Palladium-catalyzed cross-coupling reaction of thioglycosides with (hetero)aryl halides

Article abstract of DOI:10.1002/adsc.201200695

α- and β-thioglycosides serve as effective nucleophiles for Buchwald-Hartwig cross-coupling reactions using functionalized (hetero)aryl halides. The functional group tolerance on the electrophilic partner is typically high, both benzyl and acetate protect

Full text of DOI:10.1002/adsc.201200695

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DOI: 10.1002/adsc.201200695
Palladium-Catalyzed Cross-Coupling Reaction of Thioglycosides
with (Hetero)aryl Halides
Etienne Brachet,a Jean-Daniel Brion,a Samir Messaoudi,a,* and Mouad Alamia,*
a
Univ Paris-Sud, CNRS, BioCIS-UMR 8076, LabEx LERMIT, Laboratoire de Chimie Thꢀrapeutique, Facultꢀ de
Pharmacie, 5 rue J.-B. Clꢀment, 92296 Chꢁtenay-Malabry, France
Fax : (+33)-146-83-58-28; e-mail: samir.messaoudi@u-psud.fr or mouad.alami@u-psud.fr
Received: August 3, 2012; Revised: November 7, 2012; Published online: February 1, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200695.
Abstract: a- and b-thioglycosides serve as effective all cases studied. The efficiency of this general proto-
nucleophiles for Buchwald–Hartwig cross-coupling col was well demonstrated by the synthesis of 4-
reactions using functionalized (hetero)aryl halides. methyl-7-thioumbelliferyl-b-d-cellobioside
The functional group tolerance on the electrophilic CB).
partner is typically high, both benzyl and acetate
ꢀ
(MUS-
protecting groups on the carbohydrate are tolerated, Keywords: C S bond formation; ACTHNUGTRNEUNG(hetero)aryl hal-
and anomer selectivities of thioglycosides are high in ides; palladium catalysis; thioglycosides
Introduction
While much effort has been spent on construction
of specific thiooligosaccharides and thiopeptides,[1c]
The biological relevance of sulfur-containing carbohy- relatively little attention has been devoted to synthe-
drates is gaining substantial attention in a wide array sis of (hetero)arylthioglycosides. These derivatives are
of biological studies.[1] Thioglycoside derivatives have more routinely prepared by treating per-O-acetylated
been investigated extensively as mimetics of biologi- glycosyl precursors with a thiophenol in the presence
cally relevant O-glycosides. S-glycosides are much of a Lewis acid,[3] or by substituting the halogen atom
more stable than O-glycosides to both chemical and of an acetohaloglycoside with a thiolate anion[4]
enzymatic degradation and are utilized as enzyme in- (Scheme 1a). These procedures suffer from the use of
hibitors in various biochemical studies.[2]
an excess of harsh acidic reagents, and are generally
restricted in substrate scope with respect to thiophe-
Scheme 1.
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Etienne Brachet et al.
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nols. In addition, reactions can be lengthy, and unde- note, compound 3b arises from the aryl migration be-
sired anomeric mixtures are occasionally observed.[5] tween the metal center and coordinated phosphine in
An appealing option to access (hetero)arylthioglyco- the Pd(II) complex. This reactivity is quite rare but
sides 3 would be the use of thioglycosides as nucleo- has nevertheless already been reported.[11] To circum-
philes in transition metal-catalyzed reactions vent the formation of 3b, an extensive screening of
(Scheme 1b).
various reaction parameters (base, ligand and solvent)
To the best of our knowledge, only one report de- was conducted. Screening of other carbonate bases
scribed the preparation of arylthioglycosides by cou- such as K2CO3 gave a similar result (63%, entry 2).
pling of per-O-acetylated sugar thiols with activated We were delighted to find that the use of organic
o-iodoaryltriazenes.[6] To be successful, the reaction bases such as (i-Pr)2NH, (i-Pr)2NEt or Et3N leads to
required the use of stoichiometric amounts of CuI. improvement of performance of the coupling reaction
Only activated o-iodoaryltriazenes were used, thus with yields up to 98% (entries 3–5). With Et3N as the
limiting the scope of the reaction.[7] Attempted cou- base, the screening reactions with respect to the
plings with unactivated aryl iodides failed.[6] There- ligand revealed that the bidentate phosphine Xant-
fore, the development of general and selective proto- phos L1 is superior to all other choices, providing 3a
cols to give a more efficient and direct access to (het- in a quantitative yield (entry 5). Other ligands were
ero)arylthioglycosides 3 is still desirable.
detrimental to the reaction (entries 6–9). Finally, after
Continuing our longstanding interest in developing screening other parameters (solvent and amount of
novel metal-catalyzed carbon-heteroatom bond form- base), optimal conditions were found to require 1a
ing reactions,[8] we decided to explore the ability of a- (1.5 equiv.), 2a (1 equiv.), Pd
ACTHNUTRGNEU(NG OAc)2 (3 mol%), Xant-
and b-thioglycosides to participate as nucleophiles in phos (1.5 mol%), NEt3 (1 equiv.), dioxane in a sealed
[9]
a Pd-catalyzed C S cross-coupling reaction with Schlenk tube at 1008C for 1 h (entry 11).[12] Accord-
ꢀ
a wide variety of (hetero)aryl halides (Scheme 1b). ingly, 3a was formed in 99% yield without any anome-
From a synthetic viewpoint, this coupling is a substan- rization. A control experiment revealed that both pal-
tially daunting task because of the added functionality ladium catalyst and ligand were necessary for the cou-
and stereochemical complexity of carbohydrates. To pling to occur as no product could be formed in the
the best of our knowledge, there is no report describ- absence of Pd
ACHTUNGRTENN(UNG OAc)2 or L1.
ing the formation of these (hetero)aryl thioglycosides Motivated by these results, we next explored the
(3) using this idea. Herein, we report our success in scope of the coupling reaction of b-thioglucose 1a
the development of such a general and unprecedented with various (hetero)aryl iodides and bromides. Grati-
protocol that accommodates a wider combination of fyingly, all the arylations proceeded cleanly and selec-
aglycon groups (e.g., aryl, heteroaryl, heterocyclic) at tively in excellent yields. As depicted in Table 2, 1a
the sulfur atom of thioglycosides. This selective cou- was readily coupled with aryl bromides and iodides
pling competes with the standard preparation of ar- having para and meta electron-donating or electron-
ylthioglycosides by reaction of thiophenols with an ac- withdrawing substituents to give thioglycosylated
tivated sugar since, with respect to aryl partners, halo- products in good to excellent yields with complete b-
genated (hetero)aromatic compounds are more selectivity (entries 1–3, 6–8 and 10–15). In addition,
widely commercially available than thiophenol deriva- the sterically demanding ortho substitution pattern
tives.[10]
was tolerated toward the coupling reaction of 1a,
leading to b-thioglycosylated derivatives in excellent
yields (entries 4, 5 and 9), regardless of the electronic
nature of the substituents. As shown in Table 2, the
presence of a free amino (entry 2) or hydroxy group
Results and Discussion
ꢀ
To determinate the feasibility of this C S bond for- (entries 3 and 15) on the aryl halides 2 did not inter-
mation process, we examined the coupling of perace- fere with the outcome of the present reaction. Inter-
tylated b-thioglucose 1a with 4-iodoanisole 2a under estingly, the thioglycosylation procedure was tolerant
various palladium catalysts, ligand sources, bases and of a diverse array of electrophilic functional groups
solvents. Representative results from this study are [e.g., NO2, CHO, CO2Et, COMe, CH=NAr, CONR2,
summarized in Table 1. The reaction of 1a (1.5 equiv.) C(Me)=NNHTs], providing the corresponding b-ar-
with 2a (1 equiv.) was first investigated under the con- ylthioglycosides with yields ranging from 61% to
ditions of our previously reported procedure[8a,b] 98%. Aryl halides 2l–n revealed an excellent chemical
ꢀ
ꢀ
[PdACHTUNGTRENNUNG(OAc)2, Xantphos, Cs2CO3, 1,4-dioxane, 1008C]. selectivity of the C I bond over the C Br bond or N-
However, this transformation was inefficient and re- tosylhydrazone function,[13] which could enjoy further
sulted in concomitant formation of the expected b-ar- metal-catalyzed functionalization processes[14] (en-
ylthioglycoside 3a, together with by-product 3b in tries 11–13). Extending the glycosylation method to
92:08 ratio (Table 1, entry 1). After a tedious separa- heteroaromatic halides proved to be also successful
tion, 3a was isolated in an acceptable 66% yield. Of (entries 16–21). Halopyridines 2q, 2r, 2-iodothiophene
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Palladium-Catalyzed Cross-Coupling Reaction of Thioglycosides with (Hetero)aryl Halides
Table 1. Optimization of the coupling reaction of 1a with 2a under various conditions.[a]
Entry
Ligand
Base
Solvent
Conversion[b] [%]
Ratio[c] 3a/3b
Yield[d] [%]
1
2
3
4
5
6
7
8
L1
L1
L1
L1
L1
L2
L3
L4
L5
L1
L1
Cs2CO3
K2CO3
ACHTUNGTRENNUNG
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
dioxane
toluene
dioxane
100
100
100
100
100
52
0
0
0
100
100
92:08
89:11
100:0
100:0
100:0
–
–
–
–
66
63
98
98
99
–
–
–
–
ACHTUNGTRENNUNG
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
9
10
11
100:0
100:0
95
99[e,f,g]
[a]
Reaction conditions: 1a (0.375 mmol), 2a (0.25 mmol), PdACTHNUGTREN(NUNG OAc)2 (10 mol%), ligand (5 mol%), base (0.75 mmol) in sol-
vent (1.5 mL) were heated in a sealed Schlenk tube at 1008C.
Conversion was determined by H NMR on the crude reaction mixture and is based on the chemical shift of the proton
[b]
[c]
1
signal (ppm) at the C-2 position of the aromatic ring (2a: d=6.68, 3a: d=6.82).
1
Ratio was determined by H NMR in the crude reaction mixture and is based on the chemical shift of the proton signal
(ppm) at the anomeric position (3a: d=4.54, 3b: d=4.70).
Yield of isolated product.
Reaction was carried out in the presence of PdACTHNUTRGNEUNG(OAc)2 (3 mol%), L1 (1.5 mol%) and Et3N (1 equiv.). Compound 3a was
[d]
[e]
formed in 95% yield when reaction was carried out with Pd2dba3 (3 mol%), L1 (3 mol%). No reaction occurred when
Pd2dba3 (3 mol%) was used alone without L1.
[f]
A 72% yield of 3a was obtained when using only 1 mol% of PdACHTUNGTRENNUNG
[g]
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
2s and 3-bromoquinoline 2t were good partners with with respect to the sugar configuration as per-O-ace-
1a under our optimized conditions, furnishing the de- tylated 1-thio-b-d-galactose 1e and 1-thio-b-d-ribose
sired heteroaromatic thioglycosides 3q–t in yields 1f gave the corresponding products 4a–c in good to
ranging from 88 to 95% (entries 16–19). In addition, excellent yields (76–99%). The coupling procedure is
the reaction was found to proceed successfully when not limited only to thiols with the anomeric b configu-
heterocyclic halides were used, such as 3-iodoquino- ration, but also works successfully with thiols of the
lone 2u and 3-iodochromone 2v leading to glycosylat- a configuration (Scheme 2, 4). Moreover, there were
ed products 3u and 3v in excellent yields (entries 20 no significant reactivity differences between a- and b-
and 21).
anomers, as similar yields were obtained from the
In a further set of experiments, we investigated the coupling of b-benzylated thioglucopyranose 1b and a-
scope and generality of the method for a range of benzylated thioglucopyranose 1d with 4-iodoaceto-
mono- and dithiosaccharides 1a–g (Figure 1).
phenone (78% and 81% yields, respectively).
As depicted in Scheme 2, coupling reactions pro-
Importantly, there is no significant impact of pro-
ceeded cleanly in high yields without any significant tecting groups on the reactivity of the thiosugar deriv-
side reaction such as anomerization of the resulting atives since benzyl-protected carbohydrate 1b reacts
arylthioglycosides. The reaction seems to be general similarly as the O-acetylated derivative 1a furnishing
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Table 2. Palladium-catalyzed coupling of b-thioglucose 1a with (hetero)aryl halides 2.[a]
Entry
G
b-Arylthioglycosides Yield
(3)
Entry
E
b-Arylthioglycosides
(3)
Yield
[%][b]
[%][b]
1
2
3
99
12
13
14
84
90
87
90
99
4
98
15
72
5
6
98
91
16
17
84
88
7
8
9
61
86
98
18
19
20
88
95
88
10
96
95
21
22
89
86
11
[a]
Reactions of 1a (0.375 mol) with (hetero)aryl haldies 2 (0.25 mmol) were performed in a sealed Schlenk tube at 1008C
for 1 h in dioxane (1.5 mL) in the presence of Pd
Yield of isolated product.
ACHTUNGTRENN(NUG OAc)2 (5 mol%), Xantphos (2.5 mol%), and Et3N (0.25 mmol).
[b]
the coupling product 4d in a good 78% yield. More furnished exclusively b-anomer 4f in a good yield
interestingly, coupling of unprotected b-d-thioglucose (66%, Scheme 2) without any significant side product
1c with 4- iodoanisole under our optimized conditions resulting from O-arylation under Pd-catalysis.[15] A lit-
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Palladium-Catalyzed Cross-Coupling Reaction of Thioglycosides with (Hetero)aryl Halides
(isoCA-4),[16] and phenstatin,[17] two highly promising
cytotoxic and antitubulin agents, were each selectively
thioglycosylated with 1-thio-b-d-galactose 1e under
our optimized conditions. The couplings furnished b-
thioglycosides 7 and 8 with excellent efficiency (yields
up to 97%). In addition, subjection of 6-iodocarbox-
AHCTUNGTREGaNNUN mide quinolinone 9 to 1a under our protocol similar-
ly resulted in the rapid preparation of the thioglyco-
side 10 analogue of 6BrCaQ, a potent hsp90 inhibitor
developed in our group.[18] In the context of drug dis-
covery, this strategy offers the potential for rapid test-
ing of thioglycosylated analogues for biological activi-
ty from a single late-stage synthetic product.
Figure 1. Thiosaccharides 1a–g used in this study
Finally, the synthetic potential of this protocol was
well illustrated by the preparation of 4-methyl-7-thio-
erature search did not uncover any other metal-cata- umbelliferyl-b-d-cellobioside (MUS-CB),[19] a fluores-
lyzed coupling of a free thioglucose nucleophile with cent non-hydrolyzable substrate analogue for cellu-
C
G
ACHTUNGTRENNUNG
peracetylated b-d-disaccharides 1h derived from d- our optimized conditions to give acetylated MUS-CB
cellobiose octaacetate. The exclusive 1,2-trans b-thio- 12 in an excellent 87% yield with exclusive b-selectiv-
glycoside 4g was obtained in 77% yield within 1 h and ity (Scheme 4). Further deprotection of acetoxy
the stereochemistry of the 1!4’ glycosidic bond re- groups[19] furnished MUS-CB in 75% yield.
mained intact.As depicted in Scheme 2, coupling reac-
tions proceeded cleanly in high yields without any sig-
nificant side reaction such as anomerization of the re- Conclusions
sulting arylthioglycosides. Ultimately, a major benefit
of our thioglycosylation procedure its amenability to In conclusion, we have developed a general and selec-
late-stage synthetic applications. To demonstrate this tive method for the thioglycosylation of highly func-
potential, biologically active molecules were subjected tionalized (hetero)aryl halides. To the best of our
2
ꢀ
to our coupling protocol to obtain their thioglycoside knowledge the C
G
analogues (Scheme 3). For instance, compounds 5 and first time, directly by using thioglycosides as a nucleo-
6 which are analogues of isocombretastatin A-4 phile partner in the presence of commercially avail-
Scheme 2. Palladium-catalyzed coupling of various thiosaccharides 1a–g with aryl iodides 2a.
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Etienne Brachet et al.
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Scheme 3. Direct thioglycosylation of biologically active molecules.
Scheme 4. Synthesis of 4-methyl-7-thioumbelliferyl-b-d-cellobioside (MUS-CB).
able Pd
optimized reaction conditions allow us to prepare
thiosugar-based derivatives that accommodate
a wider combination of aglycone groups (e.g., aryl,
heteroaryl, heterocyclic) at the sulfur atom of the
sugar moiety. The value of this transformation has
been highlighted via the thioglycosylation of biologi-
cally active molecules. We expect this simple and gen-
eral protocol to be of broad utility for the synthesis
and development of new medicinal agents.
ACHTUNGTRENNUNG(OAc)2/Xantphos as the catalyst system. Our
High resolution mass spectra (HR-MS) were recorded on
a Bruker MicroTOF spectrometer, using ESI with methanol
as the carrier solvent. Nominal and exact m/z values are re-
ported in Daltons. (Hetero)aryl halides are commercially
available. Thiosaccharides 1a–f[21–23] were synthesized as ac-
cording to literature protocols.
G
3
Analytical Data for Thioglycosides 1a–g
Compound 1a:[21] (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-
mercaptotetrahydro-2H-pyran-3,4,5-triyl
triacetate:
1H NMR (300 MHz, CDCl3): d=5.13 (dt, J=19.2, 9.3 Hz,
2H), 4.96 (t, J=9.4 Hz, 1H), 4.54 (t, J=9.8 Hz, 1H), 4.24
(dd, J=12.5, 4.8 Hz, 1H), 4.11 (dd, J=12.4, 2.0 Hz, 1H),
3.71 (ddd, J=9.8, 4.7, 2.0 Hz, 1H), 2.30 (d, J=9.9 Hz, 1H),
2.08 (s, 3H), 2.07 (s, 3H), 2.01 (s, 3H), 1.99 (s, 3H).
Experimental Section
General Experimental Methods
The compounds were all identified by usual physical meth-
Compound 1b:[22] (2S,3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-
6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-thiol: H NMR
1
1
1
ods, e.g., H NMR, 13C NMR (J-MOD), IR, MS (ESI). H
and 13C NMR spectra were measured in CDCl3 or DMSO-d6
with a Bruker Avance-300. H chemical shifts are reported
(200 MHz, CDCl3): d=7.44–7.09 (m, 20H), 5.03–4.76 (m,
5H), 4.64–4.44 (m, 4H), 3.76–3.60 (m, 3H), 3.54–3.37 (m,
2H), 2.31 (d, J=8.0 Hz, 1H).
1
in ppm from an internal standard TMS or of residual chloro-
form (7.27 ppm). 13C chemical shifts are reported in ppm
from the central peak of deuteriochloroform (77.14). IR
spectra were measured on a Bruker Vector 22 spectropho-
tometer. MS were recorded on a Micromass spectrometer.
Analytical TLC was performed on Merck precoated silica
gel 60F plates. Merck silica gel 60 (0.015–0.040 mm) was
used for column chromatography. Melting points were re-
corded on a Bꢃchi B-450 apparatus and are uncorrected.
Compound 1c:[21] (2R,3S,4S,5R,6S)-2-(hydroxymethyl)-6-
mercaptotetrahydro-2H-pyran-3,4,5-triol:
1H NMR
(300 MHz, methanol-d4): d=3.28 (m, 4H), 3.64(dd, J=12.0,
5.1 Hz, 1H), 3.84 (dd, J=12.1, 1.8 Hz, 1H), 4.41 (d,J=
9.3 Hz, 1H).
Compound 1d:[22] (2R,3R,4S,5R,6R)-3,4,5-tris(benzyloxy)-
1
6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-thiol: H NMR
(200 MHz, CDCl3): d=7.45–7.00 (m, 20H), 5.71 (t, J=
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Palladium-Catalyzed Cross-Coupling Reaction of Thioglycosides with (Hetero)aryl Halides
4.7 Hz, 1H), 4.94–4.38 (m, 9H), 4.22–4.10 (m, 1H), 3.90–
3.45 (m, 4H), 1.85 (d, J=4.7 Hz, 1H).
(1.5 mL) was added through the septum. The septum was re-
placed with a teflon screwcap. The Schlenk tube was sealed,
and the mixture was stirred at 1008C for 1 h. The resulting
suspension was cooled to room temperature and filtered
through celite eluting with ethyl acetate. The filtrate was
concentrated and purification of the residue by silica gel
column chromatography gave the desired product 3.
Compound 1e:[21] Compound 1e: (2R,3S,4S,5R,6S)-2-(ace-
toxymethyl)-6-mercaptotetrahydro-2H-pyran-3,4,5-triyl tria-
1
cetate: H NMR (300 MHz, CDCl3): d=5.42 (d, J=3.3 Hz,
1H), 5.17 (t, J=9.8 Hz, 1H), 5.00 (dd, J=10.1, 3.4 Hz, 1H),
4.52 (t, J=9.8 Hz, 1H), 4.11 (d, J=6.7 Hz, 2H), 3.93 (t, J=
6.5 Hz, 1H), 2.36 (d, J=9.9 Hz, 1H), 2.15 (s, 3H), 2.08 (s,
3H), 2.04 (s, 3H), 1.97 (s, 3H).
Compound 1f:[23] This substrate is not enough stable for
its characterization and was used immediately after its prep-
aration.
Analytical Data for Arylthioglycosides 3
Compound 3a: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-[(4-
methoxyphenyl)thio]tetrahydro-2H-pyran-3,4,5-triyl triace-
tate: Rf =0.3 (cyclohexane/AcOEt, 5:5); white-yellow solid;
mp 76–788C; [a]D24: +47.0 (c 1.0, CHCl3); 1H NMR
(300 MHz, CDCl3): d=7.42 (d, J=8.9 Hz, 2H), 6.82 (d, J=
8.9 Hz, 2H), 5.18 (t, J=9.4 Hz, 1H), 4.97 (t, J=9.8 Hz, 1H),
4.86 (t, J=9.6 Hz, 1H), 4.54 (d, J=10.0 Hz, 1H), 4.30–4.06
(m, 2H), 3.79 (s, 3H), 3.72–3.60 (m, 1H), 2.08 (s, 3H), 2.05
(s, 3H), 1.98 (s, 3H), 1.96 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=170.63 (C=O), 170.27 (C=O), 169.46 (C=O),
169.32 (C=O), 160.55 (C), 136.63 (2CH), 120.96 (C), 114.51
(2CH), 85.77 (CH), 75.84 (CH), 74.18 (CH), 70.00 (CH),
68.30 (CH), 62.18 (CH2), 55.43 (CH), 20.89 (CH3), 20.84
(CH3), 20.68 (2CH3); IR (neat): n=3457, 3361, 3262, 3193,
Preparation of (2S,3S,4R,5S,6R)-2-(Acetoxymethyl)-
6-{[(2R,3R,4S,5R,6S)-4,5-diacetoxy-2-(acetoxymeth-
yl)-6-mercaptotetrahydro-2H-pyran-3-yl]oxy}tetra-
hydro-2H-pyran-3,4,5-triyl Triacetate (1g)
Thiourea (5.5 g, 72.0 mmol, 1.5 equiv.) and 2,3,6,2’,3’,4’,6’-
hepta-O-acetyl-a-cellobiosyl
bromide[19]
(48.0 mmol,
1 equiv.) were dissolved in acetone (100 mL) under Ar. The
reaction mixture was heated to 608C. After 2 h, a white
solid precipitated. This was removed by filtration and the fil-
trate returned to reflux. This process was repeated until the
solid ceased to precipitate. (If the product does not precipi-
tate after 4 h stirring, acetone was removed under vacuum).
The solid 2,3,6,2’,3’,4’,6’-hepta-O-acetyl-a-cellobiosyl 1-iso-
thiouronium bromide (22.6 mmol, 1 equiv.) formed and
Na2S2O5 (6.0 g, 31.7 mmol, 1.4 equiv.) were added to a stirred
mixture of DCM (100 mL) and H2O (50 mL). The reaction
mixture was heated to reflux under Ar. After 3 h, T.L.C.
(cyclohexane/ethyl acetate; 1:1) indicated the formation of
product (Rf 0.5) with complete consumption of the starting
material (Rf 0.0). The reaction mixture was cooled to room
temperature and the phases separated. The aqueous layer
was re-extracted with DCM (2ꢄ100 mL), dried over
MgSO4, filtered and concentrated under vacuum to afford
1g as a white crystalline solid; yield: 22.6 mmol (100%).
Rf =0.5 (cyclohexane/AcOEt, 5:5); white-yellow solid; mp
195–1978C; [a]D24: ꢀ103.0 (c 1.0, CHCl3); 1H NMR
(300 MHz, CDCl3): d=5.42 (d, J=3.3 Hz, 1H), 5.17 (t, J=
9.8 Hz, 1H), 5.00 (dd, J=10.1, 3.4 Hz, 1H), 4.52 (t, J=
9.8 Hz, 1H), 4.11 (d, J=6.7 Hz, 2H), 3.93 (t, J=6.5 Hz,
1H), 2.36 (d, J=9.9 Hz, 1H), 2.15 (s, 3H), 2.08 (s, 3H), 2.04
(s, 3H), 1.97 (s, 3H); 13C NMR (75 MHz, CDCl3): d=
2358, 2216, 2219, 1755, 1739, 1711, 1592, 1246, 1175 cmꢀ1
;
HR-MS (ESI): m/z= 493.1128, calcd. for C21H26NaO10S;
493.1139.
Compound 3b: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-
(phenylthio)tetrahydro-2H-pyran-3,4,5-triyl triacetate: Rf =
0.36 (cyclohexane:AcOEt, 7:3); white-yellow solid; mp 112–
1148C; [a]2D4: ꢀ16.0 (c 1.0, CHCl3); 1H NMR (300 MHz,
CDCl3): d=7.45–7.41 (m, 2H), 7.31–7.18 (m, 3H), 5.16 (t,
J=9.3 Hz, 1H), 4.94 (dt, J=19.3, 9.6 Hz, 2H), 4.65 (d, J=
10.1 Hz, 1H), 4.16 (dd, J=12.6, 5.2 Hz, 1H), 4.11 (dd, J=
12.5, 2.9 Hz, 1H), 3.66 (ddd, J = 10.0, 4.9, 2.8 Hz, 1H), 2.01
(s, 3H), 2.01 (s, 3H), 1.95 (s, 3H), 1.92 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=170.57 (C=O), 170.19 (C=O), 169.43
(C=O), 169.28 (C=O), 133.17 (2CH), 131.71 (C), 128.99
(2CH), 128.46 (CH), 85.76 (CH), 75.86 (CH), 74.03 (CH),
70.02 (CH), 68.30 (CH), 62.20 (CH2), 20.77 (2CH3), 20.62
(2CH3); IR (neat): n=3448, 3236, 2355, 2198, 1999, 1753,
1741, 1482, 1366, 1250, 1090 cmꢀ1.
Compound 3c: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-({3-
[(tert-butyldimethylsilyl)oxy]-4-methoxyphenyl}thio)tetrahy-
dro-2H-pyran-3,4,5-triyl triacetate: Rf =0.57 (cyclohex-
170.61ACHTUNGTRENNUNG(C=O), 170.44 (C=O), 170.33 (C=O), 170.00 (C=O),
169.80 (C=O), 169.44 (C=O), 169.21 (C=O), 100.94 (CH),
78.62 (CH), 77.33 (CH), 76.40 (CH), 73.89 (CH), 73.32
(CH), 73.03 (CH), 72.12 (CH), 71.70 (CH), 67.87 (CH),
62.22 (CH2), 61.67 (CH2), 21.00 (CH3), 20.86 (CH3), 20.79
(CH3), 20.66 (4CH3); IR (neat): n=3414, 3392, 3293, 3216,
2216, 2146, 2033, 1964, 1734, 1367, 1210, 1034 cmꢀ1; MS
(APCI+): m/z=653.0 [M+H]+.
A
1H NMR (300 MHz, CDCl3): d=7.04 (dd, J=8.3, 2.2 Hz,
1H), 6.98 (d, J=2.2 Hz, 1H), 6.75 (d, J=8.4 Hz, 1H), 5.17
(t, J=9.3 Hz, 1H), 4.99 (t, J=9.8 Hz, 1H), 4.94–4.82 (m,
1H), 4.56 (d, J=10.1 Hz, 1H), 4.20 (dd, J=12.3, 4.9 Hz,
1H), 4.09 (dd, J=12.3, 2.4 Hz, 1H), 3.77 (s, 3H), 3.64 (ddd,
J=10.0, 4.8, 2.4 Hz, 1H), 2.06 (s, 3H), 2.04 (s, 3H), 1.97 (s,
3H), 1.95 (s, 3H), 0.96 (s, 9H), 0.13 (d, J=2.0 Hz, 6H);
13C NMR (75 MHz, CDCl3): d=170.65 (C=O), 170.24 (C=
O), 169.41 (C=O), 169.22 (C=O), 152.05 (C), 145.02 (C),
128.36 (CH), 127.00 (CH), 121.40 (C), 112.07 (CH), 86.20
(CH), 75.84 (CH), 74.11 (CH), 70.01 (CH), 68.21 (CH),
62.14 (CH2), 55.48 (CH), 25.73 (CH3), 20.83 (CH3), 20.78
(CH3), 20.64 (2CH3), 18.48, ꢀ4.57 (2CH3); IR (neat): 3474,
3260, 3174, 2194, 2013, 1991, 1756, 1502, 1442, 1304, 1271,
1137, 1029, 949 cmꢀ1.
General Procedure for Palladium-Catalyzed Coupling
of b-Thioglucose 1a with (Hetero)aryl Halides 2
A flame-dried resealable Schlenk tube was charged with
PdACHTUNGTRENNUNG(OAc)2 (5 mol%), Xantphos (2.5 mol%), thiosugar
1 (0.375 mmol), (hetero)aryl halide 2 (0.25 mmol), and Et3N
(0.25 mmol). The Schlenk tube was capped with a rubber
septum, evacuated and backfilled with argon; then, dioxane
Adv. Synth. Catal. 2013, 355, 477 – 490
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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483

Etienne Brachet et al.
FULL PAPERS
Compound 3d: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-
[(4-aminophenyl)thio]tetrahydro-2H-pyran-3,4,5-triyl triace-
tate: Rf =0.27 (cyclohexane/AcOEt, 5:5); white-yellow
solid; mp 73–758C; [a]2D4: ꢀ14.0 (c 1.0, CHCl3); 1H NMR
(300 MHz, CDCl3): d=7.29 (d, J=8.6 Hz, 2H), 6.62 (d, J=
8.6 Hz, 2H), 5.18 (t, J=9.3 Hz, 1H), 4.98 (t, J=9.8 Hz, 1H),
4.93–4.76 (m, 1H), 4.51 (d, J=10.0 Hz, 1H), 4.25–4.09 (m,
2H), 3.70–3.59 (m, 1H), 3.34 (brs, NH2), 2.09 (s, 3H), 2.07
(s, 3H), 2.00 (s, 3H), 1.97 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=170.76 (C=O), 170.36 (C=O), 169.54 (C=O),
169.41 (C=O), 145.33 (C), 136.59 (2CH), 119.84 (C), 116.47
(2CH), 86.02 (CH), 75.87 (CH), 74.26 (CH), 70.05 (CH),
68.37 (CH), 62.26 (CH2), 20.94 (2CH3), 20.72 (2CH3); IR
(neat): n=3462, 3403, 3303, 3267, 2383, 2193, 1984, 1755,
1741, 1709, 1645, 1598, 1566, 1550, 1499, 1428, 1366, 1207,
130.51 (CH), 128.54 (CH), 126.70 (CH), 86.51 (CH), 75.81
(CH), 74.08 (CH), 70.30 (CH), 68.45 (CH), 62.36 (CH2),
21.01 (CH3), 20.79 (2CH3), 20.68 (2CH3); IR (neat): n=
3458, 3399, 3351, 3138, 2372, 2185, 2127, 2008, 1971, 1755,
1746, 1435, 1366, 1247, 1366, 1090 cmꢀ1; HR-MS (ESI):
m/z=477.1190, calcd. for C21H26NaO9S: 477.1190.
Compound 3h: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-
[(4-nitrophenyl)thio]tetrahydro-2H-pyran-3,4,5-triyl triace-
tate: Rf =0.71 (cyclohexane/AcOEt, 5:5); yellow solid; mp
1
180–1828C; [a]2D4: ꢀ63.0 (c 1.0, CHCl3); H NMR (300 MHz,
CDCl3): d=8.14 (d, J=9.0 Hz, 2H), 7.58 (d, J=9.0 Hz, 2H),
5.32–5.20 (m, 1H), 5.08 (d, J=9.3 Hz, 1H), 5.02 (d, J=
9.1 Hz, 1H), 4.86 (d, J=10.1 Hz, 1H), 4.34–4.12 (m, 2H),
3.93–3.59 (m, 1H), 2.09 (s, 3H), 2.07 (s, 3H), 2.03 (s, 3H),
1.99 (s, 3H); 13C NMR (75 MHz, CDCl3): d=170.49 (C=O),
170.13 (C=O), 169.42 (C=O), 169.29 (C=O), 147.17 (C),
141.79 (C), 131.16 (2CH), 123.98 (2CH), 84.46 (CH), 76.24
(CH), 73.73 (CH), 69.73 (CH), 68.14 (CH), 62.18 (CH2),
20.84 (CH3), 20.75 (CH3), 20.65 (2CH3); IR (neat): n=3475,
3453, 3346, 2275, 2219, 2187, 2047, 1752, 1717, 1698, 1685,
1651, 1558, 1542, 1476, 1375, 1342 cmꢀ1; HR-MS (ESI):
m/z=508.0860, calcd. for C20H23NNaO11S: 508.0884.
1092 cmꢀ1
;
HR-MS (ESI): m/z=478.1128, calcd. for
C20H25NNaO9S: 478.1142.
Compound 3e: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-[(3-
hydroxyphenyl)thio]tetrahydro-2H-pyran-3,4,5-triyl triace-
tate: Rf =0.14 (DCM/AcOEt, 95:5); white-yellow solid; mp
1
120–1228C; [a]2D4: ꢀ10.0 (c 1.0, CHCl3); H NMR (300 MHz,
CDCl3): d=7.15 (t, J=7.8 Hz, 1H), 7.05–6.94 (m, 2H),
6.85–6.73 (m, 1H), 6.34 (brs, OH), 5.22 (t, J=9.3 Hz, 1H),
5.00 (dt, J=19.4, 9.8 Hz, 2H), 4.70 (d, J=10.1 Hz, 1H),
4.30–4.17 (m, 2H), 3.80–3.63 (m, 1H), 2.09 (s, 3H), 2.07 (s,
3H), 2.01 (s, 3H), 1.98 (s, 3H); 13C NMR (75 MHz, CDCl3):
d=171.33 (C=O), 170.43 (C=O), 169.63 (2C=O), 156.26
(C), 132.57 (C), 129.96 (CH), 124.91 (CH), 120.14 (CH),
115.81 (CH), 85.39 (CH), 75.93 (CH), 74.11 (CH), 70.10
(CH), 68.43 (CH), 62.29 (CH2), 20.86 (2CH3), 20.69 (2CH3);
IR (neat): n=3346, 2247, 2182, 2165, 1982, 1755, 1581, 1477,
1441, 1366, 1251, 1092, 1034 cmꢀ1; HR-MS (ESI): m/z=
479.0989, calcd. for C20H24NaO10S: 479.0982.
Compound 3i: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-[(4-
formylphenyl)thio]tetrahydro-2H-pyran-3,4,5-triyl triacetate:
Rf =0.17 (cyclohexane/AcOEt, 7:3); white-yellow solid; mp
1
110–1128C; [a]24: +37.0 (c 1.0, CHCl3); H NMR (300 MHz,
CDCl3): d=9.9D8 (s, 1H), 7.80 (d, J=8.1 Hz, 2H), 7.58 (d,
J=8.2 Hz, 2H), 5.26 (t, J=9.3 Hz, 1H), 5.05 (td, J=9.5,
7.0 Hz, 2H), 4.86 (d, J=10.1 Hz, 1H), 4.24 (dd, J=12.4,
5.3 Hz, 1H), 4.18 (dd, J=12.3, 2.4 Hz, 1H), 3.90–3.65 (m,
1H), 2.08 (s, 3H), 2.06 (s, 3H), 2.02 (s, 3H), 1.99 (s, 3H);
13C NMR (75 MHz, CDCl3): d=191.29 (CHO), 170.54 (C=
O), 170.17 (C=O), 169.44 (C=O), 169.30 (C=O), 141.04 (C),
135.39 (C), 131.00 (2CH), 130.06 (2CH), 84.74 (CH), 76.14
(CH), 73.84 (CH), 69.83 (CH), 68.24 (CH), 62.25 (CH2),
20.84 (CH3), 20.77 (CH3), 20.66 (2CH3); IR (neat): n=3435,
3217, 2212, 2142, 2001, 1755, 1700, 1592, 1367, 1212, 1089,
Compound 3f: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-[(2-
methoxyphenyl)thio]tetrahydro-2H-pyran-3,4,5-triyl triace-
tate: Rf =0.27 (cyclohexane/AcOEt, 7:3); white-yellow solid;
mp 117–1198C; [a]D24: +5.0 (c 1.0, CHCl3); 1H NMR
(300 MHz, CDCl3): d=7.46 (dd, J=7.7, 1.4 Hz, 1H), 7.34–
7.21 (m, 1H), 6.98–6.78 (m, 2H), 5.22 (t, J=9.3 Hz, 1H),
5.05(t, J=8.9 Hz, 1H), 4.99 (t, J=8.9 Hz, 1H), 4.79 (d, J=
10.0 Hz, 1H), 4.21 (dd, J=12.3, 5.2 Hz, 1H), 4.12 (dd, J=
12.2, 2.3 Hz, 1H), 3.84 (s, 3H), 3.77–3.62 (m, 1H), 2.05 (s,
3H), 2.04 (s, 3H), 2.01 (s, 3H), 1.98 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=170.66 (C=O), 170.32 (C=O), 169.47
(C=O), 169.38 (C=O), 158.59 (C), 133.74 (CH), 129.72
(CH), 121.15 (CH), 120.14 (C), 111.16 (CH), 84.41 (CH),
75.87 (CH), 74.25 (CH), 70.26 (CH), 68.44 (CH), 62.36
(CH2), 55.87 (CH), 20.81 (2CH3), 20.70 (2CH3); IR (neat):
n=3321, 2357, 2330, 2208, 2169, 2046, 2000, 1984, 1754,
1581, 1480, 1432, 1366, 1214, 1039 cmꢀ1; HR-MS (ESI): m/
z=493.1143, calcd. for C21H26NaO10S: 493.1139.
Compound 3g: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-(o-
tolylthio)tetrahydro-2H-pyran-3,4,5-triyl triacetate: Rf =0.42
(cyclohexane/AcOEt, 6:4); white-yellow solid; mp 102–
1048C; [a]2D4: ꢀ15.0 (c 1.0, CHCl3); 1H NMR (300 MHz,
CDCl3): d=7.51 (d, J=7.4 Hz, 1H), 7.24–7.08 (m, 3H), 5.23
(dd, J=19.8, 10.5 Hz, 1H), 5.11–4.96 (m, 2H), 4.67 (d, J=
10.1 Hz, 1H), 4.21 (dd, J=12.3, 5.5 Hz, 1H), 4.12 (dd, J=
12.3, 2.5 Hz, 1H), 3.72–3.59 (m, 1H), 2.39 (s, 3H), 2.07 (s,
3H), 2.05 (s, 3H), 2.00 (s, 3H), 1.99 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=170.60 (C=O), 170.24 (C=O), 169.46
(C=O), 169.36 (C=O), 140.55 (C), 133.29 (CH), 132.00 (C),
1039 cmꢀ1
;
HR-MS (ESI): m/z=491.0973, calcd. for
C21H24NaO10S: 491.0982.
Compound 3j: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-{[4-
(ethoxycarbonyl)phenyl]thio}tetrahydro-2H-pyran-3,4,5-triyl
triacetate: Rf =0.58 (cyclohexane/AcOEt, 5:5); white-yellow
1
solid; mp 112–1148C; [a]2D4: +43.0 (c 1.0, CHCl3); H NMR
(300 MHz, CDCl3): d=7.94 (d, J=8.6 Hz, 2H), 7.48 (d, J=
8.6 Hz, 2H), 5.23 (t, J=9.3 Hz, 1H), 5.10–4.90 (m, 2H), 4.80
(d, J=10.0 Hz, 1H), 4.35 (q, J=7.1 Hz, 2H), 4.22 (dd, J=
12.3, 5.2 Hz, 1H), 4.15 (dd, J=12.3, 2.5 Hz, 1H), 3.76 (ddd,
J=9.9, 5.1, 2.6 Hz, 1H), 2.06 (s, 3H), 2.05 (s, 3H), 2.00 (s,
3H), 1.97 (s, 3H), 1.36 (t, J=7.1 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d=170.54 (C=O), 170.14 (C=O), 169.40
(C=O), 169.25 (C=O), 166.01 (C=O), 138.42 (C), 131.08
(2CH), 130.00 (2CH), 129.89 (C), 85.00 (CH), 76.03 (CH),
73.88 (CH), 69.89 (CH), 68.24 (CH), 62.20 (CH2), 61.21
(CH2), 20.78 (CH3), 20.75 (CH3), 20.62 (2CH3), 14.38 (CH3);
IR (neat): n=3380, 3341, 3324, 3099, 2337, 2273, 2169, 2104,
2016, 1757, 1716, 1216, 1040 cmꢀ1; HR-MS (ESI): m/z=
535.1246, calcd. for C23H28NaO11S: 535.1245.
Compound 3k: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-{[2-
(ethoxycarbonyl)phenyl]thio}tetrahydro-2H-pyran-3,4,5-triyl
triacetate: Rf =0.29 (cyclohexane/AcOEt, 7:3); white-yellow
1
solid; mp 120–1228C; [a]2D4: ꢀ53.0 (c 1.0, CHCl3); H NMR
(300 MHz, CDCl3): d=7.86 (d, J=7.8 Hz, 1H), 7.56 (d, J=
484
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Adv. Synth. Catal. 2013, 355, 477 – 490

Palladium-Catalyzed Cross-Coupling Reaction of Thioglycosides with (Hetero)aryl Halides
8.1 Hz, 1H), 7.41 (t, J=7.7 Hz, 1H), 7.26 (t, J=7.5 Hz, 1H),
5.26 (t, J=8.8 Hz, 1H), 5.15–5.03 (m, 2H), 4.87 (d, J=
10.1 Hz, 1H), 4.40–4.27 (m, 2H), 4.26–4.08 (m, 2H), 3.86–
3.73 (m, 1H), 2.05 (s, 3H), 2.01 (s, 3H), 2.00 (s, 3H), 1.98 (s,
3H), 1.36 (t, J=7.1 Hz, 3H); 13C NMR (75 MHz, CDCl3):
136.63 (C), 134.54 (2CH), 132.97 (2CH), 131.47 (2CH),
130.57 (C), 126.37 (C), 122.53 (2CH), 85.85 (CH), 76.41
(CH), 74.57 (CH), 70.93 (CH), 69.34 (CH), 63.07 (CH2),
20.81 (2CH3), 20.68 (CH3), 20.63 (CH3); IR (neat): n=3477,
3452, 3259, 2407, 2328, 2212, 2146, 2110, 2025, 2007, 1952,
d=170.54 (C=O), 170.20 (C=O), 169.44 (C=O), 169.18 (C= 1755, 1626, 1583, 1488, 1367, 1248, 1217, 1039 cmꢀ1; HR-MS
O), 166.44 (C=O), 136.72 (C), 132.18 (CH), 131.11 (C),
130.79 (CH), 129.13 (CH), 126.32 (CH), 84.46 (CH), 75.81
(CH), 74.07 (CH), 69.88 (CH), 68.43 (CH), 62.44 (CH2),
61.48 (CH2), 20.77 (CH3), 20.69 (CH3), 20.65 (2CH3), 14.31
(CH3); IR (neat): n=3386, 2370, 2342, 2208, 2153, 2044,
2029, 1752, 1708, 1467, 1367, 1290, 1251, 1213, 1110,
(ESI): m/z= 622.0741,calcd. for C27H29BrNO9S: 622.0741.
Compound 3o: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-{[4-
(1-{2-tosylhydrazono}ethyl)phenyl]thio}tetrahydro-2H-
pyran-3,4,5-triyl triacetate: Rf =0.12 (cyclohexane/AcOEt,
7:3); white-yellow solid; mp 204–2068C; [a]2D4: +30.0 (c 1.0,
1
CHCl3); H NMR (300 MHz, CDCl3): d=8.34 (s, 1H), 7.88
1039 cmꢀ1
;
HR-MS (ESI): m/z=535.1258, calcd. for
(d, J=8.3 Hz, 2H), 7.55 (d, J=8.5 Hz, 2H), 7.41 (d, J=
8.5 Hz, 2H), 7.29 (d, J=8.1 Hz, 2H), 5.22 (t, J=9.3 Hz,
1H), 5.07–4.89 (m, 2H), 4.71 (d, J=10.1 Hz, 1H), 4.21 (dd,
J=12.3, 5.0 Hz, 1H), 4.15 (dd, J=12.3, 2.5 Hz, 1H), 3.73
(m, 1H), 2.38 (s, 3H), 2.05 (s, 3H), 2.04 (s, 6H), 2.00 (s,
3H), 1.96 (s, 3H); 13C NMR (75 MHz, CDCl3): d=170.53
(C=O), 170.11 (C=O), 169.39 (C=O), 169.26 (C=O), 151.52
(C=N), 144.17 (C), 137.17 (C), 135.46 (C), 133.40 (C), 132.30
(2CH), 129.62 (2CH), 128.02 (2CH), 126.65 (2CH), 85.29
(CH), 75.81 (CH), 73.84 (CH), 69.90 (CH), 68.17 (CH),
62.12 (CH2), 21.58 (CH3), 20.71 (2CH3), 20.55 (2CH3), 13.39
(CH3); IR (neat): n=3468, 3381, 3332, 3131, 2169, 1755,
C23H28NaO11S: 535.1245.
Compound 3l: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-[(4-
acetylphenyl)thio]tetrahydro-2H-pyran-3,4,5-triyl triacetate:
Rf =0.42 (cyclohexane/AcOEt, 5:5); white-yellow solid; mp
1
129–1318C; [a]2D4: +54.0 (c 1.0, CHCl3); H NMR (300 MHz,
CDCl3): d=7.86 (d, J=8.3 Hz, 2H), 7.51 (d, J=8.3 Hz, 2H),
5.24 (t, J=9.3 Hz, 1H), 5.03 (dt, J=19.3, 9.6 Hz, 2H), 4.82
(d, J=10.0 Hz, 1H), 4.23 (dd, J=12.4, 5.2 Hz, 1H), 4.16 (dd,
J=12.3, 2.4 Hz, 1H), 3.78 (ddd, J=10.0, 5.1, 2.5 Hz, 1H),
2.57 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H), 2.01 (s, 3H), 1.98 (s,
3H); 13C NMR (75 MHz, CDCl3): d=197.18 (C=O), 170.53
(C=O), 170.14 (C=O), 169.42 (C=O), 169.27 (C=O), 138.89
(C), 136.28 (C), 131.16 (2CH), 128.79 (2CH), 84.87 (CH),
76.06 (CH), 73.87 (CH), 69.86 (CH), 68.23 (CH), 62.20
(CH2), 26.64 (CH3), 20.81 (CH3), 20.76 (CH3), 20.64 (2CH3);
IR (neat): n=3425, 3314, 3285, 3177, 3098, 3035, 2514, 1755,
1682, 1368, 1214, 1039 cmꢀ1; HR-MS (ESI): m/z=505.1139,
calcd. for C22H26NaO10S: 505.1132.
1710, 1596, 1494, 1366, 1307, 1249, 1211, 1167, 1085 cmꢀ1
;
HR-MS (ESI): m/z=651.1674, calcd. for C29H35N2O11S2:
651.1677.
Compound 3p: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-{[4-
(morpholine-4-carbonyl)phenyl]thio}tetrahydro-2H-pyran-
3,4,5-triyl triacetate: Rf =0.45 (AcOEt); white-yellow solid;
mp 101–1038C; [a]D24: ꢀ17.0 (c 1.0, CHCl3); 1H NMR
(300 MHz, CDCl3): d=7.53 (d, J=8.1 Hz, 2H), 7.35 (d, J=
8.1 Hz, 2H), 5.23 (t, J=9.3 Hz, 1H), 5.11–4.91 (m, 2H), 4.73
(d, J=10.1 Hz, 1H), 4.34–4.03 (m, 2H), 3.92–3.29 (m, 9H),
2.08 (s, 3H), 2.07 (s, 3H), 2.02 (s, 3H), 1.99 (s, 3H);
13C NMR (75 MHz, CDCl3): d=170.61 (C=O), 170.22 (C=
O), 169.76 (C=O), 169.51 (C=O), 169.32 (C=O), 135.14 (C),
134.46 (C), 132.66 (2CH), 127.83 (2CH), 85.49 (CH), 76.08
(CH), 73.99 (CH), 69.96 (CH), 68.29 (CH), 66.99 (4CH2),
62.24 (1CH2), 20.85 (2CH3), 20.69 (2CH3); IR (neat): n=
3266, 2361, 2154, 1981, 1755, 1740, 1710, 1631, 1596, 1430,
1364, 1280, 1211, 1114 cmꢀ1; HR-MS (ESI): m/z=576.11498,
calcd. for C25H31NNaO11S: 576.1510.
Compound 3m: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-
[(3-bromophenyl)thio]tetrahydro-2H-pyran-3,4,5-triyl triace-
tate: Rf = 0.75 (cyclohexane/AcOEt, 5:5); white-yellow
1
solid; mp = 81–838C; [a]24: ꢀ23.0 (c 1.0, CHCl3); H NMR
(300 MHz, CDCl3): d=7.D64 (t, J=1.7 Hz, 1H), 7.43 (ddd,
J=8.0, 1.9, 1.0 Hz, 1H), 7.47–7.34 (m, J=13.9, 7.8, 1.7,
1.0 Hz, 1H), 7.39 (ddd, J=7.8, 1.6, 1.0 Hz, 1H), 7.16 (t, J=
7.9 Hz, 1H), 5.22 (t, J=9.3 Hz, 1H), 5.02 (t, J=9.8 Hz, 1H),
4.98–4.90 (m, J=10.0, 9.3 Hz, 1H), 4.70 (d, J=10.1 Hz, 1H),
4.29–4.08 (m, 2H), 3.74 (ddd, J=10.0, 5.0, 2.7 Hz, 1H), 2.08
(s, 3H), 2.06 (s, 3H), 2.00 (s, 3H), 1.97 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=170.68 (C=O), 170.16 (C=O), 169.42
(C=O), 169.26 (C=O), 135.30 (CH), 134.01 (C), 131.51
(CH), 131.43 (CH), 130.27 (CH), 122.68 (C), 85.43 (CH),
76.02 (CH), 73.92 (CH), 69.90 (CH), 68.19 (CH), 62.20
(CH2), 20.87 (CH3), 20.77 (CH3), 20.63 (2CH3); IR (neat):
2361, 1755, 1737, 1577, 1559, 1432, 1366, 1246, 1087, 1062,
Compound 3q: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-{[4-
(3-hydroxybut-1-yn-1-yl)phenyl]thio}tetrahydro-2H-pyran-
3,4,5-triyl triacetate: Rf =0.64 (cyclohexane/AcOEt, 5:5);
white-yellow solid; mp 139–1418C; [a]2D4: +45.0 (c 1.0,
1
CHCl3); H NMR (300 MHz, CDCl3): d=7.42 (d, J=8.5 Hz,
1030 cmꢀ1
;
HR-MS (ESI): m/z=541.0121, calcd. for
2H), 7.35 (d, J=8.4 Hz, 2H), 5.22 (t, J=9.3 Hz, 1H), 5.10–
4.88 (m, 2H), 4.80–4.65 (m, 2H), 4.30–4.02 (m, 2H), 3.82–
3.64 (m, 1H), 2.09 (s, 3H), 2.07 (s, 3H), 2.02 (s, 3H), 1.99 (s,
3H), 1.55 (d, J=6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3):
d=170.65 (C=O), 170.27 (C=O), 169.49 (C=O), 169.35 (C=
O), 132.56 (2CH), 132.46 (C), 132.14 (2CH), 122.83 (C),
92.56 (C), 85.53 (CH), 83.39 (C), 76.04 (CH), 74.02 (CH),
70.02 (CH), 68.33 (CH), 62.28 (CH2), 58.99 (CH), 24.49
(CH3), 20.86 (2CH3), 20.70 (2CH3); IR (neat): n=3492,
2245, 2201, 2159, 2122, 1755, 1745, 1491, 1366, 1248, 1209,
1088, 1032 cmꢀ1; HR-MS (ESI): m/z=531.1291, calcd. for
C24H28NaO10S: 531.1295.
C20H23BrNaO9S: 541.0138.
Compound 3n: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-({4-
[(E)-(4-bromobenzylidene)amino]phenyl}thio)tetrahydro-
2H-pyran-3,4,5-triyl triacetate: Rf =0.44 (cyclohexane/
AcOEt, 7:3); white-yellow solid; mp 167–1698C; [a]2D4:
1
ꢀ39.0 (c 1.0, CHCl3); H NMR (300 MHz, acetone): d=8.62
(s, 1H), 7.92 (d, J=8.5 Hz, 2H), 7.72 (d, J=8.4 Hz, 2H),
7.58 (d, J=8.5 Hz, 2H), 7.27 (d, J=8.5 Hz, 2H), 5.34 (t, J=
9.4 Hz, 1H), 5.15–4.85 (m, 3H), 4.24 (dd, J=12.3, 5.4 Hz,
1H), 4.17 (dd, J=12.3, 2.5 Hz, 1H), 4.05 (ddd, J=9.8, 5.4,
2.5 Hz, 1H), 2.05 (s, 6H), 2.00 (s, 3H), 1.94 (s, 3H);
13C NMR (75 MHz, acetone): d=170.77 (C=O), 170.35 (C=
O), 170.12 (C=O), 169.81 (C=O), 160.63 (CH), 152.62 (C),
Compound 3r: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-
(pyridin-4-ylthio)tetrahydro-2H-pyran-3,4,5-triyl triacetate:
Adv. Synth. Catal. 2013, 355, 477 – 490
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
485

Etienne Brachet et al.
FULL PAPERS
Rf =0.10 (cyclohexane/AcOEt, 7:3); white-yellow solid; mp
20.88 (CH3), 20.79 (CH3), 20.66 (2CH3); IR (neat): n=3427,
3340, 3199, 2559, 2368, 2209, 2162, 2032, 1993, 1755, 1367,
1213, 1038 cmꢀ1; HR-MS (ESI): m/z=492.1321, calcd. for
C23H26NO9S: 492.1323.
Compound 3v: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-[(1-
benzyl-4-oxo-1,4-dihydroquinolin-3-yl)thio]tetrahydro-2H-
pyran-3,4,5-triyl triacetate: Rf =0.17 (cyclohexane/AcOEt,
1
135–1378C; [a]24: ꢀ16.0 (c 1.0, CHCl3); H NMR (300 MHz,
CDCl3): d=8.4D8 (brs, 2H), 7.30 (d, J=4.9 Hz, 2H), 5.29 (t,
J=9.2 Hz, 1H), 5.10 (td, J=9.8, 2.9 Hz, 2H), 4.95 (d, J=
10.1 Hz, 1H), 4.25 (dd, J=12.4, 5.5 Hz, 1H), 4.18 (dd, J=
12.4, 2.3 Hz, 1H), 3.97–3.72 (m, 1H), 2.08 (s, 3H), 2.05 (s,
3H), 2.04 (s, 3H), 2.00 (s, 3H); 13C NMR (75 MHz, CDCl3):
d=170.52 (C=O), 170.15 (C=O), 169.45 (C=O), 169.34 (C= 5:5); white-yellow solid; mp 90–928C; [a]2D4: ꢀ30.0 (c 1.0,
O), 149.34 (2CH), 145.58 (C), 123.65 (2CH), 83.70 (CH),
76.21 (CH), 73.73 (CH), 69.74 (CH), 68.25 (CH), 62.29
(CH2), 20.82 (CH3), 20.74 (CH3), 20.68 (2CH3); IR (neat):
n=3449, 2361, 2335, 2150, 1746, 1740, 1575, 1485, 1434,
1409, 1366, 1209, 1089, 1063, 1033 cmꢀ1; HR-MS (ESI):
m/z=442.1151, calcd. for C19H24NO9S: 442.1166.
CHCl3); 1H NMR (300 MHz, CDCl3): d=8.43 (dd, J=8.0,
1.3 Hz, 1H), 8.14 (s, 1H), 7.57–7.46 (m, 1H), 7.39–7.27 (m,
5H), 7.14 (m, 2H), 5.35 (s, 2H), 5.29–5.13 (m, 1H), 5.07–
4.92 (m, 3H), 4.12 (dd, J=12.3, 4.7 Hz, 1H), 4.00 (dd, J=
12.3, 2.2 Hz, 1H), 3.60 (ddd, J=10.0, 4.6, 2.3 Hz, 1H), 2.11
(s, 3H), 1.97 (s, 3H), 1.96 (s, 3H), 1.80 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=176.03 (C=O), 170.52 (C=O), 170.06
(C=O), 169.94 (C=O), 169.50 (C=O), 149.57 (CH), 139.77
(C), 134.91 (C), 132.46 (CH), 129.37 (2CH), 128.57 (CH),
127.54 (CH), 126.70 (C), 126.14 (2CH), 124.65 (CH), 116.35
(CH), 109.46 (C), 82.57 (CH), 75.79 (CH), 74.14 (CH), 70.23
(CH), 68.46 (CH), 61.86 (CH2), 56.70 (CH2), 20.94 (CH3),
20.65 (2CH3), 20.55 (CH3); IR (neat): n=3469, 3354, 3128,
Compound 3s: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-[(3-
nitropyridin-2-yl)thio]tetrahydro-2H-pyran-3,4,5-triyl triace-
tate: Rf =0.25 (cyclohexane/AcOEt, 6:4); white-yellow
1
solid; mp 67–698C; [a]2D4: +113.0 (c 1.0, CHCl3); H NMR
(300 MHz, CDCl3): d=8.69 (dd, J=4.6, 1.6 Hz, 1H), 8.49
(dd, J=8.3, 1.5 Hz, 1H), 7.30 (dd, J=8.3, 4.6 Hz, 1H), 6.03
(d, J=10.3 Hz, 1H), 5.42–5.21 (m, 2H), 5.13 (t, J=9.5 Hz,
1H), 4.19 (dd, J=12.5, 4.6 Hz, 1H), 4.03 (dd, J=12.4,
2.2 Hz, 1H), 3.93–3.82 (m, 1H), 2.00 (s, 3H), 1.99 (s, 3H),
1.98 (s, 3H), 1.97 (s, 3H); 13C NMR (75 MHz, CDCl3): d=
170.49 (C=O), 170.14 (C=O), 169.34 (C=O), 169.22 (C=O),
154.21 (C), 153.05 (CH), 142.30 (C), 133.98 (CH), 120.17
(CH), 79.83 (CH), 75.94 (CH), 74.34 (CH), 68.89 (CH),
68.21 (CH), 61.88 (CH2), 20.64 (2CH3), 20.57 (2CH3); IR
(neat): n=3457, 3410, 3316, 3099, 2264, 2204, 2182, 2040,
2019, 1963, 1755, 1747, 1588, 1559, 1520, 1402, 1367, 1342,
1249, 1214, 1061 cmꢀ1; HR-MS (ESI): m/z=509.0829, calcd.
for C19H22N2NaO11S: 509.0837.
2334, 2196, 1967, 1753, 1622, 1601, 1546, 1487, 1225 cmꢀ1
;
HR-MS (ESI): m/z=620.1562, calcd. for C30H31NNaO10S:
620.1566.
Compound 3w: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-
[(4-phenyl-2H-chromen-3-yl)thio]tetrahydro-2H-pyran-3,4,5-
triyl triacetate: Rf =0.35 (cyclohexane/AcOEt, 7:3); white-
yellow solid; mp 170–1728C; [a]2D4: +37.0 (c 1.0, CHCl3);
1H NMR (300 MHz, CDCl3): d=7.46–7.31 (m, 3H), 7.21–
7.05 (m, 3H), 6.87 (d, J=8.1 Hz, 1H), 6.79 (td, J=7.5,
1.0 Hz, 1H), 6.65 (dd, J=7.7, 1.5 Hz, 1H), 5.16 (t, J=
9.3 Hz, 1H), 5.04 (d, J=9.8 Hz, 1H), 5.00 (s, 2H), 4.88 (t,
J=9.6 Hz, 1H), 4.55 (d, J=10.2 Hz, 1H), 4.26–4.11 (m,
2H), 3.71 (ddd, J=9.9, 5.4, 2.7 Hz, 1H), 2.11 (s, 3H), 2.02
(s, 3H), 1.96 (s, 3H), 1.68 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=170.75 (C=O), 170.23 (C=O), 169.47 (C=O),
169.25 (C=O), 153.99 (C), 141.28 (C), 136.13 (2CH), 129.93
(CH), 128.25 (2CH), 128.00 (CH), 126.96 (CH), 124.68 (C),
121.66 (CH), 121.66 (C), 116.05 (2CH), 85.79 (CH), 76.07
(CH), 73.78 (CH), 70.14 (CH), 69.41 (CH2), 68.30 (CH),
62.32 (CH2), 20.81 (CH3), 20.68 (2CH3), 20.47 (CH3); IR
Compound 3t: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-
(thiophen-2-ylthio)tetrahydro-2H-pyran-3,4,5-triyl triacetate:
Rf =0.26 (cyclohexane/AcOEt, 7:3); white-yellow solid; mp
1
85–878C; [a]2D4: +15.0 (c 1.0, CHCl3); H NMR (300 MHz,
CDCl3): d=7.44 (dd, J=5.4, 1.2 Hz, 1H), 7.20 (dd, J=3.6,
1.2 Hz, 1H), 7.01 (dd, J=5.4, 3.6 Hz, 1H), 5.19 (t, J=
9.4 Hz, 1H), 4.99 (t, J=9.8 Hz, 1H), 4.91 (t, J=9.6 Hz, 1H),
4.50 (d, J=9.9 Hz, 1H), 4.31–4.08 (m, 2H), 3.81–3.56 (m,
1H), 2.10 (s, 3H), 2.07 (s, 3H), 2.00 (s, 3H), 1.97 (s, 3H);
13C NMR (75 MHz, CDCl3): d=170.71 (C=O), 170.30 (C= (neat): n=3470, 3157, 2157, 2024, 1973, 1755, 1682, 1592,
O), 169.48 (C=O), 169.32 (C=O), 136.76 (CH), 131.69 (CH),
127.62 (CH), 127.25 (C), 85.62 (CH), 76.03 (CH), 74.11
(CH), 69.76 (CH), 68.21 (CH), 62.13 (C), 20.89 (2CH3),
20.70 (2CH3); IR (neat): n=3433, 3365, 3000, 2359, 2042,
2019, 1755, 1738, 1365, 1247, 1207, 1090, 1059 cmꢀ1; HR-MS
(ESI): m/z=469.0607, calcd. for C18H22NaO9S2: 469.0603.
Compound 3u: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-
(quinolin-3-ylthio)tetrahydro-2H-pyran-3,4,5-triyl triacetate:
Rf =0.37 (cyclohexane/AcOEt, 5:5); white-yellow solid; mp
69–718C; [a]2D4: ꢀ22.0 (c 1.0, CHCl3); 1H NMR (300 MHz,
CDCl3): d=8.96 (s, 1H), 8.42 (s, 1H), 8.19 (d, J=8.5 Hz,
1H), 7.85 (d, J=8.2 Hz, 1H), 7.79 (t, J=7.7 Hz, 1H), 7.62
(t, J=7.5 Hz, 1H), 5.22 (t, J=9.3 Hz, 1H), 4.96 (dd, J=18.4,
9.4 Hz, 2H), 4.71 (d, J=10.0 Hz, 1H), 4.20 (m, 2H), 3.81–
3.64 (m, 1H), 2.13 (s, 3H), 2.03 (s, 3H), 2.00 (s, 3H), 1.97 (s,
3H); 13C NMR (75 MHz, CDCl3): d=170.73 (C=O), 170.21
(C=O), 169.43 (C=O), 169.40 (C=O), 154.23 (CH), 147.41
(C), 142.24 (CH), 130.72 (CH), 129.31 (CH), 128.02 (C),
127.91 (CH), 127.55 (CH), 124.43 (C), 84.90 (CH), 76.17
(CH), 73.90 (CH), 70.03 (CH), 68.16 (CH), 62.00 (CH2),
1483, 1453, 1365, 1090 cmꢀ1; HR-MS (ESI): m/z=593.1458,
calcd. for C29H30NaO10S: 593.1452.
General Procedure for Palladium-Catalyzed Coupling
of Thioglycosides 1b–g with Aryl Iodides 2
A flame-dried resealable Schlenk tube was charged with
PdACTHUNTRGENNG(U OAc)2 (5 mol%), Xantphos (2.5 mol%), thiosugar 1b–g
(0.375 mmol), (hetero)aryl halide 2 (0.25 mmol), and Et3N
(0.25 mmol). The Schlenk tube was capped with a rubber
septum, evacuated and backfilled with argon; then, dioxane
(1.5 mL) was added through the septum. The septum was re-
placed with a teflon screwcap. The Schlenk tube was sealed,
and the mixture was stirred at 1008C for 1 h. The resulting
suspension was cooled to room temperature and filtered
through celite eluting with ethyl acetate. The filtrate was
concentrated and purification of the residue by silica gel
column chromatography gave the desired product 4.
486
asc.wiley-vch.de
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 477 – 490

Palladium-Catalyzed Cross-Coupling Reaction of Thioglycosides with (Hetero)aryl Halides
(2CH), 127.82 (2CH), 86.80 (CH), 86.39 (CH), 80.90 (CH),
Analytical Data for Arylthioglycosides 4
79.31 (CH), 77.88 (CH), 75.99 (CH2), 75.67 (CH2), 75.24
(CH2), 73.60 (CH2), 69.16 (CH2), 26.65 (CH3); IR (neat): n=
3324, 3255, 3226, 3206, 2168, 1756, 1680, 1589, 1496, 1453,
1398, 1358, 1263, 1213, 1096 cmꢀ1; HR-MS (ESI): m/z=
697.2588, calcd. for C42H42NaO6S: 697.2594.
Compound 4a: (2R,3S,4S,5R,6S)-2-(acetoxymethyl)-6-[(4-
methoxyphenyl)thio]tetrahydro-2H-pyran-3,4,5-triyl triace-
tate: Rf =0.28 (cyclohexane/AcOEt, 7:3); colorless oil; [a]2D4:
ꢀ13.0 (c 1.0, CHCl3); H NMR (300 MHz, CDCl3): d=7.47
1
(d, J=8.4 Hz, 2H), 6.85 (d, J=8.4 Hz, 2H), 5.38 (d, J=
3.2 Hz, 1H), 5.17 (t, J=9.9 Hz, 1H), 5.02 (dd, J=9.9,
3.3 Hz, 1H), 4.56 (d, J=9.8 Hz, 1H), 4.17 (dd, J=11.2,
6.9 Hz, 1H), 4.09 (dd, J=11.2, 6.4 Hz, 1H), 3.88 (t, J=
6.6 Hz, 1H), 3.80 (s, 3H), 2.11 (s, 3H), 2.09 (s, 3H), 2.03 (s,
3H), 1.96 (s, 3H); 13C NMR (75 MHz, CDCl3): d=170.49
(C=O), 170.30 (C=O), 170.19 (C=O), 169.54 (C=O), 160.41
(C), 136.06 (2CH), 122.19 (C), 114.50 (2CH), 87.12 (CH),
74.47 (CH), 72.23 (CH), 67.49 (CH), 67.38 (CH), 61.67
(CH2), 55.48 (CH3), 21.02 (CH3), 20.81 (CH3), 20.74 (2CH3);
IR (neat): n=3488, 3404, 3221, 2574, 2252, 2014, 1749, 1370,
1244, 1220 cmꢀ1; HR-MS (ESI): m/z=493.1135, calcd. for
C21H26NaO10S: 493.1139.
Compound 4e: 1-(4-{[(2R,3R,4S,5R,6R)-3,4,5-tris(benzy-
loxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl]thio}-
phenyl)ethanone: Rf =0.20 (cyclohexane/AcOEt, 9:1);
white-yellow solid; mp 59–618C; [a]2D4: +59.0 (c 1.0, CHCl3);
1H NMR (300 MHz, CDCl3): d=7.73 (d, J=8.4 Hz, 2H),
7.44 (d, J=8.4 Hz, 2H), 7.35–6.97 (m, 21H), 5.70 (d, J=
4.6 Hz, 1H), 4.92 (d, J=10.8 Hz, 1H), 4.75 (t, J=10.3 Hz,
2H), 4.69–4.57 (m, 2H), 4.49 (d, J=11.9 Hz, 1H), 4.42 (d,
J=10.8 Hz, 1H), 4.33 (d, J=11.9 Hz, 1H), 4.23–4.08 (m,
1H), 3.92–3.75 (m, 2H), 3.72–3.57 (m, 2H), 3.50 (dd, J=
10.7, 1.5 Hz, 1H), 2.47 (s, 3H); 13C NMR (75 MHz, CDCl3):
d=197.41 (C=O), 141.98 (C), 138.68 (C), 138.24 (C), 137.90
(C), 137.61 (C), 135.10 (C), 129.51 (CH), 128.80 (CH),
128.61 (CH), 128.53 (11CH), 128.26 (CH), 128.16 (CH),
128.12 (CH), 128.00 (4CH), 127.87 (CH), 127.82 (CH),
85.72 (CH), 82.67 (CH), 79.68 (CH), 77.41 (CH), 75.95
(CH2), 75.28 (CH2), 73.55 (CH2), 72.92 (CH2), 71.62 (CH),
68.63 (CH2), 26.63 (CH3); IR (neat): n=3345, 3157, 2369,
2356, 2230, 2125, 2013, 1982, 1915, 1681, 1588, 1453, 1359,
1262, 1097 cmꢀ1; HR-MS (ESI): m/z=697.2582, calcd, for
C42H42NaO6S: 697.2594.
Compound 4b: (2R,3S,4S,5R,6S)-2-(acetoxymethyl)-6-{[4-
(trifluoromethyl)phenyl]thio}tetrahydro-2H-pyran-3,4,5-triyl
triacetate: Rf =0.45 (cyclohexane/AcOEt, 6:4); white-yellow
solid; mp 70–728C; [a]2D4: ꢀ14.0 (c 1.0, CHCl3); 1H NMR
(300 MHz, CDCl3): d=7.58 (d, J=8.4 Hz, 2H), 7.52 (d, J=
8.5 Hz, 2H), 5.48–5.33 (m, 1H), 5.21 (t, J=9.9 Hz, 1H), 5.04
(dd, J=9.9, 3.3 Hz, 1H), 4.76 (d, J=9.9 Hz, 1H), 4.12 (m,
2H), 3.97 (dd, J=9.5, 3.4 Hz, 1H), 2.08 (s, 3H), 2.05 (s,
3H), 2.01 (s, 3H), 1.94 (s, 3H); 13C NMR (75 MHz, CDCl3):
d=170.30 (C=O), 170.08 (C=O), 169.97 (C=O), 169.39 (C=
O), 137.55 (C), 131.80 (2CH), 129.90 (q, J=33.0 Hz, C),
125.66 (CH), 125.66 (CH), 123.88 (q, J=258.75 Hz, C),
85.44 (CH), 74.69 (CH), 71.89 (CH), 67.22 (CH), 67.07
(CH), 61.71 (CH2), 20.76 (CH3), 20.63 (CH3), 20.55 (2CH3);
19F NMR (188 MHz, CDCl3): d=ꢀ60.94; IR (neat): n=
3465, 3361, 2574, 2347, 2252, 2197, 2014, 1986, 1749, 1370,
1244, 1220 cmꢀ1; HR-MS (ESI): m/z=531.0919, calcd. for
C21H23F3NaO9S: 531.0907.
Compound 4c: (2R,3R,4R,5S)-2-(acetoxymethyl)-5-[(4-
methoxyphenyl)thio]tetrahydrofuran-3,4-diyl diacetate: Rf =
0.58 (cyclohexane/AcOEt, 5:5); colorless oil; [a]2D4: ꢀ18.0 (c
1.0, CHCl3); 1H NMR (300 MHz, CDCl3): d=7.40 (d, J=
8.9 Hz, 2H), 6.84 (d, J=8.9 Hz, 2H), 5.49 (m, 1H), 5.05–
4.93 (m, 2H), 4.88 (dd, J=7.2, 2.9 Hz, 1H), 4.12 (dd, J=
11.6, 4.2 Hz, 1H), 3.79 (s, 3H), 3.77–3.68 (m, 1H), 2.10 (s,
3H), 2.08 (s, 3H), 2.03 (s, 3H); 13C NMR (75 MHz, CDCl3):
d=169.88 (C=O), 169.76 (C=O), 169.37 (C=O), 160.38 (C),
135.97 (2CH), 121.47 (C), 114.74 (2CH), 84.19 (CH), 68.29
(CH), 67.54 (CH), 66.57 (CH), 63.56 (CH2), 55.44 (CH3),
20.88 (CH3), 20.83 (2CH3); IR (neat): n=3288, 3221, 2448,
2365, 2214, 2167, 2086, 2032, 2012, 1748, 1593, 1495, 1372,
1248, 1067 cmꢀ1; HR-MS (ESI): m/z=421.0916, calcd. for
C18H22NaO8S: 421.0928.
Compound 4f: (2R,3S,4S,5R,6S)-2-(hydroxymethyl)-6-[(4-
methoxyphenyl)thio]tetrahydro-2H-pyran-3,4,5-triol:
Rf =
1
0.38 (DCM/MeOH, 85:15); white oil; H NMR (300 MHz,
acetone): d=7.52 (d, J=8.8 Hz, 2H), 6.88 (d, J=8.8 Hz,
2H), 4.46 (d, J=9.6 Hz, 1H), 4.41 (brs, 2H), 3.83 (d, J=
10.2 Hz, 1H), 3.78 (s, 3H), 3.66 (d, J=12.3 Hz, 1H), 3.50–
3.40 (m, 1H), 3.32 (d, J=5.4 Hz, 2H), 3.16 (t, J=9.1 Hz,
1H), 3.03 (s, 2H); 13C NMR (75 MHz, acetone): d=160.61
(C), 135.89 (2CH), 124.15 (C), 115.05 (2CH), 89.02 (CH),
81.38 (CH), 79.38 (CH), 73.19 (CH), 71.26 (CH), 62.90
(CH2), 55.59 (CH3); IR (neat): n=3331, 3240, 3155, 2533,
2202, 2119, 2020, 2002, 1756, 1592, 1494, 1460, 1287, 1218,
1177, 1106 cmꢀ1; HR-MS (ESI): m/z=325.0708, calcd. for
C13H18NaO6S: 325.0716.
Compound 4g: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-
{[(2R,3R,4S,5R,6S)-4,5-diacetoxy-2-(acetoxymethyl)-6-[(4-
methoxyphenyl)thio]tetrahydro-2H-pyran-3-yl]oxy}tetrahy-
dro-2H-pyran-3,4,5-triyl triacetate: Rf =0.36 (cyclohexane/
AcOEt, 5:5); white-yellow solid; mp 190–1928C; [a]2D4:
1
ꢀ20.0 (c 1.0, CHCl3); H NMR (300 MHz, CDCl3): d=7.38
(d, J=8.5 Hz, 2H), 6.79 (d, J=8.6 Hz, 2H), 5.18–4.96 (m,
3H), 4.82 (dt, J=19.3, 8.9 Hz, 2H), 4.57–4.41 (m, 3H), 4.32
(dd, J=12.5, 4.1 Hz, 1H), 4.08–3.92 (m, 2H), 3.76 (s, 3H),
3.69–3.48 (m, 3H), 2.06 (s, 3H), 2.05 (s, 3H), 2.02 (s, 3H),
1.97 (s, 3H), 1.96 (s, 6H), 1.93 (s, 3H); 13C NMR (75 MHz,
CDCl3): d=170.46 (C=O), 170.21 (2C=O), 169.76 (C=O),
169.53 (C=O), 169.29 (C=O), 168.99 (C=O), 160.41 (C),
136.59 (2CH), 121.05 (C), 114.37 (2CH), 100.75 (CH), 85.51
(CH), 76.78 (CH), 76.28 (CH), 73.72 (CH), 72.97 (CH),
71.99 (CH), 71.65 (CH), 70.16 (CH), 67.84 (CH), 61.87
(CH2), 61.58 (CH2), 55.36 (CH3), 20.89 (CH3), 20.84 (CH3),
20.65 (CH3), 20.56 (4CH3); IR (neat): n=3354, 3248, 3206,
3111, 3081, 2313, 2168, 2089, 1986, 1970, 1757, 1496, 1368,
1215, 1041 cmꢀ1; HR-MS (ESI): m/z=781.1970, calcd. for
C33H42NaO18S: 781.1984.
Compound 4d: 1-(4-{[(2S,3R,4S,5R,6R)-3,4,5-tris(benzy-
loxy)-6-[(benzyloxy)methyl]tetrahydro-2H-pyran-2-yl]thio}-
phenyl)ethanone: Rf =0.27 (cyclohexane/AcOEt, 7:3);
white-yellow solid; mp 118–1208C; [a]2D4: ꢀ13.0 (c 1.0,
1
CHCl3); H NMR (300 MHz, CDCl3): d=7.68 (d, J=8.2 Hz,
2H), 7.51 (d, J=8.3 Hz, 2H), 7.31–6.98 (m, 20H), 4.91–4.60
(m, 6H), 4.58–4.34 (m, 3H), 3.81–3.34 (m, 6H), 2.45 (s,
3H); 13C NMR (75 MHz, CDCl3): d=197.37 (C=O), 141.43
(C), 138.41 (C), 138.29 (C), 138.05 (C), 137.89 (C), 135.41
(C), 129.86 (CH), 128.88 (CH), 128.59 (12CH), 128.51
(2CH), 128.29 (CH), 128.07 (CH), 128.01 (2CH), 127.89
Adv. Synth. Catal. 2013, 355, 477 – 490
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
487

Etienne Brachet et al.
FULL PAPERS
2H), 7.76 (d, J=1.6 Hz, 1H), 7.56 (dd, J=8.7, 1.7 Hz, 1H),
7.28 (d, J=10.3 Hz, 1H), 6.96 (d, J=8.7 Hz, 2H), 5.21 (dd,
J=15.2, 5.7 Hz, 1H), 4.93 (dt, J=29.5, 9.7 Hz, 2H), 4.73–
4.57 (m, 1H), 4.29–4.07 (m, 2H), 3.85 (s, 3H), 3.80 (s, 3H),
3.82–3.73 (m, 1H), 2.10 (s, 3H), 2.07 (s, 3H), 1.98 (s, 3H),
1.94 (s, 3H); 13C NMR (75 MHz, CDCl3): d=170.71 (C=O),
170.17 (C=O), 169.42 (C=O), 165.29 (C=O), 162.87 (C=O),
158.13 (C=O), 135.77 (C), 134.22 (CH), 134.09 (CH), 129.20
(2CH), 128.60 (C), 126.28 (C), 124.82 (C), 121.71 (C),
119.31 (CH), 114.52 (CH), 114.08 (2CH), 85.34 (CH), 76.17
(CH), 75.96 (CH), 73.98 (CH), 69.78 (CH), 68.03 (CH),
62.04 (CH2), 55.56 (CH3), 30.56 (CH3), 20.86 (2CH3), 20.64
(2CH3); IR (neat): n=3416, 3215, 3014, 2219, 2181, 2044,
1965, 1755, 1674, 1640, 1527, 1485, 1363, 1248, 1212,
General Procedure for Palladium-Catalyzed Coupling
of Thioglycosides with Biologically Active Molecules
5, 6, 9 and 11
A flame-dried resealable Schlenk tube was charged with
PdACHTUNGTRENNUNG(OAc)2 (5 mol%), Xantphos (2.5 mol%), thiosugar
1 (0.375 mmol), 5, 6, 9 or 11 (0.25 mmol), and Et3N
(0.25 mmol). The Schlenk tube was capped with a rubber
septum, evacuated and backfilled with argon; then, dioxane
(1.5 mL) was added through the septum. The septum was re-
placed with a teflon screwcap. The Schlenk tube was sealed,
and the mixture was stirred at 1008C for 1 h. The resulting
suspension was cooled to room temperature and filtered
through celite eluting with ethyl acetate. The filtrate was
concentrated and purification of the residue by silica gel
column chromatography gave the desired product 7, 8, 10
and 12.
1176 cmꢀ1
;
HR-MS (ESI): m/z=693.1724, calcd. for
C32H34N2NaO12S: 693.1725.
Compound 12: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-
{[(2R,3R,4S,5R,6S)-4,5-diacetoxy-2-(acetoxymethyl)-6-[(4-
methyl-2-oxo-2H-chromen-7-yl)thio]tetrahydro-2H-pyran-3-
yl]oxy}tetrahydro-2H-pyran-3,4,5-triyl triacetate: Rf =0.45
(cyclohexane/AcOEt, 4:6); white-yellow solid; mp 210–
2128C; [a]2D4: ꢀ5.0 (c 1.0, CHCl3); 1H NMR (300 MHz,
CDCl3): d=7.46 (m, 2H), 7.23 (dd, J=8.3, 1.7 Hz, 1H), 6.24
(d, J=1.0 Hz, 1H), 5.35–4.85 (m, 5H), 4.79 (d, J=10.1 Hz,
1H), 4.56 (d, J=11.5 Hz, 1H), 4.50 (d, J=7.9 Hz, 1H), 4.35
(dd, J=12.5, 4.2 Hz, 1H), 4.11 (dd, J=11.9, 5.3 Hz, 1H),
4.01 (dd, J=12.4, 2.0 Hz, 1H), 3.81–3.69 (m, 2H), 3.65 (ddd,
J=9.7, 4.0, 2.1 Hz, 1H), 2.39 (s, 3H), 2.18 (s, 3H), 2.04 (s,
6H), 2.02 (s, 3H), 1.98 (s, 6H), 1.95 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=170.58 (C=O), 170.51 (C=O), 170.24
(C=O), 169.72 (C=O), 169.53 (C=O), 169.38 (C=O), 169.15
(C=O), 160.25 (C=O), 153.63 (C), 151.92 (C), 138.04 (C),
126.45 (CH), 124.70 (CH), 119.20 (C), 118.36 (CH), 115.20
(CH), 100.90 (CH), 84.67 (CH), 77.16 (CH), 76.29 (CH),
73.51 (CH), 73.00 (CH), 72.10 (CH), 71.67 (CH), 69.83
(CH), 67.85 (CH), 62.12 (CH2), 61.63 (CH2), 20.94 (CH3),
20.76 (CH3), 20.72 (CH3), 20.61 (4CH3), 18.65 (CH3); IR
(neat): n=3339, 2197, 2110, 2045, 2021, 1740, 1709, 1603,
1384, 1364, 1210, 1167, 1032, 955 cmꢀ1; HR-MS (ESI): m/z=
811.2102, calcd. for C36H43O19S: 811.2114.
Compound 7: (2R,3S,4S,5R,6S)-2-(acetoxymethyl)-6-({2-
methoxy-5-[1-(3,4,5-trimethoxyphenyl)vinyl]phenyl}thio)te-
trahydro-2H-pyran-3,4,5-triyl triacetate: Rf =0.43 (cyclohex-
ane/AcOEt, 7:3); white-yellow solid; mp 84–868C; [a]2D4:
1
+22.0 (c 1.0, CHCl3); H NMR (300 MHz, CDCl3): d=7.57
(d, J=2.2 Hz, 1H), 7.23 (dd, J=8.5, 2.2 Hz, 1H), 6.84 (d,
J=8.5 Hz, 1H), 6.53 (s, 2H), 5.44–5.22 (m, 4H), 5.07 (dd,
J=9.9, 3.4 Hz, 1H), 4.83 (d, J=10.0 Hz, 1H), 4.06 (dd, J=
6.7, 3.4 Hz, 3H), 3.89 (s, 3H), 3.87 (s, 3H), 3.81 (s, 6H), 2.11
(s, 3H), 2.06 (s, 3H), 1.98 (s, 3H), 1.97 (s, 3H); 13C NMR
(75 MHz, CDCl3): d=170.42 (C=O), 170.33 (C=O), 170.13
(C=O), 169.52 (C=O), 158.08 (C), 153.04 (2C), 149.15 (C),
137.17 (C), 134.37 (C), 132.86 (CH), 129.42 (CH), 120.70
(C), 113.08 (C), 110.63 (CH), 105.82 (2CH), 85.36 (CH),
74.49 (CH), 72.14 (CH), 67.52 (CH), 67.29 (CH), 61.42
(CH2), 60.98 (CH), 56.30 (2CH3), 56.03 (CH3), 20.87
(2CH3), 20.70 (2CH3); IR (neat): n=3431, 3379, 3159, 3095,
2482, 224, 2128, 1922, 1753, 1368, 1223, 1126 cmꢀ1; HR-MS
(ESI): m/z=663.2098, calcd. for C32H39O13S: 663.2166.
Compound 8: (2R,3S,4S,5R,6S)-2-(acetoxymethyl)-6-{[2-
methoxy-5-(3,4,5-trimethoxybenzoyl)phenyl]thio}tetrahydro-
2H-pyran-3,4,5-triyl triacetate: Rf =0.32 (cyclohexane/
AcOEt, 9:1); white-yellow solid; mp 108–1108C; [a]2D4:
1
+61.0 (c 1.0, CHCl3); H NMR (300 MHz, CDCl3): d=8.01
(d, J=2.1 Hz, 1H), 7.71 (dd, J=8.5, 2.1 Hz, 1H), 6.98 (s,
2H), 6.91 (d, J=8.6 Hz, 1H), 5.45–5.36 (m, 1H), 5.27 (t, J=
10.0 Hz, 1H), 5.06 (dd, J=9.9, 3.4 Hz, 1H), 4.88 (d, J=
10.0 Hz, 1H), 3.99–4.02 (m, 2H), 3.93 (s, 3H), 3.90 (s, 3H),
3.85 (s, 6H), 2.10 (s, 3H), 2.05 (s, 3H), 1.95 (s, 3H), 1.93 (s,
3H); 13C NMR (75 MHz, CDCl3): d=193.91 (C=O), 170.43
(C=O), 170.29 (C=O), 170.06 (C=O), 169.57 (C=O), 161.13
(C), 152.91 (C), 141.89 (C), 134.03 (CH), 132.88 (C), 131.86
(CH), 130.74 (C), 122.10 (C), 109.88 (CH), 107.52 (2CH),
84.69 (CH), 74.49 (CH), 71.96 (CH), 67.18 (CH), 61.40
(CH2), 61.02 (CH), 56.39 (3CH3), 56.23 (CH3), 20.87 (CH3),
20.69 (CH3), 20.63 (2CH3); IR (neat): n=3439, 3323, 3270,
3204, 3131, 2358, 2159, 2027, 1942, 1751, 1647, 1582, 1502,
1413, 1368, 1225 cmꢀ1; HR-MS (ESI): m/z=687.1708, calcd.
for C31H36NaO14S: 687.1718.
Procedure for Deprotection of Compound 12
A solution of compound 12 (0.150 g, 0.185 mmol) under
argon was dissolved in methanol (12 mL) and a solution
[1M] of sodium methoxide (1 mL) was added at 08C. The
resultant mixture was stirred continuously for 8 h at room
temperature. The solution was treated with Amberlyst
15(H+) resin until pH 5 and filtered through celite eluting
with methanol. Then, the filtrate was concentrated and
dried under vacuum to give the desired MUS-CB product;
yield: 0.72 g (75%).
Compound MUS-CB: 7-{[(2S,3R,4R,5S,6R)-3,4-dihy-
droxy-6-(hydroxymethyl)-5-{[(2S,3R,4S,5S,6R)-3,4,5-trihy-
droxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy}te-
trahydro-2H-pyran-2-yl]thio}-4-methyl-2H-chromen-2-one:
Rf =0 (AcOEt); white-yellow oil; 1H NMR (300 MHz,
DMSO/D2O, 9:1): d=7.66 (d, J=8.3 Hz, 1H), 7.43–7.31 (m,
2H), 6.29 (d, J=1.0 Hz, 1H), 4.88 (d, J=9.8 Hz, 1H), 4.28
(d, J=7.8 Hz, 1H), 3.78–3.34 (m, 14H), 3.19 (m, 3H), 3.11–
2.91 (m, 2H), 2.37 (s, 3H). 13C NMR (75 MHz, DMSO):
d=159.69 (C=O), 153.10 (2C), 140.62 (C), 125.47 (CH),
Compound 10: (2R,3R,4S,5R,6S)-2-(acetoxymethyl)-6-{[3-
(4-methoxybenzamido)-1-methyl-2-oxo-1,2-dihydroquinolin-
6-yl]thio}tetrahydro-2H-pyran-3,4,5-triyl triacetate: Rf =0.4
(cyclohexane/AcOEt, 5:5); white-yellow solid; mp 107–
1
1098C; [a]2D4: ꢀ35.0 (c 1.0, in CHCl3); H NMR (300 MHz,
CDCl3): d=9.27 (s, 1H), 8.80 (s, 1H), 7.88 (d, J=8.7 Hz,
488
asc.wiley-vch.de
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 477 – 490

Palladium-Catalyzed Cross-Coupling Reaction of Thioglycosides with (Hetero)aryl Halides
124.31 (CH), 117.50 (C), 115.39 (CH), 113.56 (CH), 103.07
(CH), 85.28 (CH), 79.75 (CH), 78.89 (CH), 76.84 (CH),
76.50 (CH), 76.28 (CH), 73.34 (CH), 72.19 (CH), 70.07
(CH), 61.07 (CH2), 60.24 (CH2), 18.03 (CH3). IR (neat): n=
3400, 3369, 3303, 3286, 3161, 2953, 1569, 2460, 2078, 1973,
1718, 1601, 677 cmꢀ1; HR-MS (ESI): m/z=539.1170, calcd.
for C22H28NaO12S: 539.1199.
see: P. S. Herradura, K. A. Pendola, R. K. Guy, Org.
Lett. 2000, 2, 2019–2022.
[7] The presence of a triazene group ortho to the iodide is
crucial for a successful course of reaction; see: ref.[6]
[8] a) D. Audisio, S. Messaoudi, J.-F. Peyrat, J.-D. Brion,
M. Alami, Tetrahedron Lett. 2007, 48, 6928–6932; b) S.
Messaoudi, D. Audisio, J.-D. Brion, M. Alami, Tetrahe-
dron 2007, 63, 10202–10210; c) D. Audisio, S. Messaou-
di, J.-F. Peyrat, J.-D. Brion, M. Alami, J. Org. Chem.
2011, 76, 4995–5005; d) M. A. Soussi, D. Audisio, S.
Messaoudi, O. Provot, J.-D. Brion, M. Alami, Eur. J.
Org. Chem. 2011, 5077–5088.
Acknowledgements
[9] <For a recent review, see: I. P. Beletskaya, V. P. Anani-
The CNRS is gratefully acknowledged for financial support
of this research and Ministꢀre (MENRT) for a doctoral fel-
lowship to EB. Our laboratory BioCIS-UMR 8076 is
a member of the Laboratory of Excellence LERMIT sup-
ported by a grant from ANR (ANR-10-LABX-33).
kov, Chem. Rev. 2011, 111, 1596–1636. Selected repre-
ꢀ
sentative examples for the Pd-catalyzed C S cross-cou-
pling reaction see: a) T. Migita, T. Shimizu, Y. Asami,
J. Shiobara, Y. Kato, M. Kosugi, Bull. Chem. Soc. Jpn.
1980, 53, 1385–1389; b) U. Schopfer, A. Schlapbach,
Tetrahedron 2001, 57, 3069–3073; c) G. Y. Li, G. Zheng,
A. F. Noonan, J. Org. Chem. 2001, 66, 8677–8688; d) M.
Murata, S. L. Buchwald, Tetrahedron 2004, 60, 7397–
7403; e) T. Itoh, T. Mase, Org. Lett. 2004, 6, 4587–4590;
f) M. A. Fernandez-Rodroeguez, Q. Shen, J. F. Hartwig,
J. Am. Chem. Soc. 2006, 128, 2180–2181; g) M. A. Fer-
nandez-Rodroeguez, Q. Shen, J. F. Hartwig, Chem. Eur.
J. 2006, 12, 7782–7796; h) C. C. Eichman, J. P. Stambuli,
J. Org. Chem. 2009, 74, 4005–4008; i) M. A. Fernꢅndez-
Rodrꢆguez, J. F. Hartwig, J. Org. Chem. 2009, 74, 1663–
1672; j) C. Bryan, J. Braunger, M. Lautens, Angew.
Chem. 2009, 121, 7198–7202; Angew. Chem. Int. Ed.
2009, 48, 7064–7068; k) M. Fernꢅndez-Rodrꢆguez, J.
Hartwig, Chem. Eur. J. 2010, 16, 2355–2359; l) A.
van den Hoogenband, J. W. Lange, R. P. Bronger, A. R.
Stoit, S. W. Tupstra, Tetrahedron Lett. 2010, 51, 6877–
6881.
References
[1] For general reviews, see: a) H. Driguez, Thiooligosac-
charides in glycobiology. Glycoscience Synthesis of Sub-
strate Analogs and Mimetics, in: Topics in Current
Chemistry, Springer, Berlin, Vol. 187, pp 85–116, 1997,;
b) Z. J. Witczak, Curr. Med. Chem. 1999, 6, 165–178;
c) K. Pachamuthu, R. R. Schmidt, Chem. Rev. 2006,
106, 160–187; d) M. Samuni-Blank, I. Izhaki, M. D.
Dearing, Y. Gerchman, B. Trabelcy, A. L. W. H. Kara-
sov, Z. Arad, Curr. Biol. 2012, 22, 1218–1220.
[2] a) C. S. Rye, S. G. Withers, Carbohydr. Res. 2004, 339,
699–703; b) B. B. Metaferia, B. J. Fetterolf, S. Shazad-
ul-Hussan, M. Moravec, J. A. Smith, S. Ray, M.-T. Gu-
tierrez-Lugo, C. A. Bewley, J. Med. Chem. 2007, 50,
6326–6336; c) F. Castaneda, A. Burse, W. Boland,
R. K.-H. Kinne, Int. J. Med. Sci. 2007, 4, 131–139.
[3] a) R. Furneaux, R. Ferrier, Methods Carbohydr. Chem.
1980, 8, 251–253; b) K. C. Nicolaou, J. L. Randall, G. T.
Furst, J. Am. Chem. Soc. 1985, 107, 5556–5558; c) S. K.
Das, J. Roy, K. A. Reddy, C. Abbineni, Carbohydr. Res.
2003, 338, 2237–2240; d) C.-A. Tai, S. S. Kulkarni, S.-C.
Hung, J. Org. Chem. 2003, 68, 8719–8722; e) C.-A. Tai,
S. S. Kulkarni, S. C. Hung, J. Org. Chem. 2003, 68,
8719–8722; f) S. K. Das, J. Roy, K. A. Reddy, C. Abbi-
neni, Carbohydr. Res. 2003, 338, 2237–2240; g) G. Agni-
hotri, P. Tiwari, A. K. Misra, Carbohydr. Res. 2005, 340,
1393–1396.
[4] a) E. Fischer, K. Delbruek, Ber. Dtsch. Chem. Ges.
1909, 42, 1476–1482; b) M. Blanc-Muesser, J. Defaye,
H. Driguez, Carbohydr. Res. 1978, 67, 305–328; c) M.
Apparu, M. Blanc-Muesser, J. Defaye, H. Driguez,
Can. J. Chem. 1981, 59, 314–320.
[5] S-S. Weng, Y-D. Lin, C-T. Chen, Org. Lett. 2006, 8,
5633–5636.
[6] P. Naus, L. Leseticky, S. Smrcek, I. Tislerova, M. Sticha,
Synlett 2003, 2117–2122. Only one example was report-
ed with respect to the Chan–Lam type-coupling of per-
O-acetylated 1-thio-b-d-glucose with phenylboronic
[10] The most common method for preparing thiophenols
involves the lithiation of aromatic halides and trapping
of the organolithium intermediates with elemental
sulfur.
[11] a) K. C. Kong, C. H. Cheng, J. Am. Chem. Soc. 1991,
113, 6313–63155; b) L. Pellegatti, E. Vedrenne, J.-M.
Leger, C. Jarry, S. Routier, J. Comb. Chem. 2010, 12,
604–608; c) S. Messaoudi, J.-D. Brion, M. Alami, Org.
Lett. 2012, 14, 1496–1499.
[12] The use of Pd
ACHTUNGERTN(NUNG OAc)2 (3 mol%)/L1 (3 mol%) and Pd-
AHCTUNGTRENNUNG
product 3a in 58% and 74% yields, respectively.
ꢀ
[13] For C S bond forming reaction from N-tosylhydra-
zones, see: a) Q. Ding, B. Cao, J. Yuan, X. Liu, Y.
Peng, Org. Biomol. Chem. 2011, 9, 748–751; b) X.-W.
Feng, J. Wang, J. Zhang, J. Yang, N. Wang, X.-Q. Yu,
Org. Lett. 2010, 12, 4408–4411; c) J. Barluenga, M.
Tomas-Gamasa, F. Aznar, C. Valdes, Eur. J. Org. Chem.
2011, 1520–1526.
ꢀ
[14] For selected examples of C C bond forming reaction
from N-tosylhydrazones, see: a) J. Barluenga, P. Moriel,
C. Valdes, F. Aznar, Angew. Chem. 2007, 119, 5683–
5686; Angew. Chem. Int. Ed. 2007, 46, 5587–5590;
b) W.-Y. Yu, Y.-T. Tsoi, Z. Zhou, A. S. C. Chan, Org.
Lett. 2009, 11, 469–472; c) J. Barluenga, M. Tomas-
Gamasa, F. Aznar, C. Valdes, Chem. Eur. J. 2010, 16,
12801–12803; d) B. Trꢀguier, A. Hamze, O. Provot, J.-
acid in the presence of excess of CuACTHNUTRGENUN(G OAc)2 (1.5 equiv.)
in DMF at elevated temperature (1538C). The yield of
the formed product was moderate (51%), but no spec-
tral data are available in the supporting information,
Adv. Synth. Catal. 2013, 355, 477 – 490
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
489

Etienne Brachet et al.
FULL PAPERS
D. Brion, M. Alami, Tetrahedron Lett. 2009, 50, 6549–
6552; e) X. Zhao, J. Jing, K. Lu, Y. Zhang, J. Wang,
Chem. Commun. 2010, 46, 1724–1726; f) E. Brachet, A.
Hamze, J.-F. Peyrat, J.-D. Brion, M. Alami, Org. Lett.
2010, 12, 4042–4045; g) X. Zhao, G. Wu, Y. Zhang, J.
tovo, O. Provot, C. Mousset, D. Veau, J. Rodrigo, J.
Bignon, J.-M. Liu, J. Wdzieczak-Bakala, S. Thoret, J.
Dubois, J.-D. Brion, M. Alami, ChemMedChem 2011, 6,
2179–2191.
[17] a) G. R. Pettit, B. Toki, D. L. Herald, P. Verdier-Pinard,
M. R. Boyd, E. Hamel, R. K. Pettit, J. Med. Chem.
1998, 41, 1688–1695; b) J.-P. Liou, J.-Y. Chang, C.-W.
Chang, C.-Y. Chang, N. Mahindroo, F.-M. Kuo, H.-P.
Hsieh, J. Med. Chem. 2004, 47, 2897–2905.
[18] D. Audisio, S. Messaoudi, L. Ceigeikowski, J.-F. Peyrat,
J.-D. Brion, D. Methy-Gonnot, C. Radanyi, J.-M.
Renoir, M. Alami, ChemMedChem 2011, 6, 804–815.
[19] B. K. Barr, R. J. Holewinski, Biochemistry 2002, 41,
4447–4452.
[20] C. Bao, G. Fan, Q. Lin, B. Li, S. Cheng, Q. Huang, L.
Zhu, Org. Lett. 2012, 14, 572–575.
[21] N. Floyd, B. Vijayakrishnan, J. R. Koeppe, B. G. Davis,
Angew. Chem. 2009, 121, 7938–7942; Angew. Chem.
Int. Ed. 2009, 48, 7798–7802.
ꢀ
Wang, J. Am. Chem. Soc. 2011, 133, 3296–3299. For C
O bond forming reaction, see: h) J. Barluenga, M.
Tomas-Gamasa, F. Aznar, C. Valdes, Angew. Chem.
2010, 122, 5113–5116; Angew. Chem. Int. Ed. 2010, 49,
ꢀ
4993–4996; for C N bond forming reaction, see: i) A.
Hamze, B. Trꢀguier, J.-D. Brion, M. Alami, Org.
Biomol. Chem. 2011, 9, 6200–6204.
[15] a) L. Salvi, N. R. Davis, S. Z. Ali, S. L. Buchwald, Org.
Lett. 2012, 14, 170–173; b) K. W. Anderson, T. Ikawa,
R. E. Tundel, S. L. Buchwald, J. Am. Chem. Soc. 2006,
128, 10694–10695; c) A. V. Vorogushin, X. Huang, S. L.
Buchwald J. Am. Chem. Soc. 2005, 127, 8146–8149.
[16] a) S. Messaoudi, B. Trꢀguier, A. Hamze, O. Provot, J.-F.
Peyrat, J. R. Rodrigo De Losada, J.-M. Liu, J. Bignon,
J. Wdzieczak-Bakala, S. Thoret, J. Dubois, J.-D. Brion,
M. Alami, J. Med. Chem. 2009, 52, 4538–4542; b) A.
Hamze, A. Giraud, S. Messaoudi, O. Provot, J.-F.
Peyrat, J. Bignon, J.-M. Liu, J. Wdzieczak-Bakala, S.
Thoret, J. Dubois, J.-D. Brion, M. Alami, ChemMed-
Chem 2009, 4, 1912–1924; c) A. Hamze, E. Rasolfonja-
[22] G. J. L. Bernardes, D. P. Gamblin, B. G. Davis, Angew.
Chem. 2006, 118, 4111–4115; Angew. Chem. Int. Ed.
2006, 45, 4007–4011.
[23] M. Gao, Y. Chen, S. Tan, J. H. Reibenspies, R. A. Zin-
garo, Heteroat. Chem. 2008, 19, 199–206.
490
asc.wiley-vch.de
ꢂ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 477 – 490