C-Glycosyl Styrene Type Compounds by Pd-Catalyzed Cross-Coupling Reactions of Anhydro-Aldose Tosylhydrazones with Benzyl Bromides

Article abstract of DOI:10.1002/adsc.201801059

C-Glycopyranosyl styrene type compounds are valuable synthetic intermediates whose syntheses are known in rather lengthy procedures. Herein palladium-catalyzed cross-couplings of O-peracylated 2,6-anhydro-aldose tosylhydrazones with benzyl bromides were studied under thermic conditions in the presence of LiOtBu. The reactions gave the corresponding C-glycopyranosyl styrenes in up to 59% yields. The transformations represent a new, short synthetic sequence to get this type of glycomimetic compounds in 4–5 steps from a free aldose. (Figure presented.).

Full text of DOI:10.1002/adsc.201801059

Title: C-Glycosyl styrene type compounds by Pd-catalyzed cross-
coupling reactions of anhydro-aldose tosylhydrazones with
benzyl bromides
Authors: Tímea Kaszás, Marietta Tóth, Peter Langer, and László
Somsák
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Adv. Synth. Catal. 10.1002/adsc.201801059
Link to VoR: http://dx.doi.org/10.1002/adsc.201801059

10.1002/adsc.201801059
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
C-Glycosyl styrene type compounds by Pd-catalyzed cross-
coupling reactions of anhydro-aldose tosylhydrazones with
benzyl bromides
Tímea Kaszás,a,b Marietta Tóth,a Peter Langer,b and László Somsáka*
a
Department of Organic Chemistry, University of Debrecen, POB 400, H-4002 Debrecen, Hungary
(*phone: +3652512900 ext 22348, fax: +3652512744, e-mail: somsak.laszlo@science.unideb.hu)
Department of Chemistry, University of Rostock, Albert-Einstein-Str. 3a, 18059 Rostock, Germany
b
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. C-Glycopyranosyl styrene type compounds are
valuable synthetic intermediates whose syntheses are known
in rather lengthy procedures. Herein palladium-catalyzed
cross-couplings of O-peracylated 2,6-anhydro-aldose
tosylhydrazones with benzyl bromides were studied under
thermic conditions in the presence of LiOtBu. The reactions
gave the corresponding C-glycopyranosyl styrenes in up to
59 % yields. The transformations represent a new, short
synthetic sequence to get this type of glycomimetic
compounds in 4-5 steps from a free aldose.
Keywords: Alkenes; Anhydro-aldose tosylhydrazones;
Carbenes; Carbohydrates; Cross-coupling; C-C coupling;
C-Glycosides.
possibility is represented by the direct C-glycosylation of
glycosyl fluoride A with potassium styryl trifluoroborate,[9]
the irradiation of glycosylcobaloximes B in the presence of
alkenes,[15] while in the intramolecular approaches radical-
induced cyclization of the 2-phenylethynylsiloxy-
glucopyranosylphenylselenide[16] C or 2-alkynylsiloxy-
Introduction
C-Glycosyl compounds are present in nature, among
synthetic derivatives, and active ingredients of marketed
drugs, and their chemistry as well as already realized and
potential applications have been comprehensively
reviewed recently.[1-3]
glycopyranosylphenylsulfones[17]
D
followed
by
desilylation gave styrenes F.
Among many types of C-glycosyl derivatives C-
glycosyl styrenes F (Scheme 1) are versatile starting
compounds of e. g. C-glycosyl-aldehydes (highly
appreciated intermediates for the synthesis of complex C-
glycosyl derivatives),[4-6] cis- and trans-fused allylic and
vinylic bicyclic ethers,[7, 8] (structural elements of marine
toxins[9]), pyranopyran carbohydrate amino acids (building
blocks of glyco- and peptidomimetic compounds),[10, 11]
analogues of uridine-5’-diphosphate (UDP) sugar
derivatives[12] (potential glycosyltransferase inhibitors), C-
linked glycosyl coumarins and isocoumarins[13] (e. g.
antibacterial, anticancer agents) and (parts of) natural
products such as ambruticin[5] (an antifungal antibiotic) or
lasonolide A[14] (anticancer activity).
The known synthetic routes to access C-glycopyranosyl
styrenes F are summarized in Scheme 1. One of the
applied approaches is the construction of the C-C bond
between the anomeric carbon and the aglycon part of the
molecules. Among these methods inter- and intramolecular
variants can also be found. Thus, the intermolecular
The most frequently applied method for the preparation
of C-glycopyranosyl styrenes F is the partial reduction of
the acetylene moiety in E by employing Lindlar catalyst[4, 7,
8, 10, 11]
or zinc.[18] Arylethynyl derivatives E can be
obtained directly from a glycopyranosyl bromide or
chloride or in a two-step reaction from 1,2-anhydro
aldopyranose derivatives or lactones, as detailed in the
above references.
In other syntheses the construction of the C=C bond in
styrenes F are realized in one step: dehydration reaction of
O-perbenzylated or O-peracetylated 1-phenyl-2-(-D-
glucopyranosyl)ethanol H, prepared from free aldoses in
three-step reactions[6] or the Julia olefination of the O-
perbenzylated -C-glucopyranosyl aldehyde I resulted in
C-glycopyranosyl styrenes F.[13] Another possibility is the
formation of the C=C bond in a cross-metathesis reaction
between a vinyl -C-D-galactopyranoside J with alkenes in
the presence of Hoveyda-Grubbs II catalyst and CuI.[19]
1
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801059
Advanced Synthesis & Catalysis
Scheme 1. Synthetic routes toward C-glycopyranosyl styrenes F (for details see text).
From a synthetic point of view, most of the above
methods lack generality, need special starting materials or
reagents prepared in lengthy reaction sequences, therefore,
a mild catalytic methodology to prepare C-glycopyranosyl
styrene derivatives from starting compounds easily
available in any monosaccharide configuration would be
desirable.
In the last decade tosylhydrazones emerged as reaction
partners in various cross-coupling reactions.[20-24] In recent
years we have studied the utility of anhydro-aldose
reaction
with
2.5
mol%
(Pd2(dba)3)
tris(dibenzylideneacetone)dipalladium(0)
catalyst in the presence of P(2-furyl)3 and LiOtBu in 1,4-
dioxane at reflux temperature or in toluene at 80 C as
°
suggested in the literature for aromatic coupling partners[31]
gave compound 2a in very low (entry 6) or moderate yield
(entry 7), respectively. Further optimization of the reaction
conditions revealed that the yields could be significantly
improved by raising the amount of benzyl bromide (entries
8 and 9). The optimized reaction conditions are shown in
entry 9, under which the coupling product 2a could be
obtained in 48% yield. In almost every cases the formation
of exo-glucal 3 and N-benzylated tosylhydrazone 4a as by-
products were observed.
tosylhydrazones
G readily obtained from glycosyl
cyanides.[25-27] Thus, metal free couplings of G with
alcohols, phenols, carboxylic acids,[28] and thiols,[29] as
well as Pd-catalyzed cross couplings with aryl bromides[30]
were studied. Herein we disclose our experiences with Pd-
catalyzed reactions between G and benzyl bromides which
provide a new, alternative, and shorter reaction pathway to
C-glycopyranosyl styrenes F.
With the optimized conditions in hand, the scope of the
reaction was first explored with tosylhydrazone 1 and a
variety of substituted benzyl bromides (Table 2). The
reactions afforded the corresponding styrenes in low to
medium yields. The substitution pattern of the aromatic
ring with electron-donating and electron-withdrawing
groups and ortho, meta or para position of the substituents
had only a moderate effect on the yields (entries 1-10).
Similarly to previous findings, the formation of exo-glucal
3 and N-benzylated tosylhydrazone 4 could never be
avoided. Further by-products having no carbohydrate
residue were also observed in these reactions, and in one
case, from the reaction in entry 3, this compound was
isolated and proved to be 3-methoxybenzyl-4-
methylphenyl-sulfone 5c clearly formed by the reaction of
the toluenesulfinate anion with the corresponding benzyl
bromide (see mechanistic proposal later).
Results and Discussion
At the outset, we chose O-perbenzoylated C-(-D-
glucopyranosyl)formaldehyde tosylhydrazone 1[26, 27] and
benzyl bromide as the substrates to optimize the reductive
coupling reaction (Table 1). Initially, it was observed that
using 5 mol% (Pd(OAc)2) with (LiOtBu) as the base in
o
1,4-dioxane at 70 C the expected coupling product 2a
could be isolated, albeit in only very low yield (Table 1,
entry 1). Other ligands such as di(1-adamantyl)-n-
butylphosphine
(CataCXium
A)
and
1,3-
A
further optimization was performed with 4-
bis(diphenylphosphino)propane (DPPP) were found to be
also effective (entries 3 and 5, respectively), however, the
yield did not improve. On the other hand tri(2-
furyl)phosphine (P(2-furyl)3) and 1,1’-ferrocenediyl-
bis(diphenylphosphine) (DPPF) gave somewhat better
results (entries 2 and 4, respectively). Performing the
cyanobenzyl bromide (Table 3) which was the reagent in
one of the relatively low yielding reactions. Application of
a higher ratio of the Pd2(dba)3 catalyst (10 mol%) and the
P(2-furyl)3 ligand (40 mol%) resulted in somewhat better
yields (entry 2). Nevertheless, raising the quantities in an
2
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801059
Advanced Synthesis & Catalysis
extraordinary way (50 mol% Pd2(dba)3 catalyst and 400
mol% P(2-furyl)3 ligand, entry 3) doubled the yield.
Application of 40 mol% P(2-furyl)3 ligand with various
Pd-catalysts did not affect the yields significantly (entries
4-7). Next, the effect of the ligands was also examined.
The use of Pd2(dba)3 catalyst (10 mol%) with CataCXium
8, 10, 11, respectively), nevertheless, better results were
achieved with DPPP and PPh3 (entries 9, 12). Similarly to
the other reactions, formation of by-products 3, 4j and type
5 could not be avoided.
A,
DPPF
and
2-dicyclohexylphosphino-2’,4’,6’-
triisopropylbiphenyl (XPhos) diminished the yields (entries
Table 1. Optimization of reaction conditions
Yield (%)
Pd catalyst
(mol %)
Ligand
(mol %)
Ph-CH2-Br LiOtBu
T
(°C)
Entry
Solvent
(equiv.)
(equiv.)
2
3
3
4
4
1
2
3
4
5
6
7
8
9
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd(OAc)2 (5)
Pd2(dba)3 (2.5)
Pd2(dba)3 (2.5)
Pd2(dba)3 (2.5)
Pd2(dba)3 (2.5)
XPhos (20)
P(2-furyl)3 (20)
CataCXium A (20)
DPPF (20)
1
1
1
1
1
1
1
3
6
3
3
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
1,4-dioxane
70
70
70
70
70
15
in
traces
25
3
nda
in
traces
in
traces
in
3
4
2
3
24
3
DPPP (20)
3
7
traces
P(2-furyl)3 (20)
P(2-furyl)3 (20)
P(2-furyl)3 (20)
P(2-furyl)3 (20)
3
1,4-dioxane 101
4
nda
2
nda
3
toluene
80
70
70
32
22
48
3
1.5
1.5
1,4-dioxane
1,4-dioxane
nda
11
nda
nda
a Not detectable
3
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801059
Advanced Synthesis & Catalysis
Table 2. Pd-catalyzed coupling of tosylhydrazone 1 with benzyl bromides
Yield (%)
R-C6H4-CH2-Br
(equiv.)
LiOtBu
(equiv.)
Entry
R
2
3
11
6
4
1
2
H
4-CH3
3-CH3O
4-Cl
6
6
6
6
6
6
6
6
6
6
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
48
40
10
40
42
54
32
36
20d
27
nda
11
31
14
nda
nda
5
a
b
c
d
e
f
3b
4
nda
5
5
3-Cl
6
6
4-Br
4
7
3-Br
11c
20
g
h
i
8
2-Br
2
in
traces
9
4-NO2
4-CN
16c
17c
10
16c
j
a Not detectable
b By-product containing no carbohydrate residue isolated from the reaction:
5c
c Yields calculated on the basis of the 1H NMR spectra of the worked-up reaction mixture.
d Based on the 1H NMR spectrum of the crude mixture formation of an equal amount of the Z isomer was observed.
4
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801059
Advanced Synthesis & Catalysis
Table 3. Optimization of the reaction conditions of Pd-catalyzed coupling of tosylhydrazone 1 with 4-cyanobenzyl
bromide
Yield (%)
Pd catalyst
(mol %)
Ligand
(mol %)
4-CN-C6H4-CH2-Br LiOtBu
Entry
(equiv.)
(equiv.)
2j
27
35
55
32
30
36
24
14
42a
22a
21
40
3
16a
12
5
4j
17a
21
7
1
2
Pd2(dba)3 (2.5)
Pd2(dba)3 (10)
Pd2(dba)3 (50)
Pd(OAc)2 (19)
Pd(CH3CN)2Cl2 (10)
Pd(PPh3)2Cl2 (10)
Pd(PPh3)4 (10)
Pd2(dba)3 (10)
Pd2(dba)3 (10)
Pd2(dba)3 (10)
Pd2(dba)3 (10)
Pd2(dba)3 (10)
P(2-furyl)3 (20)
P(2-furyl)3 (40)
P(2-furyl)3 (400)
P(2-furyl)3 (40)
P(2-furyl)3 (40)
P(2-furyl)3 (40)
P(2-furyl)3 (40)
CataCXium A (40)
DPPP (40)
6
3
6
6
6
6
6
6
6
6
6
6
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
1.5
3
4
10
4
18
20
53
27
63
29a
28a
28
17
5
6
1
7
16
13
20
8
9
in
traces
in
traces
in
10
11
12
DPPF (40)
XPhos (40)
PPh3 (40)
traces
a Yields calculated on the basis of the 1H NMR spectra of the worked-up reaction mixture.
The examinations were extended to the D-galacto
configured tosylhydrazone 6 (Table 4). The corresponding
styrene 7a was isolated in good yield (entry 1). The
substrates bearing both electron-donating (entries 2, 3) and
electron-withdrawing (entries 4, 5) substituents on the
aromatic ring could afford the corresponding products 7b-e
in low to medium yields. There was no clear correlation
between the yields and the arene substitution pattern (meta
or para positions, compare entries 2-3 and 4-5). The exo-
galactal 8 and the substituted tosylhydrazone 9 by-products
were isolated from the reaction mixtures in almost every
case.
Some trials were conducted with allyl bromide,
propargyl bromide and n-butyl bromide to explore the
possibility of extending the reaction to aliphatic coupling
partners. However, these experiments gave only very
complex mixtures from which no discrete product could be
isolated except for the reaction with allyl bromide which
furnished the N-allyl tosylhydrazone 10 in a low yield
(18 %).
10
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801059
Advanced Synthesis & Catalysis
Table 4. Pd-catalyzed coupling of tosylhydrazone 6 with benzyl bromides
Yield (%)
R-C6H4-CH2-Br
(equiv.)
LiOtBu
(equiv.)
Entry
R
7
8
5
9
nda
nda
7
1
2
3
4
H
6
3
6
6
6
1.5
2.2
1.5
1.5
1.5
59
39
25
59
31
a
b
c
4-CH3
3-CH3
3-Cl
7b
3
3
nda
9
d
e
in
traces
5
4-Br
a Not detectable
b Yields calculated on the basis of the 1H NMR spectra of the worked-up reaction mixture.
The configuration of the double bonds in compounds 2
and 7 was E as followed from the vicinal coupling
constants of the olefinic protons (2: H-1 6.74–6.59 ppm,
H-2 6.36–6.14 ppm, J1,2 15.9–15.8 Hz; 7: H-1 6.66–6.60
ppm, H-2 6.12–6.06 ppm, J1,2 15.9–15.8 Hz). This was
corroborated by a n. O. e. measurement for 2a (Fig. 1) to
show spatial vicinity of the indicated protons that is
possible only in the E configuration of the double bond.
with a benzylpalladium complex XII (formed in the usual
way by oxidative addition of the benzyl bromide to a Pd(0)
complex XI) to yield VIII. On the other hand, direct
formation of VIII is also possible from VI. Intermediate
VIII may also result in III by a H-shift, thereby providing
an alternative route to the formation of the exo-glycal by-
product III. Whether III is formed from VII or VIII
cannot be proven on the basis of the present data, probably
both routes may be operative. Rearrangement of VIII to
IX is followed by a β-hydride elimination. From the two
possibilities loss of Hb is preferred to that of Ha due to the
formation of the conjugated system resulting in the target
compounds IV and the Pd-complex X. Loss of HBr from X
closes the catalytic cycle.
This complex system of reactions may account for the
medium yields of the target compounds. Since the benzyl
bromide reaction partner can participate in two competing
transformations toward II and XIII besides XII, even its
relatively high proportion does not lead to high
conversions. On the other hand, the essential carbene
intermediate VII is also subject of an intramolecular (to
III) and an intermolecular (to VIII) reaction, and
monomolecular transformations used to be faster than
bimolecular ones. In the light of these competing reaction
pathways the obtained yields of IV can be considered as
satisfactory.
Taking into account that the starting anhydro-aldose
tosylhydrazones of several configurations are available
from a free aldose in 3-4 well established steps which
generally need no chromatographic purification, except in
some cases for the tosylhydrazone itself, this method gives
Figure 1. Characteristic nuclear Overhauser effects in C-
glucopyranosyl styrene (E)-2a.
A mechanistic proposal to explain the formation of the
desired C-glycosyl styrenes and the observed by-products
is outlined in Scheme 2. The starting tosylhydrazone I is
deprotonated to lithium-salt V which by acting as a
nucleophile reacts with the benzyl bromide to give the N-
benzylated tosylhydrazone II. Loss of a toluenesulfinate
ion from V results in a diazo compound VI. The TsLi can
react with the benzyl bromide to sulfone XIII observed in
each reaction and isolated in one case. Diazo compound VI
on loss of nitrogen gives carbene VII which can undergo
an intramolecular C-H insertion to give the exo-glycal III.
Alternatively, VII may enter the catalytic cycle by reacting
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801059
Advanced Synthesis & Catalysis
the target C-glycosyl styrene type compounds in a
remarkably short reaction sequence.
Scheme 2. Mechanistic proposal for the coupling of C-(β-D-glycopyranosyl)formaldehyde tosylhydrazones with benzyl
bromides and the formation of by-products.
Organics, particle size: (0.050–0.200 mm, 60A) was
Conclusion
applied. 1,4-Dioxane was distilled from sodium
benzophenone ketyl and stored over sodium wires.
Pd-Catalyzed cross-couplings of anhydro-aldose
tosylhydrazones and benzyl bromides give C-
glycopyranosyl styrenes as the main products with
unavoidable formation of exo-glycals and other by-
General procedure for the synthesis of -(C-2,3,4,6-
tetra-O-acyl-β-D-glycopyranosyl)styrenes (2, 7)
A (bromomethyl)benzene (3 or 6 mmol, specified with the
products of nucleophilic substitution. The yields of the
transformations vary between 10-59 %, nevertheless, this
synthetic route represents a significantly shorter sequence
to the target compounds from a free aldose in comparison
to the known methods.
particular compounds), LiOtBu base (2.2 or 1.5 mmol,
specified with the particular compounds), P(2-furyl)3
ligand (20 mol%) and Pd2(dba)3 catalyst (2.5 mol%) were
added to abs. 1,4-dioxane (8 mL). The suspension was
stirred and heated to 70 °C (bath temp) under an inert (Ar,
N2) atmosphere and then a solution of tosylhydrazone (1 or
6 (1 mmol)) in abs. 1,4-dioxane (15 mL) was added
dropwise in 20 min. When TLC (1:2 EtOAc–hexane or 1:2
EtOAc–heptane; 1:1 EtOAc–hexane or 1:1 EtOAc–
heptane) indicated complete consumption of the starting
compound (2.5 h‒22 h), the mixture was cooled and the
insoluble material filtered off through a pad of celite and
washed thoroughly with abs. 1,4-dioxane (3 × 20 mL). The
solvent was removed under reduced pressure, and the
residue was purified by column chromatography (neutral
Al2O3) with eluents indicated for the particular compounds
to give -(C-2,3,4,6-tetra-O-acyl-β-D-glycopyranosyl)
styrenes.
Experimental Section
General methods
Optical rotations were determined with a Perkin–Elmer
241 polarimeter at room temperature. NMR spectra were
recorded with Bruker Avance 250 II (250/63 MHz for
1
1H/13C), Bruker Avance 300 III (300/75 MHz for H/13C),
Bruker 360 AM Avance (360/90 MHz for 1H/13C) or
Bruker DRX 400 (400/100 MHz for 1H/13C) spectrometers.
Chemical shifts are referenced to TMS as the internal
reference (1H), or to the residual solvent signals (1H, 13C).
The assignments of the 1H and 13C NMR signals of
compounds 2, 4, 7, 9 were performed by their COSY
(2a,d,k, 4b,d, 7a,e, 9e), HSQC (2a,d,k, 4b,d, 7a,e, 9e) and
HMBC (2a,d,k, 4b,d, 7a,e, 9e) spectra. Mass spectra were
obtained by an Agilent GC 7890A / MS 5975C or by an
Agilent HP GC / MS 5890 / 5973 instrument (EI, 70 eV)
by GC inlet or by a MX-1321 and Finnigan MAT 95 XP
(Thermo Electron Corp., San Jose, CA, USA) instruments
(EI, 70 eV) by direct inlet or by an Agilent 1969A Time-
of-Flight or a maXis II UHR ESI-QTOF MS instrument
(Bruker) operated in positive ion ESI mode. TLC was
performed on DCAlurolle Kieselgel 60 F254 (Merck).
TLC plates were visualized under UV light, and by gentle
heating. For column chromatography Kieselgel 60 (Merck,
particle size (0.063–0.200 mm) or Al2O3 neutral (Across
(E)-3,7-Anhydro-4,5,6,8-tetra-O-benzoyl-1,2-dideoxy-1-
phenyl-D-glycero-D-gulo-oct-1-enitol ((E)--(C-2,3,4,6-
tetra-O-benzoyl-β-D-glucopyranosyl)styrene) (2a)
Prepared from tosylhydrazone 1 (0.20 g, 0.26 mmol),
(bromomethyl)benzene (6 equiv., 0.18 mL, 0.26 g, 1.54
mmol) and LiOtBu (1.5 equiv., 0.03 g, 0.39 mmol)
according to General procedure (4h). Purified by column
chromatography (1:8 EtOAc–heptane) to yield 85 mg
(48 %) of 2a as a white amorphous product. Rf: 0.39 (1:2
1
EtOAc–hexane); [α]D –31 (c 0.65, CHCl3). H NMR (400
MHz, CDCl3) δ 8.14–7.68 (8H, m, aromatics), 7.64–7.06
(17H, m, aromatics), 6.69 (1H, d, J1,2 15.9 Hz, H-1), 6.20
(1H, dd, J2,3 7.3 Hz, H-2), 5.98 (1H, pseudo t, J5,6 9.5 Hz,
H-5), 5.76 (1H, pseudo t, J6,7 9.7 Hz, H-6), 5.54 (1H,
pseudo t, J4,5 9.8 Hz, H-4), 4.67 (1H, dd, J8a,8b 12.3 Hz, H-
8a), 4.51 (1H, dd, H-8b), 4.39 (1H, dd, J3,4 9.5 Hz, H-3),
4.21 (1H, ddd, J7,8a 3.1, J7,8b 4.8 Hz, H-7). 13C NMR (100
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801059
Advanced Synthesis & Catalysis
MHz, CDCl3) δ 166.4, 166.1, 165.5, 165.4 (4×CO), 135.2
(C-1), 136.7–126.1 (aromatics), 124.3 (C-2), 80.0 (C-3),
76.2 (C-7), 74.3 (C-5), 72.4 (C-4), 69.9 (C-6), 63.5 (C-8).
HR-ESI-MS positive mode (m/z): calcd. for:
[M+Na]+=705.2095, found: [M+Na]+=705.2096; C42H34O9
(682.22).
(m/z):
calcd.
for:
[M+Na]+=903.2558,
found:
[M+Na]+=903.2566; C50H44N2O11S (880.27).
(E)-3,7-Anhydro-4,5,6,8-tetra-O-benzoyl-1,2-dideoxy-
1-(3-methoxyphenyl)-D-glycero-D-gulo-oct-1-enitol ((E)-
-(C-2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl)-3-
2,6-Anhydro-N1-benzyl-3,4,5,7-tetra-O-benzoyl-D-
glycero-D-gulo-heptose tosylhydrazone (N1-benzyl-C-
(2,3,4,6-tetra-O-benzoyl-β-D-
methoxystyrene) (2c)
Prepared from tosylhydrazone 1 (0.20 g, 0.26 mmol), 1-
bromomethyl-3-methoxybenzene (6 equiv., 0.22 mL, 0.31
g, 1.54 mmol) and LiOtBu (1.5 equiv., 0.03 g, 0.39 mmol)
according to General procedure (19h). Purified by column
chromatography (1:8 EtOAc–hexane) to yield 19 mg
(10 %) of 2c as a yellow amorphous product. Rf: 0.31 (1:2
glucopyranosyl)formaldehyde tosylhydrazone) (4a)
Isolated as a by-product beside 2a from the previous
reaction mixture by column chromatography (1:8 EtOAc–
hexane) to yield 5 mg (3 %) of 4a as a white amorphous
product. Rf: 0.10 (1:2 EtOAc–hexane); [α]D –8 (c 0.10,
1
EtOAc–hexane); [α]D –25 (c 0.60, CHCl3). H NMR (400
MHz, CDCl3) δ 8.11–7.78 (8H, m, aromatics), 7.62–7.23
(12H, m, aromatics), 7.18–7.11 (1H, m, aromatic), 6.99–
6.72 (3H, m, aromatics), 6.66 (1H, d, J1,2 15.9 Hz, H-1),
6.18 (1H, dd, J2,3 7.3 Hz, H-2), 5.97 (1H, pseudo t, J5,6 9.8
Hz, H-5), 5.75 (1H, pseudo t, J6,7 9.8 Hz, H-6), 5.53 (1H,
pseudo t, J4,5 9.5 Hz, H-4), 4.65 (1H, dd, J8a,8b 12.3 Hz, H-
8a), 4.50 (1H, dd, H-8b), 4.39 (1H, dd, J3,4 9.2 Hz, H-3),
4.21 (1H, ddd, J7,8a 2.8, J7,8b 4.8 Hz, H-7), 3.75 (3H, s, O–
CH3). 13C NMR (100 MHz, CDCl3) δ 166.4, 166.1, 165.4
(4×CO), 135.0 (C-1), 137.7–110.0 (aromatics), 124.6 (C-2),
80.0 (C-3), 76.2 (C-7), 74.3 (C-5), 72.4 (C-4), 69.9 (C-6),
63.5 (C-8), 55.3 (O–CH3). HR-ESI-MS positive mode
1
CHCl3). H NMR (360 MHz, CDCl3) δ 8.13–7.69 (8H, m,
aromatics), 7.67–7.12 (19H, m, aromatics), 6.93 (2H, d, J
8.2 Hz, aromatics), 6.82 (1H, d, J1,2 6.6 Hz, H-1), 5.87 (1H,
pseudo t, J4,5 9.8 Hz, H-4), 5.61 (1H, pseudo t, J5,6 9.7 Hz,
H-5), 5.33 (1H, pseudo t, J3,4 9.7 Hz, H-3), 4.83 (1H, d,
JCH2a,CH2b 16.7 Hz, CH2a), 4.70 (1H, d, CH2b), 4.52 (1H, dd,
J7a,7b 12.2 Hz, H-7a), 4.38 (1H, dd, H-7b), 4.34 (1H, dd, J2,3
9.7 Hz, H-2), 4.11 (1H, ddd, J6,7a 2.8, J6,7b 4.8 Hz, H-6),
2.23 (3H, s, CH3). 13C NMR (90 MHz, CDCl3) δ 166.3,
165.9, 165.4, 165.3 (4×CO), 139.8 (C-1), 144.5–125.5
(aromatics), 78.8 (C-2), 76.3 (C-6), 73.9 (C-4), 70.9 (C-3),
69.5 (C-5), 63.3 (C-7), 51.2 (CH2), 21.8 (CH3). HR-ESI-
MS positive mode (m/z): calcd. for: [M+Na]+=889.2402,
found: [M+Na]+=889.2386; C49H42N2O11S (866.25).
(m/z):
calcd.
for:
[M+Na]+=735.2201,
found:
[M+Na]+=735.2199; C43H36O10 (712.23).
2,6-Anhydro-3,4,5,7-tetra-O-benzoyl-N1-(3-
methoxybenzyl)-D-glycero-D-gulo-heptose
(E)-3,7-Anhydro-4,5,6,8-tetra-O-benzoyl-1,2-dideoxy-1-
(4-methylphenyl)-D-glycero-D-gulo-oct-1-enitol ((E)--
(C-2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl)-4-
tosylhydrazone (N1-3-methoxybenzyl-C-(2,3,4,6-tetra-
O-benzoyl-β-D-glucopyranosyl)formaldehyde
methylstyrene) (2b)
tosylhydrazone) (4c)
Prepared from tosylhydrazone 1 (0.20 g, 0.26 mmol), 1-
bromomethyl-4-methylbenzene (6 equiv., 0.29 g, 1.54
mmol) and LiOtBu (1.5 equiv., 0,03 g, 0.39 mmol)
according to General procedure (16h). Purified by column
chromatography (1:7 EtOAc–hexane) to yield 72 mg
(40 %) of 2b as a pale yellow amorphous product. Rf: 0.42
Isolated as a by-product beside 2c from the previous
reaction mixture by column chromatography (1:8 EtOAc–
hexane) to yield 72 mg (31 %) of 4c as a yellow
amorphous product. Rf: 0.23 (1:2 EtOAc–hexane); [α]D –2
1
(c 0.45, CHCl3). H NMR (400 MHz, CDCl3) δ 8.28–7.69
(8H, m, aromatics), 7.64–7.04 (16H, m, aromatics), 6.92
(2H, d, J 8.2 Hz, aromatics), 6.86 (1H, d, J1,2 6.7 Hz, H-1),
6.83–6.72 (2H, m, aromatics), 5.88 (1H, pseudo t, J4,5 9.7
Hz, H-4), 5.62 (1H, pseudo t, J5,6 10.0 Hz, H-5), 5.34 (1H,
pseudo t, J3,4 9.7 Hz, H-3), 4.82 (1H, d, JCH2a,CH2b 16.6 Hz,
CH2a), 4.64 (1H, d, CH2b), 4.53 (1H, dd, J7a,7b 12.3 Hz, H-
7a), 4.39 (1H, dd, H-7b), 4.34 (1H, dd, J2,3 9.9 Hz, H-2),
4.12 (1H, ddd, J6,7a 2.4, J6,7b 5.2 Hz, H-6), 3.68 (3H, s, O–
CH3), 2.22 (3H, s, CH3). 13C NMR (90 MHz, CDCl3) δ
166.3, 165.9, 165.4, 165.3 (4×CO), 140.0 (C-1), 160.4–
111.5 (aromatics), 78.8 (C-2), 76.3 (C-6), 73.8 (C-4), 70.9
(C-3), 69.4 (C-5), 63.4 (C-7), 55.3 (O–CH3), 51.3 (CH2),
21.8 (CH3). HR-ESI-MS positive mode (m/z): calcd. for:
1
(1:2 EtOAc–hexane); [α]D –20 (c 0.55, CHCl3). H NMR
(400 MHz, CDCl3) δ 8.13–7.76 (8H, m, aromatics), 7.57–
6.91 (16H, m, aromatics), 6.66 (1H, d, J1,2 15.9 Hz, H-1),
6.14 (1H, dd, J2,3 7.4 Hz, H-2), 5.97 (1H, pseudo t, J5,6 10.1
Hz, H-5), 5.75 (1H, pseudo t, J6,7 9.8 Hz, H-6), 5.53 (1H,
pseudo t, J4,5 9.7 Hz, H-4), 4.66 (1H, dd, J8a,8b 12.2 Hz, H-
8a), 4.50 (1H, dd, H-8b), 4.38 (1H, dd, J3,4 9.3 Hz, H-3),
4.21 (1H, ddd, J7,8a 2.9, J7,8b 4.8 Hz, H-7), 2.28 (3H, s,
CH3). 13C NMR (100 MHz, CDCl3) δ 166.4, 166.1, 165.4
(4×CO), 135.2 (C-1), 145.3–125.1 (aromatics), 123.2 (C-2),
80.2 (C-3), 76.2 (C-7), 74.4 (C-5), 72.4 (C-4), 69.9 (C-6),
63.5 (C-8), 21.3 (CH3). HR-ESI-MS positive mode (m/z):
calcd.
for:
[M+Na]+=719.2252,
found:
[M+Na]+=919.2507,
C50H44N2O11S (896.26).
found:
[M+Na]+=919.2508;
[M+Na]+=719.2249; C43H36O9 (696.24).
2,6-Anhydro-3,4,5,7-tetra-O-benzoyl-N1-(4-
4-Methylphenyl-3-methoxybenzyl sulfone (5c)
methylbenzyl)-D-glycero-D-gulo-heptose tosylhydrazone
Isolated as a by-product beside 2c from the previous
reaction mixture by column chromatography (1:8 EtOAc–
hexane) to yield 40 mg (56 %) of 5c as a yellow
(N1-4-methylbenzyl-C-(2,3,4,6-tetra-O-benzoyl-β-D-
glucopyranosyl)formaldehyde tosylhydrazone) (4b)
Isolated as a by-product beside 2b from the previous
reaction mixture by column chromatography (1:7 EtOAc–
hexane) to yield 25 mg (11 %) of 4b as a white amorphous
product. Rf: 0.36 (1:2 EtOAc–hexane); [α]D –22 (c 0.60,
1
amorphous product. H NMR (360 MHz, CDCl3) δ 7.53
(2H, d, J 8.2 Hz, Ts), 7.24 (2H, d, J 8.1 Hz, Ts), 7.20–7.10
(1H, m, aromatic), 6.85 (1H, d, J 7.3 Hz, aromatic), 6.68–
6.58 (2H, m, aromatics), 4.26 (2H, s, CH2), 3.71 (3H, s, O–
CH3), 2.41 (3H, s, CH3). 13C NMR (90 MHz, CDCl3) δ
140.4–114.5 (aromatics), 63.1 (O–CH3), 55.3 (CH2), 21.7
(CH3). HR-ESI-MS positive mode (m/z): calcd. for:
1
CHCl3). H NMR (400 MHz, CDCl3) δ 8.17–7.69 (8H, m,
aromatics), 7.67–7.12 (14H, m, aromatics), 7.11–6.88 (6H,
m, aromatics), 6.85 (1H, d, J1,2 6.6 Hz, H-1), 5.87 (1H,
pseudo t, J4,5 9.8 Hz, H-4), 5.61 (1H, pseudo t, J5,6 9.7 Hz,
H-5), 5.34 (1H, pseudo t, J3,4 9.7 Hz, H-3), 4.78 (1H, d,
JCH2a,CH2b 16.5 Hz, CH2a), 4.66 (1H, d, CH2b), 4.52 (1H, dd,
J7a,7b 12.2 Hz, H-7a), 4.39 (1H, dd, H-7b), 4.34 (1H, dd, J2,3
10.1 Hz, H-2), 4.11 (1H, ddd, J6,7a 2.5, J6,7b 4.5 Hz, H-6),
2.27 (3H, s, CH3), 2.23 (3H, s, CH3-Ts). 13C NMR (100
MHz, CDCl3) δ 166.3, 165.9, 165.4, 165.3 (4×CO), 139.7
(C-1), 144.0–126.3 (aromatics), 78.8 (C-2), 76.2 (C-6),
73.9 (C-4), 70.9 (C-3), 69.4 (C-5), 63.9 (C-7), 51.1 (CH2),
21.8 (CH3-Ts), 21.2 (CH3). HR-ESI-MS positive mode
[M+Na]+=299.0712,
C15H16O3S (276.08).
found:
[M+Na]+=299.0710;
(E)-3,7-Anhydro-4,5,6,8-tetra-O-benzoyl-1-(4-
chlorophenyl)-1,2-dideoxy-D-glycero-D-gulo-oct-1-enitol
((E)--(C-2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl)-
4-chlorostyrene) (2d)
Prepared from tosylhydrazone 1 (0.20 g, 0.26 mmol), 1-
bromomethyl-4-chlorobenzene (6 equiv., 0.32 g, 1.54
8
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801059
Advanced Synthesis & Catalysis
mmol) and LiOtBu (1.5 equiv., 0.03 g, 0.39 mmol)
according to General procedure (4.5h). Purified by column
chromatography (1:8 EtOAc–hexane) to yield 74 mg
(40 %) of 2d as an orange amorphous product. Rf: 0.44
according to General procedure (4h). Purified by column
chromatography (1:8 EtOAc–heptane) to yield 107 mg
(54 %) of 2f as a yellow amorphous product. Rf: 0.36 (1:2
1
EtOAc–hexane); [α]D –49 (c 2.10, CHCl3). H NMR (300
1
(1:2 EtOAc–hexane); [α]D –17 (c 0.35, CHCl3). H NMR
MHz, CDCl3) δ 8.09–7.75 (8H, m, aromatics), 7.58–7.16
(14H, m, aromatics), 7.09 (2H, d, J 8.5 Hz, aromatics),
6.59 (1H, d, J1,2 15.9 Hz, H-1), 6.16 (1H, dd, J2,3 7.2 Hz,
H-2) 5.96 (1H, pseudo t, J5,6 9.6 Hz, H-5), 5.73 (1H,
pseudo t, J6,7 9.9 Hz, H-6), 5.49 (1H, pseudo t, J4,5 9.6 Hz,
H-4), 4.65 (1H, dd, J8a,8b 12.2 Hz, H-8a), 4.48 (1H, dd, H-
8b), 4.36 (1H, dd, J3,4 9.2 Hz, H-3), 4.19 (1H, ddd, J7,8a 2.9,
J7,8b 4.8 Hz, H-7). 13C NMR (63 MHz, CDCl3) δ 166.3,
166.1, 165.5, 165.4 (4×CO), 133.7 (C-1), 135.5–122.0
(aromatics), 125.1 (C-2), 79.8 (C-3), 76.2 (C-7), 74.2 (C-5),
72.4 (C-4), 69.8 (C-6), 63.4 (C-8). HR-ESI-MS positive
mode (m/z): calcd. for: [M+Na]+=783.1200, found:
[M+Na]+=783.1219; C42H33BrO9 (760.13).
(400 MHz, CDCl3) δ 8.19–7.77 (8H, m, aromatics), 7.66–
7.06 (16H, m, aromatics), 6.63 (1H, d, J1,2 15.9 Hz, H-1),
6.17 (1H, dd, J2,3 7.2 Hz, H-2), 5.98 (1H, pseudo t, J5,6 9.5
Hz, H-5), 5.75 (1H, pseudo t, J6,7 9.9 Hz, H-6), 5.51 (1H,
pseudo t, J4,5 9.8 Hz, H-4), 4.67 (1H, dd, J8a,8b 12.3 Hz, H-
8a), 4.50 (1H, dd, H-8b), 4.38 (1H, dd, J3,4 9.5 Hz, H-3),
4.21 (1H, ddd, J7,8a 2.9, J7,8b 4.8 Hz, H-7). 13C NMR (100
MHz, CDCl3) δ 166.3, 166.1, 165.5, 165.4 (4×CO), 134.6
(C-1), 136.5–126.1 (aromatics), 125.0 (C-2), 79.9 (C-3),
76.2 (C-7), 74.2 (C-5), 72.4 (C-4), 69.8 (C-6), 63.4 (C-8).
HR-ESI-MS positive mode (m/z): calcd. for:
[M+Na]+=739.1705,
C42H33ClO9 (716.18).
found:
[M+Na]+=739.1705;
(E)-3,7-Anhydro-4,5,6,8-tetra-O-benzoyl-1-(3-
bromophenyl)-1,2-dideoxy-D-glycero-D-gulo-oct-1-enitol
((E)-3-bromo--(C-2,3,4,6-tetra-O-benzoyl-β-D-
2,6-Anhydro-3,4,5,7-tetra-O-benzoyl-N1-(4-
chlorobenzyl)-D-glycero-D-gulo-heptose tosylhydrazone
(N1-4-chlorobenzyl-C-(2,3,4,6-tetra-O-benzoyl-β-D-
glucopyranosyl)styrene) (2g)
glucopyranosyl)formaldehyde tosylhydrazone) (4d)
Isolated as a by-product beside 2d from the previous
reaction mixture by column chromatography (1:8 EtOAc–
hexane) to yield 33 mg (14 %) of 4d as a yellow
amorphous product. Rf: 0.30 (1:2 EtOAc–hexane); [α]D –
Prepared from tosylhydrazone 1 (0.20 g, 0.26 mmol), 1-
bromomethyl-3-bromobenzene (6 equiv., 0.39 g, 1.54
mmol) and LiOtBu (1.5 equiv., 0.03 g, 0.39 mmol)
according to General procedure (20h). Purified by column
chromatography (1:7 EtOAc–hexane) to yield 63 mg
(32 %) of 2g as a yellow amorphous product. Rf: 0.39 (1:2
1
17 (c 0.30, CHCl3). H NMR (400 MHz, CDCl3) δ 8.12–
1
7.67 (8H, m, aromatics), 7.65–7.11 (14H, m, aromatics),
7.09–6.89 (6H, m, aromatics), 6.80 (1H, d, J1,2 6.6 Hz, H-
1), 5.88 (1H, pseudo t, J4,5 9.6 Hz, H-4), 5.62 (1H, pseudo t,
J5,6 10.0 Hz, H-5), 5.34 (1H, pseudo t, J3,4 9.8 Hz, H-3),
4.75 (1H, d, JCH2a,CH2b 16.8 Hz, CH2a), 4.68 (1H, d, CH2b),
4.54 (1H, dd, J7a,7b 12.4 Hz, H-7a), 4.40 (1H, dd, H-7b),
4.34 (1H, dd, J2,3 9.9 Hz, H-2), 4.13 (1H, ddd, J6,7a 2.8, J6,7b
4.9 Hz, H-6), 2.23 (3H, s, CH3). 13C NMR (100 MHz,
CDCl3) δ 166.2, 165.9, 165.4, 165.3 (4×CO), 139.9 (C-1),
145.3–127.6 (aromatics), 78.7 (C-2), 76.3 (C-6), 73.7 (C-4),
70.8 (C-3), 69.4 (C-5), 63.3 (C-7), 50.5 (CH2), 21.8 (CH3).
HR-ESI-MS positive mode (m/z): calcd. for:
EtOAc–hexane); [α]D –20 (c 0.45, CHCl3). H NMR (400
MHz, CDCl3) δ 8.13–7.78 (8H, m, aromatics), 7.62–6.99
(16H, m, aromatics), 6.60 (1H, d, J1,2 15.9 Hz, H-1), 6.19
(1H, dd, J2,3 7.0 Hz, H-2), 5.99 (1H, pseudo t, J5,6 9.5 Hz,
H-5), 5.76 (1H, pseudo t, J6,7 9.8 Hz, H-6), 5.52 (1H,
pseudo t, J4,5 9.8 Hz, H-4), 4.67 (1H, dd, J8a,8b 12.3 Hz, H-
8a), 4.51 (1H, dd, H-8b), 4.40 (1H, dd, J3,4 9.2 Hz, H-3),
4.23 (1H, ddd, J7,8a 2.3, J7,8b 4.7 Hz, H-7). 13C NMR (90
MHz, CDCl3) δ 166.3, 166.0, 165.4, 165.3 (4×CO), 133.8
(C-1), 145.3–122.4 (aromatics), 125.3 (C-2), 79.6 (C-3),
76.2 (C-7), 74.3 (C-5), 72.4 (C-4), 69.8 (C-6), 63.4 (C-8).
HR-ESI-MS positive mode (m/z): calcd. for:
[M+Na]+=923.2012,
C49H41ClN2O11S (900.21).
found:
[M+Na]+=923.2016;
[M+Na]+=783.1200,
C42H33BrO9 (760.13).
found:
[M+Na]+=783.1211;
2,6-Anhydro-3,4,5,7-tetra-O-benzoyl-N1-(3-
(E)-3,7-Anhydro-4,5,6,8-tetra-O-benzoyl-1-(3-
chlorophenyl)-1,2-dideoxy-D-glycero-D-gulo-oct-1-enitol
((E)--(C-2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl)-
3-chlorostyrene) (2e)
bromobenzyl)-D-glycero-D-gulo-heptose tosylhydrazone
(N1-3-bromobenzyl-C-(2,3,4,6-tetra-O-benzoyl-β-D-
glucopyranosyl)formaldehyde tosylhydrazone) (4g)
Isolated as a by-product beside 2g from the previous
reaction mixture by column chromatography (1:7 EtOAc–
hexane) to yield 13 mg (5 %) of 4g as a white amorphous
product. Rf: 0.31 (1:2 EtOAc–hexane); [α]D –7 (c 0.29,
Prepared from tosylhydrazone 1 (0.20 g, 0.26 mmol), 1-
bromomethyl-3-chlorobenzene (6 equiv., 0.20 mL, 0.32 g,
1.54 mmol) and LiOtBu (1.5 equiv., 0.03 g, 0.39 mmol)
according to General procedure (4.5h). Purified by column
chromatography (1:8 EtOAc–heptane) to yield 78 mg
(42 %) of 2e as a yellow amorphous product. Rf: 0.39 (1:2
1
CHCl3). H NMR (400 MHz, CDCl3) δ 8.12–7.71 (8H, m,
aromatics), 7.67–7.19 (16H, m, aromatics), 7.18–6.88 (4H,
m, aromatics), 6.82 (1H, d, J1,2 6.6 Hz, H-1), 5.89 (1H,
pseudo t, J4,5 9.9 Hz, H-4), 5.63 (1H, pseudo t, J5,6 9.9 Hz,
H-5), 5.34 (1H, pseudo t, J3,4 9.6 Hz, H-3), 4.80 (1H, d,
JCH2a,CH2b 16.8 Hz, CH2a), 4.65 (1H, d, CH2b), 4.54 (1H, dd,
J7a,7b 12.3 Hz, H-7a), 4.40 (1H, dd, H-7b), 4.34 (1H, dd, J2,3
9.9 Hz, H-2), 4.13 (1H, ddd, J6,7a 2.8, J6,7b 5.1 Hz, H-6),
2.22 (3H, s, CH3). 13C NMR (100 MHz, CDCl3) δ 166.4,
165.9, 165.5, 165.3 (4×CO), 133.3 (C-1), 144.5–123.1
(aromatics), 78.8 (C-2), 76.3 (C-6), 73.7 (C-4), 71.0 (C-3),
69.4 (C-5), 63.3 (C-7), 50.6 (CH2), 21.8 (CH3). HR-ESI-
MS positive mode (m/z): calcd. for: [M+Na]+=967.1507,
found: [M+Na]+=967.1519; C49H41BrN2O11S (944.16).
1
EtOAc–hexane); [α]D –35 (c 0.70, CHCl3). H NMR (250
MHz, CDCl3) δ 8.12–7.74 (8H, m, aromatics), 7.63–6.92
(16H, m, aromatics), 6.60 (1H, d, J1,2 15.9 Hz, H-1), 6.18
(1H, dd, J2,3 7.0 Hz, H-2), 5.97 (1H, pseudo t, J5,6 9.8 Hz,
H-5), 5.73 (1H, pseudo t, J6,7 9.8 Hz, H-6), 5.50 (1H,
pseudo t, 1H, J4,5 9.5 Hz, H-4), 4.65 (1H, dd, J8a,8b 12.2 Hz,
H-8a), 4.48 (1H, dd, H-8b), 4.36 (1H, dd, J3,4 9.2 Hz, H-3),
4.19 (1H, ddd, J7,8a 2.9, J7,8b 5.0 Hz, H-7). 13C NMR (63
MHz, CDCl3) δ 166.3, 166.1, 165.4, 165.3 (4×CO), 133.5
(C-1), 145.5–125.2 (aromatics), 124.9 (C-2), 79.6 (C-3),
76.2 (C-7), 74.2 (C-5), 72.4 (C-4), 69.8 (C-6), 63.4 (C-8).
HR-ESI-MS positive mode (m/z): calcd. for:
[M+Na]+=739.1705,
C42H33ClO9 (716.18).
found:
[M+Na]+=739.1710;
(E)-3,7-Anhydro-4,5,6,8-tetra-O-benzoyl-1-(2-
bromophenyl)-1,2-dideoxy-D-glycero-D-gulo-oct-1-enitol
((E)-2-bromo--(C-2,3,4,6-tetra-O-benzoyl-β-D-
(E)-3,7-Anhydro-4,5,6,8-tetra-O-benzoyl-1-(4-
bromophenyl)-1,2-dideoxy-D-glycero-D-gulo-oct-1-enitol
((E)-4-bromo--(C-2,3,4,6-tetra-O-benzoyl-β-D-
glucopyranosyl)styrene) (2h)
Prepared from tosylhydrazone 1 (0.20 g, 0.26 mmol), 1-
bromomethyl-2-bromobenzene (6 equiv., 0.39 g, 1.54
mmol) and LiOtBu (1.5 equiv., 0.03 g, 0.39 mmol)
according to General procedure (21h). Purified by column
chromatography (1:7 EtOAc–hexane) to yield 71 mg
glucopyranosyl)styrene) (2f)
Prepared from tosylhydrazone 1 (0.20 g, 0.26 mmol), 1-
bromomethyl-4-bromobenzene (6 equiv., 0.39 g, 1.54
mmol) and LiOtBu (1.5 equiv., 0.03 g, 0.39 mmol)
9
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801059
Advanced Synthesis & Catalysis
(N1-4-nitrobenzyl-C-(2,3,4,6-tetra-O-benzoyl-β-D-
(36 %) of 2h as pale yellow amorphous product. Rf: 0.43
1
(1:2 EtOAc–hexane); [α]D –13 (c 0.40, CHCl3). H NMR
glucopyranosyl)formaldehyde tosylhydrazone) (4i)
Isolated as a by-product beside 2i from the previous
reaction mixture by column chromatography (1:8 EtOAc–
hexane) to yield 39 mg (16 %) of 4i as a yellow amorphous
product. Rf: 0.23 (1:2 EtOAc–hexane); [α]D –4 (c 0.60,
CHCl3). 1H NMR (400 MHz, CDCl3) δ 8.23–7.61 (12H, m,
aromatics), 7.60–7.20 (14H, m, aromatics), 6.98 (2H, d, J
8.3 Hz, aromatics), 6.75 (1H, d, J1,2 6.6 Hz, H-1), 5.88 (1H,
pseudo t, J4,5 9.7 Hz, H-4), 5.63 (1H, pseudo t, J5,6 9.6 Hz,
H-5), 5.31 (1H, pseudo t, J3,4 9.6 Hz, H-3), 4.85 (2H,s,
CH2), 4.56 (1H, dd, J7a,7b 12.4 Hz, H-7a), 4.39 (1H, dd, H-
7b), 4.35 (1H, dd, J2,3 9.9 Hz, H-2), 4.13 (1H, ddd, J6,7a 2.6,
J6,7b 5.3 Hz, H-6), 2.25 (3H, s, CH3). 13C NMR (100 MHz,
CDCl3) δ 166.2, 165.9, 165.5, 165.3 (4×CO), 140.4 (C-1),
147.8–123.5 (aromatics), 78.6 (C-2), 76.4 (C-6), 73.6 (C-4),
70.9 (C-3), 69.3 (C-5), 63.1 (C-7), 50.5 (CH2), 21.8 (CH3).
HR-ESI-MS positive mode (m/z): calcd. for:
(360 MHz, CDCl3) δ 8.23–7.73 (8H, m, aromatics), 7.68–
7.13 (15H, m, aromatics), 7.11–7.04 (1H, m, aromatic),
7.01 (1H, d, J1,2 15.8 Hz, H-1), 6.13 (1H, dd, J2,3 7.3 Hz,
H-2) 5.99 (1H, pseudo t, J5,6 9.9 Hz, H-5), 5.75 (1H,
pseudo t, J6,7 9.9 Hz, H-6), 5.53 (1H, pseudo t, J4,5 9.6 Hz,
H-3), 4.68 (1H, dd, J8a,8b 12.2 Hz, H-8a), 4.50 (1H, dd, H-
8b), 4.45 (1H, dd, J3,4 9.2 Hz, H-3), 4.23 (1H, ddd, J7,8a 2.8,
J7,8b 4.9 Hz, H-5). 13C NMR (100 MHz, CDCl3) δ 166.4,
166.1, 165.6, 165.4 (4×CO), 133.8 (C-1), 136.4–123.4
(aromatics), 127.3 (C-2), 79.9 (C-3), 76.2 (C-7), 74.3 (C-5),
72.3 (C-4), 69.9 (C-6), 63.4 (C-8). HR-ESI-MS positive
mode (m/z): calcd. for: [M+Na]+=783.1200, found:
[M+Na]+=783.1211; C42H33BrO9 (760.13).
2,6-Anhydro-3,4,5,7-tetra-O-benzoyl-N1-(2-
bromobenzyl)-D-glycero-D-gulo-heptose tosylhydrazone
[M+Na]+=934.2252,
found:
[M+Na]+=934.2245;
(N1-2-bromobenzyl-C-(2,3,4,6-tetra-O-benzoyl-β-D-
C49H41N3O13S (911.24).
glucopyranosyl)formaldehyde tosylhydrazone) (4h)
Isolated as a by-product beside 2h from the previous
reaction mixture by column chromatography (1:7 EtOAc–
hexane) to yield 4 mg (2 %) of 4h as a white amorphous
product. Rf: 0.27 (1:2 EtOAc–hexane); [α]D +3 (c 0.60,
CHCl3).1H NMR (400 MHz, CDCl3) δ 8.15–7.70 (8H, m,
aromatics), 7.69–7.19 (14H, m, aromatics), 7.15–6.89 (6H,
m, aromatics), 6.84 (1H, d, J1,2 6.6 Hz, H-1), 5.86 (1H,
pseudo t, J4,5 9.7 Hz, H-4), 5.61 (1H, pseudo t, J5,6 9.8 Hz,
H-5), 5.34 (1H, pseudo t, J3,4 9.7 Hz, H-3), 4.78 (1H, d,
JCH2a,CH2b 16.5 Hz, CH2a), 4.65 (1H, d, CH2b), 4.52 (1H, dd,
J7a,7b 12.3 Hz, H-7a), 4.40 (1H, dd, H-7b), 4.34 (1H, dd, J2,3
9.9 Hz, H-2), 4.11 (1H, ddd, J6,7a 2.8, J6,7b 5.0 Hz, H-6),
2.23 (3H, s, CH3). 13C NMR (100 MHz, CDCl3) δ 166.3,
165.9, 165.3 (4×CO), 139.5 (C-1), 144.8–120.7
(aromatics), 78.7 (C-2), 76.3 (C-6), 73.9 (C-4), 70.8 (C-3),
69.4 (C-5), 63.3 (C-7), 51.1 (CH2), 21.8 (CH3). HR-ESI-
MS positive mode (m/z): calcd. for: [M+Na]+=967.1507,
found: [M+Na]+=967.1506; C49H41BrN2O11S (944.16).
(E)-3,7-Anhydro-4,5,6,8-tetra-O-benzoyl-1-(4-
cyanophenyl)-1,2-dideoxy-D-glycero-D-gulo-oct-1-enitol
((E)-4-cyano--(C-2,3,4,6-tetra-O-benzoyl-β-D-
glucopyranosyl)styrene) (2j)
Prepared from tosylhydrazone 1 (0.20 g, 0.26 mmol), 4-
bromomethyl benzonitrile (6 equiv., 0.30 g, 1.54 mmol),
LiOtBu (1.5 equiv., 0.03 g, 0.39 mmol), P(2-furyl)3 (4
equiv., 0.24 g, 1.02 mmol) and Pd2(dba)3 (50 mol%, 0.12 g,
0.13 mmol) according to General procedure (20.5h).
Purified by column chromatography (1:8 EtOAc–hexane)
to yield 100 mg (55 %) of 2j as a pale yellow amorphous
product. Rf: 0.26 (1:2 EtOAc–hexane); [α]D –45 (c 1.75,
CHCl3).1H NMR (400 MHz, CDCl3) δ 8.16–7.74 (8H, m,
aromatics), 7.62–7.18 (16H, m, aromatics), 6.69 (1H, d,
J1,2 15.9 Hz, H-1), 6.31 (1H, dd, J2,3 6.8 Hz, H-2), 6.00 (1H,
pseudo t, J5,6 9.6 Hz, H-5), 5.76 (1H, pseudo t, J6,7 9.9 Hz,
H-6), 5.51 (1H, pseudo t, J4,5 9.7 Hz, H-4), 4.69 (1H, dd,
J8a,8b 12.3 Hz, H-8a), 4.51 (1H, dd, H-8b), 4.42 (1H, dd, J3,4
9.6 Hz, H-3), 4.23 (1H, ddd, J7,8a 2.8, J7,8b 4.8 Hz, H-7).
13C NMR (100 MHz, CDCl3) δ 166.3, 166.0, 165.5, 165.3
(4×CO), 132.6 (C-1), 140.7–118.7 (aromatics), 128.2 (C-2),
111.6 (CN), 79.3 (C-3), 76.3 (C-7), 74.1 (C-5), 72.4 (C-4),
69.7 (C-6), 63.3 (C-8). HR-ESI-MS positive mode (m/z):
3,7-Anhydro-4,5,6,8-tetra-O-benzoyl-1,2-dideoxy-1-(4-
nitrophenyl)-D-glycero-D-gulo-oct-1-enitol (-(C-
2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyl)-4-
nitrostyrene) (2i)
calcd.
for:
[M+Na]+=730.2048,
found:
Prepared from tosylhydrazone 1 (0.20 g, 0.26 mmol), 1-
bromomethyl-4-nitrobenzene (6 equiv., 0.33 g, 1.54 mmol)
and LiOtBu (1.5 equiv., 0.03 g, 0.39 mmol) according to
General procedure (19h). Purified by column
chromatography (1:7 EtOAc–hexane) to yield 74 mg
(40 %) (E/Z = 1:1) of 2i as an orange amorphous product.
[M+Na]+=730.2038; C43H33NO9 (707.22).
2,6-Anhydro-3,4,5,7-tetra-O-benzoyl-N1-(4-
cyanobenzyl)-D-glycero-D-gulo-heptose tosylhydrazone
1
(N1-4-cyanobenzyl-C-(2,3,4,6-tetra-O-benzoyl-β-D-
Rf: 0.34 (1:2 EtOAc–hexane). E isomer: H NMR (400
MHz, CDCl3) δ 8.32–7.68 (8H, m, aromatics), 7.66–7.13
(16H, m, aromatics), 6.74 (1H, d, J1,2 15.9 Hz, H-1), 6.36
(1H, dd, J2,3 6.7 Hz, H-2), 6.00 (1H, pseudo t, J5,6 10.0 Hz,
H-5), 5.76 (1H, pseudo t, J6,7 9.9 Hz, H-6), 5.51 (1H,
pseudo t, J4,5 9.6 Hz, H-4), 4.69 (1H, dd, J8a,8b 12.4 Hz, H-
8a), 4.50 (1H, dd, H-8b), 4.43 (1H, dd, J3,4 9.9 Hz, H-3),
4.22 (1H, ddd, J7,8a 2.7, J7,8b 5.0 Hz, H-7). 13C NMR (100
MHz, CDCl3) δ 166.3, 166.0, 165.5, 165.4 (4×CO), 147.6–
110.7 (C-1, C-2, aromatics), 79.3 (C-3), 76.3 (C-7), 73.9
glucopyranosyl)formaldehyde tosylhydrazone) (4j)
Isolated as a by-product beside 2j from the previous
reaction mixture by column chromatography (1:8 EtOAc–
hexane) to yield 15 mg (7 %) of 4j as a pale yellow
amorphous product. Rf: 0.14 (1:2 EtOAc–hexane); [α]D –9
1
(c 1.40, CHCl3). H NMR (400 MHz, CDCl3) δ 8.16–7.70
(8H, m, aromatics), 7.68–7.13 (18H, m, aromatics), 6.97
(2H, d, J 8.2 Hz, aromatics), 6.75 (1H, d, J1,2 6.6 Hz, H-1),
5.89 (1H, pseudo t, J4,5 9.5 Hz, H-4), 5.63 (1H, pseudo t,
J5,6 10.0 Hz, H-5), 5.32 (1H, pseudo t, J3,4 9.8 Hz, H-3),
4.80 (2H, s, CH2), 4.56 (1H, dd, J7a,7b 12.3 Hz, H-7a), 4.39
(1H, dd, H-7b), 4.35 (1H, dd, J2,3 9.8 Hz, H-2), 4.14 (1H,
ddd, J6,7a 2.7, J6,7b 4.9 Hz, H-6), 2.24 (3H, s, CH3). 13C
NMR (100 MHz, CDCl3) δ 166.2, 165.8, 165.4, 165.2
(4×CO), 140.2 (C-1), 145.5–118.2 (aromatics), 111.9 (CN),
78.5 (C-2), 76.3 (C-6), 73.6 (C-4), 70.8 (C-3), 69.3 (C-5),
63.1 (C-7), 50.6 (CH2), 21.8 (CH3). HR-ESI-MS positive
mode (m/z): calcd. for: [M+Na]+=914.2354, found:
[M+Na]+=914.2358; C50H41N3O11S (891.25).
1
(C-5), 72.4 (C-4), 69.7 (C-6), 63.3 (C-8). Z isomer: H
NMR (400 MHz, CDCl3) δ 8.32–7.68 (8H, m, aromatics),
7.66–7.13 (16H, m, aromatics), 6.81 (1H, d, J1,2 11.6 Hz,
H-1), 6.01 (1H, dd, J2,3 2.5 Hz, H-2), 5.89 (1H, pseudo t,
J5,6 9.6 Hz, H-5), 5.69 (1H, pseudo t, J6,7 9.9 Hz, H-6), 5.64
(1H, pseudo t, J4,5 9.7 Hz, H-4), 4.66 (1H, dd, J7,8a 2.5,
J8a,8b 12.6 Hz, H-8a), 4.56–4.45 (2H, m, H-3, H-8b), 4.27–
4.15 (1H, m, H-7). 13C NMR (100 MHz, CDCl3) δ 166.3,
166.0, 165.4 (4×CO), 147.6–110.7 (C-1, C-2, aromatics),
76.4 (C-7), 74.5 (C-3), 74.1 (C-5), 72.5 (C-4), 69.8 (C-6),
63.7 (C-8). HR-ESI-MS positive mode (m/z): calcd. for:
[M+Na]+=750.1946,
C42H33NO11 (727.21).
found:
[M+Na]+=750.1939;
(E)-4,5,6,8-Tetra-O-acetyl-3,7-anhydro-1,2-dideoxy-1-
phenyl-D-glycero-L-manno-oct-1-enitol ((E)--(C-
2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)styrene)
(7a)
2,6-Anhydro-3,4,5,7-tetra-O-benzoyl-N1-(4-
nitrobenzyl)-D-glycero-D-gulo-heptose tosylhydrazone
10
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801059
Advanced Synthesis & Catalysis
Prepared from tosylhydrazone 6 (0.20 g, 0.38 mmol),
(bromomethyl)benzene (6 equiv., 0.27 mL, 0.39 g, 2.27
mmol) and LiOtBu (1.5 equiv., 0.05 g, 0.57 mmol)
according to General procedure (4h). Purified by column
chromatography (1:2 EtOAc–heptane) to yield 98 mg
(59 %) of 7a as an orange amorphous product. Rf: 0.42
Isolated as a by-product beside 7c from the previous
reaction mixture by column chromatography (1:4 EtOAc–
heptane) to yield 16 mg (7 %) of 9c as a white amorphous
product. Rf: 0.36 (1:1 EtOAc–heptane); [α]D –10 (c 0.35,
CHCl3).1H NMR (250 MHz, CDCl3) δ 7.83 (2H, d, J 8.3
Hz, aromatics), 7.34 (2H, d, J 8.0 Hz, aromatics), 7.25–
6.97 (4H, m, aromatics), 6.66 (1H, d, J1,2 6.5 Hz, H-1),
5.39 (1H, dd, J5,6 0.8 Hz, H-5), 5.10–5.00 (2H, strongly
coupled, H-3, H-4), 4.94 (1H, d, JCH2a,CH2b 16.9 Hz, CH2a),
4.60 (1H, d, CH2b), 4.03 (1H, dd, J7a,7b 12.5 Hz, H-7a), 3.98
(1H, dd, H-7b), 3.93 (1H, strongly coupled, H-2), 3.86 (1H,
ddd, J6,7a 6.5, J6,7b 6.8 Hz, H-6), 2.43 (3H, s, CH3-Ts), 2.34
(3H, s, CH3), 2.10, 2.02, 1.95, 1.65 (12H, 4s, 4×CH3). 13C
NMR (63 MHz, CDCl3) δ 170.5, 170.3, 170.1 (4×CO),
139.9 (C-1), 144.5–123.3 (aromatics), 79.0 (C-2), 74.4 (C-
6), 71.3 (C-4), 67.6 (C-5), 67.0 (C-3), 61.6 (C-7), 51.1
(CH2), 21.7 (CH3-Ts), 21.6 (CH3), 20.8, 20.7, 20.3
(4×CH3). HR-ESI-MS positive mode (m/z): calcd. for:
1
(1:1 EtOAc–hexane); [α]D –3 (c 0.55, CHCl3). H NMR
(400 MHz, CDCl3) δ 7.40–7.14 (5H, m, aromatics), 6.66
(1H, d, J1,2 15.9 Hz, H-1), 6.11 (1H, dd, J2,3 7.8 Hz, H-2),
5.48 (1H, dd, J6,7 0.9 Hz, H-6), 5.25 (1H, pseudo t, J4,5 10.2
Hz, H-4), 5.13 (1H, dd, J5,6 3.4 Hz, H-5), 4.17 (1H, dd,
J8a,8b 13.5 Hz, H-8a), 4.13 (1H, dd, H-8b), 4.02 (1H, dd, J3,4
9.8 Hz, H-3), 4.00 (1H, ddd, J7,8a 6.6, J7,8b 6.6 Hz, H-7),
2.18, 2.05, 2.00, 1.95 (12H, 4s, 4×CH3). 13C NMR (100
MHz, CDCl3) δ 170.5, 170.4, 170.3, 169.8 (4×CO), 135.1
(C-1), 136.0–111.0 (aromatics), 124.3 (C-2), 80.3 (C-3),
74.1 (C-7), 71.8 (C-5), 68.8 (C-4), 67.8 (C-6), 61.8 (C-8),
20.8, 20.7 (4×CH3). HR-ESI-MS positive mode (m/z):
calcd.
for:
[M+Na]+=434.1469,
found:
[M+Na]+=655.1932,
found:
[M+Na]+=655.1948;
[M+Na]+=457.1468; C22H26O9 (434.16). NMR spectra are
identical with those reported.[6]
C30H26N2O11S (632.20).
(E)-4,5,6,8-Tetra-O-acetyl-3,7-anhydro-(3-
chlorophenyl)-1,2-dideoxy-1-D-glycero-L-manno-oct-1-
enitol ((E)--(C-2,3,4,6-tetra-O-acetyl-β-D-
(E)-4,5,6,8-Tetra-O-acetyl-3,7-anhydro-1,2-dideoxy-1-
(4-methylphenyl)-D-glycero-L-manno-oct-1-enitol ((E)-
-(C-2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-4-
galactopyranosyl)-3-chlorostyrene) (7d)
methylstyrene) (7b)
Prepared from tosylhydrazone 6 (0.20 g, 0.38 mmol), 1-
bromomethyl-3-chlorobenzene (6 equiv., 0.30 mL, 0.47 g,
2.27 mmol) and LiOtBu (1.5 equiv., 0.05 g, 0.57 mmol)
according to General procedure (4.5h). Purified by column
chromatography (1:4 EtOAc–heptane) to yield 104 mg
(59 %) of 7d as a yellow amorphous product. Rf: 0.42 (1:1
EtOAc–hexane); [α]D –2 (c 0.80, CHCl3).1H NMR (250
MHz, CDCl3) δ 7.60–7.12 (4H, m, aromatics), 6.59 (1H, d,
J1,2 15.9 Hz, H-1), 6.12 (1H, dd, J2,3 7.5 Hz, H-2), 5.47 (1H,
dd, J6,7 1.1 Hz, H-6), 5.23 (1H, pseudo t, J4,5 10.2 Hz, H-4),
5.11 (1H, dd, J5,6 3.3 Hz, H-5), 4.17–4.10 (2H, m, H-8a, H-
8b), 4.05–3.93 (2H, m, H-3, H-7), 2.17, 2.04, 1.99, 1.96
(12H, 4s, 4×CH3). 13C NMR (63 MHz, CDCl3) δ 170.6,
170.4, 170.3, 169.8 (4×CO), 133.5 (C-1), 145.4–124.8
(aromatics), 125.0 (C-2), 79.9 (C-3), 74.3 (C-7), 71.8 (C-5),
68.8 (C-4), 67.8 (C-6), 61.9 (C-8), 20.9, 20.8 (4×CH3).
HR-ESI-MS positive mode (m/z): calcd. for:
Prepared from tosylhydrazone 6 (0.10 g, 0.19 mmol), 1-
bromomethyl-4-methylbenzene (3 equiv., 0.11 g, 0.57
mmol) and LiOtBu (2.2 equiv., 0.03 g, 0.42 mmol)
according to General procedure (2.5h). Purified by column
chromatography (1:5 EtOAc–heptane) to yield 33 mg
(39 %) of 7b as an orange amorphous product. Rf: 0.45
1
(1:1 EtOAc–hexane); [α]D –7 (c 0.70, CHCl3). H NMR
(360 MHz, CDCl3) δ 7.37–6.98 (4H, m, aromatics), 6.62
(1H, d, J1,2 15.8 Hz, H-1), 6.06 (1H, dd, J2,3 7.9 Hz, H-2),
5.48 (1H, dd, J6,7 0.8 Hz, H-6), 5.24 (1H, pseudo t, J4,5 10.2
Hz, H-4), 5.11 (1H, dd, J5,6 3.4 Hz, H-5), 4.14 (2H, m, H-
8a, H-8b), 4.03–3.93 (2H, m, H-3, H-7), 2.34 (3H, s, CH3),
2.18, 2.06, 2.00, 1.95 (12H, 4s, 4×CH3). 13C NMR (75
MHz, CDCl3) δ 170.7, 170.5, 170.4, 169.9 (4×CO), 135.3
(C-1), 138.5–125.2 (aromatics), 123.4 (C-2), 80.6 (C-3),
74.3 (C-7), 71.9 (C-5), 68.9 (C-4), 67.9 (C-6), 62.0 (C-8),
21.4 (CH3), 20.9, 20.8 (4×CH3). HR-ESI-MS positive
mode (m/z): calcd. for: [M+Na]+=471.1626, found:
[M+Na]+=471.1626; C23H28O9 (448.17).
[M+Na]+=491.1079,
C22H25ClO9 (468.12).
found:
[M+Na]+=491.1077;
(E)-4,5,6,8-Tetra-O-acetyl-3,7-anhydro-1-(4-
bromophenyl)-1,2-dideoxy-D-glycero-L-manno-oct-1-
enitol ((E)-4-bromo--(C-2,3,4,6-tetra-O-acetyl-β-D-
galactopyranosyl)styrene) (7e)
(E)-4,5,6,8-Tetra-O-acetyl-3,7-anhydro-1,2-dideoxy-1-
(3-methylphenyl)-D-glycero-L-manno-oct-1-enitol ((E)-
-(C-2,3,4,6-tetra-O-acetyl-β-D-galactopyranosyl)-3-
methylstyrene) (7c)
Prepared from tosylhydrazone 6 (0.20 g, 0.38 mmol), 1-
bromomethyl-4-bromobenzene (6 equiv., 0.57 g, 2.27
mmol) and LiOtBu (1.5 equiv., 0.05 g, 0.57 mmol)
according to General procedure (2.5h). Purified by column
chromatography (1:4 EtOAc–heptane) to yield 59 mg
(31 %) of 7e as a pale yellow amorphous product. Rf: 0.42
(1:1 EtOAc–hexane); [α]D –7 (c 0.80, CHCl3).1H NMR
(400 MHz, CDCl3) δ 7.44 (2H, d, J 8.4 Hz, aromatics),
7.23 (2H, d, J 8.4 Hz, aromatics), 6.60 (1H, d, J1,2 15.9 Hz,
Prepared from tosylhydrazone 6 (0.20 g, 0.38 mmol), 1-
bromomethyl-3-methylbenzene (6 equiv., 0.31 mL, 0.42 g,
2.27 mmol) and LiOtBu (1.5 equiv., 0.05 g, 0.57 mmol)
according to General procedure (2.5h). Purified by column
chromatography (1:4 EtOAc–heptane) to yield 43 mg
(25 %) of 7c as a white amorphous product. Rf: 0.45 (1:1
1
EtOAc–hexane); [α]D –6 (c 0.35, CHCl3). H NMR (250
MHz, CDCl3) δ 7.36–6.95 (4H, m, aromatics), 6.61 (1H, d,
J1,2 15.9 Hz, H-1), 6.09 (1H, dd, J2,3 7.8 Hz, H-2), 5.47 (1H, H-1), 6.11 (1H, dd, J2,3 7.7 Hz, H-2), 5.48 (1H, dd, J6,7 0.8
dd, J6,7 1.1 Hz, H-6), 5.24 (1H, pseudo t, J4,5 10.2 Hz, H-4),
5.11 (1H, dd, J5,6 3.4 Hz, H-5), 4.21–4.09 (2H, m, H-8a, H-
8b), 4.06–3.93 (2H, m, H-3, H-7), 2.33 (3H, s, CH3), 2.17,
2.04, 1.99, 1.94 (15H, 5s, 5×CH3). 13C NMR (63 MHz,
CDCl3) δ 170.6, 170.4, 170.3, 169.8 (4×CO), 135.4 (C-1),
138.4–124.0 (aromatics), 124.2 (C-2), 80.4 (C-3), 74.2 (C-
7), 71.9 (C-5), 68.9 (C-4), 67.9 (C-6), 61.9 (C-8), 21.5
(CH3), 20.9, 20.8 (4×CH3). HR-ESI-MS positive mode
Hz, H-6), 5.23 (1H, pseudo t, J4,5 10.2 Hz, H-4), 5.12 (1H,
dd, J5,6 3.3 Hz, H-5), 4.19–4.09 (2H, m, H-8a, H-8b), 4.01
(1H, dd, J2,3 9.7 Hz, H-3), 3.98 (1H, ddd, J6,7a 6.6, J6,7b 6.3
Hz, H-7), 2.18, 2.05, 2.00, 1.95 (12H, 4s, 4×CH3). 13C
NMR (63 MHz, CDCl3) δ 170.6, 170.4, 170.3, 169.8
(4×CO), 133.8 (C-1), 145.4–122.8 (aromatics), 125.3 (C-2),
80.1 (C-3), 74.3 (C-7), 71.8 (C-5), 68.8 (C-4), 67.8 (C-6),
61.9 (C-9), 20.9, 20.8 (4×CH3). HR-ESI-MS positive mode
(m/z):
calcd.
for:
[M+Na]+=471.1626,
found:
(m/z):
calcd.
for:
[M+Na]+=535.0574,
found:
[M+Na]+=471.1631; C23H28O9 (448.17).
[M+Na]+=535.0571; C22H25BrO9 (512.07).
3,4,5,7-Tetra-O-acetyl-2,6-anhydro-N1-(3-
methylbenzyl)-D-glycero-L-manno-heptose
3,4,5,7-Tetra-O-acetyl-2,6-anhydro-N1-(4-
bromobenzyl)-D-glycero-L-manno-heptose
tosylhydrazone (N1-3-methylbenzyl-C-(2,3,4,6-tetra-O-
acetyl-β-D-galactopyranosyl)formaldehyde
tosylhydrazone) (9c)
tosylhydrazone (N1-4-bromobenzyl-C-(2,3,4,6-tetra-O-
acetyl-β-D-galactopyranosyl)formaldehyde
tosylhydrazone) (9e)
11
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801059
Advanced Synthesis & Catalysis
Isolated as a by-product beside 7e from the previous
reaction mixture by column chromatography (1:4 EtOAc–
heptane) to yield 24 mg (9 %) of 9e as a yellow amorphous
product. Rf: 0.36 (1:1 EtOAc–hexane); [α]D –8 (c 0.60,
CHCl3).1H NMR (400 MHz, CDCl3) δ 7.82 (2H, d, J 8.3
Hz, aromatics), 7.49 (2H, d, J 8.4 Hz, aromatics), 7.35 (2H,
d, J 8.1 Hz, aromatics), 7.16 (2H, d, J 8.4 Hz, aromatics),
6.61 (1H, d, J1,2 6.5 Hz, H-1), 5.40 (1H, dd, J5,6 1.0 Hz, H-
5), 5.04 (1H, dd, J4,5 4.8 Hz, H-4), 5.03 (1H, pseudo t, J3,4
10.2 Hz, H-3), 4.92 (1H, d, JCH2a,CH2b 16.9 Hz, CH2a), 4.56
(1H, d, CH2b), 4.03 (1H, dd, J7a,7b 13.4 Hz, H-7a), 4.00 (1H,
dd, H-7b), 3.92 (1H, strongly coupled, H-2), 3.87 (1H, ddd,
J6,7a 6.8, J6,7b 6.3 Hz, H-6), 2.44, (3H, s, CH3-Ts), 2.12,
2.03, 1.96, 1.64 (12H, 4s, 4×CH3). 13C NMR (63 MHz,
CDCl3) δ 170.9, 170.5, 170.2, 170.1 (4×CO), 140.2 (C-1),
144.7–121.6 (aromatics), 78.9 (C-2), 74.5 (C-6), 71.1 (C-4),
67.5 (C-5), 67.1 (C-3), 61.6 (C-7), 50.5 (CH2), 21.7 (CH3-
Ts), 20.8, 20.7, 20.3 (4×CH3). HR-ESI-MS positive mode
[6]
[7]
[8]
V. Khatri, A. Kumar, B. Singh, S. Malhotra, A. K.
Prasad, J. Org. Chem. 2015, 80, 11169-11174.
M. A. Leeuwenburgh, H. S. Overkleeft, G. A. van
der Marel, J. H. van Boom, Synlett 1997, 1263-1264.
M. A. Leeuwenburgh, C. Kulker, H. I. Duynstee, H.
S. Overkleeft, G. A. van der Marel, J. H. van Boom,
Tetrahedron 1999, 55, 8253-8262.
J. Zeng, S. Vedachalam, S. Xiang, X.-W. Liu, Org.
Lett. 2011, 13, 42-45.
G. M. Grotenbreg, A. W. Tuin, M. D. Witte, M. A.
Leeuwenburgh, J. H. van Boom, G. A. van der
Marel, H. S. Overkleeft, M. Overhand, Synlett 2004,
0904-0906.
M. D. P. Risseeuw, G. M. Grotenbreg, M. D. Witte,
A. W. Tuin, M. A. Leeuwenburgh, G. A. Van der
Marel, H. S. Overkleeft, M. Overhand, Eur. J. Org.
Chem. 2006, 3877-3886.
B. Waldscheck, M. Streiff, W. Notz, W. Kinzy, R.
R. Schmidt, Angew. Chem., Int. Ed. 2001, 40, 4007-
4011.
K. Sudarshan, I. S. Aidhen, Eur. J. Org. Chem.
2017, 34-38.
D. J. Hart, S. Patterson, J. P. Unch, Synlett 2003,
1334-1338.
A. Ghosez, T. Göbel, B. Giese, Chem. Ber. 1988,
121, 1807-1811.
G. Stork, H. S. Suh, G. Kim, J. Am. Chem. Soc.
1991, 113, 7054-7056.
D. Mazéas, T. Skrydstrup, O. Doumeix, J.-M. Beau,
Angew. Chem. Int. Ed. Engl. 1994, 33, 1383.
J. Désiré, A. Veyrières, Carbohydr. Res. 1995, 268,
177-186.
I. Šnajdr, K. Parkan, F. Hessler, M. Kotora, Beilstein
J. Org. Chem. 2015, 11, 1392-1397.
J. Barluenga, C. Valdes, Angew. Chem. Int. Edit.
2011, 50, 7486-7500.
Z. Shao, H. Zhang, Chem. Soc. Rev. 2012, 41, 560-
572.
Q. Xiao, Y. Zhang, J. B. Wang, Acc. Chem. Res.
2013, 46, 236-247.
D. Qiu, F. Y. Mo, Y. Zhang, J. B. Wang, in
Advances in Organometallic Chemistry, Vol 67, Vol.
67 (Ed.: P. J. Perez), 2017, pp. 151-219.
Y. Xia, D. Qiu, J. B. Wang, Chem. Rev. 2017, 117,
13810-13889.
[9]
[10]
[11]
[12]
(m/z):
calcd.
for:
[M+Na]+=719.0881,
found:
[M+Na]+=719.0879; C29H33BrN2O11S (696.10).
N1-Allyl-2,6-anhydro-3,4,5,7-tetra-O-benzoyl-D-glycero-
D-gulo-heptose tosylhydrazone (N1-allyl-C-(2,3,4,6-
tetra-O-benzoyl-β-D-glucopyranosyl)formaldehyde
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
tosylhydrazone) (10)
Prepared from tosylhydrazone 1 (0.20 g, 0.26 mmol), 3-
bromoprop-1-ene (6 equiv., 0.13 mL, 0.19 g, 1.54 mmol)
and LiOtBu (1.5 equiv., 0.03 g, 0.39 mmol) according to
General procedure (22h). Purified by column
chromatography (1:8 EtOAc–hexane) to yield 40 mg
(18 %) of 10 as a yellow amorphous product. Rf: 0.33 (1:2
1
EtOAc–hexane); [α]D +1 (c 0.79, CHCl3). H NMR (400
MHz, CDCl3) δ 8.14–7.69 (8H, m, aromatics), 7.63–7.20
(14H, m, aromatics), 6.94 (1H, d, J1,2 6.7 Hz, H-1), 6.86
(2H, d, J 8.1 Hz, aromatics), 5.93 (1H, pseudo t, J4,5 9.7 Hz,
H-4), 5.69 (1H, pseudo t, J5,6 10.0 Hz, H-5), 5.66–5.59 (1H,
m, CH), 5.46 (1H, pseudo t, J3,4 9.7 Hz, H-3), 5.20–5.07
(2H, m, CH2), 4.58 (1H, dd, J7a,7b 12.3 Hz, H-7a), 4.45 (1H,
dd, H-7b), 4.39 (1H, dd, J2,3 9.8 Hz, H-2), 4.36–4.26 (1H,
m, CH2a), 4.25–4.18 (1H, m, CH2b), 4.17 (1H, ddd, J6,7a 2.5,
J6,7b 5.0 Hz, H-6), 2.19 (3H, s, CH3). 13C NMR (100 MHz,
CDCl3) δ 166.3, 165.9, 165.5, 165.3 (4×CO), 139.5 (C-1),
144.0–126.5 (aromatics, CH), 118.4 (CH2), 78.9 (C-2),
76.3 (C-6), 73.8 (C-4), 71.0 (C-3), 69.4 (C-5), 63.3 (C-7),
49.0 (CH2), 21.7 (CH3). HR-ESI-MS positive mode (m/z):
calcd.
for:
[M+Na]+=839.2245,
found:
[M+Na]+=839.2240; C45H40N2O11S (816.24).
Acknowledgements
[24]
[25]
[26]
[27]
This work was supported by the National Research,
Development and Innovation Office of Hungary (Grant
K109450), by the EU co-financed by the European
Regional Development Fund under the projects GINOP-
2.3.2-15-2016-00008 and GINOP-2.3.3-15-2016-00004, as
well as by the Alexander von Humboldt Foundation
(Germany).
M. Tóth, L. Somsák, Tetrahedron Lett. 2001, 42,
2723-2725.
M. Tóth, K. E. Kövér, A. Bényei, L. Somsák, Org.
Biomol. Chem. 2003, 1, 4039-4046.
M. Tóth, L. Somsák, D. Goyard, in Carbohydrate
Chemistry: Proven Synthetic Methods, Vol. 1 (Ed.:
P. Kováč), CRC Press, Boca Raton, 2012, pp. 355-
365.
T. Kaszás, M. Tóth, S. Kun, L. Somsák, RSC Adv.
2017, 7, 10454-10462.
T. Kaszás, M. Tóth, L. Somsák, New. J. Chem.
2017, 41, 13871-13880.
References
[28]
[29]
[30]
[31]
[1]
É. Bokor, S. Kun, D. Goyard, M. Tóth, J.-P. Praly,
S. Vidal, L. Somsák, Chem. Rev. 2017, 117, 1687-
1764.
T. Kaszás, A. Ivanov, M. Tóth, P. Ehlers, P. Langer,
L. Somsák, Carbohydr. Res. 2018, 466, 30-38.
Q. Xiao, J. Ma, Y. Yang, Y. Zhang, J. B. Wang,
Org. Lett. 2009, 11, 4732-4735.
[2]
[3]
[4]
[5]
Y. Yang, B. Yu, Chem. Rev. 2017, 117, 12281-
12356.
K. Kitamura, Y. Ando, T. Matsumoto, K. Suzuki,
Chem. Rev. 2018, 118, 1495-1598.
M. E. L. Sánchez, V. Michelet, I. Besnier, J.-P.
Genêt, Synlett 1994, 705-708.
V. Michelet, K. Adiey, S. Tanier, G. Dujardin, J.-P.
Genêt, Eur. J. Org. Chem. 2003, 2947-2958.
12
This article is protected by copyright. All rights reserved.

10.1002/adsc.201801059
Advanced Synthesis & Catalysis
FULL PAPER
C-Glycosyl styrene type compounds by Pd-
catalyzed cross-coupling reactions of anhydro-
aldose tosylhydrazones with benzyl bromides
Adv. Synth. Catal. Year, Volume, Page – Page
Tímea Kaszás, Marietta Tóth, Peter Langer, and
László Somsák*
13
This article is protected by copyright. All rights reserved.