Facile Cu-free Sonogashira cross-coupling of nucleoside C-6 arylsulfonates with terminal alkynes

Article abstract of DOI:10.1016/j.tet.2010.08.032

The combination of PdCl₂[CH₃CN]₂ with XPhos is an efficient catalytic system for the Sonogashira-type cross-coupling of 2′-deoxyguanosine O⁶-arylsulfonates with terminal alkynes. The reactions generally proceed under mild conditions requiring no Cu co-catalyst to give the corresponding C-6-alkynylated deoxynucleosides in moderate to good yields.

Full text of DOI:10.1016/j.tet.2010.08.032

Tetrahedron 66 (2010) 7919e7926
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Facile Cu-free Sonogashira cross-coupling of nucleoside C-6 arylsulfonates
with terminal alkynes
*
Felix N. Ngassa , Jamie M. Gomez, Brandon E. Haines, Michael J. Ostach, Jared W. Hector,
Lindsay J. Hoogenboom, Chelsea E. Page
Department of Chemistry, Grand Valley State University, 1 Campus Drive, Allendale, MI 49401, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 5 July 2010
Received in revised form 10 August 2010
Accepted 11 August 2010
Available online 18 August 2010
The combination of PdCl2[CH3CN]2 with XPhos is an efficient catalytic system for the Sonogashira-type
cross-coupling of 20-deoxyguanosine O6-arylsulfonates with terminal alkynes. The reactions generally
proceed under mild conditions requiring no Cu co-catalyst to give the corresponding C-6-alkynylated
deoxynucleosides in moderate to good yields.
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
cross-coupling alkynylation of nucleosides, reported thus far, have
involved the use of halopurine nucleosides as electrophiles
The acetylenic moiety is commonly found in a number of natural
products and biologically active molecules.1 Once incorporated in
organic molecules, the acetylenic core can serve as important syn-
thetic intermediates because alkynes can undergo a wide variety of
reactions. As a result, this has prompted interest in the design of
efficient synthetic methods for the incorporation of the acetylenic
unit in organic molecules. One such method for the incorporation of
the acetylenic unit in organic molecules is the Sonogashira cross-
coupling method.2 In recent years, the Sonogashira reaction has
undoubtedly become one of the most widely used reactions in or-
ganic synthesis for the formation of a C(sp)eC(sp2) bond. In the
original Sonogashira cross-coupling reaction, a terminal alkyne is
coupled with an aryl or vinyl halide or triflate, using a palladium
catalyst and a Cu(I) salt as co-catalyst.3 Various modifications of the
original Sonogashira cross-coupling reaction have been reported in
the past decade.4e15
The modification of nucleosides continues to be an important
area in organic research due to the wide variety of applications
that modified nucleosides possess and the biological importance
of nucleosides in general. For example, modified nucleosides have
been shown to act as enzyme inhibitors and antagonists, and have
the potential to be lowly toxic, yet effective as antiviral and anti-
cancer agents.16,17 Modified nucleoside analogs, substituted at the
C-6 position, have been reported to possess a wide range of bi-
ological activities.18e22 The alkynylation of nucleosides by the
Sonogashira cross-coupling reaction is well documented in the
literature.15,21,23e26 However, most of the successful Sonogashira
reacting with terminal alkynes.
An important modification of the Sonogashira cross-coupling
reaction we have been exploring in our lab, for the synthesis of
modified nucleosides, is the Cu-free method.15 The use of copper
is sometimes limited by the formation of insoluble copper ace-
tylides, which are potentially explosive. In addition, Buchwald
and co-workers reported the potential oligomerization of the
alkyne starting material when using a copper co-catalyst in the
conventional Sonogashira cross-coupling method.4 Historically,
the identity of the group being displaced in a Sonogashira-type
cross-coupling has been a halide. However, examples have been
cited in the literature in which the halogen has been replaced
with a sulfonate as the leaving group in the synthesis of modi-
fied nucleosides. For example, the facile displacement of a sulfo-
nate on the C-6 position of nucleosides by oxygen and nitrogen
nucleophiles has been reported.27 An analogous Suzuki-type
cross-coupling has been developed in which nucleoside arylsul-
fonates were reacted with arylboronic acids to create a new CeC
bond at the C-6 position of 20-deoxyguanosine.28
The use of tosylates as the leaving group in a Sonogashira-type
cross-coupling, especially in the coupling of non-nucleosidic aro-
matic compounds with terminal acetylenes, has been reported.4,29
A Cu-free Pd-catalyzed cross-coupling of vinyl tosylates with ter-
minal acetylenes has been reported by Fu and co-workers.29 Simi-
larly, Gelman and co-workers reported the first Sonogashira-type
cross-coupling of aryl tosylates with terminal alkynes under Cu-free
conditions.4 However, to the best of our knowledge, there has been
no literature precedence on the displacement of sulfonates in gen-
eral, and tosylates in particular, on nucleosides using terminal
alkynes through a Sonogashira-type cross-coupling.
* Corresponding author. E-mail address: ngassaf@gvsu.edu (F.N. Ngassa).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.08.032

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F.N. Ngassa et al. / Tetrahedron 66 (2010) 7919e7926
To add to the current state of knowledge in the field, our group
Following sulfonation, the dG sulfonates were coupled with
phenylacetylene for initial optimization using a Cu-free Sonoga-
shira-type cross-coupling reaction. The reactivities of protected
20-deoxyguanosine p-toluenesulfonate and protected 20-deoxy-
guanosine mesitylenesulfonate were compared and results showed
a greater reactivity of 20-deoxyguanosine p-toluenesulfonate, per-
haps due tothe steric hindrance of the mesitylenesulfonate. We then
used 20-deoxyguanosine p-toluenesulfonate as the nucleoside
starting material for the optimization experiments.
has been particularly interested in investigating the development of
efficient methods to synthesize C-6-alkynyl-substituted nucleo-
sides. As a part of our ongoing interest in transition metal-mediated
syntheses of modified nucleosides,30 we recently reported a modi-
fied Sonogashira-type cross-coupling in the C-6-alkynylation of
protected 20-deoxyadenosine.15 Therefore, in this work, we setout to
evaluate both the conventional Sonogashira cross-coupling method
and the modified versions, in the coupling of protected 20-deoxy-
guanosine sulfonates with terminal acetylenes, toward the synthe-
sis of C-6-alkynylated deoxynucleosides. Herein, we report our
initial results that show a convenient Sonogashira-type cross-cou-
pling of protected 20-deoxyguanosine sulfonates with terminal
acetylenes to afford C-6-alkynyl-substituted nucleosides.
In the optimization experiments, several different combinations
of palladium species, ligands, bases, and solvents were investigated.
Three different Pd species, PdPCl2[CH3CN]2, Pd(PPh3)4, and
PdCl2(PPh3)2, and three ligands, L-1, L-2, and L-3 were investigated
(Fig. 2). Two bases Cs2CO3 and Et3N were used while CH3CN, DMF,
dioxane, DME, toluene, and THF were investigated as possible
solvents. The use of Cs2CO3 was discontinued after poor solubility
and very low percent yields were recorded each time the base was
used during the optimization experiments. The use of Et3N as the
organic base gave better results with all the solvents tested. Among
the solvents examined, THF, based on solubility and percentage
recovery of product, turned out to be the best and was used
throughout the optimization. The ligands and Pd species were se-
lected for this experiment because they had been used effectively in
experiments similar to this one in previously published work.4,15
For preliminary studies, we used 5 mol % Pd species, 15 mol %
ligand, and 4.5 equiv Et3N as base for the coupling of 20-deoxy-
guanosine sulfonates with phenylacetylene in THF at 90 ꢀC. In the
course of the optimization experiments, it was noticed that the
combination of any of the Pd species with any of the ligands and
Et3N in THF resulted in product formation (Table 1). When Pd
(Ph3P)4 was used as the Pd species, a better yield was obtained
using L-3 (Table 1, entry 3), which is consistent with results from
our previous work, albeit, Et3N was used in this case and not Cs2CO3
due to solubility problems. The yields for the same Pd species were
rather low using L-1 and L-2 (Table 1, entries 1 and 2). When the Pd
species was switched to PdCl2(PPh3)2, a much better yield was
obtained with L-1, albeit, the yields were comparable between L-1
and L-2 (Table 1, entries 4 and 5). However, the yield with L-3
dropped from 85% (Table 1, entry 3) to 57% (Table 1, entry 6) when
the Pd species Pd(Ph3P)4 was replaced with PdCl2(PPh3)2. The use of
PdCl2(CH3CN)2 as the Pd species resulted in a much better yield of
86% using L-1 in just 8 h (Table 1, entry 7). When the same reaction
was run, under the same set of conditions as in entry 7, for 24 h,
a slightly lower yield of 79% was obtained. Comparatively, the
yields were much lower with L-2 and L-3 when PdCl2(CH3CN)2 was
used as the Pd species (Table 1, entries 8 and 9). Although the effect
of the ligands on the different Pd species has not been investigated
at this time, it can be deduced from the optimization experiments
that L-1 works best with PdCl2(CH3CN)2, L-2 works best with
2. Results and discussion
Our synthetic strategy toward the C-6-alkynylated deoxy-
ribonucleoside derivatives involved a Sonogashira-type cross-cou-
pling of protected 20-deoxyguanosine sulfonates with terminal
acetylenes. Initial attempts to sulfonate the unprotected 20-deox-
yguanosine resulted in a complex mixture of products probably due
to the reactivity of the polar hydroxyl groups with the sulfonyl
chloride. We then decided to protect the hydroxyl groups prior to
sulfonation. In order to obtain the deoxyribonucleoside starting
material for cross-coupling, the hydroxyl groups of commercially
available 20-deoxyguanosine (dG) were protected as the silyl ether
using tert-butyldimethylsilyl chloride (TBDMS-Cl), imidazole, and
DMF. The O6 position of the protected dG was then sulfonated using
either 2-mesitylenesulfonyl chloride or p-toluenesulfonyl chloride
(Fig. 1).
O
O
O
Ar
S
N
N
N
N
NH2
TBDMSO
O
OTBDMS
1a: Ar = 2,4,6-trimethylphenyl
1b: Ar = 4-methylphenyl
Figure 1. Structures of nucleoside arylsulfonates synthesized from 20-deoxyguanosine
and evaluated.
PdCl2(PPh3)2
PdCl2(CH3CN)2
Pd(Ph3P)4
Pd-species:
PCy2
iPr
P(tert-Bu)2
PCy2
OMe
Ligands:
iPr
MeO
iPr
XPhos
L-1
S-Phos
L-2
JohnPhos
L-3
Figure 2. Pd-species and ligands investigated. The symbol Cy2 stands for dicyclohexyl.

F.N. Ngassa et al. / Tetrahedron 66 (2010) 7919e7926
7921
PdCl2(PPh3)2, and L-3 works best with Pd(Ph3P)4 (Table 1, entries 3,
5, and 7). It should be noted that although the yields of entry 3 and
7, 85% and 86%, respectively, are comparable, we chose the system
in entry 7 because of less time required for reaction completion and
because the Pd species and ligand were more readily available to us.
We also decided to investigate the optimum Pd-species/ligand
ratio. Thus, using the optimized reaction conditions, we carried
out reactions with different ratios of PdCl2(CH3CN)2 and L-1
with or without CuI (Table 2).
Table 1
Optimization study for the Sonogashira cross-coupling of phenylacetylene with 20-deoxyguanosine p-toluenesulfonate
O
O
S
O
N
N
N
N
N
Pd-Ligand, Et3N
N
N
NH2
N
NH2
TBDMSO
THF, 90oC, N2
TBDMSO
O
O
1b
3a
OTBDMS
OTBDMS
Entry
Pd-species
Ligand
Time (h)
Yield (%)a,b
1
2
3
4
5
6
7
8
9
Pd(Ph3P)4
Pd(Ph3P)4
Pd(Ph3P)4
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
PdCl2(CH3CN)2
L-1
L-2
L-3
L-1
L-2
L-3
L-1
L-2
L-3
24
24
24
24
24
24
8
49
34
85
76
73
57
86
53
48
24
24
a
The percentage yield is the calculated yield of the recovered product from an average of two runs.
Reactions were carried out in THF at 90 ꢀC, with 1.0 equiv of protected 20-deoxyguanosine p-toluenesulfonate, 1.5 equiv of phenylacetylene, 0.05 equiv of Pd-species,
b
0.15 equiv of ligand, and 4.5 equiv of Et3N. L-1: XPhos; L-2: S-Phos; L-3: JohnPhos.
Table 2
Optimization of catalyst-ligand ratio in the coupling of 20-deoxyguanosine sulfonates with phenylacetylene
O
O
S
O
PdCl2(CH3CN)2, XPhos
N
N
N
N
N
Et3N
N
N
NH2
N
NH2
TBDMSO
THF, 90oC, N2
TBDMSO
O
O
1b
3a
OTBDMS
OTBDMS
Entry
CuI (mol %)
Pd-species (mol %)
Ligand (mol %)
Yield (%)a,b
1
2
3
4
5
6
0
5
10
15
0
5
5
10
15
10
15
15
30
45
30
7.5
86
83
63
58
75
72
0
2.5
a
The percentage yield is the calculated yield of the recovered product after two runs. The Pd-species is PdCl2(CH3CN)2. Ligand (L-1) is 2-dicyclohexylphosphino-20,40,60-
triisopropylbiphenyl (XPhos). All reactions were run for 24 h except in entry 6 where it took 36 h for reaction completion.
b
Reactions were carried out with 1.0 equiv of protected 20-deoxyguanosine p-toluenesulfonate, 1.5 equiv of phenylacetylene, 4.5 equiv of Et3N, and L-1 as XPhos.
Our preliminary experiments established the combination of
PdCl2(CH3CN)2/L-1 and Et3N in THF at 90 ꢀC as the optimal
conditions for the Sonogashira-type cross-coupling of 20-deoxy-
guanosine sulfonates with phenylacetylene. Since CuI is com-
monly used in the conventional Sonogashira cross-coupling
reactions, and since we are using sulfonates for the first time
as the leaving group in a Sonogashira-type cross-coupling, we
decided to investigate if the use of CuI would be more efficient.
The most effective catalytic system was the use of 5 mol %
PdCl2(CH3CN)2, 15 mol % L-1 under Cu-free conditions (Table 2,
entry 1). When 5 mol % CuI was used in the presence of 5 mol %
PdCl2(CH3CN)2and 15 mol % L-1, there was no significant change in
the yield from 86% to 83% (Table 2, entry 2). Increasing the catalyst
loading did not result in improvement in the yield but rather the
yield decreased. At 10 mol % CuI, 10 mol % PdCl2(CH3CN)2, and
30 mol % L-1, the yield of product decreased to 63% (Table 2,

7922
F.N. Ngassa et al. / Tetrahedron 66 (2010) 7919e7926
entry 3). With
a
catalyst loading of 15 mol % CuI, 15 mol %
Our optimized reaction conditions were used to study the scope of
the Sonogashira-type cross-coupling of 20-deoxyguanosine p-tolue-
nesulfonate with various terminal acetylenes incorporating a wide
arrayoffunctional groups(Tables 3 and4). All thearomatic acetylenes
investigated, withtheexceptionof2-nitrophenylacetylene, reactedto
give products in good to excellent yields (Table 3). We found that
aromatic acetylenes containing electron-releasing groups were more
reactive with 20-deoxyguanosine p-toluenesulfonate (Table 3, entries
2, 3, 5, and 6). Among the aromatic acetylenes containing electron-
releasing groups, the ortho-substituted derivatives (Table 3, entries 2
and 3) gave better yields than the para-substituted derivatives
(Table 3, entries 5 and 6). Two aromatic acetylenes containing elec-
tron-withdrawing groups, an ortho-substituted nitro group (Table 3,
PdCl2(CH3CN)2, and 45 mol % L-1, only a modest yield of 58% was
obtained (Table 2, entry 4). This proved to us that the reaction should
be carried out effectively under Cu-free conditions. Therefore, as
a logical next step, we decided to investigate the optimum ratio for
the Pd-species and L-1. Increasing the catalyst loading to 10 mol %
PdCl2(CH3CN)2, 30 mol % L-1 under Cu-free conditions resulted in
a decrease in the yield from 86% to 75% (Table 2, entry 5). Also, de-
creasing the catalyst loading to 2.5 mol % PdCl2(CH3CN)2, 7.5 mol %
L-1 under Cu-free conditions resulted in 72% yield of product with
reaction only complete after 36 h (Table 2, entry 6). Therefore, we
established that the most effective catalytic system is the use of
5 mol % PdCl2(CH3CN)2 and 15 mol % L-1 under Cu-free conditions.
Table 3
Sonogashira-type cross-coupling of aromatic acetylenes with 20-deoxyguanosine p-toluenesulfonate
R
N
O
O
S
O
XPhos (15 mol %)
N
N
N
N
N
N
PdCl2(CH3CN)2 (5 mol %)
N
NH2
NH2
TBDMSO
+
R
TBDMSO
O
Et3N
O
THF, 90oC, N2
3a-i
1b
OTBDMS
OTBDMS
Time (h)
8
Entry
1
Product
Yield (%)a
86
R
3a
2
3
3b
3c
10
10
91
95
CH3
OCH3
NO2
4
5
3d
3e
24
12
0
74
CH3
6
7
3f
12
24
82
51
OCH3
CHO
3g
8
3h
3i
10
12
85
59
9
N
a
Reactions were carried out in THF at 90 ꢀC, nucleoside concentration was 0.148 mmol in 2 mL THF. Reactions were carried out with 1.0 equiv of protected 20-deoxy-
guanosine p-toluenesulfonate, 1.5 equiv of terminal alkyne, 0.05 equiv of PdCl2(CH3CN)2, 0.15 equiv of XPhos, and 4.5 equiv of Et3N.

F.N. Ngassa et al. / Tetrahedron 66 (2010) 7919e7926
7923
entry 4) and a para-substituted formyl group (Table 3, entry 7),
were investigated. The ortho-substituted aromatic acetylene did not
result in any product formation; instead a substantial amount of
starting material was isolated (Table 3, entry 4). However, the para-
substituted aromatic acetylene gave a modest 51% yield of product
formation (Table 3, entry 7). To explore the versatility of our
optimized cross-coupling conditions, we decided to investigate the
reactivity of terminal acetylenes containing an extended aromatic
system or heterocycle. The extended aromatic terminal acetylene,
1-ethynylnaphthalene, gave the cross-coupling product 3h in 85%
yield (Table 3, entry 8). The reactivity of N-heteroaryl acetylene was
also investigated. For example, 3-pyridinyl acetylene reacted with
20-deoxyguanosine p-toluenesulfonate to give the cross-coupling
product 3i in 59% yield (Table 3, entry 9).
(Table 4, entries 1ꢁ3). The use of a more substituted aliphatic
acetylene, 3,3-dimethyl-1-butyne, resulted in no product formation
after 24 h (Table 4, entry 4). However, the use of a substrate,
1-pentyne, substituted at the fifth carbon with a chloro- or cyano-
group resulted in a slight increase in the yield of the cross-coupled
products 4e and 4f (Table 4, entries 5 and 6). The optimized
reaction condition also tolerated acid sensitive functional groups,
such as OTHP ether containing terminal acetylene (Table 4, entry 7).
For example, the reaction of the terminal acetylene 2-(prop-
2-ynyloxy)tetrahydro-2H-pyran with 20-deoxyguanosine p-tolue-
nesulfonate resulted in the cross-coupled product 4g obtained in a
modest 55% yield (Table 4, entry 7). The terminal acetylene,
1-ethynylcyclopentanol also reacted with 20-deoxyguanosine
p-toluenesulfonate to give 75% of the cross-coupled product 4h
Table 4
Sonogashira-type cross-coupling of aliphatic acetylenes with 20-deoxyguanosine p-toluenesulfonate
R
O
O
S
O
XPhos (15 mol %)
N
N
N
N
N
N
PdCl2(CH3CN)2 (5 mol %)
N
NH2
N
NH2
TBDMSO
+
R
TBDMSO
O
Et3N
O
THF, 90oC, N2
4a-j
1b
OTBDMS
OTBDMS
Entry
1
Product
Time (h)
12
Yield (%)a
66
R
4a
2
3
4
4b
4c
4d
12
12
24
63
58
0
5
6
4e
4f
10
10
70
69
Cl
CN
7
8
4g
4h
12
12
55
75
O
O
OH
9
4i
4j
12
12
72
79
Si
10
Si
a
Reactions were carried out in THF at 90 ꢀC, nucleoside concentration was 0.148 mmol in 2 mL THF. Reactions were carried out with 1.0 equiv of protected 20-deoxy-
guanosine p-toluenesulfonate, 1.5 equiv of terminal alkyne, 0.05 equiv of PdCl2(CH3CN)2, 0.15 equiv of XPhos, and 4.5 equiv of Et3N.
After successfully applying our optimized reaction conditions to
the cross-coupling of aromatic acetylenes, we then investigated the
cross-coupling of aliphatic acetylenes (Table 4). With simple unsub-
stituted aliphatic acetylenes, moderate to good yields were obtained
in the cross-coupling with 20-deoxyguanosine p-toluenesulfonate
(Table 4, entry 8). Terminal alkynes having the silyl moiety, tert-
butyl(ethynyl)dimethylsilane and triethyl(ethynyl)silane, also reac-
ted with 20-deoxyguanosine p-toluenesulfonate to afford moderate
to good yields of the cross-coupling products 4i and 4j, respectively
(Table 4, entries 9 and 10).

7924
F.N. Ngassa et al. / Tetrahedron 66 (2010) 7919e7926
3. Conclusion
NH2), 4.60e4.57 (m, 1H, 30), 3.98 (app q, 1H, 40, Jz3.3 Hz), 3.80 (dd,
1H, 50, J¼4.4, 11.3 Hz), 3.74 (dd, 1H, 50, J¼3.3, 11.3 Hz), 2.63e2.55 (m,
1H, 20), 2.60 (s, 3H, CH3), 2.40e2.33 (m, 1H, 20), 0.90, 0.89 (2s, 18H,
SiC(CH3)3), 0.09, 0.06 (2s, 12H, Si((CH3)2)); 13C NMR (75 MHz,
In summary, we have developed a Cu-free Sonogashira-type
cross-coupling of terminal acetylenes of varying functionality with
the O6-arylsulfonyl derivative of 20-deoxyguanosine. The reactions
generally proceed to completion within 24 h, afford moderate to
good yields, and are tolerant to different functional groups. Efforts
are underway to optimize the reaction conditions further and ex-
pand the scope to incorporate other nucleosides and terminal
acetylenes.
CDCl3) d: 159.3, 153.5, 141.7, 141.3, 133.1, 131.2, 130.1, 129.5, 125.7,
122.4, 121.4, 87.9, 87.0, 83.8, 72.1, 62.9, 40.9, 26.1, 25.9, 21.0, 18.5,
18.1, ꢁ4.6, ꢁ5.4. HRMS exact mass calculated for C31H47N5O3Si2
(MþþH) 594.3217, found 594.3275.
4.3.3. 2-Amino-6-[2-(methoxy)phenylethynyl]-9-[20-deoxy-30,50-bis-
O-(tert-butyldimethylsilyl)-b-D-erythro-pentafuranosyl]purine
4. Experimental section
4.1. General methods
(3c). Yellow oil (95%), Rf (8% EtOAc in CH2Cl2)¼0.11. 1H NMR
(300 MHz, CDCl3)
d: 8.07 (s, 1H, AreH), 7.65 (d, 1H, AreH, J¼9.1 Hz),
7.36e7.33 (m, 1H, AreH), 6.93e6.91 (m, 2H, AreH), 6.34 (t, 1H, 10,
J¼6.1 Hz), 5.41 (br s, 2H, NH2), 4.60e4.56 (m,1H, 30), 3.98 (app q,1H,
40, Jz3.6 Hz), 3.94 (s, 3H, OCH3), 3.81 (dd,1H, 50, J¼4.1,11.3 Hz), 3.75
(dd, 1H, 50, J¼3.3, 11.3 Hz), 2.61e2.53 (m, 1H, 20), 2.40e2.32 (m, 1H,
20), 0.91, 0.90 (2s,18H, SiC(CH3)3), 0.10, 0.07 (2s,12H, Si((CH3)2)); 13C
All reactions were carried out in oven-dried glassware under
a nitrogen atmosphere. All the reagents were obtained from
commercial sources and were used without further purification.
Thin-layer chromatography was performed on silica gel plates
containing fluorescent indicator. Column chromatographic sepa-
ration was performed using 230e400 mesh silica gel. 1H NMR
spectra (300 MHz) and 13C data (75 MHz) were obtained in CDCl3
or DMSO-d6. Coupling constants (J) are reported in Hertz (Hz).
The sugar protons are numbered 10ꢁ50 starting at the anomeric
carbon and moving along the carbon chain to the primary car-
binol carbon.
NMR (75 MHz, CDCl3) d: 161.1, 159.3, 153.5, 141.3, 134.7, 131.6, 129.2,
128.5, 120.5, 111.1, 110.7, 94.5, 87.9, 83.8, 72.1, 62.9, 56.0, 41.1, 29.8,
25.9, 18.5, 18.1, ꢁ4.7, ꢁ5.3. HRMS exact mass calculated for
C31H47N5O4Si2 (MþþH) 610.3167, found 610.3233.
4.3.4. 2-Amino-6-[4-(methyl)phenylethynyl]-9-[20-deoxy-30,50-bis-
O-(tert-butyldimethylsilyl)-b-D-erythro-pentafuranosyl]purine
(3e). Brown oil (74%), Rf (5% EtOAc in CH2Cl2)¼0.25. 1H NMR
(300 MHz, CDCl3)
d
: 8.07 (s, 1H, AreH), 7.57 (d, 2H, AreH, J¼8.3 Hz),
4.2. Typical procedure for the cross-coupling of
20-deoxyguanosine sulfonates with terminal alkynes
7.14 (d, 2H, AreH, J¼7.4 Hz), 6.32 (t, 1H, 10, J¼6.1 Hz), 5.16 (br s, 2H,
NH2), 4.58e4.57 (m,1H, 30), 3.98 (app q,1H, 40, Jz3.3 Hz), 3.81e3.74
(m, 2H, 50), 2.60e2.52 (m, 1H, 20), 2.37 (s, 3H, CH3), 2.27e2.00
(m, 1H, 20), 0.89, 0.88 (2s, 18H, SiC(CH3)3), 0.08, 0.05 (2s, 12H, Si
The Pd species (0.0074 mmol), ligand (0.0222 mmol), 20-deox-
yguanosine sulfonate (0.1484 mmol), Et3N (0.666 mmol), and THF
(2 mL) were placed in the reaction vial. The vial was flushed with N2
gas and stirred at room temperature for 30 min. Half of the terminal
alkyne was added to the vial (0.111 mmol). The vial was flushed
with N2 gas and stirred in an oil bath at 90 ꢀC for 30 min. The
second half of the terminal alkyne was added to the vial
(0.111 mmol). The vial was flushed with N2 gas and stirred in an oil
bath at 90 ꢀC until completion of reaction. The reaction mixture was
then cooled to room temperature, diluted with EtOAc, and washed
with water. The combined organic layers were dried with anhy-
drous Na2SO4. After concentration, the residue was purified by
column chromatography on silica gel, packed with CH2Cl2, and
eluting sequentially with 2% EtOAc/CH2Cl2, 5% EtOAc/CH2Cl2, and
8% EtOAc/CH2Cl2 to give the desired product.
((CH3)2)); 13C NMR (75 MHz, CDCl3)
d: 159.0, 153.6, 141.6, 140.5,
138.1, 132.8, 129.3, 128.5, 118.3, 98.5, 88.0, 83.9, 82.4, 72.1, 62.9, 41.0,
25.9, 21.8, 18.5, 18.1, ꢁ4.7, ꢁ5.4. HRMS exact mass calculated for
C31H47N5O3Si2 (MþþH) 594.3217, found 594.3271.
4.3.5. 2-Amino-6-[4-(methoxy)phenylethynyl]-9-[20-deoxy-30,50-bis-
O-(tert-butyldimethylsilyl)-b-D-erythro-pentafuranosyl]purine
(3f). Brown oil (82%), Rf (5% EtOAc in CH2Cl2)¼0.12. 1H NMR
(300 MHz, CDCl3)
d
: 8.07 (s, 1H, AreH), 7.65 (d, 2H, AreH, J¼8.5 Hz),
6.88 (d, 2H, AreH, J¼8.8 Hz), 6.34 (t, 1H, 10, J¼6.6 Hz), 5.14 (br s, 2H,
NH2), 4.60e4.56 (m, 1H, 30), 3.99 (app q, 1H, 40, Jz3.5 Hz), 3.83 (s,
3H, OCH3), 3.81 (dd, 1H, 50, J¼4.1, 11.3 Hz), 3.75 (dd, 1H, 50, J¼3.3,
11.3 Hz), 2.64e2.55 (m, 1H, 20), 2.40e2.33 (m, 1H, 20), 0.91, 0.90 (2s,
18H, SiC(CH3)3), 0.10, 0.07 (2s, 12H, Si((CH3)2)); 13C NMR (75 MHz,
CDCl3) d: 161.1, 158.8, 153.6, 141.6, 134.7, 133.2, 129.0, 115.0, 114.2,
4.3. Experimental data
113.5, 88.0, 84.0, 82.0, 72.1, 62.9, 55.4, 41.0, 25.9, 18.5, 18.1, ꢁ4.7,
ꢁ5.3. HRMS exact mass calculated for C31H47N5O4Si2 (MþþH)
610.3167, found 610.3225.
4.3.1. 2-Amino-6-[phenylethynyl]-9-[20-deoxy-30,50-bis-O-(tert-bu-
tyldimethylsilyl)-b-D-erythro-pentafuranosyl]purine (3a). Brown oil
(86%), Rf (5% EtOAc in CH2Cl2)¼0.33. 1H NMR (300 MHz, CDCl3)
d:
4.3.6. 2-Amino-6-[4-(formyl)phenylethynyl]-9-[20-deoxy-30,50-bis-O-
8.10 (s, 1H, AreH), 7.71e7.69 (m, 2H, AreH,), 7.38e7.35 (m, 3H,
AreH), 6.34 (t, 1H, 10, J¼6.3 Hz), 5.27 (br s, 2H, NH2), 4.59e4.56 (m,
1H, 30), 3.99 (app q,1H, 40, Jz3.3 Hz), 3.81 (dd,1H, 50, J¼4.1, 11.3 Hz),
3.75 (dd, 1H, 50, J¼3.3, 11.3 Hz), 2.62e2.54 (m, 1H, 20), 2.40e2.33 (m,
1H, 20), 0.92, 0.89 (2s, 18H, SiC(CH3)3), 0.11, 0.07 (2s, 12H, Si
(tert-butyldimethylsilyl)-b-D-erythro-pentafuranosyl]purine
(3g). Brown oil (51%), Rf (5% EtOAc in CH2Cl2)¼0.22. 1H NMR
(300 MHz, CDCl3) d: 10.03 (s, 1H, CHO), 8.14 (s, 1H, AreH), 7.87 (2d,
4H, AreH, J¼8.3 Hz), 6.35 (t, 1H, 10, J¼6.6 Hz), 5.21 (br s, 2H, NH2),
4.61e4.57 (m, 1H, 30), 4.00 (app q, 1H, 40, Jz3.3 Hz), 3.83 (dd, 1H, 50,
J¼4.1, 11.3 Hz), 3.76 (dd, 1H, 50, J¼3.3, 11.3 Hz), 2.63e2.54 (m, 1H, 20),
2.42e2.35 (m, 1H, 20), 0.91, 0.90 (2s, 18H, SiC(CH3)3), 0.10, 0.08 (2s,
((CH3)2)); 13C NMR (75 MHz, CDCl3)
d: 158.9, 153.7, 141.8, 140.2,
132.9, 130.1, 129.1, 128.5, 128.4, 121.3, 88.0, 83.9, 72.1, 62.9, 41.1, 26.1,
25.9, 18.5, 18.1, ꢁ4.6, ꢁ5.3. HRMS exact mass calculated for
C30H45N5O3Si2 (MþþH) 580.3061, found 580.3128.
12H, Si((CH3)2)); 13C NMR (75 MHz, CDCl3)
d: 191.3, 164.5, 159.2,
154.3, 136.5, 134.2, 133.4, 133.3, 129.5, 129.2, 128.5, 88.1, 84.1, 72.1,
62.8, 41.3, 26.1, 25.7, 18.5, 18.1, ꢁ4.7, ꢁ5.4. HRMS exact mass cal-
culated for C31H45N5O4Si2 (MþþH) 608.3010, found 608.3080.
4.3.2. 2-Amino-6-[2-(methyl)phenylethynyl]-9-[20-deoxy-30,50-bis-
O-(tert-butyldimethylsilyl)-b-D-erythro-pentafuranosyl]purine
(3b). Yellow oil (91%), Rf (5% EtOAc in CH2Cl2)¼0.25. 1H NMR
4.3.7. 2-Amino-6-[naphthalene-1-ylethynyl]-9-[20-deoxy-30,50-bis-
(300 MHz, CDCl3)
d
: 8.07 (s, 1H, AreH), 7.64 (d, 1H, AreH, J¼7.7 Hz),
O-(tert-butyldimethylsilyl)-b-D-erythro-pentafuranosyl]purine
7.30e7.14 (m, 3H, AreH), 6.34 (t, 1H, 10, J¼6.3 Hz), 5.29 (br s, 2H,
(3h). Brown oil (85%), Rf (5% EtOAc in CH2Cl2)¼0.13. 1H NMR

F.N. Ngassa et al. / Tetrahedron 66 (2010) 7919e7926
7925
(300 MHz, CDCl3)
d
: 8.63 (d, 1H, AreH, J¼8.5 Hz), 8.15 (s, 1H, AreH),
(4e). Yellow oil (70%), Rf (5% EtOAc in CH2Cl2)¼0.13. 1H NMR
7.96e7.85 (m, 3H, AreH), 7.66e7.61 (m, 1H, AreH), 7.56e7.44 (m, 2H,
AreH), 6.37 (t,1H,10, J¼6.5 Hz), 5.26 (br s, 2H, NH2), 4.63e4.59 (m,1H,
30), 4.01 (app q, 1H, 40, Jz3.4 Hz), 3.83 (dd, 1H, 50, J¼4.1, 11.3 Hz), 3.77
(dd,1H, 50, J¼3.3,11.3 Hz), 2.66e2.57 (m,1H, 20), 2.43e2.34 (m,1H, 20),
0.92, 0.90 (2s,18H, SiC(CH3)3), 0.11, 0.09 (2s,12H, Si((CH3)2)); 13C NMR
(300 MHz, CDCl3)
d
: 8.06 (s, 1H, AreH), 6.31 (t, 1H, 10, J¼6.5 Hz), 5.18
(br s, 2H, NH2), 4.56e4.55 (m, 1H, 30), 3.98e3.94 (m, 1H, 40),
3.83e3.75 (m, 2H, 50), 3.70 (t, 2H, J¼7.4 Hz), 2.75 (t, 2H, J¼7.0 Hz),
2.59e2.51 (m,1H, 20), 2.38e2.31 (m,1H, 20), 2.18e2.09 (m, 2H), 0.89,
0.88 (2s, 18H, SiC(CH3)3), 0.08, 0.06 (2s, 12H, Si((CH3)2)); 13C NMR
(75 MHz, CDCl3)
d: 162.5, 152.3, 150.6, 149.8,146.1, 135.6,134.6, 133.8,
(75 MHz, CDCl3) d: 158.6, 155.9, 154.6, 145.6, 140.4, 134.0, 129.7,
124.7,120.4,108.6, 88.3, 86.8, 84.4, 71.8, 62.7, 41.9, 38.0, 29.7, 25.8, 24.1,
18.5, 18.1, ꢁ4.7, ꢁ5.3. HRMS exact mass calculated for C34H47N5O3Si2
(MþþH) 630.3217, found 630.3290.
129.0, 117.1, 87.9, 84.0, 72.0, 62.9, 41.0, 25.8, 21.8, 18.5, 18.1, ꢁ4.7,
ꢁ5.4. HRMS exact mass calculated for C27H46ClN5O3Si2 (MþþH)
580.2828, found 580.2880.
4.3.8. 2-Amino-6-[pyridin-3-ylethynyl]-9-[20-deoxy-30,50-bis-O-
4.3.13. 2-Amino-6-[hex-5-ynenitrile]-9-[20-deoxy-30,50-bis-O-(tert-
(tert-butyldimethylsilyl)-
b
-
D
-erythro-pentafuranosyl]purine
butyldimethylsilyl)-b-D-erythro-pentafuranosyl]purine (4f). Brown
(3i). Brown oil (59%), Rf (5% EtOAc in CH2Cl2)¼0.20. 1H NMR
oil (69%), Rf (5% EtOAc in CH2Cl2)¼0.16. 1H NMR (300 MHz, CDCl3)
d:
(300 MHz, CDCl3)
d
: 8.95 (s, 1H, AreH), 8.65 (br s, 1H, AreH), 8.28
8.12 (s, 1H, AreH), 6.32 (t, 1H, 10, J¼6.6 Hz), 5.37 (br s, 2H, NH2),
4.57e4.55 (m, 1H, 30), 3.99 (app q, 1H, 40, Jz3.0 Hz), 3.82 (dd, 1H, 50,
J¼3.8, 11.3 Hz), 3.74 (dd, 1H, 50, J¼2.5, 11.3 Hz), 2.76 (t, 2H, J¼6.6 Hz),
2.62 (t, 2H, J¼6.6 Hz), 2.56e2.50 (m, 1H, 20), 2.40e2.33 (m, 1H, 20),
2.10e2.01 (m, 2H), 0.90, 0.89 (2s, 18H, SiC(CH3)3), 0.09, 0.07 (2s,
(s, 1H, AreH), 8.08 (d, 1H, AreH, J¼7.7 Hz), 7.39e7.35 (m,1H, AreH),
6.34 (t, 1H, 10 J¼6.6 Hz), 5.92 (br s, 2H, NH2), 4.60e4.56 (m, 1H, 30),
4.02 (app q, 1H, 40, Jz3.0 Hz), 3.85 (dd, 1H, 50, J¼3.6, 11.3 Hz), 3.77
(dd, 1H, 50, J¼3.0, 11.3 Hz), 2.57e2.49 (m, 1H, 20), 2.45e2.37 (m, 1H,
20), 0.91, 0.90 (2s,18H, SiC(CH3)3), 0.10, 0.09 (2s,12H, Si((CH3)2)); 13C
12H, Si((CH3)2)); 13C NMR (75 MHz, CDCl3)
d: 158.4, 153.9, 142.3,
NMR (75 MHz, CDCl3)
d
: 159.3,150.7,149.9,149.3,144.7,140.5,139.8,
141.1, 129.3, 119.0, 88.1, 84.2, 84.0, 72.1, 62.0, 41.2, 26.1, 25.8, 24.1,
19.1, 18.2, 18.1, 16.5, ꢁ4.7, ꢁ5.4. HRMS exact mass calculated for
C28H46N6O3Si2 (MþþH) 571.3170, found 571.3227.
129.3, 123.6, 116.5, 84.5, 83.8, 83.7, 74.6, 71.9, 62.8, 41.3, 25.9, 18.5,
18.2, ꢁ5.8, ꢁ5.4. HRMS exact mass calculated for C29H44N6O3Si2
(MþþH) 581.3013, found 581.3086.
4.3.14. 2-Amino-6-[3-(tetrahydro-2H-pyran-2-yloxy)prop-1-ynyl]-
4.3.9. 2-Amino-6-[pent-1-ynyl]-9-[20-deoxy-30,50-bis-O-(tert-bu-
9-[20-deoxy-30,50-bis-O-(tert-butyldimethylsilyl)-
b
-
D
-erythro-penta-
furanosyl]purine (4g). Brown oil (55%), Rf (5% EtOAc in CH2Cl2)¼
0.17. 1H NMR (300 MHz, CDCl3) : 8.08 (s, 1H, AreH), 6.32 (t, 1H, 10,
tyldimethylsilyl)-b-D-erythro-pentafuranosyl]purine (4a). Yellow oil
(66%), Rf (5% EtOAc in CH2Cl2)¼0.12. 1H NMR (300 MHz, CDCl3)
d:
d
8.07 (s, 1H, AreH), 6.31 (t, 1H, 10, J¼6.6 Hz), 5.33 (br s, 2H, NH2),
4.58e4.54 (m, 1H, 30), 3.98 (app q, 1H, 40, Jz3.3 Hz), 3.81 (dd, 1H, 50,
J¼4.1, 11.3 Hz), 3.74 (dd, 1H, 50, J¼3.0, 11.3 Hz), 2.59e2.51 (m, 1H, 20),
2.54 (t, 2H, J¼7.1 Hz), 2.39e2.31 (m, 1H, 20), 1.77e1.65 (m, 2H), 1.05
(t, 3H, J¼7.3 Hz), 0.90, 0.89 (2s,18H, SiC(CH3)3), 0.09, 0.07 (2s,12H, Si
J¼6.6 Hz), 5.15 (br s, 2H, NH2), 4.92 (s, 1H,), 4.58 (s, 2H), 4.01e3.97
(m, 1H, 30), 3.89e3.72 (m, 4H, 40, 50, and 2H), 3.58e3.53 (m, 1H, 50),
2.60e2.52 (m, 1H, 20), 2.39e2.27 (m, 1H, 20), 1.84e1.42 (m, 6H), 0.90,
0.89 (s, 18H, SiC(CH3)3), 0.09, 0.07 (2s, 12H, Si((CH3)2)); 13C NMR
(75 MHz, CDCl3) d: 159.4, 149.7, 145.2, 142.3, 130.2, 88.0, 84.1, 83.8,
((CH3)2)); 13C NMR (75 MHz, CDCl3)
d
: 158.7, 155.9, 154.5, 146.6,
75.3, 72.1, 62.9, 62.1, 54.7, 41.0, 30.2, 26.1, 25.8, 25.4, 19.01, 18.5, 18.1,
ꢁ4.6, ꢁ5.4. HRMS exact mass calculated for C30H51N5O5Si2 (MþþH)
618.3429, found 618.3484.
140.4, 134.0, 129.7, 129.0, 117.1, 87.9, 84.0, 72.0, 62.9, 41.0, 26.0, 21.8,
18.5,18.1, ꢁ4.7, ꢁ5.3. HRMS exact mass calculated for C27H47N5O3Si2
(MþþH) 546.3217, found 546.3290.
4.3.15. 2-Amino-6-[1-(ethynyl)cyclopentanol]-9-[20-deoxy-30,50-bis-
4.3.10. 2-Amino-6-[hex-1-ynyl]-9-[20-deoxy-30,50-bis-O-(tert-bu-
O-(tert-butyldimethylsilyl)-b-D-erythro-pentafuranosyl]purine
tyldimethylsilyl)-
b
-
D
-erythro-pentafuranosyl]purine (4b). Brown oil
(4h). Brown oil (75%), Rf (5% EtOAc in CH2Cl2)¼0.19. 1H NMR
(63%), Rf (5% EtOAc in CH2Cl2)¼0.25. 1H NMR (300 MHz, CDCl3)
d:
(300 MHz, CDCl3)
d
: 8.16 (s, 1H, AreH), 6.30 (t, 1H, 10, J¼6.6 Hz), 5.25
8.03, (s, 1H, AreH), 6.31 (t, 1H, 10, J¼6.6 Hz), 5.07 (br s, 2H, NH2),
4.59e4.55 (m 1H, 30), 3.98 (app q, 1H, 40, Jz3.4 Hz), 3.80 (dd, 1H, 50,
J¼4.1, 11.2 Hz), 3.74 (dd, 1H, 50, J¼3.6, 11.2 Hz), 2.57e2.53 (m, 3H, 20,
and CH2), 2.37e2.35 (m,1H, 20),1.72e1.62 (m, 2H),1.54e1.42 (m, 2H),
1.24 (t, 3H, J¼7.1 Hz), 0.92, 0.89 (2s, 18H, SiC(CH3)3), 0.09, 0.06 (2s,
(br s, 2H, NH2), 4.59e4.56 (m, 1H, 30), 4.20 (br s, 1H, OH), 3.97 (app
q, 1H, 40, Jz3.3 Hz), 3.78 (dd, 1H, 50, J¼4.4, 11.3 Hz), 3.72 (dd, 1H, 50,
J¼3.6, 11.3 Hz), 2.68e2.59 (m, 1H, 20), 2.37e2.31 (m, 1H, 20),
2.17e2.06 (m, 4H) 1.92e1.85 (m, 2H), 1.81e1.74 (m, 2H), 0.90, 0.87
(2s, 18H, SiC(CH3)3), 0.09, 0.05 (2s, 12H, Si((CH3)2)); 13C NMR
12H, Si((CH3)2)); 13C NMR (75 MHz, CDCl3)
d: 158.4, 153.7, 141.2,
(75 MHz, CDCl3) d: 159.5, 153.2, 142.1, 141.4, 129.3, 102.2, 87.9, 84.0,
140.6,132.4, 129.7, 129.2, 128.7, 88.0, 83.9, 71.9, 62.9, 41.0, 29.8, 26.0,
25.7, 22.3, 19.2, 18.2, ꢁ4.7, ꢁ5.7. HRMS exact mass calculated for
C28H49N5O3Si2 (MþþH) 560.3374, found 560.3444.
74.4, 72.2, 63.0, 60.5, 53.5, 42.4, 25.8, 23.8, 18.1, 14.3, ꢁ4.6, ꢁ5.4.
HRMS exact mass calculated for C29H49N5O4Si2 (MþþH) 588.3323,
found 588.3377.
4.3.11. 2-Amino-6-[oct-1-ynyl]-9-[20-deoxy-30,50-bis-O-(tert-butyldi-
4.3.16. 2-Amino-6-[tert-butyldimethylsilylethynyl]-9-[20-deoxy-30,50-
methylsilyl)-
b
-
D
-erythro-pentafuranosyl]purine (4c). Brown oil
bis-O-(tert-butyldimethylsilyl)-b-D-erythro-pentafuranosyl]purine
(58%), Rf (5% EtOAc in CH2Cl2)¼0.29. 1H NMR (300 MHz, CDCl3)
d:
(4i). Yellow oil (72%), Rf (5% EtOAc in CH2Cl2)¼0.24. 1H NMR
8.04 (s, 1H, AreH), 6.31 (t, 1H, 10, J¼6.6 Hz), 5.12 (br s, 2H, NH2),
4.59e4.55 (m, 1H, 30), 3.98 (app q, 1H, 40, Jz3.3 Hz), 3.81 (dd, 1H, 50,
J¼4.1, 11.3 Hz), 3.74 (dd, 1H, 50, J¼3.3, 11.3 Hz), 2.61e2.52 (m, 3H, 20,
and CH2), 2.38e2.31 (m, 1H, 20), 1.73e1.63 (m, 2H), 1.49e1.40
(m, 2H), 1.31e1.24 (m, 7H), 0.90, 0.87 (2s, 18H, SiC(CH3)3), 0.09, 0.07
(300 MHz, CDCl3)
d
: 8.09 (s,1H, AreH), 6.30 (t,1H,10, J¼6.6 Hz), 5.35
(br s, 2H, NH2), 4.59e4.54 (m, 1H, 30), 3.98 (app q, 1H, 40, Jz3.3 Hz),
3.81e3.70 (m, 2H, 50), 2.59e2.50 (m, 1H, 20), 2.39e2.31 (m, 1H, 20),
1.03 (s, 9H), 0.90, 0.89 (2s, 18H, SiC(CH3)3), 0.25 (s, 6H), 0.09, 0.06
(2s,12H, Si((CH3)2)); 13C NMR (75 MHz, CDCl3)
d: 159.6, 150.2, 146.7,
(2s,12H, Si((CH3)2)); 13C NMR (75 MHz, CDCl3)
d
: 153.8,142.0,132.4,
142.3, 132.1, 129.2, 88.0, 83.9, 72.1, 62.9, 40.9, 26.3, 26.0, 25.8, 18.5,
18.1, 16.8, ꢁ4.7, ꢁ4.8, ꢁ5.4. HRMS exact mass calculated for
C30H55N5O3Si3 (MþþH) 618.3613, found 618.3669.
129.7, 128.8, 128.6, 87.7, 84.0, 72.1, 62.9, 41.2, 31.7, 29.8, 28.1, 26.0,
25.6, 22.4, 20.0, 18.5, 18.1, 13.8, ꢁ4.5, ꢁ5.7. HRMS exact mass cal-
culated for C30H53N5O3Si2 (MþþH) 588.3687, found 588.3758.
4.3.17. 2-Amino-6-[triethylsilylethynyl]-9-[20-deoxy-30,50-bis-O-
4.3.12. 2-Amino-6-[5-chloropent-1-ynyl]-9-[20-deoxy-30,50-bis-O-
(tert-butyldimethylsilyl)-
(tert-butyldimethylsilyl)-b-D-erythro-pentafuranosyl]purine
b
-
D
-erythro-pentafuranosyl]purine
(4j). Orange oil (79%), Rf (5% EtOAc in CH2Cl2)¼0.23. 1H NMR

7926
F.N. Ngassa et al. / Tetrahedron 66 (2010) 7919e7926
: 8.05 (s,1H, AreH), 6.29 (t,1H,10, J¼6.6 Hz), 5.25
3. For recent reviews on the Sonogashira cross-coupling reactions, see: (a) Agro-
(300 MHz, CDCl3)
d
foglio, L. A.; Gillaizeau, I.; Saito, Y. Chem. Rev. 2003, 103, 1879; (b) Doucet, H.;
Hierso, J.-C. Angew. Chem., Int. Ed. 2007, 46, 834; (c) Chinchilla, R.; Nájera, C. Chem.
Rev. 2007, 107, 874; (d) Plenio, H. Angew. Chem., Int. Ed. 2008, 47, 6954.
4. Gelman, D.; Buchwald, S. L. Angew. Chem., Int. Ed. 2003, 42, 5993.
5. Liang, Y.; Xie, Y.-X.; Li, J.-H. J. Org. Chem. 2006, 71, 379 and references cited
therein.
(br s, 2H, NH2), 4.57e4.55 (m, 1H, 30), 3.96 (app q, 1H, 40, Jz3.3 Hz),
3.80e3.69 (m, 2H, 50), 2.59e2.50 (m, 1H, 20), 2.37e2.30 (m, 1H, 20),
1.05 (t, 9H, CH3, J¼7.8 Hz), 0.88, 0.86 (2s, 18H, SiC(CH3)3), 0.74 (q,
6H, CH2, J¼7.8 Hz), 0.08, 0.05 (2s, 12H, Si((CH3)2)); 13C NMR
(75 MHz, CDCl3) d: 159.6, 149.7, 145.2, 141.4, 129.7, 110.5, 98.6, 87.9,
6. Li, J.-H.; Li, J.-L.; Wang, D.-P.; Pi, S.-F.; Xie, Y.-X.; Zhang, M.-B.; Hu, X.-C. J. Org.
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10. For selected examples of Sonogashira cross-coupling under Cu-free conditions,
see: (a) Li, J.-H.; Zhang, X.-D.; Xie, Y.-X. Synthesis 2005, 804; (b) Gholap, A. R.;
Venkatesan, K.; Pasricha, R.; Daniel, T.; Lahoti, R. J.; Srinivasan, K. V. J. Org. Chem.
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83.7, 71.9, 62.9, 40.8, 26.1, 18.5, 18.1, 7.6, 4.2, ꢁ4.7, ꢁ5.4. HRMS exact
mass calculated for C30H55N5O3Si3 (MþþH) 618.3613, found
618.3669.
Acknowledgements
We acknowledge the generosity of the Chemistry Department at
GVSU through the use of its instrumentation facilities. We also
thank the Chemistry Department for providing financial support
through the Weldon Fund.
€
2007, 48, 7079; (d) Ljungdahl, T.; Bennur, T.; Dallas, A.; Emtenas, H.; Mår-
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Supplementary data
12. For selected examples of Sonogashira cross-coupling under Ligand-free condi-
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13. See Ref. 5.
General experimental procedures and characterization data for
all new products (1H and 13C NMR, and HRMS). In addition, 1H NMR
spectra of compounds 3a, 3b, 3c, 3e, 3f, 3g, 3h, 3i, 4a, 4b, 4c, 4e, 4f,
4g, 4h, 4i, 4j and nucleoside arylsulfonates. Supplementary data
associated with this article can be found in online version at
doi:10.1016/j.tet.2010.08.032.
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