mL). The resulting mixture was stirred at room tempera-
H,H
H,H
H,H
2
2
2
ture for 1 h, then it was filtered through Celite, and the solvent was
2
Eur. J. Org. Chem. 2017, 5357–5369
www.eurjoc.org
5364 © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
evaporated under vacuum. The residue was purified by chromatog-
raphy on silica gel (n-heptane/ethyl acetate, 60:40 to 30:70) to give
α/ꢀ-5d (181 mg, 36 %) as two anomers.
(2S ,3S,4S,5S,6R)-4,5-Bis(benzyloxy)-6-benzyloxymethyl-3-O-
P
5
(2,3,4,6-tetra-O-benzyl-
D
-glucopyranosyl)-2-phenyl-2-oxo-2λ -
[1,2]-oxaphosphinane (α/ꢀ-6a): Pd(PhCN) Cl2 (20.3 mg,
2
3
1
0.053 mmol) and AgOTf (27.2 mg, 0.106 mmol) were added to a
stirred solution of 4a (289 mg, 0.53 mmol) and 2,3,4,6-tetra-O-
Data for anomer 1: P NMR (161.97 MHz, CDCl ): δ = 35.12 (s) ppm.
3
1
3
3
H NMR (400.13 MHz, CDCl ): δ = 3.50 (dd, J = 0.6, J = 4.5 Hz,
3
H,H
H,H
3
2
benzyl-
D
-glucopyranosyl trichloroacetimidate (α/ꢀ-7c; 736 mg,
Cl (9 mL). The resulting mixture
1
H, 2′-H), 3.51 (dd, J = 4.7, J = 10.5 Hz, 1 H, 5′a-H), 3.56 (dd,
H,H H,H
3
2
3
2
1.07 mmol) in freshly distilled CH
2
2
JH,H = 6.5, J = 10.5 Hz, 1 H, 5′b-H), 3.82 (dd, J = 1.7, J =
1.3 Hz, 1 H, 5a-H), 3.82 (dd, J = 4.5, J = 7.6 Hz, 1 H, 3′-H),
H,H H,H
.98 (ddd, J = 2.4, J
H,H
H,H
H,H
3
3
was stirred at room temperature for 1 h, then it was filtered through
Celite, and the solvent was removed under vacuum. The residue
was purified by chromatography on silica gel (n-heptane/ethyl acet-
ate, 70:30 to 40:60) to give anomer α-6a (470 mg, 83 %).
1
3
(
4
4
3
2
= 3.6, J = 11.3 Hz, 1 H, 5b-H), 4.00
H,P
H,H
H,H
2
2
d, J = 11.8 Hz, 1 H, PhCH ), 4.08 (d, J = 11.8 Hz, 1 H, PhCH ),
H,H
3
2
H,H
2
3
2
.21 (t, J = 9.7, J = 9.7 Hz, 1 H, 3-H), 4.27 (d, J = 12.0 Hz,
H,H H,H H,H
3
3
3
Data for α-6a: 31P NMR (161.97 MHz, CDCl ): δ = 32.20 (s) ppm. H
1
1
H, PhCH ), 4.28 (ddd, J = 4.6, J = 6.4 Hz, J = 7.6 Hz, 1
2
H,H
H,H
H,H
3
3
3
3
H, 4′-H), 4.33 (ddd, J = 0.8, J = 2.5 Hz, J = 9.7 Hz, 1 H, 2-
NMR (400.13 MHz, CDCl ): δ = 3.37–3.41 (m, 3 H, 2′-H, 6′a-H, 6′b-
H,P
H,H
H,H
2
3
2
3
3
3
H), 4.34 (d, J = 12.0 Hz, 1 H, PhCH ), 4.39 (d, J = 11.6 Hz, 1 H), 3.53 (dd, J = 9.1, J = 10.2 Hz, 1 H, 4′-H), 3.75 (dd, J =
H,H
2
H,H
H,H
H,H
H,H
2
2
H, PhCH ), 4.44 (d, J = 11.6 Hz, 1 H, PhCH ), 4.45 (br. s, 1 H, 1′-
2.0, J
= 11.2 Hz, 1 H, 5a-H), 3.97–4.07 (m, 4 H, 3′-H, 5′-H, 3-H,
2
H,H
2
H,H
3
2
2
2
H), 4.53 (m, 1 H, 4-H), 4.54 (t, J = 2.5, J = 2.5 Hz, 1 H, 1-H),
5b-H), 4.29 (d, J = 12.1 Hz, 1 H, PhCH ), 4.38 (d, J = 11.1 Hz,
H,H
H,P
2
H,H 2 H,H
2
2
4
.60 (d, J
= 10.9 Hz, 1 H, PhCH ), 4.62 (d, J
= 12.2 Hz, 1 H,
1 H, PhCH ), 4.41–4.43 (m, 2 H, 1-H, 2-H), 4.47 (d, J = 12.1 Hz, 1
2 H,H
H,H
2
H,H
2
2
2
2
PhCH ), 4.66 (d, J = 12.2 Hz, 1 H, PhCH ), 4.72 (d, J = 12.2 Hz,
H, PhCH ), 4.52 (d, JH,H = 12.0 Hz, 1 H, PhCH ), 4.54 (d, JH,H =
2
H,H
2
H,H
2
2
2
2
2
1
1
H, PhCH ), 4.82 (d, J
= 12.2 Hz, 1 H, PhCH ), 4.92 (d, J
=
11.8 Hz, 1 H, PhCH ), 4.56–4.61 (m, 1 H, 4-H), 4.62 (d, J = 12.0 Hz,
2 H,H
2
H,H
2
H,H
2
2
0.9 Hz, 1 H, PhCH ), 7.15–7.59 (m, 33 H, CH ), 7.91–7.97 (m, 2 H,
1 H, PhCH ), 4.71 (d, J
= 10.9 Hz, 1 H, PhCH ), 4.74 (d, J
=
2
ar
2
H,H
2
H,H
13
3
2
CH ) ppm. C NMR (100.61 MHz, CDCl ): δ = 69.2 (d, J = 8.8 Hz,
C, CH -5), 71.8 (s, 1 C, CH -5′), 71.8 (s, 1 C, PhCH ), 72.0 (s, 1 C,
10.8 Hz, 1 H, PhCH ), 4.75 (d, J = 11.8 Hz, 1 H, PhCH ), 4.79 (d,
= 11.1 Hz, 1 H, PhCH ), 4.80 (d, J = 3.5 Hz, 1 H, 1′-H), 4.90
(d, J = 10.8 Hz, 1 H, PhCH ), 4.91 (d, J = 10.5 Hz, 1 H, PhCH ),
ar
3
C,P
2
H,H
2
2
3
1
J
2
2
2
H,H
2
2
H,H
2
1
PhCH ), 72.1 (d, J = 99.4 Hz, 1 C, CH-1), 72.4 (s, 1 C, PhCH ), 72.8
2
C,P
2
H,H
2
H,H
2
2
2
(
s, 1 C, PhCH ), 73.3 (s, 1 C, PhCH ), 74.1 (s, 1 C, CH-3), 75.3 (s, 1 C,
4.94 (d, J
= 10.9 Hz, 1 H, PhCH ), 4.97 (d, J = 11.5 Hz, 1 H,
2
2
H,H
2
H,H
2
PhCH ), 76.3 (d, J = 5.7 Hz, 1 C, CH-4), 78.9 (s, 1 C, CH-3′), 79.9
PhCH ), 7.01–7.07 (m, 4 H, CH ), 7.13–7.38 (m, 29 H, CH ), 7.43–
2
C,P
2 ar ar
2
(
1
s, 1 C, CH-2′), 80.1 (d, J = 5.9 Hz, 1 C, CH-2), 80.3 (s, 1 C, CH-4′),
05.6 (d, J = 2.6 Hz, 1 C, CH-1′), 126.9 (1 transition, 1 C, Cqar),
7.48 (m, 4 H, CH ), 7.59–7.63 (m, 1 H, CH ), 7.86–7.91 (m, 2 H, CH )
ar ar ar
C,P
3
13
ppm. C NMR (100.61 MHz, CDCl ): δ = 68.1 (s, 1 C, CH -6′), 68.5
C,P
3
2
3
1
27.5, 127.5, 127.5, 127.6, 127.7, 127.8, 127.8, 127.8, 127.9, 128.3, (d, J = 9.2 Hz, 1 C, CH -5), 70.4 (s, 1 C, CH-5′), 72.3 (s, 1 C, PhCH ),
C,P
2
2
3
1
1
28.3, 128.4, 128.4, 128.6 (d, JC,P = 13.2 Hz, 1 C, CH ), 133.1 (d, 73.2 (s, 1 C, PhCH ), 73.5 (s, 1 C, PhCH ), 74.2 (d, J = 96.5 Hz, 1
m 2 2 C,P
2
4
2
JC,P = 10.0 Hz, 1 C, CH ), 133.3 (d, J = 2.4 Hz, 1 C, CH ), 137.7
C, CH-1), 74.8 (d, J = 5.2 Hz, 1 C, CH-4), 74.8 (s, 1 C, PhCH ), 75.4
C,P 2
o
C,P
p
(
s, 1 C, CqBn), 137.7 (s, 1 C, CqBn), 138.0 (s, 1 C, CqBn), 138.0 (s, 1 (s, 1 C, PhCH ), 75.6 (s, 1 C, PhCH ), 76.8 (s, 1 C, PhCH ), 77.3 (s, 1
2 2 2
+
C, CqBn), 138.2 (s, 1 C, CqBn), 138.3 (s, 1 C, CqBn) ppm. MS (ES ):
m/z = 947.39 [M + H] . HRMS (ESI-QTOF): calcd. for C H O P [M 82.3 (d, J = 7.2 Hz, 1 C, CH-2), 95.3 (s, 1 C, CH-1′), 127.4, 127.5,
+
C, CH-4′), 78.3 (s, 1 C, CH-3), 78.9 (s, 1 C, CH-2′), 81.6 (s, 1 C, CH-3′),
+
2
5
8
60 10
C,P
+
H] 947.3924; found 947.3928.
127.6, 127.6, 127.7, 127.7, 127.7, 127.9, 128.1, 128.1, 128.2, 128.3,
3
Data for anomer 2: 31P NMR (161.97 MHz, CDCl ): δ = 37.38 (s) ppm.
128.3, 128.3, 128.4, 128.4, 128.9 (d, J
C,P = 13.2 Hz, 1 C, CH
m
), 129.4
),
33.4 (d, J = 2.7 Hz, 1 C, CH ), 137.7 (s, 1 C, CqBn), 137.9 (s, 1 C,
3
1
2
1
3
(d, JC,P = 132.4 Hz, 1 C, Cqar), 131.8 (d, JC,P = 10.8 Hz, 1 C, CH
o
H NMR (400.13 MHz, CDCl ): δ = 2.80 (q, J = 3.7 Hz, 1 H, 4′-H),
3
H,H
4
1
C,P
p
3
.12 (d, J = 3.7 Hz, 2 H, 5′-CH ), 3.68–3.73 (m, 2 H, 2′-H, 3′-H), 3.79
2
3
2
4
CqBn), 137.9 (s, 1 C, CqBn), 138.0 (s, 1 C, CqBn), 138.1 (s, 1 C, CqBn),
(
dd, J
= 1.6, J
= 11.4 Hz, 1 H, 5a-H), 3.95 (ddd, J = 2.0,
H,H
H,H
H,P
+
3
2
2
138.6 (s, 1 C, CqBn), 138.7 (s, 1 C, CqBn) ppm. MS (ES ): m/z =
JH,H = 4.0 Hz, J = 11.4 Hz, 1 H, 5b-H), 4.30 (d, J = 12.2 Hz, 1
H,H
H,H
3
+
H O
11P [M + H]+
68
2
1067.45 [M + H] . HRMS (ESI-QTOF): calcd. for C66
1067.4499; found 1067.4489.
H, PhCH ), 4.32 (d, J = 11.0 Hz, 1 H, PhCH ), 4.37 (t, J = 9.7 Hz,
1
1
2
H,H
2
H,H
H, 3-H), 4.38 (d, 2J
2
= 12.2 Hz, 1 H, PhCH ), 4.43 (d, JH,H =
H,H
2
2.1 Hz, 1 H, PhCH ), 4.44 (dd, J = 2.3, J = 9.7 Hz, 1 H, 2-H), Data for ꢀ-6a: 31P NMR (161.97 MHz, CDCl ): δ = 33.78 (s) ppm. H
3
3
1
2
H,H
H,H
3
.53 (d, 2JH,H = 12.4 Hz, 1 H, PhCH ), 4.58 (m, 1 H, 4-H), 4.61 (d,
NMR (400.13 MHz, CDCl ): δ = 3.13 (ddd, J = 2.2, J = 4.2 Hz,
JH,H = 9.7 Hz, 1 H, 5′-H), 3.20 (dd, J = 2.2, J = 10.7 Hz, 1 H,
H,H H,H
3
3
4
2
3 H,H H,H
2
2
3
3
3
JH,H = 12.3 Hz, 1 H, PhCH ), 4.67 (d, J
.74 (d, J
= 11.0 Hz, 1 H, PhCH ),
2
H,H
2
2
2
3
3
4
= 12.1 Hz, 1 H, PhCH ), 4.74 (d, J
= 12.3 Hz, 1 H,
6′a-H), 3.23 (dd, J
= 4.2, J
= 10.7 Hz, 1 H, 6′b-H), 3.32 (dd,
H,H
2
H,H
H,H
H,H
3
2
3
3
3
3
PhCH ), 4.76 (dd, J = 2.3, J = 8.6 Hz, 1 H, 1-H), 4.79 (s, 2 H,
PhCH ), 4.99 (d, J = 12.4 Hz, 1 H, PhCH ), 5.42 (d, J = 3.9 Hz,
1
JH,H = 9.5.0, J = 9.5 Hz, 1 H, 4′-H), 3.32 (dd, J = 7.7, J
=
2
H,H
H,P
H,H
H,H
H,H
2
3
3
3
9.2 Hz, 1 H, 2′-H), 3.41 (dd, J = 9.0, J = 9.0 Hz, 1 H, 3′-H), 3.69
= 11.2 Hz, 1 H, 5a-H), 3.89 (ddd, J = 2.4,
JH,H = 2.5 Hz, J = 11.2 Hz, 1 H, 5b-H), 3.92–3.97 (m, 1 H, 3-H),
2
H,H
2
H,H
H,H
H,H
3
2
4
H, 1′-H), 7.10–7.34 (m, 32 H, CH ), 7.49–7.53 (m, 1 H, CH ), 8.03– (dd, J
.08 (m, 2 H, CH ) ppm. C NMR (100.61 MHz, CDCl ): δ = 69.2 (d,
JC,P = 7.8 Hz, 1 C, CH -5), 69.2 (s, 1 C, CH -5′), 71.7 (s, 1 C, PhCH ),
2.1 (d, J = 103.7 Hz, 1 C, CH-1), 72.5 (s, 1 C, PhCH ), 73.1 (s, 1
= 2.0, J
ar
ar
H,H
H,H H,P
1
3
3
2
8
ar
3
H,H
3
2
2
4.05 (d, J
= 12.0 Hz, 1 H, PhCH ), 4.12 (d, J
PhCH ), 4.26–4.34 (m, 2 H, 1-H, 2-H), 4.35 (d, J
= 12.0 Hz, 1 H,
= 10.6 Hz, 1 H,
2
2
2
H,H
2
H,H
1
2
7
C,P
2
2
H,H
3
2
C, PhCH ), 73.3 (s, 1 C, PhCH ), 73.4 (s, 1 C, PhCH ), 74.8 (d, J
=
PhCH ), 4.46 (d, J = 12.1 Hz, 1 H, PhCH ), 4.47–4.53 (m, 1 H, 4-
H), 4.54 (d, J = 12.1 Hz, 1 H, PhCH ), 4.63 (d, J = 10.9 Hz, 1
2
2
2
C,P
2
H,H
2
2
2
1
.7 Hz, 1 C, CH-3), 75.1 (s, 1 C, PhCH ), 75.7 (s, 1 C, CH), 76.2 (d,
JC,P = 5.6 Hz, 1 C, CH-4), 77.3 (s, 1 C, CH), 80.9 (s, 1 C, CH-4′), 82.2 H, PhCH ), 4.63 (d, JH,H = 10.6 Hz, 1 H, PhCH ), 4.63 (d, JH,H
2
H,H 2 H,H
2
2
2
=
2
2
2
3
2
(d, J = 6.2 Hz, 1 C, CH-2), 103.4 (d, J = 5.8 Hz, 1 C, CH-1′),
10.1 Hz, 1 H, PhCH ), 4.67 (d, J = 10.9 Hz, 1 H, PhCH ), 4.74 (d,
C,P
C,P
2
H,H
2
2
1
3
1
1
1
1
26.4 (d, J = 141.4 Hz, 1 C, Cq ), 127.2, 127.4, 127.5, 127.5, 127.5,
27.5, 127.6, 127.6, 127.7, 127.8, 128.0, 128.0, 128.0, 128.1, 128.2, (d, J = 11.4 Hz, 1 H, PhCH ), 4.83 (d, J = 10.9 Hz, 1 H, PhCH ),
28.3, 128.3, 128.36, 128.56, 132.68 (d, JC,P = 2.7 Hz, 1 C, CHp),
33.81 (d, J = 10.1 Hz, 1 C, CH ), 137.7 (s, 1 C, CqBn), 137.9 (s, 1
J
H,H
2
= 7.7 Hz, 1 H, 1′-H), 4.75 (d, J = 10.1 Hz, 1 H, PhCH ), 4.78
C,P
ar
H,H
2
2
H,H
2
H,H
2
4
2
2
4.84 (d, J
= 10.9 Hz, 1 H, PhCH ), 5.07 (d, J = 11.4 Hz, 1 H,
H,H
2
H,H
2
PhCH ), 6.99–7.02 (m, 2 H, CH ), 7.10–7.38 (m, 36 H, CH ), 7.80–
C,P
o
2 ar ar
13
C, CqBn), 138.1 (s, 1 C, CqBn), 138.2 (s, 1 C, CqBn), 138.4 (s, 1 C,
CqBn), 138.7 (s, 1 C, CqBn) ppm. MS (ES ): m/z = 947.39 [M + H] .
HRMS (ESI-QTOF): calcd. for C H O P [M + H] 947.3924; found 73.4 (s, 1 C, PhCH ), 74.4 (d, J = 106.1 Hz, 1 C, CH-1), 74.6 (d,
9
7.85 (m, 2 H, CH ) ppm. C NMR (100.61 MHz, CDCl ): δ = 68.5 (d,
ar 3
+
+
3
JC,P = 9.0 Hz, 1 C, CH -5), 69.2 (s, 1 C, CH -6′), 73.2 (s, 1 C, PhCH ),
2 2 2
+
1
5
8
60 10
2
C,P
2
47.3920.
JC,P = 5.1 Hz, 1 C, CH-4), 74.7 (s, 1 C, CH-5′), 75.1 (s, 1 C, PhCH2),
Eur. J. Org. Chem. 2017, 5357–5369
www.eurjoc.org
5365
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
7
5.2 (s, 1 C, PhCH ), 75.4 (s, 1 C, PhCH ), 75.6 (s, 1 C, PhCH ), 75.9
ture for 1 h, then it was filtered through Celite, and concentrated
under vacuum. The crude mixture was triturated with diethyl ether,
and the resulting precipitate was dissolved in CH Cl . The mixture
2
2
2
(s, 1 C, PhCH ), 77.9 (s, 1 C, CH), 78.5 (s, 1 C, CH-3), 82.4 (s, 1 C, CH),
2
2
3
8
6
1
1
1
4.0 (d, J = 7.2 Hz, 1 C, CH-2), 84.4 (s, 1 C, CH-3′), 103.3 (d, J
.2 Hz, 1 C, CH-1′), 126.9 (1 transition, 1 C, Cq ), 127.4, 127.5, 127.6,
27.6, 127.7, 127.8, 127.9, 128.0, 128.0, 128.1, 127.2, 128.3, 128.3, reduced pressure to give pure ꢀ-6c (262 mg, 57 %). P NMR
28.3, 128.4, 128.4, 128.4, 128.4, 132.1 (d, J = 10.3 Hz, 1 C, CHo),
=
C,P
C,P
2
2
was filtered, and the solvent was removed from the filtrate under
ar
3
1
2
1
(161.97 MHz, CDCl ): δ = 33.13 (s) ppm. H NMR (400.13 MHz,
C,P
3
4
32.8 (d, J = 2.7 Hz, 1 C, CH ), 137.9 (s, 1 C, CqBn), 137.9 (s, 1 C,
CDCl ): δ = 1.89 (s, 3 H, CH ), 1.97 (s, 3 H, CH ), 1.98 (s, 3 H, CH ),
C,P
p
3
3
3
3
2
3
3
CqBn), 138.0 (s, 1 C, CqBn), 138.1 (s, 1 C, CqBn), 138.2 (s, 1 C, CqBn),
2.00 (s, 3 H, CH ), 3.36 (ddd, JH,H = 2.5, JH,H = 4.8 Hz, JH,H =
10.0 Hz, 1 H, 5′-H), 3.45 (dd, J = 2.5, J = 12.2 Hz, 1 H, 6′a-H),
3
+
1
2
1
1
1
38.4 (s, 1 C, CqBn), 138.5 (s, 1 C, CqBn) ppm. MS (ES ): m/z =
H,H
H,H
+
+
1
2
2
067.45 [M + H] . HRMS (ESI-QTOF): calcd. for C H O P [M + H]
3.60 (dd, J
= 4.8, J
= 12.2 Hz, 1 H, 6′b-H), 3.77 (dd, J
=
6
6
68 11
H,H
H,H
H,H
3
3
4
067.4499; found 1067.4503.
2.0, J = 11.2 Hz, 1 H, 5a-H), 3.98 (ddd, J = 2.4, J = 2.4 Hz,
H,H
H,H
H,H
2
3
3
JH,P = 11.2 Hz, 1 H, 5b-H), 4.04 (t, J = 9.7, J = 9.7 Hz, 1 H, 3-
H,H
H,H
(
2S ,3R,4S,5S,6R)-4,5-Bis(benzyloxy)-6-benzyloxymethyl-3-O-
P
3
2
3
H), 4.20 (dd, J = 4.8, J = 10.4 Hz, 1 H, 1-H), 4.38 (ddd, J =
5
H,P
H,H
H,P
(
2,3,4,6-tetra-O-benzyl-
D
-glucopyranosyl)-2-phenyl-2-oxo-2λ -
3
3
2
2
1
1
1
.7, J = 9.4 Hz, J = 10.4 Hz, 1 H, 2-H), 4.53 (d, J = 12.0 Hz,
H,H H,H H,H
[
1,2]-oxaphosphinane (α/ꢀ-6b): Pd(PhCN) Cl (20.3 mg,
2 2
2
H, PhCH ), 4.58 (m, 1 H, 4-H), 4.63 (d, JH , H = 12.0 Hz,
H, PhCH ), 4.73 (d, J = 11.0 Hz, 1 H, PhCH ), 4.87–4.93 (m, 5 H,
′-H,4′-H, and 3 H of PhCH ), 5.00 (dd, J = 7.8, J = 9.5 Hz, 1
H, 2′-H), 5.07 (t, J = 9.3, J = 9.3 Hz, 1 H, 3′-H), 7.21–7.24 (m,
2
0
.053 mmol) and AgOTf (27.2 mg, 0.106 mmol) were added to a
2
2
H,H
2
stirred solution of 4b (289 mg, 0.53 mmol) and 2,3,4,6-tetra-O-
benzyl- -glucopyranosyl trichloroacetimidate (α/ꢀ-7c; 736 mg,
.07 mmol) in freshly distilled CH Cl (9 mL). The resulting mixture
3
3
2
H,H
H,H
D
3
3
H,H
H,H
1
2
2
2
7
H, CH ), 7.28–7.38 (m, 13 H, CH ), 7.44–7.49 (m, 2 H, CH ), 7.56–
ar
ar
ar
3
was stirred at room temperature for 1 h, then it was filtered through
Celite, and the solvent was removed under vacuum. The residue
was purified by chromatography on silica gel (n-heptane/ethyl acet-
ate, 60:40 to 40:60) to give α-6b (117 mg, 21 %).
.60 (m, 1 H, CHar), 7.83–7.88 (m, 2 H, CHar) ppm. 1 C NMR
(
100.61 MHz, CDCl ): δ = 20.51 (s, 1 C, CH ), 20.6 (s, 1 C, CH ), 20.6
3 3 3
(
4
s, 1 C, CH ), 20.7 (s, 1 C, CH ), 62.0 (s, 1 C, CH -6′), 68.0 (s, 1 C, CH-
3 3 2
3
′), 68.4 (d, J = 9.2 Hz, 1 C, CH -5), 71.4 (s, 1 C, CH-2′), 71.6 (s, 1
C,P 2
Data for α-6b: 31P NMR (161.97 MHz, CDCl ): δ = 36.43 (s) ppm. H C, CH-5′), 73.1 (s, 1 C, CH-3′), 73.4 (s, 1 C, PhCH
NMR (400.13 MHz, CDCl ): δ = 1.73 (dt, J = 2.5, J = 10.0 Hz, 5.2 Hz, 1 C, CH-4), 75.4 (s, 1 C, PhCH
1
), 74.6 (d, JC,P
), 76.3 (d, JC,P = 104.3 Hz, 1 C,
2
2
=
3
2
3
3
1
3
H,H
H,H
3
3
2
1
H, 5′-H), 3.10 (d, J = 2.5 Hz, 2 H, 6′-CH ), 3.38 (dd, J = 9.1,
CH-1), 76.3 (s, 1 C, PhCH
1 C, CH-2), 100.7 (d, 3
C,P = 4.6 Hz, 1 C, CH-1′), 127.2 (d,
139.7 Hz, 1 C, Cqar), 127.4, 127.5, 127.7, 127.8, 128.1, 128.1, 128.2,
2
), 78.5 (s, 1 C, CH-3), 83.0 (d, JC,P = 6.9 Hz,
H,H
2
H,H
3
3
3
1
JH,H = 10.0 Hz, 1 H, 4′-H), 3.45 (dd, J = 3.6, J = 9.8 Hz, 1 H,
J
J =
C,P
H,H
H,H
3
3
3
2
′-H), 3.65 (dd, J = 9.1, J = 9.8 Hz, 1 H, 3′-H), 3.88 (dd, J
=
H,H
H,H
H,H
2
4
3
2
1
J
.8, J = 11.4 Hz, 1 H, 5a-H), 4.06 (ddd, J = 2.4, J = 3.5 Hz,
128.3, 128.4, 128.5, 128.7, 132.2 (d, JC,P = 10.2 Hz, 1 C, CH
o
), 133.2
), 137.6 (s, 1 C, CqBn), 137.8 (s, 1 C, CqBn),
137.9 (s, 1 C, CqBn), 168.8 [s, 1 C, Cq(OAc)], 169.2 [s, 1 C, Cq(OAc)],
H,H
H,P
H,H
2
2
4
= 11.4 Hz, 1 H, 5b-H), 4.29 (d, J = 11.3 Hz, 1 H, PhCH ), 4.34 (d, JC,P = 2.8 Hz, 1 C, CH
H,H
2
H,H 2
p
2
(d, J = 11.1 Hz, 1 H, PhCH ), 4.35 (d, J = 12.0 Hz, 1 H, PhCH ),
H,H
2
H,H
2
3
3
2
+
+
4
.48 (dd, J = 2.0, J = 9.6 Hz, 1 H, 2-H), 4.53 (d, J = 12.0 Hz,
170.3 [s, 1 C, Cq(OAc)] ppm. MS (ES ): m/z = 875.30 [M + H] . HRMS
H,H
H,H
3
H,H
3
+
1
H, PhCH ), 4.54 (dd, J = 9.6, J = 10.0 Hz, 1 H, 3-H), 4.57 (d,
(ESI-QTOF): calcd. for C46
H
52
O
15P [M + H] 875.3044; found
(2S ,3S,4S,5S,6R)-4,5-Dihydroxy-6-hydroxymethyl-3-O-(ꢀ-D-ribo-
P
2
H,H
H,H
2
2
JH,H = 12.5 Hz, 1 H, PhCH ), 4.63 (m, 1 H, 4-H), 4.66 (d, JH,H
=
875.3047.
2
2
1
1.1 Hz, 1 H, PhCH ), 4.66 (d, J = 12.1 Hz, 1 H, PhCH ), 4.75 (d,
2
H,H
2
2
2
JH,H = 11.3 Hz, 1 H, PhCH ), 4.76 (d, J
= 10.8 Hz, 1 H, PhCH ),
2
H,H
2
furanosyl)-2-phenyl-2-oxo-2λ5-[1,2]-oxaphosphinane (10; one
anomer): Pd/C (10 %; 300 mg) was added to a stirred solution of
5c (one anomer; 154 mg, 0.16 mmol) in EtOAc (4 mL) and absolute
EtOH (20 mL). The resulting mixture was stirred overnight at room
temperature under a hydrogen atmosphere. The mixture was then
filtered through Celite, and the filtrate was evaporated under vac-
3
2
2
4
1
.79 (dd, J = 2.0, J = 9.1 Hz, 1 H, 1-H), 4.80 (d, J = 11.1 Hz,
H,H
H,P
H,H
2
2
H, PhCH ), 4.84 (d, J
= 10.8 Hz, 1 H, PhCH ), 4.84 (d, J
=
2
H,H
2
H,H
2
1
2.1 Hz, 1 H, PhCH ), 4.89 (d, J = 12.5 Hz, 1 H, PhCH ), 4.95 (d,
2
H,H
2
2
3
JH,H = 11.1 Hz, 1 H, PhCH ), 5.68 (d, JH,H = 3.6 Hz, 1 H, 1′-H),
2
13
7
.12–7.48 (m, 38 H, CH ), 7.94–7.99 (m, 2 H, CH ) ppm. C NMR
ar ar
3
(100.61 MHz, CDCl ): δ = 67.9 (s, 1 C, CH -6′), 69.4 (d, J = 9.1 Hz,
31
3
2
C,P
uum to give 10 (one anomer; 60 mg, 94 %). P NMR (161.97 MHz,
1
1
7
C, CH -5), 69.4 (d, J = 103.3 Hz, 1 C, CH-1), 70.3 (s, 1 C, CH-5′),
1
2
C,P
[D ]methanol): δ = 38.65 (s) ppm. H NMR (400.13 MHz, [D ]meth-
4
4
1.4 (s, 1 C, PhCH ), 73.4 (s, 2 C, PhCH ), 73.5 (s, 1 C, PhCH ), 74.3
3
2
3
2
2
2
anol): δ = 2.87 (dd, J = 5.0, J = 12.2 Hz, 1 H, 5′a-H), 3.43 (dd, J =
(
s, 1 C, PhCH ), 74.5 (s, 1 C, CH-3), 75.2 (s, 1 C, PhCH ), 75.2 (s, 1 C,
2
2
2
3.0, J = 12.2 Hz, 1 H, 5′b-H), 3.70–3.82 (m, 2 H, 4′-H, 3-H), 3.86–4.28
2
PhCH ), 76.5 (s, 1 C, CH-4′), 76.7 (d, J = 5.7 Hz, 1 C, CH-4), 79.2
2
C,P
(m, 7 H), 5.10 (s, 1 H, 1′-H), 7.57–7.61 (m, 2 H, CH ), 7.68–7.71 (m,
ar
2
(
s, 1 C, CH-2′), 80.2 (s, 1 C, CH-3′), 82.6 (d, J = 5.7 Hz, 1 C, CH-2),
13
C,P
1 H, CH ), 7.90–7.95 (m, 2 H, CH ) ppm. C NMR (100.61 MHz,
ar ar
9
1
7.5 (d, 3JC,P = 8.4 Hz, 1 C, CH-1′), 125.9 (1 transition, 1 C, Cqar),
26.9, 127.1, 127.3, 127.3, 127.4, 127.5, 127.5, 127.6, 127.6, 127.7,
3
[D ]methanol): δ = 62.6 (d, J = 9.1 Hz, 1 C, CH -5), 63.2 (s, 1 C,
4
C,P
2
2
CH -5′), 71.3 (s, 1 C, CH-3), 71.6 (s, 1 C, CH-3′), 76.4 (d, J = 5.9 Hz,
C, CH), 76.5 (s, 1 C, CH-2′), 77.2 (d, J = 102.3 Hz, 1 C, CH-1),
79.0 (d, J = 5.7 Hz, 1 C, CH), 84.9 (s, 1 C, CH-4′), 109.4 (d, J
3.6 Hz, 1 C, CH-1′), 128.8 (d, J = 138.0 Hz, 1 C, Cq ), 129.7 (d,
JC,P = 13.6 Hz, 1 C, CH ), 133.4 (d, J = 10.4 Hz, 1 C, CH ), 134.6
d, J = 2.4 Hz, 1 C, CH ) ppm. MS (ES ): m/z = 407.11 [M + H] .
HRMS (ESI-QTOF): calcd. for C H O P [M + H] 407.1107; found
2
C,P
1
27.8, 128.1, 128.1, 128.3, 128.3, 128.3, 128.4, 128.4, 128.6, 128.9 (d,
1
1
C,P
3
2
J
= 13.3 Hz, 1 C, CH ), 132.9 (d, J = 10.0 Hz, 1 C, CH ), 133.7
2
3
C,P
4
m
C,P
o
=
C,P
C,P
(d, J = 2.7 Hz, 1 C, CH ), 137.4 (s, 1 C, CqBn), 137.8 (s, 1 C, CqBn),
1
C,P
p
C,P
ar
1
38.3 (s, 1 C, CqBn), 138.3 (s, 1 C, CqBn), 138.4 (s, 1 C, CqBn), 138.7
3
2
m
C,P
o
+
(s, 1 C, CqBn), 139.0 (s, 1 C, CqBn) ppm. MS (ES ): m/z = 1067.45 [M
4
+
+
(
C,P p
+
+
+
H] . HRMS (ESI-QTOF): calcd. for C H O P [M + H] 1067.4499;
+
6
6
68 11
16 24 10
found 1067.4501.
407.1101.
(
(
[
2S ,3S,4S,5S,6R)-4,5-Bis(benzyloxy)-6-benzyloxymethyl-3-O-
(2S ,3S,4S,5S,6R)-4,5-Dihydroxy-6-hydroxymethyl-3-O-(2,3:5,6-
P
P
5
2,3,4,6-tetra-O-acetyl-ꢀ-
D
-glucopyranosyl)-2-phenyl-2-oxo-2λ -
di-O-isopropylidene-α-
D-mannofuranosyl)-2-phenyl-2-oxo-2λ5-
1,2]-oxaphosphinane (ꢀ-6c): Pd(PhCN) Cl (10.2 mg, 0.027 mmol)
[1,2]-oxaphosphinane (α-11) and (2S ,3S,4S,5S,6R)-4,5-
2
2
P
and AgOTf (13.6 mg, 0.053 mmol) were added to a stirred solution
of 4a (289 mg, 0.53 mmol) and 2,3,4,6-tetra-O-acetylglucosyl tri-
chloroacetimidate (α-7d; 523 mg, 1.06 mmol) in freshly distilled
CH Cl (9 mL). The resulting mixture was stirred at room tempera-
Dihydroxy-6-hydroxymethyl-3-O-(2,3-O-isopropylidene-α-D-
mannofuranosyl)-2-phenyl-2-oxo-2λ5-[1,2]-oxaphosphinane (α-
12): Pd/C (10 %; 117 mg) was added to a solution of α-5a (100 mg,
0.127 mmol) in EtOAc (2.5 mL) and absolute EtOH (19 mL). The
2
2
Eur. J. Org. Chem. 2017, 5357–5369
www.eurjoc.org
5366
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
3
2
resulting mixture was stirred overnight at room temperature under
a hydrogen atmosphere. The mixture was then filtered through Cel-
ite, and the filtrate was concentrated under vacuum. Water was
added to the residue, and the aqueous phase was washed with
2JH,H = 11.4 Hz, 1 H, 6′b-H), 3.66 (dd, J = 2.0, J = 11.2 Hz, 1
H,H
H,H
4
3
2
H, 5a-H), 3.79 (ddd, J = 2.0, J = 3.5 Hz, J = 11.2 Hz, 1 H,
5b-H), 3.88 (dd, JH,H = 9.4, JH,H = 10.0 Hz, 1 H, 3-H), 4.14 (ddd,
JH,P = 2.9, J = 9.4 Hz, J = 10.2 Hz, 1 H, 2-H), 4.32–3.37 (m, 1
diethyl ether (1 ×). The aqueous phase was concentrated under re- H, 4-H), 4.40 (d, J = 12.0 Hz, 1 H, PhCH ), 4.47 (d, J = 7.7 Hz,
H,P
H,H
H,H
3
3
3
3
3
H,H
H,H
2
3
H,H
2
H,H
2
duced pressure, and the resulting solid was purified by chroma-
1 H, 1′-H), 4.48 (d, 2J
= 12.0 Hz, 1 H, PhCH ), 4.58 (d, JH,H =
H,H
2
2
3
tography on silica gel (CH Cl /iPrOH, 100:00 to 50:50) to give α-11
11.1 Hz, 1 H, PhCH ), 4.60 (dd, J = 4.1, J = 10.2 Hz, 1 H, 1-H),
2
2
2 H,P H,H
2
2
(28 mg, 43 %), and α-12 (5 mg, 8 %).
4.71 (d, J
= 10.1 Hz, 1 H, PhCH ), 4.79 (d, J
= 10.1 Hz, 1 H, PhCH ), 7.08–7.23 (m, 13 H,
CH ), 7.28–7.31 (m, 2 H, CH ), 7.44–7.49 (m, 2 H, CH ), 7.57–7.62
m, 1 H, CH ), 7.79–7.85 (m, 2 H, CH ) ppm. C NMR (100.61 MHz,
D ]methanol): δ = 62.8 (s, 1 C, CH -6′), 69.8 (d, J = 9.5 Hz, 1 C,
CH -5), 71.6 (s, 1 C, CH-4′), 74.4 (s, 1 C, PhCH ), 75.1 (s, 1 C, CH-2′),
= 11.1 Hz, 1 H,
H,H
2
H,H
2
PhCH ), 5.04 (d, J
Data for α-11: 31P NMR (161.97 MHz, [D ]methanol): δ = 34.97 (s)
2
H,H
2
4
1
ar
ar
ar
ppm. H NMR (400.13 MHz, [D ]methanol): δ = 1.25 (s, 3 H, CH ),
4
3
13
(
[
ar ar
1
.27 (s, 3 H, CH ), 1.33 (s, 3 H, CH ), 1.39 (s, 3 H, CH ), 3.76 (dd,
3 3 3
3
3
3
4
2
C,P
JH,H = 9.2, J = 10.1 Hz, 1 H, 3-H), 3.90–4.03 (m, 5 H, 6′a-H, 5a-
H, 5b-H, 2-H, 6′b-H), 4.11 (dd, J = 4.1, J = 10.1 Hz, 1 H, 1-H),
H,H
2
3
2
2
H,P
H,H
1
7
5.8 (d, J = 104.8 Hz, 1 C, CH-1), 76.3 (s, 1 C, PhCH ), 77.0 (d,
3
C
,
P
2
4
5
7
.21–4.29 (m, 3 H, 4′-H, 5′-H, 4-H), 4.50 (s, 1 H, 1′-H), 4.55 (d, J
=
H,H
2
JC,P = 5.4 Hz, 1 C, CH-4), 77.2 (s, 1 C, PhCH ), 77.7 (s, 1 C, CH-3′),
7.9 (s, 1 C, CH-5′), 79.3 (s, 1 C, CH-3), 84.7 (d, J = 7.2 Hz, 1 C,
CH-2), 104.7 (d, J = 4.7 Hz, 1 C, CH-1′), 128.2 (d, J = 139.6 Hz,
C, Cq ), 128.7, 128.8, 128.8, 129.1, 129.3, 129.4, 129.4, 129.5, 129.5,
3
3
2
.9 Hz, 1 H, 2′-H), 4.72 (dd, JH,H = 3.1, J
= 5.9 Hz, 1 H, 3′-H),
H,H
2
7
C,P
.60–7.65 (m, 2 H, CH ), 7.71–7.76 (m, 1 H, CH ), 7.93–7.98 (m, 2 H,
ar
ar
3
1
13
C,P
C,P
CH ) ppm. C NMR (100.61 MHz, [D ]methanol): δ = 24.7 (s, 1 C,
ar
4
1
1
ar
CH ), 25.6 (s, 1 C, CH ), 26.1 (s, 1 C, CH ), 26.9 (s, 1 C, CH ), 62.6 (d,
3
3
3
3
2
4
29.7, 133.3 (d, J = 10.7 Hz, 1 C, CH ), 134.7 (d, J = 2.9 Hz, 1
3
C,P
o
C,P
JC,P = 9.4 Hz, 1 C, CH -5), 67.9 (s, 1 C, CH -6′), 71.4 (s, 1 C, CH-3),
4.3 (s, CH-5′), 74.9 (s, 1 C, CH-2), 75.4 (d, J = 100.8 Hz, 1 C, CH-
), 79.3 (d, J = 5.6 Hz, 1 C, CH-4), 80.7 (s, 1 C, CH-3′), 82.1 (s, 1 C,
CH-4′), 86.2 (s, 1 C, CH-2′), 106.7 (d, J = 1.7 Hz, 1 C, CH-1′), 110.2
2
2
C, CH ), 139.2 (s, 1 C, CqBn), 139.4 (s, 1 C, CqBn), 139.7 (s, 1 C, CqBn)
1
p
7
1
C,P
+
+
ppm. MS (ES ): m/z = 707.26 [M + H] . HRMS (ESI-QTOF): calcd. for
2
C,P
+
C H O P [M + H] 707.2621; found 707.2626.
3
38 44 11
C,P
(
2S ,3S,4S,5S,6R)-4,5-Bis(benzyloxy)-6-acetoxymethyl-3-
acetoxy-2-phenyl-2-oxo-2λ -[1,2]oxaphosphinane (14): A solu-
[
s, 1 C, Cq(CH ) ], 113.7 [s, 1 C, Cq(CH ) ], 128.9 (1 transition, 1 C,
P
3
2
3
3 2
5
2
Cq ), 130.3 (d, J = 13.2 Hz, 1 C, CH ), 133.0 (d, J = 10.8 Hz,
ar
C,P
m
C,P
4
+
tion of freshly fused ZnCl (2.51 g, 18.4 mmol) in Ac O/AcOH (6 mL,
1
5
5
C, CH ), 135.1 (d, J = 2.7 Hz, 1 C, CH ) ppm. MS (ES ): m/z =
17.18 [M + H] . HRMS (ESI-QTOF): calcd. for C H O P [M + H]
2
2
o
C,P
p
+
+
2:1) was added to a stirred solution of oxaphosphinane 4a (1.00 g,
.84 mmol) in Ac O/AcOH (6 mL, 2:1). The reaction mixture was
stirred at room temperature for 5 h, and then water was added. The
mixture was extracted with CH Cl (3 ×). The combined organic
layer was washed with a saturated solution of sodium carbonate,
and water. The organic phase was dried with MgSO , and concen-
trated under vacuum. The residue was then washed with a mixture
of pentane and acetone (7:3) to give pure product 14 (883 mg,
9 %) as white crystals. P NMR (161.97 MHz, CDCl ): δ = 32.23 (s)
2
3 34 11
1
17.1839; found 517.1843.
2
Data for α-12: 31P NMR (161.97 MHz, [D ]methanol): δ = 34.97 (s)
4
2
2
1
ppm. H NMR (400.13 MHz, [D ]methanol): δ = 1.14 (s, 6 H, 2 CH ),
4
3
3
2
3
3
2
1
5
4
2
.45 (dd, J
= 5.8, J
= 11.8 Hz, 1 H, 6′a-H), 3.57 (dd, J
=
H,H
H,H
H,H
4
2
3
3
.8, J = 11.8 Hz, 1 H, 6′b-H), 3.64 (dd, J = 9.1, J = 10.1 Hz,
H,H
H,H
H,H
3
3
2
H, 3-H), 3.69 (ddd, J = 2.8, J = 5.8 Hz, J = 9.3 Hz, 1 H,
′-H), 3.79–3.86 (m, 3 H, 2-H, 5a-H, 5b-H), 3.97–4.00 (m, 1 H, 4′-H),
= 10.2 Hz, 1 H, 1-H), 4.14 (dddd, J
.5, J = 3.5, J = 4.4, J = 10.1 Hz, 1 H, 4-H), 4.38 (s, 1 H, 1′-
H,H
H,H
H,H
31
8
3
2
3
3
.00 (dd, J = 3.8, J
=
1
H,P
H,H
H,H
ppm. H NMR (400.13 MHz, CDCl ): δ = 1.92 (s, 3 H, CH ), 2.07 (s, 3
3
3
3
3
3
3
3
H,P
H,H
H,H
H, CH ), 3.92 (dd, J
= 9.1, J = 10.2 Hz, 1 H, 3-H), 4.37 (ddd,
JH,P = 1.7, J = 4.0 Hz, J = 12.3 Hz, 1 H, 5-H), 4.40 (ddd, J
3
H,H H,H
3
3
3
H), 4.42 (d, J
= 5.9 Hz, 1 H, 2′-H), 4.66 (dd, J
= 3.5, J
=
4
3
2
3
H,H
H,H
H,H
=
H,H
H,H
H,P
5
7
.9 Hz, 1 H, 3′-H), 7.49–7.54 (m, 2 H, CH ), 7.60–7.64 (m, 1 H, CH ),
3
3
4
ar
ar
3.2, J = 9.1 Hz, J = 10.5 Hz, 1 H, 2-H), 4.45 (ddd, J = 0.5,
H,H H,H H,P
1
3
.81–7.87 (m, 2 H, CH ) ppm. C NMR (100.61 MHz, [D ]methanol):
3
2
2
ar
4
JH,H = 2.3 Hz, J = 12.3 Hz, 1 H, 5′-H), 4.65 (d, J = 10.8 Hz, 1
H,H H,H
3
δ = 23.5 (s, 1 C, CH ), 24.8 (s, 1 C, CH ), 61.2 (d, J = 9.4 Hz, 1 C,
3
3
3
3
3
C,P
H, PhCH ), 4.69 (m, J = 2.3, J = 4.0 Hz, J = 10.2 Hz, 1 H,
2 H,H H,H H,H
CH -5), 64.0 (s, 1 C, CH -6′), 69.0 (s, 1 C, CH-5′), 70.0 (s, 1 C, CH-3),
2
2
2
2
4-H), 4.78 (d, J = 11.3 Hz, 1 H, PhCH ), 4.92 (d, J = 11.3 Hz, 1
H,H 2 H,H
H, PhCH ), 4.94 (d, J = 10.8 Hz, 1 H, PhCH ), 5.54 (dd, J = 1.1,
JH,H = 10.5 Hz, 1 H, 1-H), 7.26–7.39 (m, 10 H, CH ), 7.49–7.54 (m, 2
H, CH ), 7.61–7.65 (m, 1 H, CH ), 7.80–7.85 (m, 2 H, CH ) ppm.
2
1
7
1
3.5 (d, J = 2.2 Hz, 1 C, CH-2), 74.0 (d, J = 92.9 Hz, 1 C, CH-
), 77.8 (d, J = 5.5 Hz, 1 C, CH-4), 79.5 (s, 1 C, CH-4′), 79.6 (s, 1 C,
CH-3′), 84.5 (s, 1 C, CH-2′), 105.4 (d, J = 1.8 Hz, 1 C, CH-1′), 112.1
s, 1 C, Cq(CH ) ], 128.0 (d, JC,P = 133.8 Hz, 1 C, Cq ), 128.8 (d,
2
2
C,P
2
C,P
2
H,H
2
H,P
3
C,P
ar
3
13
C,P
C
ar
ar
ar
1
[
3
2
ar
NMR (100.61 MHz, CDCl ): δ = 20.4 (s, 1 C, CH ), 20.8 (s, 1 C, CH ),
3 3 3
3
2
JC,P = 13.3 Hz, 1 C, CH ), 131.6 (d, J = 10.8 Hz, 1 C, CH ), 133.7
3
1
m
C,P
o
62.8 (d, J = 9.5 Hz, 1 C, CH -5), 70.4 (d, J = 101.8 Hz, 1 C, CH-
1), 73.4 (d, J = 5.2 Hz, 1 C, CH-4), 75.6 (s, 1 C, PhCH ), 76.3 (s, 1
C,P
2
2
C,P
+
+
(
d, 4JC,P = 2.8 Hz, 1 C, CH ) ppm. MS (ES ): m/z = 477.15 [M + H] .
p
C,P
2
+
HRMS (ESI-QTOF): calcd. for C H O P [M + H] 477.1526; found
2
2
0
30 11
C, PhCH ), 78.0 (s, 1 C, CH-3), 81.8 (d, J = 5.0 Hz, 1 C, CH-2), 126.3
2 C,P
4
77.1528.
1
(
1
CH
(
d, J = 140.2 Hz, 1 C, Cq ), 127.6, 127.9, 128.2, 128.3, 128.6, 128.6,
C,P ar
3
2
28.8 (d, J = 13.8 Hz, 1 C, CH ), 131.8 (d, J = 10.7 Hz, 1 C,
C,P m C,P
(
D
2S ,3S,4S,5S,6R)-4,5-Bis(benzyloxy)-6-benzyloxymethyl-3-O-(ꢀ-
-glucopyranosyl)-2-phenyl-2-oxo-2λ -[1,2]-oxaphosphinane
P
4
5
o
), 133.8 (d, JC,P = 2.9 Hz, 1 C, CH
p
), 137.0 (s, 1 C, CqBn), 137.7
3
s, 1 C, CqBn), 169.6 [d, J = 3.8 Hz, 1 C, Cq(OAc)], 170.4 [s, 1 C,
Cq(OAc)] ppm. MS (ES ): m/z = 539.18 [M + H] . HRMS (ESI-QTOF):
calcd. for C H O P [M + H] 539.1835; found 539.1841.
C,P
(
ꢀ-13): Sodium methoxide (1
M solution in methanol; 1.5 mL) was
+
+
added to a solution of ꢀ-6c (0.17 g, 0.194 mmol) in methanol (3 mL)
+
29 32 8
under N . The reaction mixture was stirred at room temperature for
2
1
h, and then it was neutralised with HCl (1
M
aq.). The methanol
(2S ,3S,4S,5S,6R)-4,5-Bis(benzyloxy)-6-hydroxymethyl-3-
P
5
was removed under vacuum. The resulting suspension was ex- hydroxy-2-phenyl-2-oxo-2λ -[1,2]oxaphosphinane (15):
tracted with EtOAc, and the solution was concentrated under vac-
uum to give ꢀ-13 (103 mg, 75 %). P NMR (161.97 MHz, CDCl3):
Potassium tert-butoxide (22.5 mg, 0.20 mmol) was added to a
stirred solution of diester 14 (0.54 g, 1.00 mmol) in MeOH (22 mL).
The reaction mixture was stirred at room temperature for 1 h, and
3
1
1
δ = 35.04 (s) ppm. H NMR (400.13 MHz, [D ]methanol): δ = 2.85
4
3
3
3
(
ddd, J = 2.3, J = 5.9 Hz, J = 9.7 Hz, 1 H, 5′-H), 2.93 (dd,
then HCl (1
M aq.) was added to neutralise the base. The mixture
H,H
H,H
H,H
3
3
3
2
JH,H = 8.6, J
= 9.7 Hz, 1 H, 4′-H), 2.96 (dd, J
= 5.9, J
=
was filtered, and the filter residue was washed with cold CH Cl .
H,H
H,H
H,H
2
2
3
3
1
3
1.4 Hz, 1 H, 6′a-H), 3.02 (dd, J = 7.7, J = 9.3 Hz, 1 H, 2′-H), The filtrate was concentrated to give pure product 15 (386 mg,
.12 (dd, J = 8.6, J = 9.3 Hz, 1 H, 3′-H), 3.27 (dd, J = 2.3, 85 %). P NMR (161.97 MHz, DMSO): δ = 35.62 (s) ppm. H NMR
H,H H,H
3
3
3
31
1
H,H
H,H
H,H
Eur. J. Org. Chem. 2017, 5357–5369
www.eurjoc.org
5367
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
3
(
400.13 MHz, DMSO): δ = 3.70–3.78 (m, 2 H, 5-CH ), 3.80 (dd, J
=
line ID29. R. B. thanks the Averroès-ERASMUS MUNDUS pro-
gram for her PhD mobility fellowship.
2
H,H
3
3
3
9
.1, J = 10.0 Hz, 1 H, 3-H), 3.97 (ddd, J = 2.6, J = 9.1 Hz,
JH,H = 10.2 Hz, 1 H, 2-H), 4.07 (d, J = 10.2 Hz, 1 H, 1-H), 4.14–
.19 (m, 1 H, 4-H), 4.67 (d, JH,H = 10.8 Hz, 1 H, PhCH ), 4.78 (d,
= 10.8 Hz, 1 H, PhCH2),
.93 (d, J = 11.2 Hz, 1 H, PhCH ), 5.06 (br. s, 1 H, OH), 5.91 (br.
H,H H,P H,H
3
3
H,H
2
4
2
Keywords: Glycosylation · Carbohydrates · Disaccharides ·
Glycomimetics · Phosphorus · Glycosides
2
2
JH,H = 11.2 Hz, 1 H, PhCH ), 4.80 (d, J
2
H,H
2
4
H,H
2
s, 1 H, OH), 7.24–7.36 (m, 10 H, CH ), 7.56–7.60 (m, 2 H, CH ),
ar
ar
13
[1] A. Varki, R. D. Cummings, J. D. Esko, H. H. Freeze, P. Stanley, C. R. Bertozzi,
G. W. Hart, M. E. Etzler (Eds.), Essentials of Glycobiology, 2nd ed., CSH
Press, New York, 2009.
7
.66–7.70 (m, 1 H, CH ), 7.85–7.90 (m, 2 H, CH ) ppm. C NMR
ar ar
3
(
100.61 MHz, DMSO): δ = 60.5 (d, JC,P = 9.2 Hz, 1 C, CH -5), 70.4 (d,
JC,P = 102.6 Hz, 1 C, CH-1), 74.4 (s, 1 C, PhCH ), 74.9 (s, 1 C, PhCH ),
2
1
2
2
[
2] a) C.-H. Wong (Ed.), Carbohydrate-Based Drug Discovery, Wiley–VCH,
Weinheim, 2003; b) D. H. Dube, C. R. Bertozzi, Nat. Rev. Drug Discov.
2
2
7
8
5.9 (d, J = 5.0 Hz, 1 C, CH-4), 77.5 (s, 1 C, CH-3), 83.5 (d, J
.1 Hz, 1 C, CH-2), 127.3, 127.6, 127.7, 128.0, 128.2, 128.4 (d, J
=
=
C,P
C,P
1
C,P
2005, 4, 477–488; c) S. Takayama, S. Chung, Y. Igarashi, Y. Ichikawa, A.
3
1
30.1 Hz, 1 C, Cq ), 128.5 (d, J = 12.7 Hz, 1 C, CH ), 131.8 (d,
ar
C,P
m
Sepp, R. Lechler, J. Wua, T. Hayashia, G. Siuzdaka, C. Wong, Bioorg. Med.
Chem. 1999, 7, 401–409; d) K. Ohtsubo, J. D. Marth, Cell 2006, 126, 855–
67; e) N. Taniguchi, Y. Kizuka in Glycosylation and Cancer (Eds.: R. Drake,
L. Ball), Elsevier, 2015, pp. 11–51.
2
4
JC,P = 10.1 Hz, 1 C, CH ), 133.0 (d, J = 2.1 Hz, 1 C, CH ), 138.1
o
C,P
p
+
(s, 1 C, CqBn), 138.7 (s, 1 C, CqBn) ppm. MS (ES ): m/z = 455.16 [M
+
+
+
H] . HRMS (ESI-QTOF): calcd. for C H O P [M + H] 455.1632;
25 28 6
[
[
3] J. E. Hudak, C. R. Bertozzi, Chem. Biol. 2014, 21, 16–37.
4] P. Compain, O. R. Martin, Bioorg. Med. Chem. 2001, 9, 3077–3092.
found 455.1624.
(
2S ,3S,4S,5S,6R)-4,5-Bis(benzyloxy)-6-methyl-3-O-(2,3,5-tri-O-
[5] S. Roscales, J. Plumet, Int. J. Carbohydr. Chem. 2016, 1–42.
[6] Y. Kajihara, H. Hashimoto, H. Kodama, Carbohydr. Res. 1992, 229, C5–C9.
P
5
benzyl-
D-ribofuranosyl)-2-phenyl-2-oxo-2λ -[1,2]-oxaphos-
[
7] a) S. Hanessian, O. Rogel, J. Org. Chem. 2000, 65, 2667–2674; b) A. Ferry,
X. Guinchard, P. Retailleau, D. Crich, J. Am. Chem. Soc. 2012, 134, 12289–
phinane (16): BF ·OEt (217 μL, 1.76 mmol) was added to a stirred
solution of 15 (0.40 g, 0.88 mmol) and 2,3,5-tri-O-benzyl-
furanosyl trichloroacetimidate (7b; 2.48 g, 4.39 mmol) in CH Cl2
3
2
D-ribo-
1
2301; c) A. Ferry, G. Malik, X. Guinchard, P. Retailleau, D. Crich, J. Org.
2
Chem. 2013, 78, 6858–6867; d) A. Ferry, G. Malik, X. Guinchard, V. Vet-
vicka, D. Crich, J. Am. Chem. Soc. 2014, 136, 14852–14857.
8] V. Vinader, M. H. Haji-Abdullahi, L. H. Patterson, K. Afarinkia, PLoS One
2013, 8, e82111.
(12 mL) at 0 °C under N . After 4 h at 0 °C, further BF ·OEt (217 μL,
2 3 2
1
.76 mmol) was added, and the reaction mixture was stirred for a
[
further 6 h at 0 °C, and then for 32 h at room temperature. After
this time, a saturated aqueous solution of sodium hydrogen carb-
onate was added, and the resulting mixture was extracted with
CH Cl . The combined organic phases were dried (Na SO ), filtered,
and concentrated under vacuum. The residue was purified by chro-
matography on silica gel (n-heptane/ethyl acetate, 60:40 to 40:60)
[9] A. Varki, Glycobiology 1993, 3, 97–130.
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[
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2
2
2
4
[
3
1
to give 16 (89 mg, 11 %). P NMR (161.97 MHz, CDCl ): δ = 36.22
3
s) ppm. 1H NMR (400.13 MHz, CDCl ): δ = 3.47 (dd, JH,H = 6.1,
3
(
3
3
2
2
JH,H = 10.5 Hz, 1 H, 5′a-H), 3.54 (dd, J = 4.0, J = 10.5 Hz, 1
H,H
H,H
4
3
2
H, 5′b-H), 3.81 (ddd, J = 1.9, J = 3.8 Hz, J = 11.4 Hz, 1 H,
5
1
H, 1-H), 4.02–4.04 (m, 2 H, 3′-H, 5a-H), 4.24 (ddd, J = 2.7, J
9
H,P
H,H
H,H
3
3
3
b-H), 3.84 (dd, J = 9.3, J = 9.9 Hz, 1 H, 3-H), 3.92 (dd, J
.2, J = 4.7 Hz, 1 H, 2′-H), 4.02 (dd, J = 1.5, J = 9.8 Hz, 1
=
H,H
H,H
H,H
3
2
3
H,H
H,P
H,H
3
3
=
H,P
H,H
3
.3 Hz, J = 9.8 Hz, 1 H, 2-H), 4.34–4.39 (m, 3 H, 4′-H, PhCH ), 4.48
H,H
2
2
(d, J = 11.9 Hz, 1 H, PhCH ), 4.51–4.56 (m, 1 H, 4-H), 4.58 (s, 2 H,
H,H 2
2015, 104, 33–41; d) Z. Hassani, A. Saleh, S. Turpault, S. Khiati, W. Morelle,
2
2
PhCH ), 4.60 (d, J = 11.9 Hz, 1 H, PhCH ), 4.62 (d, J = 10.8 Hz,
1
2
H,H
2
H,H
J. Vignon, J.-P. Hugnot, E. Uro-Coste, P. Legrand, M. Delaforge, S. Loiseau,
L. Clarion, M. Lecouvey, J.-N. Volle, D. Virieux, J.-L. Pirat, H. Duffau, N.
Bakalara, Mol. Cancer Res., https://doi.org/10.1158/1541-7786.MCR-17-
0120.
2
2
H, PhCH ), 4.92 (d, J
= 11.0 Hz, 1 H, PhCH ), 4.92 (d, J
0.8 Hz, 1 H, PhCH ), 5.04 (d, J = 11.0 Hz, 1 H, PhCH ), 5.07 (d,
=
2
H,H
2
H,H
2
1
2
H,H
2
3
JH,H = 1.2 Hz, 1 H, 1′-H), 7.17–7.45 (m, 27 H, CH ), 7.56–7.60 (m, 1
ar
1
3
H, CH ), 7.81–7.86 (m, 2 H, CH ) ppm. C NMR (100.61 MHz, CDCl3):
[14] a) D. Crich, J. Org. Chem. 2011, 76, 9193–9209; b) X. Zhu, R. R. Schmidt,
Angew. Chem. Int. Ed. 2009, 48, 1900–1934; Angew. Chem. 2009, 121,
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16] a) T. Ogawa, K. Katano, K. Sasajima, M. Matsui, Tetrahedron 1981, 37,
ar
ar
3
δ = 66.7 (d, J = 9.2 Hz, 1 C, CH -5), 71.6 (s, 1 C, CH -5′), 72.2 (d,
C,P
2
2
1
JC,P = 97.0 Hz, 1 C, CH-1), 72.3 (s, 1 C, PhCH ), 72.4 (s, 1 C, PhCH ),
2
2
2
7
3.0 (s, 1 C, PhCH ), 74.9 (d, J = 5.1 Hz, 1 C, CH-4), 75.5 (s, 1 C,
2 C,P
[
[
PhCH ), 76.3 (s, 1 C, PhCH ), 77.8 (s, 1 C, CH-3), 78.5 (s, 1 C, CH-3′),
7
CH-2), 105.7 (s, 1 C, CH-1′), 126.6 (1 transition, 1 C, Cq ), 127.5,
2
2
2
9.7 (s, 1 C, CH-2′), 80.8 (s, 1 C, CH-4′), 84.2 (d, JC,P = 7.0 Hz, 1 C,
2
779–2786; b) A. M. Jansson, M. Meldal, K. Bock, J. Chem. Soc. Perkin
ar
Trans. 1 1992, 1699–1707; c) K. C. Nicolaou, N. J. Bockovich, D. R. Carcana-
gue, J. Am. Chem. Soc. 1993, 115, 8843–8844; d) S. N. Lam, J. Gervay-
Hague, J. Org. Chem. 2005, 70, 8772–8779.
1
27.5, 127.7, 127.9, 127.9, 128.2, 128.3, 128.4, 128.5, 128.5, 128.7 (d,
3
2
J
C,P
4
= 13.4 Hz, 1 C, CH ), 131.9 (d, J = 10.4 Hz, 1 C, CH ), 133.3
m C,P o
(d, J = 2.3 Hz, 1 C, CH ), 137.6 (s, 1 C, CqBn), 137.7 (s, 1 C, CqBn),
[17] B. Helferich, J. Zirner, Chem. Ber. 1962, 95, 2604–2611.
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C,P
p
1
37.8 (s, 1 C, CqBn), 138.1 (s, 1 C, CqBn), 138.3 (s, 1 C, CqBn) ppm.
+
+
MS (ES ): m/z = 857.34 [M + H] . HRMS (ESI-QTOF): calcd. for
C H O P [M + H] 857.3455; found 857.3453.
+
66 68 11
[
[
Acknowledgments
[
[
We acknowledge the European Synchrotron Radiation Facility
for the provision of synchrotron radiation facilities, and we
would like to thank David Flot for his assistance in using beam-
[
Eur. J. Org. Chem. 2017, 5357–5369
www.eurjoc.org
5368
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

Full Paper
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2
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[
[
1985, 41, 5427–5438.
8
[
[
[
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042.
Received: June 20, 2017
Eur. J. Org. Chem. 2017, 5357–5369
www.eurjoc.org
5369
© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim