Synthesis of benzamide-C-ribonucleosides by Pd-catalyzed aminocarbonylations

Article abstract of DOI:10.1016/j.tet.2009.04.006

A novel modular, efficient and practical methodology for preparation of p- and m-substituted benzamide-C-ribonucleosides was developed. Reaction of TBS-protected 3- and 4-bromophenyl-C-ribonucleosides 1 and 4 with various primary and secondary amines or N

Full text of DOI:10.1016/j.tet.2009.04.006

Tetrahedron 65 (2009) 4471–4483
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Synthesis of benzamide-C-ribonucleosides by Pd-catalyzed aminocarbonylations
ˇ
*
Martin Stefko, Radek Pohl, Michal Hocek
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Gilead Sciences & IOCB Research Center, Flemingovo nam. 2,
CZ-16610 Prague 6, Czech Republic
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel modular, efficient and practical methodology for preparation of p- and m-substituted benza-
mide-C-ribonucleosides was developed. Reaction of TBS-protected 3- and 4-bromophenyl-C-ribonucleo-
sides 1 and 4 with various primary and secondary amines or NH4Cl under atmospheric pressure of
carbon monoxide and in the presence of Pd(OAc)2 and Xantphos lead to the corresponding amides 2a–j
and 5a–j in high yields. Subsequent deprotection of silylated nucleosides by Et3N$3HF or TFA afforded
a series of free C-ribonucleosides 3a–j or 6a–j in excellent yields (20 examples).
Received 5 February 2009
Received in revised form 18 March 2009
Accepted 2 April 2009
Available online 9 April 2009
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
of echiguanine B. Originally, the carbonylation reactions required
higher pressure of CO and more reactive aryl iodides. Only recently,
C-nucleosides are important class of stable analogues of biogenic
nucleosides that find useful applications in chemical biology1 and
medicinal chemistry.2 Many of the current synthetic approaches3 to
these compounds are inefficient and nonselective and even the ef-
ficient procedures4 are not truly general. We have recently de-
veloped a new modular approach5 to C-nucleosides consisting in
the synthesis of halogenated aryl-C-nucleosides and their follow-up
functionalizations by cross-couplings, aminations, etc. and it is now
applied to the synthesis of diverse classes of nucleosides.
Buchwald et al.13 reported a highly efficient method for direct
synthesis of N-substituted benzamides from aryl bromides under
atmospheric pressure of CO in presence of Pd(OAc)2 and Xantphos.
Here we report a general and practical method for the Pd-catalyzed
aminocarbonylation of easily available 3-bromophenyl-C-ribonu-
cleoside 1 and 4-bromophenyl-C-ribonucleoside 414 at atmospheric
pressure of CO under mild conditions, to efficiently prepare wide
range of diverse N-substituted benzenecarboxamide C-nucleosides.
Carboxamide derivatives of C-nucleosides are analogues of bio-
genic nicotinamine ribonucleoside (Fig. 1) and some of them exhibit
cytostatic effect.6 Apart from five-membered heterocyclic carbox-
amides7 (tiazofurin and analogues), also simple benzamide-3-C-ri-
bonucleoside (BR) was found8 to be a strong cytostatic agent
inducing apoptosis in cancer cells.9 General mechanism of action of
these compounds is their biotransformation to analogues of NAD,
which then inhibit IMP dehydrogenase.10 Syntheses of these C-nu-
cleosides are7,8 quite difficult and low yielding and do not allow
access to large series of derivatives for SAR studies. We have envis-
aged a new approach to a series of analogues and positional isomers
of important cytostatic BR via Pd-catalyzed aminocarbonylation of
haloaryl C-nucleosides (Fig. 1).
Nicotinamide
Cytostatic analogues:
O
ribonucleoside
O
O
NH2
NH2
NH2
S
N
N
O
HO
HO
HO
O
O
OH OH
BR
OH OH
OH OH
Tiazofurin
R1
O
This study:
N
Br
R2
Palladium-catalyzed aminocarbonylations of aryl halides (or
halide equivalents) are a general tool11 for the introduction of
carboxamide function. There is only one single known example12 of
the use of aminocarbonylation in nucleoside chemistry (modifica-
tion of position 7 of 7-deazapurine nucleoside) in the total synthesis
HO
O
HO
O
OH OH
OH OH
N-substituted derivatives
and positional isomers of BR
* Corresponding author. Tel.: þ420 220183324; fax: þ420 220183559.
E-mail address: hocek@uochb.cas.cz (M. Hocek).
Figure 1. Structure of nicotinamide ribonucleoside, its cytostatic C-nucleoside ana-
logues and rationale for this study.
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.04.006

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M. Stefko et al. / Tetrahedron 65 (2009) 4471–4483
4472
2. Results and discussion
amines were more sensitive to strictly anhydrous conditions and
special precautions (i.e., finely grounded freshly dried K3PO4 and
extra dry solvent) had to be applied to get good conversions. In this
way, cyclopropyl, cyclohexyl and benzyl carboxamides 2f–h were
prepared in good yields of 86%, 84% and 79%, respectively (entries
6–8). Analogous reaction of methylamine hydrochloride gave the N-
methylcarboxamide 2i in 88% yield (entry 9).
Final deprotection of the silylated nucleosides 2a–i by treatment
with Et3N$3HF at 40 ꢀC for 2 days followed by treatment with
K2CO3 resulted in formation of the desired free nucleosides 3a–i.
Chromatographic purification of the resulting crude nucleosides on
silica gel was not practical due to significant losses of the hydro-
philic products on the column. Therefore, reverse-phase flash
chromatography was used for the final purification to give the free
nucleosides 3a–i in excellent yields (83–95%).
The first target series of compounds were benzene-3-carbox-
amide-C-nucleosides. The aminocarbonylation reactions of 3-bro-
mophenyl-C-ribonucleoside 1 with CO (1 atm) and amines were
performed under conditions analogous to the Buchwald pro-
cedure13 in presence of 5 mol % of Pd(OAc)2, Xantphos and K3PO4 in
toluene (Scheme 1, Table 1). In all cases, short reaction times (2–4 h)
were sufficient for the complete conversion of starting material.
Reactions with secondary amines proceeded very smoothly to give
the corresponding amides 2a–d in excellent yields (Table 1, entry 1–
4). Dimethyl amine hydrochloride was used as a solid equivalent of
gaseous dimethyl amine in the preparation of N,N-dimethyl-
carboxamide 2e in 84% yield (entry 5). Reactions with primary
An analogous two-step procedure was used for the preparation
of isomeric 4-substituted-benzamide-C-ribonucleosides. Also in
this case all the amines or amine hydrochlorides generally show
good reactivity under the same conditions of the amino-
carbonylation to give the carboxamide nucleosides 5a–i (Scheme 2,
Table 2). Desilylation of the TBS-protected nucleosides 5a–i by
treatment with Et3N$3HF has been performed analogously to fur-
nish the series of free C-ribonucleosides 6a–i in excellent yields
(85–95%, Table 2), after purification by reversed-phase flash
chromatography.
In order to prepare unsubstituted benzamide nucleoside 2j and
5j, several sources of ammonia have been tested in the reaction of
3-bromophenyl-C-ribonucleoside 1 under analogous conditions
(Table 3) using higher loading (10 mol %) of Pd(OAc)2. When using
LiHMDS (entry 1), no reaction occurred. The use of HCOONH4
resulted in the formation of an inseparable reaction mixture (entry
2), while the use of HMDS furnished desired amide 2j but in low
hardly reproducible yields of 5–20% (entry 3). Finally with AcONH4,
the desired 3-(carbamoylphenyl)-C-ribonucleoside 2j was pre-
pared in 76% yield (entry 4). As an alternative, gaseous ammonia
was used as a ca. 1:1 mixture with CO and the desired amide 2j was
prepared in an acceptable 62% yield (entry 5). With NH4Cl as an
ammonia surrogate, 2j was prepared in low yield of 20% but much
cleaner mixture was obtained making the isolation of the product
more straightforward (entry 6). Revising the former conditions lead
us to the use of solvent mixture toluene/DMSO (1:1). This modifi-
cation increased the yield and enabled us to reduce the reaction
time or palladium loading (to 5 mol %) (entries 7 and 8). The opti-
mized conditions then employed 5 mol % of Pd(OAc)2 and a reaction
time of 3.5 h to give 2j in 68% yield. For the aminocarbonylation of
4-bromophenyl-C-nucleoside 4 to the corresponding amide 5j, the
use of gaseous ammonia and NH4OAc gave good yields of the
product only after 14–16 h (entries 9 and 10), while the use of
O
Br
TBSO
HO
N
R1
O
O
R2
TBSO OTBS
Amine source
HO OH 3a-j
1
Et3N•3HF
40 °C THF
2 days
R1
Pd(OAc)2, Xantphos
K3PO4, CO (1 atm)
O
N
Toluene, 80 °C
TBSO
O
R2
2a-j
TBSO OTBS
Scheme 1. Aminocarbonylation of 3-bromophenyl-C-ribonucleoside 1.
Table 1
Aminocarbonylation of 3-bromophenyl-C-ribonucleoside 1a
Entry
Amine
Time Aminocarbonylation product
(h)
Deprotect.
product (yield)
R1
R2
Yield
1
2
3
4
2
2
–(CH2)4–
2a (95%)
3a (86%)
HN
HN
–(CH2)5–
2b (92%)
2c (89%)
2d (95%)
3b (93%)
3c (89%)
3d (83%)
–(CH2)2O(CH2)2–
HN
O
4
5
HN(n-Bu)2
4
2
n-Bu
n-Bu
HNMe2$HCl
Me
Me
2e (84%)b 3e (95%)
6
7
8
9
3.5
2
H
H
H
H
H
c-Pr
c-Hex
Bn
2f (86%)
2g (84%)
2h (79%)
2i (88%)
2j (68%)c
3f (89%)
3g (91%)
3h (88%)
3i (93%)
3j (90%)d
H2N
H2N
O
R1
Br
N
R2
TBSO
HO
O
O
4
H2N
TBSO OTBS
Amine source
HO OH
4
6a-j
O
R1
R2
H2NMe$HCl
2
Me
N
Pd(OAc)2, Xantphos
K3PO4, CO (1 atm)
Toluene 80 °C
Et3N•3HF
40 °C THF
2 days
10
NH4Cl
3.5
H
TBSO
O
a
Reaction conditions: 5 mol % of Pd(OAc)2, 10 mol % Xantphos, 3 equiv amine,
4 equiv K3PO4, toluene (2.5 mL/mmol), 80 ꢀC, CO (1 atm).
b
Me2NH$HCl (2 equiv) was used.
Toluene/DMSO 1:1 (3 mL/mmol) was used.
TBSO OTBS 5a-j
Scheme 2. Aminocarbonylation of 4-bromophenyl-C-ribonucleoside 4.
c
d
TFA/H2O 9:1, rt, 1.5 h.

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M. Stefko et al. / Tetrahedron 65 (2009) 4471–4483
4473
Table 2
In conclusion, the presented methodology gives a facile access to
primary and secondary benzamide-C-ribonucleosides by Pd(OAc)2/
Xanthphos catalyzed aminocarbonylation in presence of primary or
secondary amines and represents the first systematic study and
application of this reaction in nucleoside chemistry. An analogous
reaction using NH4Cl gives unsubstituted benzamides in somewhat
lower (but still acceptable) yields. In contrast to know cytostatic
unsubstituted benzamide 3j (BR),8 the N-substituted benzamide-C-
ribonucleosides 3a–3i and 6a–6i did not exert any significant cy-
tostatic activity. However, this powerful and efficient methodology
extends the repertoire of reactions for functionalization of C-nu-
cleosides in our modular approach5 and will now be used for the
synthesis of heterocyclic benzamide ribonucleosides with potential
biological activity.
Aminocarbonylation of 4-bromophenyl-C-ribonucleoside 4a
Entry
Amine
Time (h) Aminocarbonylation product Deprotect.
product (yield)
R1
R2
Yield
1
2
3
3
3
2
–(CH2)4–
5a (88%) 6a (90%)
5b (92%) 6b (91%)
HN
HN
–(CH2)5–
–(CH2)2O(CH2)2– 5c (89%)
6c (87%)
HN
O
4
5
HN(n-Bu)2
3
4
n-Bu
n-Bu
5d (95%) 6d (87%)
5e (87%)b 6e (95%)
3. Experimental
3.1. General
HNMe2$HCl
Me
Me
6
7
8
9
3
H
H
H
H
H
c-Pr
c-Hex
Bn
5f (81%)
6f (89%)
H2N
H2N
NMR spectra were recorded on 600 MHz (1H at 600.1 MHz, 13
at 150.9 MHz) and 500 MHz (499.8 and 500.0 MHz for 1H and
125.7 MHz for 13C) spectrometers. Chemical shifts (in ppm,
scale)
C
2
5g (87%) 6g (85%)
5h (86%) 6h (93%)
d
were referenced to TMS as internal standard. Coupling constants (J)
are given in hertz. The assignment of carbons was based on C,H-
HSQC and C,H-HMBC experiments. Melting points were de-
termined on a Kofler block and are uncorrected. Mass spectra were
measured using FAB (ionization by Xe, accelerating voltage 8 kV,
glycerolþthioglycelor matrix) or ESI. Pd(OAc)2, Pd(PPh3)4, Xant-
phos and all amines were purchased from commercial suppliers
and used without any further treatment. All reactions were carried
out in flame-dried glassware with magnetic stirring. K3PO4 was
finely ground and dried (630 ꢀC, 4 Torr, 1 h) prior to each use. Tol-
uene was dried by refluxing with sodium/benzophenone and
freshly distilled prior to use. DMSO was stored over molecular
sieves under argon.
3
H2N
H2NMe$HCl
3.5
Me
5i (81%)
6i (90%)
10
NH4Cl
3.5
H
5j (65%)c 6j (90%)d
a
Reaction conditions: 5 mol % of Pd(OAc)2, 10 mol % Xantphos, 3 equiv amine,
4 equiv K3PO4, toluene (2.5 mL/mmol), 80 ꢀC, CO (1 atm).
b
Me2NH$HCl (2 equiv) was used.
Toluene/DMSO 1:1 (3 mL/mmol) was used.
c
d
TFA/H2O 9:1, rt, 1.5 h.
NH4Cl proved to be the best, yielding the nucleoside 5j in 65% yield
within 3.5 h (entry 11).
3.2. General procedure for aminocarbonylation
Attempted deprotection of amides 2j and 5j by treatment with
Et3N$3HF and subsequent treatment with K2CO3 resulted in deg-
radation of final products. Therefore, an acidic cleavage by TFA/
water (9:1) mixture was used. The reaction was finished within
1.5 h at room temperature and crude nucleosides were purified by
reversed-phase chromatography to give free nucleosides 3j and 6j
in excellent 90% yields.
A flame-dried septum-sealed flask containing 3- or 4-bromo-
phenyl-C-ribonucleoside 1 or 4 (1 mmol), Pd(OAc)2 (0.05 mmol),
Xantphos (0.1 mmol), K3PO4 (4 mmol) [and an amine hydrochlo-
ride (3 mmol) in cases when solid hydrochlorides were used] was
evacuated and backfilled with CO(g). Then, toluene (2.5 mL) and an
amine (3 mmol) [in cases when liquid amines were used] were
added via syringe. The reaction mixture was stirred at room tem-
perature for 5 min and then immersed into a preheated oil bath
(80 ꢀC) and vigorously stirred until the starting material had been
completely consumed (TLC analysis, hexanes/EA 8:2). The reaction
mixture was then allowed to cool to room temperature, diluted
with Et2O, filtered through a plug of Celite (eluting with Et2O) and
concentrated under reduced pressure. The crude product was pu-
rified by flash chromatography on silica gel.
Table 3
Conversion of nucleosides 1 and 4 to carboxamides 2j and 5ja
Entry
Starting comp.
Ammonia source
Reaction time (h)
Product (yield)
1
2
3
4
5
6
7
8
1
1
1
1
1
1
1
1
4
4
4
LiHMDS
HCOONH4
HMDS
AcONH4
NH3 (g)
NH4Cl
NH4Cl
NH4Cl
NH3
AcONH4
NH4Cl
24
24
8
15
16
8
1.5
3.5
14
16
3.5
2j N.R.b
2j N.R.c
2j (5–20%)d
2j (76%)a
2j (62%)e
2j (20%)a
2j (69%)f
2j (68%)f,g
5j (69%)e
5j (60%)a
5j (65%)f,g
3.2.1. 1
tri-O-(tert-butyldimethylsilyl)-
According to the general procedure, a mixture of 3-bromo-
phenyl-C-ribonucleoside (0.502 mmol, 318 mg), Pd(OAc)2
b
-{3-[(Pyrrolidine-1-yl)carbonyl]phenyl}-1-deoxy-2,3,5-
D-ribofuranose (2a)
1
9
10
11
(5 mol %, 0.025 mmol, 5.6 mg), Xantphos (10 mol %, 0.050 mmol,
29.1 mg), pyrrolidine (1.51 mmol, 3 equiv, 0.13 mL), K3PO4
(2.01 mmol, 4 equiv, 427 mg) and toluene (1.3 mL) was heated at
80 ꢀC for 4 h. The crude product mixture was purified by flash
column chromatography on silica gel in gradient hexane/EA 100:2
to 100:16 to provide the title compound as a colourless light oil
(311 mg, 95%). HRMS (FAB) for C34H64NO5Si3: [MþH] calculated,
650.4092; found, 650.4108. 1H NMR (600.1 MHz, CDCl3): ꢁ0.43,
ꢁ0.13, 0.09, 0.11 and 0.12 (5ꢂs, 18H, CH3Si), 0.80, 0.93 and 0.94
a
Reaction conditions: 10 mol % of Pd(OAc)2, 20 mol % Xantphos, 3 equiv of am-
monia source, 4 equiv K3PO4, toluene (2.5 mL/mmol), 80 ꢀC, CO (1 atm).
b
No base was used.
Inseparable reaction mixture.
Yields were not reproducible.
1:1 Mixture of NH3(g) and CO(g) was used.
Toluene/DMSO 1:1 (3 mL/mmol) was used.
Pd(OAc)2 (5 mol %), 10 mol % Xantphos.
c
d
e
f
g

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M. Stefko et al. / Tetrahedron 65 (2009) 4471–4483
4474
(3ꢂs, 3ꢂ9H, (CH3)3C), 1.81–1.87 and 1.92–1.97 (2ꢂm, 2ꢂ2H, CH2-
pyr), 3.37 and 3.40 (2ꢂdt, 2H, Jgem¼10.6, Jvic¼6.8, CH2N-pyr), 3.63 (t,
2H, Jvic¼7.0, CH2N-pyr), 3.77 and 3.79 (2ꢂdd, 2H, Jgem¼11.1,
6). 13C NMR (150.9 MHz, CDCl3): ꢁ5.50, ꢁ5.41, ꢁ5.34, ꢁ4.50, ꢁ4.47
and ꢁ4.37 (CH3Si), 17.93, 18.06 and 18.36 (C(CH3)3), 25.83, 25.87
and 26.00 ((CH3)3C), 42.46 and 48.28 (CH2N-morph), 63.79 (CH2-
50), 66.90 (CH2O-morph), 74.04 (CH-30), 79.52 (CH-20), 82.33 (CH-
10), 86.26 (CH-40), 125.59 (CH-2), 126.44 (CH-4), 128.14 (CH-5),
128.51 (CH-6), 135.16 (C-3), 141.37 (C-1), 170.33 (CO). IR spectrum
(CCl4): 1647, 1607, 1588, 1487, 1472, 1462, 1439, 1419, 1389, 1362,
1330, 1300, 1257, 1211, 1153, 1117, 1111, 1098, 1080, 1026, 940, 888,
0
0
0
0
0
0
0
0
J5 ,4 ¼3.5, H-5 ), 3.85 (dd, 1H, J2 ,1 ¼7.9, J2 ,3 ¼4.4, H-2 ), 4.04 (td, 1H,
0
0
0
0
0
0
0
0
0
0
J4 ,5 ¼3.5, J4 ,3 ¼1.7, H0-4 ), 4.12 (dd, 1H, J3 ,2 ¼4.4, J3 ,4 ¼1.7, H-3 ), 4.80
0
0
(d, 1H, J1 ,2 ¼7.9, H-1 ), 7.33 (t, 1H, J5,4¼J5,6¼7.7, H-5), 7.41 (ddd, 1H,
J4,5¼7.7, J4,2¼1.7, J4,6¼1.4, H-4), 7.48 (ddd, 1H, J6,5¼7.7, J6,2¼1.7,
J6,4¼1.4, H-6), 7.56 (t, 1H, J2,4¼J2,6¼1.7, H-2). 13C NMR (150.9 MHz,
CDCl3): ꢁ5.52, ꢁ5.48, ꢁ5.31, ꢁ4.50, ꢁ4.48 and ꢁ4.38 (CH3Si), 17.93,
18.07 and 18.36 (C(CH3)3), 24.49 (CH2-pyr), 25.83, 25.87 and 25.98
((CH3)3C), 26.37 (CH2-pyr), 46.06 and 49.59 (CH2N-pyr), 63.76
(CH2-50), 73.95 (CH-30), 79.48 (CH-20), 82.49 (CH-10), 86.07 (CH-40),
125.41 (CH-2), 126.48 (CH-4), 127.91 (CH-5), 128.33 (CH-6), 137.15
(C-3), 140.82 (C-1), 169.71 (CO). IR spectrum (CCl4): 1636, 1607,
1587, 1485, 1472, 1463, 1446, 1409, 1390, 1361, 1343, 1308, 1255,
837, 698, 673 cmꢁ1
.
3.2.4. 1
(tert-butyldimethyl-silyl)-
According to the general procedure a mixture of 3-bromo-
phenyl-C-ribonucleoside (0.237 mmol, 150 mg), Pd(OAc)2
b-[3-(Dibutylcarbamoyl)phenyl]-1-deoxy-2,3,5-tri-O-
D
-ribofuranose (2d)
1
(5 mol %, 0.012 mmol, 2.7 mg), Xantphos (10 mol %, 0.024 mmol,
13.7 mg), dibutylamine (0.712 mmol, 3 equiv, 0.12 mL), K3PO4
(0.949 mmol, 4 equiv, 202 mg) and toluene (0.60 mL) was heated at
80 ꢀC for 4 h. The crude product mixture was purified by flash
column chromatography on silica gel in gradient hexane/EA 100:2
to 100:6 to provide the title compound as a colourless light oil
(158 mg, 95%). HRMS (FAB) for C38H74NO5Si3: [MþH] calculated,
708.4875; found, 708.4864. 1H NMR (500.0 MHz, CDCl3): ꢁ0.42,
ꢁ0.13, 0.09, 0.11 and 0.12 (5ꢂs, 18H, CH3Si), 0.78–0.81 (br m, 3H,
CH3CH2CH2CH2N), 0.81, 0.93 and 0.93 (3ꢂs, 3ꢂ9H, (CH3)3C), 0.95–
0.99 (br m, 3H, CH3CH2CH2CH2N), 1.08–1.16, 1.35–1.43, 1.43–1.50
and 1.59–1.67 (4ꢂbr m, 4ꢂ2H, CH3CH2CH2CH2N), 3.12–3.20 and
3.40–3.53 (2ꢂbr m, 2ꢂ2H, CH3CH2CH2CH2N), 3.76 (dd, 1H,
1218, 1163, 1111, 1095, 1081, 940, 837, 703, 671 cmꢁ1
.
3.2.2. 1
tri-O-(tert-butyldimethylsilyl)-
According to the general procedure, a mixture of 3-bromo-
phenyl-C-ribonucleoside (0.508 mmol, 321 mg), Pd(OAc)2
b-{3-[(Piperidine-1-yl)carbonyl]phenyl}-1-deoxy-2,3,5-
D-ribofuranose (2b)
1
(5 mol %, 0.025 mmol, 5.7 mg), Xantphos (10 mol %, 0.050 mmol,
29.4 mg), piperidine (1.52 mmol, 3 equiv, 0.15 mL), K3PO4
(2.03 mmol, 4 equiv, 432 mg) and toluene (1.3 mL) was heated at
80 ꢀC for 2 h. The crude product mixture was purified by flash
column chromatography on silica gel in gradient hexane/EA 100:2
to 100:8 to provide the title compound as a colourless light oil
(310 mg, 92%). HRMS (FAB) for: C35H66NO5Si3: [MþH] calculated,
664.4249; found, 664.4235. 1H NMR (600.1 MHz, CDCl3): ꢁ0.42,
ꢁ0.13, 0.09, 0.11 and 0.12 (5ꢂs,18H, CH3Si), 0.80 and 0.93 (2ꢂs, 27H,
(CH3)3C), 1.45–1.52 and 1.63–1.70 (2ꢂbr m, 6H, CH2-pip), 3.63–3.69
and 3.69–3.77 0(2ꢂbr m, 2ꢂ2H, CH2N-pip), 3.77 (dd, 1H, Jge0m¼10.8,
0
0
0
0
0
Jgem¼10.9, J5 b,4 ¼4.1, H-5 b), 3.79 (dd, 1H, Jgem¼10.9, J5 a,4 ¼3.5, H-
50a), 3.84 (dd, 1H,0J2 ,1 ¼7.8, J2 ,3 ¼4.4, H-2 ), 4.04 (ddd, 1H, J4 ,5 ¼4.1,
0
0
0
0
0
0
0
0
0
0
0
0
0
0
3.5, J4 ,3 ¼1.9, H-4 ), 4.12 (dd, 1H, J3 ,2 ¼4.4, J3 ,4 ¼1.9, H-3 ), 4.79 (d,
0
0
0
1H, J1 ,2 ¼7.8, H-1 ), 7.26 (dt, 1H, J4,5¼7.6, J4,2¼J4,6¼1.7, H-4), 7.32 (t,
1H, J5,4¼J5,6¼7.6, H-5), 7.36 (t, 1H, J2,4¼J2,6¼1.7, H-2), 7.47 (dt, 1H,
J6,5¼7.6, J6,2¼J6,4¼1.7, H-6). 13C NMR (125.7 MHz, CDCl3): ꢁ5.51,
ꢁ5.39, ꢁ5.27, ꢁ4.54, ꢁ4.46 and ꢁ4.39 (CH3Si), 13.70 and 13.96
(CH3CH2CH2CH2N), 17.93, 18.07 and 18.37 (C(CH3)3), 19.80 and
20.34 (CH3CH2CH2CH2N), 25.86, 25.89 and 26.00 ((CH3)3C), 29.69
and 30.87 (CH3CH2CH2CH2N), 44.45 and 48.83 (CH3CH2CH2CH2N),
63.75 (CH2-50), 73.89 (CH-30), 79.44 (CH-20), 82.54 (CH-10), 85.99
(CH-40), 124.77 (CH-2), 125.80 (CH-4), 127.52 (CH-6), 127.97 (CH-5),
137.25 (C-3), 140.96 (C-1), 171.47 (CO). IR spectrum (CCl4): 1638,
1607, 1588, 1487, 1471, 1463, 1421, 1389, 1379, 1362, 1308, 1257, 1211,
0
0
0
0
J5 b,4 ¼4.0, H-5 b), 3.79 (dd, 1H, Jgem¼10.8, J5 a,4 ¼3.5, H-5 a), 3.85
0
0
0
0
0
0
0
(dd, 1H, J2 ,1 ¼7.8, J2 ,3 ¼4.4, H-2 ), 4.04 (ddd, 1H, J4 ,5 ¼4.0, 3.5,
0
0
0
0
0
0
0
0
J4 ,3 ¼1.8, H-4 ), 4.12 (dd, 1H, J3 ,2 ¼4.4, J3 ,4 ¼1.8, H-3 ), 4.79 (d, 1H,
0
0
0
J1 ,2 ¼7.8, H-1 ), 7.28 (dt, 1H, J4,5¼7.6, J4,2¼J4,6¼1.7, H-4), 7.33 (t, 1H,
J5,4¼J5,6¼7.6, H-5), 7.42 (t, 1H, J2,4¼J2,6¼1.7, H-2), 7.48 (dt, 1H,
J6,5¼7.6, J6,2¼J6,4¼1.7, H-6). 13C NMR (150.9 MHz, CDCl3): ꢁ5.52,
ꢁ5.42, ꢁ5.31, ꢁ4.53, ꢁ4.48 and ꢁ4.40 (CH3Si), 17.92, 18.06 and
18.37 (C(CH3)3), 24.61 and 25.57 (CH2-pip), 25.83, 25.87 and 26.00
((CH3)3C), 26.55 (CH2-pip), 43.03 and 48.72 (CH2N-pip), 63.76 (CH2-
50), 73.91 (CH-30), 79.46 (CH-20), 82.50 (CH-10), 86.01 (CH-40),
125.29 (CH-2),126.22 (CH-4),127.98 and 127.99 (CH-5,6),136.32 (C-
3), 141.03 (C-1), 170.18 (CO). IR spectrum (CCl4): 1636, 1607, 1587,
1485, 1472, 1463, 1446, 1409, 1390, 1361, 1343, 1308, 1255, 1218,
1152, 1110, 1098, 1082, 940, 837, 701, 673 cmꢁ1
.
3.2.5. 1
(tert-butyldimethyl-silyl)-
According to the general procedure, a mixture of 3-bromo-
phenyl-C-ribonucleoside (0.339 mmol, 214 mg), Pd(OAc)2
b-[3-(Dimethylcarbamoyl)phenyl]-1-deoxy-2,3,5-tri-O-
D
-ribofuranose (2e)
1163, 1111, 1095, 1081, 940, 837, 703, 671 cmꢁ1
.
1
3.2.3. 1
tri-O-(tert-butyldimethylsilyl)-
According to the general procedure, a mixture of 3-bromo-
phenyl-C-ribonucleoside (0.576 mmol, 364 mg), Pd(OAc)2
b
-{3-[(Morpholine-4-yl)carbonyl]phenyl}-1-deoxy-2,3,5-
(5 mol %, 0.017 mmol, 3.8 mg), Xantphos (10 mol %, 0.034 mmol,
19.6 mg), Me2NH$HCl (0.677 mmol, 2 equiv, 55.2 mg), K3PO4
(1.35 mmol, 4 equiv, 288 mg) and toluene (0.85 mL) was heated at
80 ꢀC for 2 h. The crude product mixture was purified by flash
column chromatography on silica gel in gradient hexane/EA 100:2
to 100:10 to provide the title compound as a colourless light oil
(178 mg, 84%). HRMS (FAB) for C32H62NO5Si3: [MþH] calculated,
624.3936; found, 624.3940. 1H NMR (500.0 MHz, CDCl3): ꢁ0.43,
ꢁ0.12, 0.09, 0.11 and 0.12 (5ꢂs, 18H, CH3Si), 0.80, 0.931 and 0.935
(3ꢂs, 3ꢂ9H, (CH3)3C), 2.90–3.02 and 3.02–3.14 (2ꢂbr s, 2ꢂ3H,
D-ribofuranose (2c)
1
(5 mol %, 0.029 mmol, 6.5 mg), Xantphos (10 mol %, 0.058 mmol,
33.3 mg), morpholine (1.73 mmol, 3 equiv, 0.15 mL), K3PO4
(2.30 mmol, 4 equiv, 489 mg) and toluene (1.4 mL) was heated at
80 ꢀC for 2 h. The crude product mixture was purified by flash
column chromatography on silica gel in gradient hexane/EA 100:2
to 100:16 to provide the title compound as a colourless light oil
(340 mg, 89%). HRMS (FAB) for C34H64NO6Si3: [MþH] calculated,
666.4042; found, 666.4053. 1H NMR (600.1 MHz, CDCl3): ꢁ0.45,
ꢁ0.12, 0.096, 0.098, 0.12 and 0.13 (6ꢂs, 6ꢂ3H, CH3Si), 0.80, 0.93 and
0.94 (3ꢂs, 3ꢂ9H, (CH3)3C), 3.35–3.50, 3.53–3.67 0 and 3.67–3.90
0
0
0
0
0
0
0
CH3N), 3.78 (d, 2H, J5 ,4 ¼3.7, H-5 ), 3.85 (dd, 1H, J2 ,1 ¼7.8, J2 ,3 ¼4.4,
0
H-20), 4.04 (td, 1H, J4 ,5 ¼3.7, J4 ,3 ¼1.8, H-4 ), 4.12 (dd, 1H, J3 ,2 ¼4.4,
0
0
0
0
0
0
0
0
0
0
0
0
J3 ,4 ¼1.8, H-3 ), 4.80 (d, 1H, J1 ,2 ¼7.8, H-1 ), 7.31 (dt, 1H, J4,5¼7.6,
J4,2¼J4,6¼1.7, H-4), 7.34 (td, 1H, J5,4¼J5,6¼7.6, J5,2¼0.6, H-5), 7.46 (tt,
0
0
0
(3ꢂbr m, 8H, H-morph), 3.78 (d, 2H, J5 ,4 ¼3.6, H-5 ), 3.85 (dd, 1H,
1H, J2,4¼J2,6¼1.7, J2,5¼J2,1 ¼0.6, H-2), 7.48 (dtd, 1H, J6,5¼7.6,
J2 ,1 ¼8.0, J2 ,3 ¼4.4, H-2 ), 4.04 (td, 1H, J4 ,5 ¼3.6, J4 ,3 ¼1.6, H-4 ), 4.12
J6,2¼J6,4¼1.7, J6,1 ¼0.6, H-6). 13C NMR (125.7 MHz, CDCl3): ꢁ5.50,
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
0
(dd, 1H, J3 ,2 ¼4.4, J3 ,4 ¼1.6, H-3 ), 4.79 (d, 1H, J1 ,2 ¼8.0, H-1 ), 7.29
(dt, 1H, J4,5¼7.6, J4,2¼J4,6¼1.7, H-4), 7.35 (t, 1H, J5,4¼J5,6¼7.6, H-5),
7.46 (t, 1H, J2,4¼J2,6¼1.7, H-2), 7.51 (dt, 1H, J6,5¼7.6, J6,2¼J6,4¼1.7, H-
ꢁ5.47, ꢁ5.28, ꢁ4.49, ꢁ4.46 and ꢁ4.37 (CH3Si), 17.94, 18.08 and
18.37 (C(CH3)3), 25.84, 25.89 and 26.00 ((CH3)3C), 35.26 and 39.56
(CH3N), 63.75 (CH2-50), 73.95 (CH-30), 79.51 (CH-20), 82.50 (CH-10),

ˇ
M. Stefko et al. / Tetrahedron 65 (2009) 4471–4483
4475
86.08 (CH-40), 125.41 (CH-2), 126.43 (CH-4), 128.00 (CH-5), 128.11
(CH-6), 136.24 (C-3), 141.03 (C-1), 171.59 (CO). IR spectrum (CCl4):
1646, 1608, 1587, 1499, 1472, 1463, 1434, 1406, 1391, 1391, 1362,
1308, 1257, 1218, 1152, 1111, 1093, 1080, 939, 837, 699, 681,
3.2.8. 1
(tert-butyldimethyl-silyl)-
According to the general procedure, a mixture of 3-bromophenyl-
C-ribonucleoside (0.783 mmol, 495 mg), Pd(OAc)2 (5 mol %,
0.039 mmol, 8.8 mg), Xantphos (10 mol %, 0.078 mmol, 45.3 mg),
benzylamine (2.35 mmol, 3 equiv, 0.25 mL), K3PO4 (3.13 mmol,
4 equiv, 665 mg) and toluene (2.1 mL) was heated at 80 ꢀC for 4 h.
The crude product mixture was purified by flash column chroma-
tography on silica gel in gradient hexane/EA 100:2 to 100:10 to
provide the title compound as a white foam (377 mg, 79%). HRMS
(FAB) for C37H64NO5Si3: [MþH] calculated, 686.4092; found,
686.4087. 1H NMR (499.8 MHz, CDCl3): ꢁ0.52, ꢁ0.14, 0.09 and 0.10
(4ꢂs, 18H, CH3Si), 0.77, 0.91 and 0.94 (3ꢂs, 3ꢂ9H, (CH3)3C), 3.78 (d,
b
-[3-(Benzylcarbamoyl)phenyl]-1-deoxy-2,3,5-tri-O-
D
-ribofuranose (2h)
1
673 cmꢁ1
.
3.2.6. 1
(tert-butyldimethyl-silyl)-
According to the general procedure a mixture of 3-bromo-
phenyl-C-ribonucleoside (0.185 mmol, 120 mg), Pd(OAc)2
b
-[3-(Cyclopropylcarbamoyl)phenyl]-1-deoxy-2,3,5-tri-O-
D-ribofuranose (2f)
1
(5 mol %, 0.009 mmol, 2.1 mg), Xantphos (10 mol %, 0.018 mmol,
11.0 mg), cyclopropylamine (0.57 mmol, 3 equiv, 0.04 mL), K3PO4
(0.76 mmol, 4 equiv, 161 mg) and toluene (0.46 mL) was heated
at 80 ꢀC for 3.5 h. The crude product mixture was purified by
flash column chromatography on silica gel in gradient hexane/EA
25:1 to 8:1 to provide the title compound as a white foam
(100 mg, 86%). HRMS (ESI) for C33H61NO5Si3Na: [MþNa] calcu-
lated, 658.3756; found, 658.3748. 1H NMR (600.1 MHz, CDCl3):
ꢁ0.53, ꢁ0.14, 0.097, 0.102, 0.12 and 0.13 (6ꢂs, 6ꢂ3H, CH3Si),
0.58–0.62 (m, 2H, CH2-cycloprop), 0.82–0.92 (s, 9H, (CH3)3C),
0.87 (m, 2H, CH2-cycloprop), 0.93 and 0.94 (2ꢂs, 2ꢂ9H, (CH3)3C),
2.89 (ttd, 1H, J¼7.3, 3.9, 2.5, CH-cycloprop), 3.77–3.82 (m, 3H, H-
0
0
0
0
0
0
0
0
2H, J5 ,4 ¼3.5, H-5 ), 3.81 (dd, 1H, J2 ,1 ¼8.3, J2 ,3 ¼4.4, H-2 ), 4.04 (t0d,
0
0
0
0
0
0
0
0
0
1H, J4 ,5 ¼3.5, J4 ,3 ¼1.4, H-4 ), 4.11 (dd, 1H, J3 ,2 ¼4.4, J3 ,4 ¼1.4, H-3 ),
4.61 (dd, 1H, Jgem¼14.7, Jvic¼5.5, CHaHbPh), 4.68 (dd, 1H, Jgem¼14.7,
Jvic¼5.8, CHaHbPh), 6.36 (br dd, 1H, Jvic¼5.8, 5.5, NH), 4.80 (d, 1H,
0
0
0
J1 ,2 ¼8.3, H-1 ), 7.28–7.32 (m, 1H, H-p-Ph), 7.33–7.37 (m, 4H, H-o,m-
Ph), 7.40 (t, 1H, J5,4¼J5,6¼7.7, H-5), 7.62 (dddd, 1H, J6,5¼7.7, J6,2¼1.8,
0
J6,4¼1.2, J6,1 ¼0.4, H-6), 7.71 (t, 1H, J2,4¼J2,6¼1.8, H-2), 7.78 (ddd, 1H,
J4,5¼7.7, J4,2¼1.8, J4,6¼1.2, H-4). 13C NMR (125.7 MHz, CDCl3): ꢁ5.56,
ꢁ5.53, ꢁ5.43, ꢁ5.34, ꢁ4.50 and ꢁ4.35 (CH3Si),17.89,18.05 and 18.30
(C(CH3)3), 25.78, 25.88 and 25.94 ((CH3)3C), 44.12 (CH2Ph), 63.76
(CH2-50), 74.12 (CH-30), 79.48 (CH-20), 82.07 (CH-10), 86.55 (CH-40),
124.74 (CH-2), 126.92 (CH-4), 127.60 (CH-p-Ph), 127.97 (CH-o-Ph),
128.51 (CH-5), 128.75 (CH-m-Ph),129.99 (CH-6),134.09 (C-3), 138.15
(C-i-Ph), 141.15 (C-1), 167.23 (CO). IR spectrum (CCl4): 3459, 3357,
1673, 1607, 1588, 1538,1511, 1500,1481, 1472, 1463, 1456, 1436, 1406,
1389, 1361, 1307, 1288, 1253, 1218, 1153, 1112, 1097, 1080, 1030, 940,
20,50), 4.05 (td, 1H, J4 ,5 ¼3.2, J4 ,3 ¼1.5, H-40), 4.12 (dd, 1H,
0
0
0
0
0
0
0
0
0
0
0
0
J3 ,2 ¼4.5, J3 ,4 ¼1.5, H-3 ), 4.80 (d, 1H, J1 ,2 ¼8.3, H-1 ), 6.20 (d, 1H,
J¼2.5, NH), 7.38 (t, 1H, J5,4¼J5,6¼7.7, H-5), 7.59 (ddd, 1H, J6,5¼7.7,
J6,2¼1.8, J6,4¼1.3, H-6), 7.62 (t, 1H, J2,4¼J2,6¼1.8, H-2), 7.73 (ddd,
1H, J4,5¼7.7, J4,2¼1.8, J4,6¼1.3, H-4). 13C NMR (150.9 MHz, CDCl3):
ꢁ5.57, ꢁ5.53, ꢁ5.38, ꢁ4.48 and ꢁ4.35 (CH3Si), 6.67 and 6.82
(CH2-cycloprop), 17.91, 18.06 and 18.31 (C(CH3)3), 23.04 (CH-1-
cycloprop), 25.80, 25.88 and 25.95 ((CH3)3C), 63.77 (CH2-50),
74.14 (CH-30), 79.45 (CH-20), 82.06 (CH-10), 86.59 (CH-40), 124.43
(CH-2), 126.89 (CH-4), 128.49 (CH-5), 129.83 (CH-6), 134.15 (C-3),
141.01 (C-1), 168.79 (CO). IR spectrum (CCl4): 3454, 3346, 3094,
3011, 1678, 1663, 1608, 1588, 1524, 1504, 1472, 1463, 1436, 1425,
1406, 1389, 1362, 1305, 1285, 1257, 1218, 1152, 1112, 1098, 1081,
923, 837, 698, 671 cmꢁ1
.
3.2.9. 1
(tert-butyldimethyl-silyl)-
According to the general procedure a mixture of 3-bromo-
phenyl-C-ribonucleoside (0.549 mmol, 347 mg), Pd(OAc)2
b-[3-(Methylcarbamoyl)phenyl]-1-deoxy-2,3,5-tri-O-
D
-ribofuranose (2i)
1
940, 837, 711, 688, 671 cmꢁ1
.
(5 mol %, 0.027 mmol, 6.2 mg), Xantphos (10 mol %, 0.055 mmol,
31.8 mg), MeNH2$HCl (1.65 mmol, 3 equiv, 112 mg), K3PO4
(2.20 mmol, 4 equiv, 466 mg) and toluene (1.4 mL) was heated at
80 ꢀC for 2 h. The crude product mixture was purified by flash
column chromatography on silica gel in gradient hexane/AcOH
25:1 to 13:1 to provide the title compound as a white foam
(295 mg, 88%). HRMS (ESI) for C31H60NO5Si3: [MþH] calculated,
610.3774; found, 610.3764. 1H NMR (499.8 MHz, CDCl3): ꢁ0.52,
ꢁ0.14, 0.098, 0.102, 0.12 and 0.13 (6ꢂs, 6ꢂ3H, CH3Si), 0.79, 0.93
and 0.94 (3ꢂs, 3ꢂ9H, (CH3)3C), 3.00 (d, 3H, J¼4.9, CH3N), 3.79 (dd,
3.2.7. 1
(tert-butyldimethyl-silyl)-
According to the general procedure, a mixture of 3-bromo-
phenyl-C-ribonucleoside (0.392 mmol, 248 mg), Pd(OAc)2
b
-[3-(Cyclohexylcarbamoyl)phenyl]-1-deoxy-2,3,5-tri-O-
D-ribofuranose (2g)
1
(5 mol %, 0.019 mmol, 4.4 mg), Xantphos (10 mol %, 0.039 mmol,
22.7 mg), cyclohexylamine (1.18 mmol, 3 equiv, 0.14 mL), K3PO4
(1.57 mmol, 4 equiv, 333 mg) and toluene (1.0 mL) was heated at
80 ꢀC for 2 h. The crude product mixture was purified by flash
column chromatography on silica gel in gradient hexane/EA 50:1 to
8:1 to provide the title compound as a white foam (224 mg, 84%).
HRMS (ESI) for C36H67NO5Si3Na: [MþNa] calculated, 700.4225;
found, 700.4219. 1H NMR (600.1 MHz, CDCl3): ꢁ0.55, ꢁ0.13, 0.10,
0.11, 0.12 and 0.13 (6ꢂs, 6ꢂ3H, CH3Si), 0.79, 0.93 and 0.95 (3ꢂs,
3ꢂ9H, (CH3)3C), 1.15–1.27, 1.38–1.47, 1.63–1.69, 1.71–1.79 and 1.99–
0
0
0
0
0
1H, Jgem¼10.9, J5 b,4 ¼3.2, H-5 b), 3.81 (dd, 1H, Jge0m¼10.9, J5 a,4 ¼3.7,
H-50a), 3.82 (dd, 1H, J2 ,1 ¼0 8.3, J2 ,3 ¼4.4, H-2 ), 4.05 (ddd, 1H,
0
0
0
0
0
0
0
0
0
0
0
0
J4 ,5 ¼3.7, 3.2, J4 ,3 ¼1.4, H-4 ), 4.12 (dd, 1H, J3 ,2 ¼4.4, J3 ,4 ¼1.4, H-
30), 6.11 (br q, 1H, J¼4.9, NH), 4.81 (d, 1H, J1 ,2 ¼8.3, H-1 ), 7.39 (t,
0
0
0
1H, J5,4¼J5,6¼7.7, H-5), 7.58 (dddd, 1H, J6,5¼7.7, J6,2¼1.8, J6,4¼1.2,
0
J6,1 ¼0.5, H-6), 7.70 (t, 1H, J2,4¼J2,6¼1.8, H-2), 7.74 (ddd, 1H,
2.07 (5ꢂm, 10H, H-2,3,4,5,6-cyclohex), 3.80 (d, 2H, J5 ,4 ¼3.8, H-5 ),
J4,5¼7.7, J4,2¼1.8, J4,6¼1.2, H-4). 13C NMR (125.7 MHz, CDCl3):
ꢁ5.52, ꢁ5.45, ꢁ4.50, ꢁ4.49 and ꢁ4.34 (CH3Si), 17.91, 18.06 and
18.33 (C(CH3)3), 25.79, 25.88 and 25.94 ((CH3)3C), 26.75 (CH3N),
63.82 (CH2-50), 74.17 (CH-30), 79.54 (CH-20), 82.14 (CH-10), 86.55
(CH-40), 124.53 (CH-2), 126.85 (CH-4), 128.45 (CH-5), 129.89 (CH-
6), 134.43 (C-3), 141.05 (C-1), 168.15 (CO). IR spectrum (CCl4):
3476, 3363, 2955, 2897, 1677, 1608, 1588, 1519, 1485, 1472, 1463,
1436, 1419, 1389, 1362, 1308, 1288, 1256, 1219, 1154, 1113, 1095,
0
0
0
0
0
0
0
0
3.81 (dd, 1H, J2 ,1 ¼8.3, J2 ,3 ¼4.4, H-2 ), 3.98 (tdt, 1H, 0J¼10.8, 8.2, 3.9,
0
0
0
0
H-1-cyclohex), 4.05 (td0, 1H, J4 ,5 ¼3.8, J4 ,3 ¼1.4, H-4 ), 4.12 (dd, 1H,
0
0
0
0
0
0
0
J3 ,2 ¼4.4, J3 ,4 ¼1.4, H-3 ), 4.81 (d, 1H, J1 ,2 ¼8.3, H-1 ), 5.92 (d, 1H,
J¼8.2, NH), 7.39 (t, 1H, J5,4¼J5,6¼7.7, H-5), 7.60–7.63 (m, 2H, H-2,6),
7.73 (ddd, 1H, J4,5¼7.7, J4,2¼1.8, J4,6¼1.3, H-4). 13C NMR (150.9 MHz,
CDCl3): ꢁ5.56, ꢁ5.53, ꢁ5.34, ꢁ4.48 and ꢁ4.36 (CH3Si), 17.92, 18.07
and 18.33 (C(CH3)3), 24.98 and 25.58 (CH2-3,4,5-cyclohex), 25.84,
25.89 and 25.97 ((CH3)3C), 33.27 and 33.30 (CH2-2,6-cyclohex),
48.65 (CH-1-cyclohex), 63.77 (CH2-50), 74.11 (CH-30), 79.43 (CH-20),
82.14 (CH-10), 86.53 (CH-40), 124.57 (CH-2), 126.88 (CH-4), 128.49
(CH-5), 129.44 (CH-6), 134.75 (C-3), 140.96 (C-1), 166.51 (CO). IR
spectrum (CCl4): 3389, 3347, 3347, 2930, 2858, 1669, 1608, 1589,
1507,1480,1472,1463,1451,1435,1406,1389,1373,1361,1351,1320,
1080, 998, 940, 924, 813, 727, 691, 671 cmꢁ1
.
3.2.10. 1
tri-O-(tert-butyldimethylsilyl)-
According to the general procedure, a mixture of 4-bromo-
phenyl-C-ribonucleoside (0.223 mmol, 141 mg), Pd(OAc)2
(5 mol %, 0.011 mmol, 2.5 mg), Xantphos (10 mol %, 0.022 mmol,
b-{4-[(Pyrrolidine-1-yl)carbonyl]phenyl}-1-deoxy-2,3,5-
D-ribofuranose (5a)
4
1308, 1257, 1218, 1152, 1113, 1092, 1082, 940, 838, 672 cmꢁ1
.

ˇ
M. Stefko et al. / Tetrahedron 65 (2009) 4471–4483
4476
13 mg), pyrrolidine (0.669 mmol, 3 equiv, 0.06 mL), K3PO4
(0.893 mmol, 4 equiv, 189 mg) and toluene (0.5 mL) was heated at
80 ꢀC for 3 h. The crude product mixture was purified by flash
column chromatography on silica gel in gradient hexane/EA 100:2
to 100:16 to provide the title compound as a colourless light oil
(128 mg, 88%). HRMS (FAB) for C34H64NO5Si3: [MþH] calculated,
650.4092; found, 650.4108. 1H NMR (600.1 MHz, CDCl3): ꢁ0.43,
ꢁ0.12, 0.09, 0.12 and 0.13 (5ꢂs, 18H, CH3Si), 0.80, 0.935 and 0.941
(3ꢂs, 3ꢂ9H, (CH3)3C), 1.84–1.86 and 1.92–1.98 (2ꢂm, 2ꢂ2H, CH2-
pyr), 3.37 and 3.40 (2ꢂdt, 2H, Jgem¼10.8, Jvic¼6.8, CH2N-pyr), 3.64 (t,
ꢁ0.11, 0.09, 0.12 and 0.13 (5ꢂs, 18H, CH3Si), 0.80, 0.937 and 0.940
(3ꢂs, 3ꢂ9H, (CH3)3C), 3.33–3.49, 3.52–3.68 and 3.68–3.82 (3ꢂbr m,
0
0
0
8H, H-morph), 3.78 (dd, 1H, 0Jgem¼11.0, J5 b,4 ¼2.9, H-5 b), 3.82 (dd,
0
0
0
0
0
0
1H, Jgem¼11.0, J5 a,4 ¼3.8, H-5 a), 3.85 (dd, 1H, J2 ,1 ¼0 7.7, J2 ,3 ¼4.4, H-
20), 4.05 (ddd, 1H, J4 0,5 ¼3.8, 2.9, J4 ,3 ¼1.9, H-4 ), 4.13 (dd, 1H,
0
0
0
0
0
0
0
0
0
0
0
J3 ,2 ¼4.4, J3 ,4 ¼1.9, H-3 ), 4.80 (d, 1H, J1 ,2 ¼7.7, H-1 ), 7.34–7.38 (m,
2H, H-3,5), 7.48–7.52 (m, 2H, H-2,6). 13C NMR (125.7 MHz, CDCl3):
ꢁ5.53, ꢁ5.45, ꢁ5.38, ꢁ4.50, ꢁ4.47 and ꢁ4.43 (CH3Si), 17.93, 18.05
and 18.34 (C(CH3)3), 25.81, 25.86 and 25.97 ((CH3)3C), 42.64 and
48.26 (CH2N-morph), 63.56 (CH2-50), 66.85 (CH2O-morph), 73.79
(CH-30), 79.68 (CH-20), 82.54 (CH-10), 86.07 (CH-40), 126.93 (CH-
3,5), 126.97 (CH-2,6), 134.50 (C-4), 142.94 (C-1), 170.46 (CO). IR
spectrum (CCl4): 3930, 2957, 2897, 2858, 1645, 1615, 1574, 1509,
1482, 1462, 1456, 1423, 1408, 1389, 1362, 1300, 1280, 1258, 1219,
1187, 1154, 1118, 1110, 1095, 1080, 1026, 1018, 1011, 939, 894, 839,
0
0
0
2H, Jvic¼7.0, CH2N-pyr), 3.78 (dd, 1H, Jg0em¼11.0, J5 b,4 ¼2.9, H-5 b),
0
0
0
0
3.82 (dd, 1H, 0Jgem¼11.0, J5 a,4 ¼3.9, H-5 a), 3.85 (dd, 1H, J20,1 ¼7.6,
0
0
0
0
0
0
J2 ,3 ¼4.4, H-2 ), 4.04 (ddd, 1H, J4 ,5 ¼3.9, 2.9, J4 ,3 ¼2.0, H-4 ), 4.13
0
0
0
0
0
0
0
0
(dd,1H, J3 ,2 ¼4.4, J3 ,4 ¼2.0, H-3 ), 4.80 (d,1H, J1 ,2 ¼7.6, H-1 ), 7.47 (s,
4H, H-2,3,5,6). 13C NMR (150.9 MHz, CDCl3): ꢁ5.52, ꢁ5.43, ꢁ5.33,
ꢁ4.50, ꢁ4.46 and ꢁ4.43 (CH3Si), 17.94, 18.06 and 18.35 (C(CH3)3),
24.47 (CH2-pyr), 25.84, 25.87 and 25.98 ((CH3)3C), 26.42 (CH2-pyr),
46.18 and 49.56 (CH2N-pyr), 63.58 (CH2-50), 73.78 (CH-30), 79.64
(CH-20), 82.64 (CH-10), 85.98 (CH-40), 126.63 (CH-2,6), 126.94 (CH-
3,5), 136.49 (C-4), 142.68 (C-1), 169.73 (CO). IR spectrum (CCl4):
2955, 2930, 2896, 2885, 2858, 1634, 1614, 1574, 1513, 1485, 1472,
1463, 1463, 1420, 1405, 1392, 1362, 1343, 1257, 1227, 1213, 1186,
698, 671 cmꢁ1
.
3.2.13. 1
(tert-butyldimethyl-silyl)-
According to the general procedure a mixture of 4-bromo-
phenyl-C-ribonucleoside (0.627 mmol, 396 mg), Pd(OAc)2
b-[4-(Dibutylcarbamoyl)phenyl]-1-deoxy-2,3,5-tri-O-
D
-ribofuranose (5d)
4
(5 mol %, 0.031 mmol, 7.0 mg), Xantphos (10 mol %, 0.063 mmol,
36.3 mg), dibutylamine (1.88 mmol, 3 equiv, 0.32 mL), K3PO4
(2.51 mmol, 4 equiv, 532 mg) and toluene (1.6 mL) was heated at
80 ꢀC for 3 h. The crude product mixture was purified by flash
column chromatography on silica gel in gradient hexane/EA 100:2
to 100:6 to provide the title compound as a colourless light oil
(422 mg, 95%). HRMS (FAB) for C38H74NO5Si3: [MþH] calculated,
708.4875; found, 708.4865. 1H NMR (499.8 MHz, CDCl3): ꢁ0.44,
ꢁ0.11, 0.090, 0.092, 0.12 and 0.13 (6ꢂs, 6ꢂ3H, CH3Si), 0.77–0.82 (br
m, 3H, CH3CH2CH2CH2N), 0.81, 0.935 and 0.940 (3ꢂs, 3ꢂ9H,
(CH3)3C), 0.95–0.99 (br m, 3H, CH3CH2CH2CH2N), 1.07–1.15, 1.37–
1.43, 1.43–1.50 and 1.60–1.68 (4ꢂbr m, 4ꢂ2H, CH3CH2CH2CH2N),
3.16 and 3.47 (2ꢂbr m,0 2ꢂ2H, CH3CH2CH2CH2N), 3.78 (dd, 1H,
1153, 1112, 1112, 1095, 1081, 1020, 939, 838, 681, 672, 637 cmꢁ1
.
3.2.11. 1
tri-O-(tert-butyldimethyl-silyl)-
According to the general procedure, a mixture of 4-bromo-
phenyl-C-ribonucleoside (0.701 mmol, 443 mg), Pd(OAc)2
b
-{4-[(Piperidine-1-yl)carbonyl]phenyl}-1-deoxy-2,3,5-
D-ribofuranose (5b)
4
(5 mol %, 0.035 mmol, 7.9 mg), Xantphos (10 mol %, 0.070 mmol,
40.6 mg), piperidine (2.10 mmol, 3 equiv, 0.21 mL), K3PO4
(2.80 mmol, 4 equiv, 595 mg) and toluene (1.8 mL) was heated at
80 ꢀC for 3 h. The crude product mixture was purified by flash
column chromatography on silica gel in gradient hexane/EA 100:2
to 100:8 to provide the title compound as a colourless light oil
(431 mg, 92%). HRMS (FAB) for C35H66NO5Si3: [MþH] calculated,
664.4267; found, 664.4249. 1H NMR (499.8 MHz, CDCl3): ꢁ0.42,
ꢁ0.11, 0.09, 0.11 and 0.13 (5ꢂs, 18H, CH3Si), 0.80, 0.936 and 0.939
(3ꢂs, 3ꢂ9H, (CH3)3C), 1.44–1.52 and 1.64–1.70 (2ꢂbr m, 6H, CH2-
pip), 3.25–3.35 and 3.64–3.76 (2ꢂbr m, 2ꢂ2H, CH2N-pip), 3.78 (dd,
0
0
0
0
Jgem¼11.0, J5 b,4 ¼2.8, H-5 b), 3.82 (dd, 1H, Jgem¼11.0, J5 a,4 ¼3.8, H-
50a), 3.85 (dd, 1H,0J2 ,1 ¼7.6, J2 ,3 ¼4.4, H-2 ), 4.04 (ddd, 1H0, J4 ,5 ¼3.8,
0
0
0
0
0
0
0
0
0
0
0
0
0
2.8, J4 ,3 ¼1.9, H-4 ), 4.13 (dd, 1H, J3 ,2 ¼4.4, J3 ,4 ¼1.9, H-3 ), 4.80 (d,
0
0
0
1H, J1 ,2 ¼7.6, H-1 ), 7.37–7.32 (m, 2H, H-3,5), 7.44–7.48 (m, 2H, H-
2,6). 13C NMR (125.7 MHz, CDCl3): ꢁ5.54, ꢁ5.45, ꢁ5.31, ꢁ4.48,
ꢁ4.47 and ꢁ4.44 (CH3Si), 13.75 and 13.94 (CH3CH2CH2CH2N), 17.91,
18.06 and 18.33 (C(CH3)3), 19.79 and 20.33 (CH3CH2CH2CH2N),
25.83, 25.87 and 25.97 ((CH3)3C), 29.65 and 30.91
(CH3CH2CH2CH2N), 44.51 and 48.82 (CH3CH2CH2CH2N), 63.58
(CH2-50), 73.81 (CH-30), 79.59 (CH-20), 82.63 (CH-10), 85.98 (CH-40),
126.21 (CH-3,5), 126.75 (CH-2,6), 136.68 (C-4), 141.80 (C-1), 171.62
(CO). IR spectrum (CCl4): 2958, 2897, 1637, 1615, 1573, 1512, 1471,
1463, 1423, 1408, 1389, 1379, 1362, 1307, 1257, 1221, 1188, 1152, 1110,
0
0
0
0
0
1H, Jgem¼10.9, J5 b,4 ¼2.9, H-5 b), 3.82 (dd, 1H, Jge0m¼10.9, J5 a,4 ¼3.9,
H-50a), 3.85 (dd, 1H, J2 ,1 ¼7.6, J2 ,3 ¼4.4, H-2 ), 4.04 (ddd, 1H,
0
0
0
0
0
0
0
0
0
0
0
0
0
0
J4 ,5 ¼3.9, 2.9, J4 ,3 ¼2.1, H-4 ), 4.13 (dd, 1H, J3 ,2 ¼4.4, J3 ,4 ¼2.1, H-3 ),
0
0
0
4.80 (d, 1H, J1 ,2 ¼7.6, H-1 ), 7.32–7.35 (m, 2H, H-3,5), 7.45–7.49 (m,
2H, H-2,6). 13C NMR (125.7 MHz, CDCl3): ꢁ5.53, ꢁ5.45, ꢁ5.38,
ꢁ4.49, ꢁ4.46 and ꢁ4.43 (CH3Si), 17.94, 18.06 and 18.34 (C(CH3)3),
24.61 and 25.62 (CH2-pip), 25.82, 25.87 and 25.97 ((CH3)3C), 26.48
(CH2-pip), 43.13 and 48.75 (CH2N-pip), 63.56 (CH2-50), 73.75 (CH-
30), 79.67 (CH-20), 82.66 (CH-10), 85.95 (CH-40), 126.61 (CH-3,5),
126.80 (CH-2,6), 135.76 (C-4),142.23 (C-1),170.34 (CO). IR spectrum
(CCl4): 2951, 2930, 2897, 2887, 2858, 1638, 1615, 1574, 1512, 1472,
1463, 1454, 1443, 1429, 1410, 1389, 1370, 1362, 1352, 1310, 1288,
1273, 1258, 1219, 1187, 1153, 1110, 1095, 1080, 1029, 1021, 1003, 939,
1097, 1080, 1021, 939, 838, 700, 682, 672, 635 cmꢁ1
.
3.2.14. 1
(tert-butyldimethyl-silyl)-
According to the general procedure a mixture of 4-bromo-
phenyl-C-ribonucleoside (0.287 mmol, 181 mg), Pd(OAc)2
b-[4-(Dimethylcarbamoyl)phenyl]-1-deoxy-2,3,5-tri-O-
D
-ribofuranose (5e)
885, 852, 838, 696, 671, 635 cmꢁ1
.
4
(5 mol %, 0.014 mmol, 3.2 mg), Xantphos (10 mol %, 0.029 mmol,
16.6 mg), Me2NH$HCl (0.573 mmol, 2 equiv, 46.8 mg), K3PO4
(1.15 mmol, 4 equiv, 243 mg) and toluene (0.8 mL) was heated at
80 ꢀC for 4 h. The crude product mixture was purified by flash col-
umn chromatography on silica gel in gradient hexane/EA 100:2 to
100:16 to provide the title compound as a colourless light oil
(155 mg, 87%). HRMS (FAB) for C32H62NO5Si3: [MþH] calculated,
624.3936; found, 624.3945. 1H NMR (499.8 MHz, CDCl3): ꢁ0.42,
ꢁ0.11, 0.07, 0.09, 0.12 and 0.13 (6ꢂs, 6ꢂ3H, CH3Si), 0.80, 0.936 and
0.940 (3ꢂs, 3ꢂ9H, (CH3)3C), 2.90–3.05 and 3.05–3.15 (2ꢂbr s, 2ꢂ3H,
3.2.12. 1
tri-O-(tert-butyldimethyl-silyl)-
According to the general procedure, a mixture of 4-bromo-
phenyl-C-ribonucleoside (0.752 mmol, 475 mg), Pd(OAc)2
(5 mol %, 0.038 mmol, 8.4 mg), Xantphos (10 mol %, 0.075 mmol,
43.5 mg), morpholine (2.26 mmol, 3 equiv, 0.19 mL), K3PO4
(3.00 mmol, 4 equiv, 638 mg) and toluene (1.9 mL) was heated at
80 ꢀC for 2 h. The crude product mixture was purified by flash
column chromatography on silica gel in gradient hexane/EA 100:2
to 100:16 to provide the title compound as a colourless light oil
(448 mg, 89%). HRMS (FAB) for C34H64NO6Si3: [MþH] calculated,
666.4042; found, 666.4023. 1H NMR (499.8 MHz, CDCl3): ꢁ0.44,
b
-{4-[(Morpholine-4-yl)carbonyl]phenyl}-1-deoxy-2,3,5-
D-ribofuranose (5c)
4
0
0
0
CH3N), 3.78 (dd, 1H, Jgem¼11.0, J5 b,4 ¼2.9, H-5 b), 3.82 (dd, 1H,
0
0
0
0
0
0
0
0
Jgem¼11.0, J5 a,4 ¼3.8, H-5 a), 3.86 (dd, 1H, J2 ,1 ¼7.6, J2 ,3 ¼4.4, H-2 ),
0
0
0
0
0
0
0
4.04 (ddd, 1H, J4 ,5 ¼3.8, 2.9, J4 ,3 ¼2.0, H-4 ), 4.13 (dd, 1H, J3 ,2 ¼4.4,

ˇ
M. Stefko et al. / Tetrahedron 65 (2009) 4471–4483
4477
0
0
0
0
0
0
J3 ,4 ¼2.0, H-3 ), 4.80 (d,1H, J1 ,2 ¼7.6, H-1 ), 7.35–7.39 (m, 2H, H-3,5),
7.46–7.49 (m, 2H, H-2,6). 13C NMR (125.7 MHz, CDCl3): ꢁ5.52,
ꢁ5.44, ꢁ5.34, ꢁ4.49, ꢁ4.46 and ꢁ4.43 (CH3Si),17.94,18.06 and 18.35
(C(CH3)3), 25.83, 25.88 and 25.98 ((CH3)3C), 35.37 and 39.53 (CH3N),
63.59 (CH2-50), 73.80 (CH-30), 79.67 (CH-20), 82.63 (CH-10), 86.00
(CH-40), 126.75 (CH-2,6), 126.92 (CH-3,5), 135.57 (C-4), 142.44 (C-1),
171.65 (CO). IR spectrum (CCl4): 2956, 2897, 1644, 1616, 1574, 1513,
1489,1472,1463,1406,1390,1390,1362,1308,1258,1217,1187,1153,
1493,1472,1463,1451,1407,1389,1362,1351,1320,1304,1283,1257,
1216,1187,1152,1112,1095,1081,1018, 939, 838, 699, 670, 638 cmꢁ1
.
3.2.17. 1
(tert-butyldimethyl-silyl)-
According to the general procedure, a mixture of 4-bromo-
phenyl-C-ribonucleoside (0.641 mmol, 405 mg), Pd(OAc)2
b
-[4-(Benzylcarbamoyl)phenyl]-1-deoxy-2,3,5-tri-O-
D
-ribofuranose (5h)
4
(5 mol %, 0.032 mmol, 7.2 mg), Xantphos (10 mol %, 0.064 mmol,
37.1 mg), benzylamine (1.92 mmol, 3 equiv, 0.21 mL), K3PO4
(2.56 mmol, 4 equiv, 544 mg) and toluene (1.6 mL) was heated at
80 ꢀC for 3 h. The crude product mixture was purified by flash
column chromatography on silica gel in gradient hexane/EA 100:2
to 100:10 to provide the title compound as a white foam (378 mg,
86%). HRMS (FAB) for C37H64NO5Si3: [MþH] calculated, 686.4092;
found, 686.4097. 1H NMR (600.1 MHz, CDCl3): ꢁ0.48, ꢁ0.13, 0.09,
0.10, 0.12 and 0.13 (6ꢂs, 6ꢂ3H, CH3Si), 0.81 and 0.94 (2ꢂs, 27H,
1111, 1095, 1077, 1020, 939, 838, 701, 671, 634 cmꢁ1
.
3.2.15. 1
(tert-butyldimethyl-silyl)-
According to the general procedure, a mixture of 4-bromophenyl-
C-ribonucleoside (0.548 mmol, 346 mg), Pd(OAc)2 (5 mol %,
b
-[4-(Cyclopropylcarbamoyl)phenyl]-1-deoxy-2,3,5-tri-O-
D
-ribofuranose (5f)
4
0.027 mmol, 6.1 mg), Xantphos (10 mol %, 0.055 mmol, 31.7 mg),
cyclopropylamine (1.64 mmol, 3 equiv, 0.11 mL), K3PO4 (2.19 mmol,
4 equiv, 465 mg) and toluene (1.5 mL) was heated at 80 ꢀC for 3 h.
The crude product mixture was purified by flash column chroma-
tography on silica gel in gradient hexane/EA 100:2 to 100:12 to
provide the title compound as a white foam (283 mg, 81%). HRMS
(FAB) for C33H62NO5Si3: [MþH] calculated, 636.3936; found,
636.3951. 1H NMR (500.0 MHz, CDCl3): ꢁ0.49, ꢁ0.13, 0.089, 0.092,
0.12 and 0.13 (6ꢂs, 6ꢂ3H, CH3Si), 0.62–0.66 (m, 2H, CH2-cycloprop),
0.80 (s, 9H, (CH3)3C), 0.85–0.87 (m, 2H, CH2-cycloprop), 0.93 and 0.94
(2ꢂs, 2ꢂ9H, (CH3)3C), 2.90 (ttd, 1H, J¼7.0, 3.9, 2.9, CH-cycloprop),
0
0
0
(CH3)3C), 3.78 (dd, 1H, J0gem¼11.0, J5 b,4 ¼2.8, H-5 b), 3.81 (dd, 1H,
0
0
0
0
0
0
0
Jgem¼11.0, J5 a,4 ¼3.7, H-5 a), 3.86 (dd, 1H, 0J2 ,1 ¼7.8, J2 ,3 ¼4.4, H-2 ),
0
0
0
0
0
0
4.04 (ddd, 1H, J4 ,5 ¼3.7, 2.8, J4 ,3 ¼1.7, H-4 ), 4.13 (dd, 1H, J3 ,2 ¼4.4,
0
0
0
J3 ,4 ¼1.7, H-3 ), 4.62 and 4.64 (2ꢂdd, 2H, Jgem¼14.6, Jvic¼5.6, CH2Ph),
0
0
0
4.81 (d, 1H, J1 ,2 ¼7.8, H-1 ), 6.50 (br t, 1H, Jvic¼5.6, NH), 7.28–7.32
(m, 1H, H-p-Ph), 7.34–7.38 (m, 4H, H-o,m-Ph), 7.48–7.52 (m, 2H, H-
2,6), 7.73–7.77 (m, 2H, H-3,5). 13C NMR (150.9 MHz, CDCl3): ꢁ5.56,
ꢁ5.42, ꢁ5.38, ꢁ4.52, ꢁ4.50 and ꢁ4.43 (CH3Si), 17.86, 18.02 and
18.32 (C(CH3)3), 25.80, 25.84 and 25.96 ((CH3)3C), 44.09 (CH2Ph),
63.60 (CH2-50), 73.92 (CH-30), 79.54 (CH-20), 82.34 (CH-10), 86.20
(CH-40), 126.67 (CH-3,5), 126.98 (CH-2,6), 127.55 (CH-p-Ph), 127.97
(CH-o-Ph), 128.73 (CH-m-Ph), 133.40 (C-4), 138.19 (C-i-Ph), 144.70
(C-1), 167.11 (CO). IR spectrum (CCl4): 3460, 3356, 3089, 3067, 3033,
2956, 2897, 2887, 1672, 1657, 1614, 1575, 1523, 1514, 1472, 1455,
1407,1389,1362,1305,1295,1289,1263,1257,1217,1152,1113,1095,
0
0
0
3.78 (dd, 1H, Jgem¼11.0, J5 b,4 ¼2.8, H-5 b), 3.82 (dd, 10H, Jgem¼11.0,
0
0
0
0
0
0
0
J5 a,4 ¼3.7, H-5 a), 3.85 (dd, 1H, J2 ,1 ¼7.9, J2 ,3 ¼4.4, H-2 ), 4.04 (ddd,
0
0
0
0
0
0
0
0
0
1H, J4 ,5 ¼3.7, 2.8, J4 ,3 ¼1.7, H-4 ), 4.12 (dd, 1H, J3 ,2 ¼4.4, J3 ,4 ¼1.7, H-
30), 4.80 (d, 1H, J1 ,2 ¼7.9, H-1 ), 6.24 (br d, 1H, J¼2.9, NH), 7.47–7.51
(m, 2H, H-2,6), 7.67–7.71 (m, 2H, H-3,5). 13C NMR (125.7 MHz,
CDCl3): ꢁ5.54, ꢁ5.41, ꢁ5.38, ꢁ4.50, ꢁ4.48 and ꢁ4.41 (CH3Si), 6.76
(CH2-cycloprop), 17.89, 18.05 and 18.35 (C(CH3)3), 23.09 (CH-1-
cycloprop), 25.82, 25.86 and 25.98 ((CH3)3C), 63.63 (CH2-50), 73.97
(CH-30), 79.55 (CH-20), 82.33 (CH-10), 86.27 (CH-40), 126.54 (CH-3,5),
126.96 (CH-2,6), 133.43 (C-4), 144.64 (C-1), 168.63 (CO). IR spectrum
(CCl4): 3457, 3346, 3094, 3011, 2956, 2897, 1678, 1662, 1615, 1575,
1533,1520,1487,1472,1463,1424,1407,1389,1362,1308,1288,1258,
0
0
0
1080, 1031, 1019, 939, 838, 698, 672, 638 cmꢁ1
.
3.2.18. 1
(tert-butyldimethyl-silyl)-
According to the general procedure, a mixture of 4-bromo-
phenyl-C-ribonucleoside (0.211 mmol, 133 mg), Pd(OAc)2
b-[4-(Methylcarbamoyl)phenyl]-1-deoxy-2,3,5-tri-O-
D
-ribofuranose (5i)
4
1214,1186,1153, 1112,1095,1081,1019, 939, 838, 684, 671, 638 cmꢁ1
.
(5 mol %, 0.011 mmol, 2.4 mg), Xantphos (10 mol %, 0.021 mmol,
12.2 mg), MeNH2$HCl (0.634 mmol, 3 equiv, 42.8 mg), K3PO4
(0.845 mmol, 4 equiv, 180 mg) and toluene (0.52 mL) was heated at
80 ꢀC for 3.5 h. The crude product mixture was purified by flash
column chromatography on silica gel in gradient hexane/AcOH
83:1 to 13:1 to provide the title compound as a white foam
(208 mg, 81%). HRMS (ESI) for C31H60NO5: [MþH] calculated,
610.3774; found, 610.3771. 1H NMR (499.8 MHz, CDCl3): ꢁ0.49,
ꢁ0.13, 0.091, 0.094, 0.12 and 0.13 (6ꢂs, 6ꢂ3H, CH3Si), 0.80, 0.936
and 0.942 (3ꢂs, 3ꢂ9H, (CH3)3C), 3.02 (d, 3H, J¼4.9, CH3N), 3.78 (dd,
3.2.16. 1
(tert-butyldimethyl-silyl)-
According to the general procedure, a mixture of 4-bromo-
phenyl-C-ribonucleoside (0.653 mmol, 413 mg), Pd(OAc)2
b
-[4-(Cyclohexylcarbamoyl)phenyl]-1-deoxy-2,3,5-tri-O-
D
-ribofuranose (5g)
4
(5 mol %, 0.033 mmol, 7.3 mg), Xantphos (10 mol %, 0.065 mmol,
37.8 mg), cyclohexylamine (1.96 mmol, 3 equiv, 0.22 mL), K3PO4
(2.61 mmol, 4 equiv, 555 mg) and toluene (1.6 mL) was heated at
80 ꢀC for 2 h. The crude product mixture was purified by flash col-
umn chromatography on silica gel in gradient hexane/EA 100:2 to
100:8 to provide the title compound as a white foam (385 mg, 87%).
HRMS (FAB) for C36H68NO5Si3: [MþH] calculated, 678.4405; found,
678.4419. 1H NMR (600.1 MHz, CDCl3): ꢁ0.46, ꢁ0.13, 0.090, 0.092,
0.12 and 0.13 (6ꢂs, 6ꢂ3H, CH3Si), 0.81, 0.936 and 0.943 (3ꢂs, 3ꢂ9H,
(CH3)3C), 1.18–1.22, 1.23–1.27, 1.39–1.48, 1.63–1.69, 1.73–1.79 and
2.02–2.08 (6ꢂm, 10H, H-2,3,4,5,6-cyclohex), 3.78 (dd,1H, Jgem¼11.0,
0
0
0
0
0
1H, Jgem¼10.9, J5 b,4 ¼2.9, H-5 b), 3.82 (dd, 1H, Jge0m¼10.9, J5 a,4 ¼3.8,
H-50a), 3.85 (dd, 1H, J2 ,1 ¼7.8, J2 ,3 ¼4.4, H-2 ), 4.04 (ddd, 1H,
0
0
0
0
0
0
0
0
0
0
0
0
0
0
J4 ,5 ¼3.8, 2.9, J4 ,3 ¼1.7, H-4 ), 4.13 (dd, 1H, J3 ,2 ¼4.4, J3 ,4 ¼1.7, H-3 ),
0
0
0
4.81 (d, 1H, J1 ,2 ¼7.8, H-1 ), 6.14 (br q, 1H, J¼4.9, NH), 7.48–7.52 (m,
2H, H-2,6), 7.69–7.73 (m, 2H, H-3,5). 13C NMR (125.7 MHz, CDCl3):
ꢁ5.52, ꢁ5.41, ꢁ5.40, ꢁ4.49, ꢁ4.46 and ꢁ4.40 (CH3Si), 17.91, 18.06
and 18.36 (C(CH3)3), 25.83, 25.88 and 25.99 ((CH3)3C), 26.80
(CH3N), 63.66 (CH2-50), 74.00 (CH-30), 79.62 (CH-20), 82.36 (CH-10),
86.27 (CH-40), 126.54 (CH-3,5), 127.02 (CH-2,6), 135.75 (C-4), 144.50
(C-1), 168.01 (CO). IR spectrum (CCl4): 3477, 3357, 2956, 2897, 1675,
1662, 1615, 1574, 1547, 1530, 1500, 1472, 1463, 1414, 1407, 1389,
1362, 1303, 1290, 1274, 1257, 1216,1187, 1152, 1113, 1095, 1080, 1066,
0
0
0
0
0
0
J5 b,4 ¼2.9, H-5 b), 3.82 (dd,1H, Jgem¼11.0, J5 a,4 ¼3.8, H-5 a), 3.85 (dd,
0
0
0
0
0
1H, J2 ,1 ¼7.7, J2 ,3 ¼4.4, H-2 ), 3.98 (tdt, 1H, J¼10.7, 8.1, 4.0, H-1-
0
0
0
0
0
cyclohex), 4.04 (td, 1H,0J4 ,5 ¼3.8, 2.9, J4 ,3 ¼1.8, H-4 ), 4.13 (dd, 1H,
0
0
0
0
0
0
0
J3 ,2 ¼4.4, J3 ,4 ¼1.8, H-3 ), 4.81 (d, 1H, J1 ,2 ¼7.7, H-1 ), 5.94 (d, 1H,
J¼8.1, NH), 7.47–7.51 (m, 2H, H-2,6), 7.68–7.71 (m, 2H, H-3,5). 13C
NMR (150.9 MHz, CDCl3): ꢁ5.52, ꢁ5.39, ꢁ5.31, ꢁ4.49, ꢁ4.46 and
ꢁ4.41 (CH3Si), 17.90, 18.06 and 18.36 (C(CH3)3), 24.93 and 25.59
(CH2-3,4,5-cyclohex), 25.83, 25.87 and 25.99 ((CH3)3C), 33.27 (CH2-
2,6-cyclohex), 48.65 (CH-1-cyclohex), 63.61 (CH2-50), 73.88 (CH-30),
79.54 (CH-20), 82.45 (CH-10), 86.12 (CH-40), 126.52 (CH-3,5), 126.91
(CH-2,6), 134.15 (C-4), 144.36 (C-1), 166.36 (CO). IR spectrum (CCl4):
3451, 3347, 2953, 2930, 2898, 2858, 1667, 1614, 1574, 1538, 1520,
939, 838, 699, 671, 638 cmꢁ1
.
3.3. General procedure for the preparation of unsubstituted
benzamide nucleosides 2j and 5j using AcONH4dmethod A
A flame-dried septum-sealed flask containing 3- or 4-bromo-
phenyl-C-ribonucleoside 1 or 4 (1 mmol), Pd(OAc)2 (10 mol %,

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M. Stefko et al. / Tetrahedron 65 (2009) 4471–4483
4478
0.1 mmol), Xantphos (20 mol %, 0.2 mmol), AcONH4 (3 mmol)
(AcONH4 was not dried prior to use) and K3PO4 (4 mmol) was
evacuated and backfilled with CO(g). Then, toluene (2.5 mL) was
added via syringe. The reaction mixture was stirred at room tem-
perature for 5 min and then immersed into a preheated oil bath
(80 ꢀC) and vigorously stirred until the starting material had been
completely consumed (TLC analysis, Hexanes/EA/AcOH 7:2:1). The
reaction mixture was then allowed to cool to room temperature,
diluted with Et2O, filtered through a plug of Celite (eluting with
Et2O) and concentrated under reduced pressure. The crude product
was purified by flash chromatography on silica gel.
(CH-2), 127.12 (CH-4), 128.46 (CH-5), 130.47 (CH-6), 133.07 (C-3),
141.21 (C-1), 169.29 (CO). IR spectrum (CCl4): 3538, 3506, 3421,
3352, 3295, 3166, 2955, 2847, 1685, 1609, 1587, 1472, 1463, 1438,
1407, 1389, 1379, 1361, 1308, 1257, 1257, 1218, 1153, 1112, 1095, 1082,
940, 926, 838, 692, 672 cmꢁ1
.
Prepared according to the general procedure, method B. Starting
from (337 mg, 0.5333 mmol) using Pd(OAc)2 (5 mol %,
1
0.027 mmol, 6.0 mg), Xantphos (10 mol %, 0.053 mmol, 31.0 mg),
NH4Cl (1.60 mmol, 3 equiv, 95.6 mg), K3PO4 (2.13 mmol, 4 equiv
453 mg) and toluene/DMSO 1:1 mixture (1.9 mL). Reaction time
3.5 h. Flash chromatography in gradient hexane/AcOH 25:1 to 25:2
gave 2j as colourless light oil (216 mg, 68%).
3.4. General procedure for the preparation of unsubstituted
benzamide nucleosides 2j and 5j using NH4Cldmethod B
Prepared according to the general procedure, method C. Reaction
mixture containing 1 (107 mg, 0.1693 mmol), Pd(OAc)2 (10 mol %,
0.017 mmol, 3.8 mg), Xantphos (20 mol %, 0.034 mmol, 20 mg),
K3PO4 (0.677 mmol, 4 equiv 144 mg) was evacuated and backfilled
with CO(g)/NH3 (ca.1:1 mixture). Then toluene (0.42 mL) was added
and reaction mixture was stirred for 16 h. Flash chromatography in
gradient hexane/AcOH 25:1 to 25:2 gave 2j as colourless light oil
(63 mg, 62%).
A flame-dried septum-sealed flask containing 3- or 4-bromo-
phenyl-C-ribonucleoside
1 or 4 (1 mmol), Pd(OAc)2 (5 mol %,
0.05 mmol), Xantphos (10 mol %, 0.1 mmol), NH4Cl (3 mmol)
(NH4Cl was not dried prior to use) and K3PO4 (4 mmol) was evac-
uated and backfilled with CO(g). Then, toluene/DMSO 1:1 (3 mL)
was added via syringe. The reaction mixture was stirred at room
temperature for 5 min and then immersed into a preheated oil bath
(80 ꢀC) and vigorously stirred until the starting material had been
completely consumed (TLC analysis, Hexanes/EA/AcOH 7:2:1). The
reaction mixture was then allowed to cool to room temperature,
diluted with Et2O, filtered through a plug of Celite (eluting with
Et2O) and concentrated under reduced pressure. The crude product
was purified by flash chromatography on silica gel.
3.5.2. 1
b-[4-(Carbamoyl)phenyl]-1-deoxy-2,3,5-tri-O-
(tert-butyldimethyl-silyl)-
D
-ribofuranose (5j)
Prepared according to the general procedure, method A. Starting
from 4 (126 mg, 0.200 mmol) using Pd(OAc)2 (10 mol %, 0.02 mmol,
4.5 mg), Xantphos (20 mol %, 0.04 mmol, 23 mg), AcONH4
(0.598 mmol, 46 mg, 3 equiv), K3PO4 (0.797 mmol, 169 mg, 4 equiv)
and toluene (0.5 mL). Reaction time 16 h. Flash chromatography in
gradient hexane/AcOH 25:1 to 25:2 gave 5j as colourless light oil
(72 mg, 60%). HRMS (ESI) for C30H58NO5Si3: [MþH] calculated,
596.3592; found, 596.3617. 1H NMR (500.0 MHz, CDCl3): ꢁ0.48,
ꢁ0.13, 0.09, 0.10, 0.12 and 0.13 (6ꢂs, 6ꢂ3H, CH3Si), 0.81, 0.939 and
3.5. General procedure for the preparation of unsubstituted
benzamide nucleosides 2j and 5j using NH3(g)dmethod C
0
0
A flame-dried septum-sealed flask containing 3- or 4-bromo-
phenyl-C-ribonucleoside 1 or 4 (1 mmol), Pd(OAc)2 (10 mol %,
0.1 mmol), Xantphos (20 mol %, 0.2 mmol) was evacuated and
backfilled with CO(g)/NH3(g) mixture (approx. ratio 1:1). Then, tol-
uene (2.5 mL) was added via syringe. The reaction mixture was
stirred at room temperature for 5 min and then immersed into
a preheated oil bath (80 ꢀC) and vigorously stirred until the starting
material had been completely consumed (TLC analysis, Hexanes/EA/
AcOH 7:2:1). The reaction mixture was then allowed to cool to room
temperature, diluted with Et2O, filtered through a plug of Celite
(eluting with Et2O) and concentrated under reduced pressure. The
crude product was purified by flash chromatography on silica gel.
0.943 (3ꢂs, 3ꢂ9H, (CH3)3C), 3.78 (dd, 1H, Jgem¼11.0, J5 b,4 ¼2.8, H-
0
50b), 3.82 (dd,1H, Jgem¼11.0, J5 a,4 ¼3.7, H-5 a), 3.86 (dd,1H, J2 ,1 ¼7.9,
0
0
0
0
0
0
0
0
0
0
0
0
J2 ,3 ¼4.4, H-2 ), 4.05 (ddd,1H, J4 ,5 ¼3.7, 2.8, J4 ,3 ¼1.7, H-4 ), 4.13 (dd,
0
0
0
0
0
0
0
0
1H, J3 ,2 ¼4.4, J3 ,4 ¼1.7, H-3 ), 4.82 (d, 1H, J1 ,2 ¼7.9, H-1 ), 5.55–5.57
and 5.90–6.20 (2ꢂbr s, 2H, NH2); 7.51–7.55 (m, 2H, H-2,6), 7.75–
7.78 (m, 2H, H-3,5). 13C NMR (125.7 MHz, CDCl3): ꢁ5.52, ꢁ5.41,
ꢁ4.49, ꢁ4.46 and ꢁ4.39 (CH3Si), 17.91, 18.06 and 18.36 (C(CH3)3),
25.83, 25.88 and 25.99 ((CH3)3C), 63.66 (CH2-50), 74.02 (CH-30),
79.64 (CH-20), 82.33 (CH-10), 86.33 (CH-40), 127.08 (CH-2,6), 127.11
(CH-3,5),132.38 (C-4),145.34 (C-1),169.08 (CO). IR spectrum (CCl4):
3539, 3507, 3422, 3352, 3291, 3212, 3163, 2956, 2897, 1615, 1604,
1583, 1575, 1513, 1472, 1463, 1416, 1407, 1388, 1377, 1361, 1304, 1257,
1215, 1187, 1153, 1113, 1095, 1080, 1018, 939, 838, 672, 642 cmꢁ1
.
3.5.1. 1
(tert-butyldimethyl-silyl)-
Prepared according to the general procedure, method A. Starting
from (104 mg, 0.165 mmol) using Pd(OAc)2 (10 mol %,
b
-[3-(Carbamoyl)phenyl]-1-deoxy-2,3,5-tri-O-
Prepared according to the general procedure, method B. Starting
from 4 (312 mg, 0.494 mmol) using Pd(OAc)2 (5 mol %, 0.025 mmol,
5.5 mg), Xantphos (10 mol %, 0.050 mmol, 27 mg), NH4Cl
(1.48 mmol, 79 mg, 3 equiv), K3PO4 (1.98 mmol, 419 mg, 4 equiv)
and toluene/DMSO 1:1 mixture (1.8 mL). Reaction time 3.5 h. Flash
chromatography in gradient hexane/AcOH 25:1 to 25:2 gave 5j as
colourless light oil (192 mg, 65%).
Prepared according to the general procedure, method C. Reaction
mixture containing 4 (128 mg, 0.203 mmol), Pd(OAc)2 (10 mol %,
0.020 mmol, 4.5 mg), Xantphos (20 mol %, 0.041 mmol, 23 mg),
K3PO4 (0.810 mmol, 172 mg, 4 equiv) was evacuated and backfilled
with CO(g)/NH3 (ca.1:1 mixture). Then toluene (0.50 mL) was added
and reaction mixture was stirred for 14 h. Flash chromatography in
gradient hexane/AcOH 25:1 to 25:2 gave 5j as colourless light oil
(93 mg, 69%).
D-ribofuranose (2j)
1
0.016 mmol, 3.7 mg), Xantphos (20 mol %, 0.033 mmol, 19 mg),
AcONH4 (0.494 mmol, 3 equiv, 38 mg), K3PO4 (0.658 mmol, 4 equiv,
140 mg) and toluene (0.41 mL). Reaction time 15 h. Flash chroma-
tography in gradient hexane/AcOH 25:1 to 25:2 gave 2j as colour-
less light oil (74 mg, 76%). HRMS (FAB) for C30H57NO5Si3Na: [MþNa]
calculated, 618.3436; found, 618.3438. 1H NMR (499.8 MHz, CDCl3):
ꢁ0.51, ꢁ0.14, 0.10, 0.11, 0.12 and 0.14 (6ꢂs, 6ꢂ3H, CH3Si), 0.79, 0.94
0
0
and 0.95 (3ꢂs, 3ꢂ9H, (CH3)3C), 3.79 (dd, 1H, Jgem¼10.9, J5 b,4 ¼3.3,
0
H-50b), 3.82 (dd, 1H, Jgem¼10.9, J5 a,4 ¼3.7, H-5 a), 3.84 (dd, 1H,
0
0
0
0
0
0
0
0
0
0
0
J2 ,1 ¼8.3, J2 ,3 ¼4.4, H-2 ), 4.05 (ddd, 1H,0 J4 ,5 ¼3.7, 3.3, J4 ,3 ¼1.5, H-
40), 4.13 (dd, 1H, J3 ,2 ¼4.4, J3 ,4 ¼1.5, H-3 ), 4.82 (d, 1H, J1 ,2 ¼8.3, H-
10), 5.80–6.00 and 6.00–6.20 (2ꢂbr s, 2H, NH2), 7.41 (td, 1H,
J5,4¼J5,6¼7.7, J5,2¼0.5, H-5), 7.64 (dt, 1H, J6,5¼7.7, J6,2¼J6,4¼1.7, H-6),
7.76–7.80 (m, 2H, H-2,4). 13C NMR (125.7 MHz, CDCl3): ꢁ5.56,
ꢁ5.43, ꢁ5.44, ꢁ4.51, ꢁ4.49 and ꢁ4.34 (CH3Si), 17.90, 18.05 and
18.33 (C(CH3)3), 25.78, 25.87 and 25.95 ((CH3)3C), 63.81 (CH2-50),
74.18 (CH-30), 79.56 (CH-20), 82.05 (CH-10), 86.61 (CH-40), 125.44
0
0
0
0
0
0
3.6. General procedure for the deprotection of TBDMS-
groupdmethod A
Et3N$3HF (163
mL, 1.00 mmol, 10 equiv) was added to the solu-
tion of silylated compound 2a–i or 5a–i (0.10 mmol) in THF

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M. Stefko et al. / Tetrahedron 65 (2009) 4471–4483
4479
(1.00 mL) and the resulting mixture was stirred at 40 ꢀC for 2 days.
After the reaction was complete (monitored by TLC eluted in CHCl3/
MeOH 8:2), solvent was removed under reduced pressure, the
crude product was dissolved in water and solid K2CO3 was added
until basic pH. Solvents were removed under reduced pressure and
crude product purified by reversed-phase chromatography (H2O/
MeOH as a eluent) to obtain free C-ribonucleosides 3a–i and 6a–i.
(C-3), 141.98 (C-1), 169.19 (CO). IR spectrum (KBr): 3435, 1696, 1632,
1620, 1602, 1584, 1492, 1445, 1432, 1369, 1350, 1287, 1210, 1114,
20
1075, 1052, 1028, 887, 853, 806, 701 cmꢁ1. [
a]
ꢁ24.1 (c 4.10,
D
MeOH). Anal. Calcd for C17H23NO5$0.5H2O: C, 61.80; H, 7.32; N, 4.24.
Found: C, 61.59; H, 7.25; N, 4.14.
3.7.3. 1
b-{3-[(Morpholine-4-yl)carbonyl]phenyl}-1-deoxy-D-
ribofuranose (3c)
3.7. General procedure for the deprotection of TBDMS-
groupdmethod B
Compound 3c was prepared from 2c (180 mg, 0.270 mmol)
according to general procedure, method A, in 89% yield, as a colour-
less oil, which after lyophylization furnished white hygroscopic
powder. HRMS (FAB) for C16H22NO6: [MþH] calculated, 324.1447;
found, 324.1443. 1H NMR (500.0 MHz, DMSO-d6): 3.31–3.35 (br m,
Mixture of CF3COOH/H2O 9:1 (0.75 mL) was added to silylated
compounds 2j or 5j (0.10 mmol) and resulting homogeneous mix-
ture was stirred for 1.5 h at room temperature. After the reaction
was complete (monitored by TLC, eluted in CHCl3/MeOH 8:2) sol-
vents were removed under reduced pressure and the crude product
was co-evaporated with 3ꢂ50 mL of toluene. Subsequent purifi-
cation by reversed-phase chromatography afforded desired nucleo-
side 3j and 6j.
0
2H, CH2N-morph); 3.53 and 3.56 (2ꢂddd, 2H, Jgem¼11.8, J5 ,OH¼5.5,
0
0
0
J5 ,4 ¼4.6, H-5 ), 3.56–3.66 (br m, 6H, CH2N-morph and CH2O-
0
0
0
0
0
0
morph), 3.67 (ddd, 1H, J2 ,1 ¼7.3, J2 ,OH¼7.1, J2 ,3 ¼5.4, H-2 ), 3.83 (dt,
0
0
0
0
0
0
0
0
1H, J4 ,5 ¼4.6, J4 ,3 ¼2.8, H-4 ), 3.89 (ddd, 1H, J3 ,2 ¼5.4, J3 ,OH¼4.8,
0
0
0
0
0
0
0
J3 ,4 ¼2.8, H-3 ), 4.59 (d,1H, J1 ,2 ¼0 7.3, H-1 ), 4.87 (t,1H, JOH,5 ¼5.5, OH-
50), 4.97 (d, 1H, JOH,3 ¼4.8, OH-3 ), 5.05 (d, 1H, JOH,2 ¼7.1, OH-2 ), 7.30
(dt, 1H, J4,5¼7.5, J4,2¼J4,6¼1.5, H-4), 7.38 (dd, 1H, J5,6¼7.7, J5,4¼7.5, H-
5), 7.42 (t,1H, J2,4¼J2,6¼1.5, H-2), 7.47 (dt,1H, J6,5¼7.7, J6,2¼J6,4¼1.5, H-
6). 13C NMR (125.7 MHz, DMSO-d6): 42.26 and 47.95 (CH2N-morph),
62.22 (CH2-50), 66.33 (CH2O-morph), 71.69 (CH-30), 78.03 (CH-20),
82.69 (CH-10), 85.53 (CH-40), 124.96 (CH-2), 126.24 (CH-4), 127.71
(CH-6), 128.39 (CH-5), 135.45 (C-3), 142.09 (C-1), 169.40 (CO). IR
spectrum (KBr): 3435, 1631, 1620, 1601, 1585, 1491, 1463, 1433, 1389,
0
0
0
3.7.1. 1b-{3-[(Pyrrolidine-1-yl)carbonyl]phenyl}-1-deoxy-D-
ribofuranose (3a)
Compound 3a was prepared from 2a (306 mg, 0.471 mmol)
according to general procedure, method A, in 86% yield, as a col-
ourless oil, which after lyophylization furnished white powder, mp
115–118 ꢀC. HRMS (FAB) for C16H22NO5: [MþH] calculated,
308.1498; found, 308.1506. 1H NMR (500.0 MHz, DMSO-d6): 1.79
and 1.86 (2ꢂp, 2ꢂ2H, Jvic¼6.8, CH2-pyr), 3.33–3.39 (m, 2H, CH2N-
pyr), 3.45 (t, 2H, Jvic¼6.8, CH2N-pyr), 3.52 and 3.57 (2ꢂbr ddd, 2H,
1389, 1362, 1338, 1303, 1279, 1264, 1210, 1113, 1068, 1054, 889 cmꢁ1
.
20
[
a
]
ꢁ29.5 (c 3.86, MeOH). Anal. Calcd for C16H21NO6$0.5H2O: C,
D
57.82; H, 6.67; N, 4.21. Found: C, 58.21; H, 6.68; N, 3.90.
0
0
0
0
0
0
Jgem¼11.4, J5 ,OH¼5.5, J5 ,4 ¼4.4, H-5 ), 3.67 (br ddd, 1H, J2 ,1 ¼7.03,
0
0
0
0
0
0
0
0
J2 ,OH¼7.0, J2 ,3 ¼5.1, H-2 ), 4.82 (td, 1H, J4 ,5 ¼4.4, J4 ,3 ¼3.1, H-4 ),
3.7.4. 1
b-[3-(Dibutylcarbamoyl)phenyl]-1-deoxy-D-
0
0
0
0
0
0
3.89 (br ddd, 1H, J3 ,2 ¼5.1, J3 ,OH¼4.5, J3 ,4 ¼3.1, H-3 ), 4.59 (d, 1H,
ribofuranose (3d)
0
0
0
0
0
0
J1 ,2 ¼7.3, H-1 ), 4.87 (t, 1H, JOH,5 ¼5.5, OH-5 ), 4.97 (d, 1H, JOH,3 ¼4.5,
Compound 3d was prepared from 2d (258 mg, 0.364 mmol)
according to general procedure, method A, in 83% yield, as a colour-
less oil, which after lyophylization furnished a colourless oil. HRMS
(ESI) for C20H32NO5: [MþH] calculated, 366.2275; found, 366.2264.
1H NMR (499.8 MHz, DMSO-d6): 0.71 and 0.93 (2ꢂbt, 2ꢂ3H, Jvic¼7.1,
CH3CH2CH2CH2N), 1.02–1.10, 1.28–1.38, 1.39–1.44 and 1.50–1.60
(4ꢂbr m, 4ꢂ2H, CH3CH2CH2CH2N), 3.10 and 3.38 (2ꢂbr t, 2ꢂ2H,
OH-30), 5.04 (d, 1H, JOH,2 ¼7.0, OH-2 ), 7.38 (br dd, 1H, J5,4¼8.4,
0
0
J5,6¼6.6, H-5), 7.41 (br dt, 1H, J4,5¼8.4, J4,2¼J4,6¼2.0, H-4), 7.46 (br dt,
1H, J6,5¼6.6, J6,2¼J6,4¼2.0, H-6), 7.52 (br t, 1H, J2,4¼J2,6¼2.0, H-2). 13
C
NMR (125.7 MHz, DMSO-d6): 24.19 and 26.23 (CH2-pyr), 46.17 and
49.19 (CH2N-pyr), 62.23 (CH2-50), 71.67 (CH-30), 78.01 (CH-20),
82.78 (CH-10), 85.51 (CH-40), 124.98 (CH-2), 126.19 (CH-4), 127.80
(CH-5), 128.13 (CH-6), 137.18 (C-3), 141.78 (C-1), 168.53 (CO). IR
spectrum (KBr): 3386, 3252, 1632, 1613, 1600, 1578, 1491, 1465,
0
Jvic¼7.6, CH3CH2CH2CH2N), 3.55 (ddd, 1H, Jgem¼11.7, J5 b,OH¼5.5,
0
0
0
0
0
0
0
J5 b,4 ¼4.5, H-5 b), 3.55 (ddd, 1H, Jgem¼11.7, J5 a,4 ¼5.5, J5 a,4 ¼4.5, H-
0
50a), 3.65 (td, 1H, J2 ,1 ¼J2 ,OH¼7.2, J2 ,3 ¼5.4, H-2 ), 3.82 (td, 1H,
0
0
0
0
0
1458,1451,1422,1342,1337,1313,1220,1170,1128,1090,1059,1050,
20
1043, 1000, 877, 806, 704 cmꢁ1. [
a]
ꢁ29.5 (c 3.69, MeOH). Anal.
J4 ,5 ¼4.5, J4 ,3 ¼3.4, H-40), 3.88 (ddd, 1H, J3 ,2 ¼5.4, J3 ,OH¼4.9,
0
0
0
0
0
0
0
D
0
0
0
0
0
0
0
Calcd for C16H21NO5$0.5H2O: C, 60.75; H, 7.01; N, 4.43. Found: C,
J3 ,4 ¼3.4, H-3 ), 4.58 (d,1H, J1 ,2 ¼0 7.2, H-1 ), 4.83 (t,1H, JOH,5 ¼5.5, OH-
0
50), 4.95 (d, 1H, JOH,3 ¼4.9, OH-3 ), 5.00 (d, 1H, JOH,2 ¼7.2, OH-2 ), 7.19
0
0
60.44; H, 6.87; N, 4.22.
(ddd, 1H, J4,5¼7.5, J4,2¼1.8, J4,6¼1.3, H-4), 7.32 (tt, 1H, J2,4¼J2,6¼1.8,
0
3.7.2. 1
b
-{3-[(Piperidine-1-yl)carbonyl]phenyl}-1-deoxy-
D-
J2,5¼J2,1 ¼0.5, H-2), 7.40 (ddd,1H, J5,6¼7.7, J5,4¼7.5, J5,2¼0.5, H-5), 7.43
(dddd, 1H, J6,5¼7.7, J6,2¼1.8, J6,4¼1.3, J6,1 ¼0.6, H-6). 13C NMR
0
ribofuranose (3b)
Compound 3b was prepared from 2b (291 mg, 0.438 mmol)
according to general procedure, method A, in 93% yield, as a col-
ourless oil, which after lyophylization furnished white hygroscopic
powder. HRMS (FAB) for C17H24NO5: [MþH] calculated, 322.1654;
found, 322.1650. 1H NMR (500.0 MHz, DMSO-d6): 1.41–1.49, 1.49–
1.56 and 1.56–1.64 (3ꢂbr m, 3ꢂ2H, CH2-pip), 3.21–3.31 (br m, 2H,
(125.7 MHz, DMSO-d6): 13.62 and 14.07 (CH3CH2CH2CH2N), 19.42,
19.95, 29.47 and 30.44 (CH3CH2CH2CH2N), 43.95 and 48.23
(CH3CH2CH2CH2N), 62.21 (CH2-50), 71.62 (CH-30), 78.01 (CH-20),
82.73 (CH-10), 85.44 (CH-40), 123.89 (CH-2), 125.34 (CH-4), 126.87
(CH-6), 128.25 (CH-5), 137.27 (C-3), 141.86 (C-1), 170.62 (CO). IR
spectrum (KBr): 3351, 1633, 1614, 1603, 1585, 1493, 1428, 1378, 1310,
20
CH2N-pip), 3.52 (ddd, 1H, Jgem¼11.7, J5 b,OH¼5.5, J05 b,4 ¼4.7, H-5 b),
1204, 1166, 1111, 1076, 1054, 806, 706 cmꢁ1. [
a]
D
ꢁ34.4 (c 3.37,
0
0
0
0
0
0
0
0
3.56 (ddd, 1H, Jgem¼11.7, J5 a,4 ¼5.5, J5 a,4 ¼4.4, H-5 a), 3.53–3.58 (br
MeOH). Anal. Calcd for C20H31NO5$0.5H2O: C, 64.45; H, 8.61; N, 3.74.
0
0
0
0
0
0
m, 2H, CH2N-pip), 3.67 (ddd, 1H, J2 ,1 ¼7.3, J2 ,OH¼7.1, J2 ,3 ¼5.4, H-2 ),
Found: C, 64.52; H, 8.42; N, 3.76.
0
0
0
0
0
0
0
3.82 (ddd, 1H, J4 ,5 ¼4.7, 4.4, J4 ,3 ¼3.1, H-4 ), 3.82 (ddd, 1H, J3 ,2 ¼5.4,
0
0
0
0
0
0
0
J3 ,OH¼4.7, J3 ,4 ¼3.1, H-3 ), 4.58 (d, 1H, J1 ,2 ¼7.3, H-1 ), 4.87 (t, 1H,
3.7.5. 1
b-[3-(Dimethylcarbamoyl)phenyl]-1-deoxy-D-
0
0
0
0
JOH,5 ¼5.5, OH-5 ), 4.97 (d, 1H, JOH,3 ¼4.7, OH-3 ), 5.05 (d, 1H,
ribofuranose (3e)
0
0
JOH,2 ¼7.1, OH-2 ), 7.24 (dt,1H, J4,5¼7.6, J4,2¼J4,6¼1.5, H-4), 7.37 (t,1H,
J2,4¼J2,6¼1.5, H-2), 7.38 (t, 1H, J5,4¼J5,6¼7.6, H-5), 7.44 (dt, 1H,
J6,5¼7.6, J6,2¼J6,4¼1.5, H-6). 13C NMR (125.7 MHz, DMSO-d6): 24.32,
25.52 and 26.25 (CH2-pip), 42.54 and 48.27 (CH2N-pip), 62.26 (CH2-
50), 71.72 (CH-30); 78.02 (CH-20), 82.73 (CH-10), 85.54 (CH-40),
124.52 (CH-2), 125.81 (CH-4), 127.38 (CH-6), 128.34 (CH-5), 136.45
Compound 3e was prepared from 2e (134 mg, 0.215 mmol)
according to general procedure, method A, in 95% yield, as a col-
ourless oil, which after lyophylization furnished white powder, mp
122–125 ꢀC. HRMS (FAB) for C14H20NO5: [MþH] calculated,
282.1341; found, 282.1338. 1H NMR (500.0 MHz, DMSO-d6): 2.80–
2.92 and 2.92–3.04 (2ꢂbr s, 2ꢂ3H, CH3N), 3.53 and 3.56 (2ꢂddd,

ˇ
M. Stefko et al. / Tetrahedron 65 (2009) 4471–4483
4480
20
0
0
0
0
0
0
2H, Jgem¼11.7, J5 ,OH¼5.50, J5 ,4 ¼4.4, H-5 ), 3.68 (ddd, 1H, J2 ,1 ¼7.02,
1337, 1320, 1301, 1210, 1129, 1087, 1063, 815, 703, 695 cmꢁ1. [
a]
D
0
0
0
0
0
0
0
J2 ,OH¼7.1, J2 ,3 ¼5.4, H-2 ), 3.82 (td, 1H, J4 ,5 ¼4.4, J4 ,3 ¼3.4, H-4 ),
ꢁ11.0 (c 3.18, MeOH). Anal. Calcd for C18H25NO5$1H2O: C, 61.17; H,
0
0
0
0
0
0
3.89 (ddd, 1H, J3 ,2 ¼5.4, J3 ,OH¼4.8, J3 ,4 ¼03.4, H-3 ), 4.58 (d, 1H,
7.70; N, 3.96. Found: C, 61.27; H, 7.47; N, 3.96.
0
0
0
0
0
J1 ,2 ¼7.2, H-1 ), 4.83 (t, 1H, JOH,5 ¼5.5, OH-5 ), 4.93 (d, 1H, JOH,3 ¼4.8,
OH-30), 5.01 (d, 1H, JOH,2 ¼7.1, OH-2 ), 6.60 (ddd, 1H, J4,5¼7.6,
3.7.8. 1
b-[3-(Benzylcarbamoyl)phenyl]-1-deoxy-D-
0
0
J4,2¼1.8, J4,6¼1.3, H-4), 7.38 (dd, 1H, J5,6¼7.7, J5,4¼7.6, H-5), 7.41 (tt,
ribofuranose (3h)
0
1H, J2,4¼J2,6¼1.8, J2,5¼J2,1 ¼0.6, H-2), 7.45 (dddd, 1H, J6,5¼7.7,
Compound 3h was prepared from 2h (210 mg, 0.306 mmol)
according to general procedure, method A, in 88% yield, as a colour-
less oil, which after crystallization from EA furnished white crystals,
mp 135–137 ꢀC. HRMS (ESI) for C19H20NO5: [MꢁH] calculated,
342.1336; found, 342.1340.1H NMR (600.1 MHz, DMSO-d6): 3.55 and
J6,2¼1.8, J6,4¼1.3, J6,1 ¼0.7, H-6). 13C NMR (125.7 MHz, DMSO-d6):
0
34.90 and 39.16 (CH3N), 62.18 (CH2-50), 71.61 (CH-30), 77.91 (CH-20),
82.73 (CH-10), 85.47 (CH-40), 124.77 (CH-2), 126.00 (CH-4), 127.33
(CH-6), 128.11 (CH-5), 136.38 (C-3), 141.81 (C-1), 170.35 (CO). IR
spectrum (KBr): 3362, 3252, 3175, 1623, 1606, 1585, 1512, 1479,
0
0
0
0
3.58 (2ꢂddd, 2ꢂ1H, Jgem¼11.6, J5 ,OH¼5.6, J5 ,4 ¼4.6, H-5 ), 3.71 (ddd,
0
0
0
0
0
0
0
0
1432, 1412, 1400, 1310, 1222, 1164, 1131, 1098, 1081, 1053, 1046, 804,
1H, J2 ,1 ¼7.1, 0 J2 ,OH¼6.9, J2 ,3 ¼5.4, H-2 ), 3.83 (td, 1H, J4 ,5 ¼4.6,
20
700 cmꢁ1
.
[a
]
ꢁ28.4 (c 3.49, MeOH). Anal. Calcd for
J4 ,3 ¼3.7, H-4 ), 3.90 (ddd, 1H, J3 ,2 ¼5.4, J3 ,OH¼4.9, J3 ,4 ¼3.7, H-3 ),
0
0
0
0
0
0
0
0
D
0
0
0
C14H19NO5$0.4H2O: C, 58.28; H, 6.92; N, 4.85. Found: C, 58.58; H,
4.48 (d, 2H, J¼6.00, CH2Ph), 4.61 (d, 1H, J1 ,2 ¼7.1, H-1 ), 4.83 (t, 1H,
0
0
0
6.69; N, 4.48.
JOH,5 ¼5.6, OH-5 ), 4.94 (d, 1H, JOH,3 ¼4.9, OH-3 ), 5.03 (d, 1H,
0
0
JOH,2 ¼6.9, OH-2 ), 7.22–7.26 (m, 1H, H-p-Ph), 7.30–7.35 (m, 4H, H-
o,m-Ph), 7.43 (dd, 1H, J5,4¼7.7, J5,6¼7.6, H-5), 7.58 (dddd, 1H, J6,5¼7.6,
3.7.6. 1
b-[3-(Cyclopropylcarbamoyl)phenyl]-1-deoxy-D-
0
ribofuranose (3f)
J6,2¼1.8, J6,4¼1.3, J6,1 ¼0.5, H-6), 7.79 (ddd, 1H, J4,5¼7.7, J4,2¼1.8,
0
Compound 3f was prepared from 2f (283 mg, 0.445 mmol)
according to general procedure, method A, in 89% yield, as a col-
ourless oil, which after lyophylization furnished white hygroscopic
powder. HRMS (ESI) for C15H20NO5: [MþH] calculated, 294.1336;
found, 294.1336. 1H NMR (500.0 MHz, DMSO-d6): 0.54–0.58 and
0.66–0.72 (2ꢂm, 2ꢂ2H, CH2-cycloprop), 2.83 (tq 1H, J¼7.3, 4.0, CH-
J4,6¼1.3, H-4), 7.87 (tt,1H, J2,4¼J2,6¼1.8, J2,5¼J2,1 ¼0.6, H-2), 9.04 (t,1H,
J¼6.0, NH). 13C NMR (150.9 MHz, DMSO-d6): 42.81 (CH2Ph), 62.24
(CH2-50), 71.61 (CH-30), 77.75 (CH-20), 82.99 (CH-10), 85.45 (CH-40),
125.49 (CH-2), 126.37 (CH-4), 126.95 (CH-p-Ph), 127.40 (CH-o-Ph),
128.28 (CH-5),128.51 (CH-m-Ph),129.33 (CH-6),134.39 (C-3),139.94
(C-i-Ph), 141.85 (C-1), 166.51 (CO). IR spectrum (KBr): 3420, 3370,
0
0
0
0
cycloprop), 3.54 (ddd, 1H, Jgem¼11.7, J5 b,OH¼5.6, J5 b,4 ¼4.8, H-5 b),
3292, 1642, 1620, 1607, 1581, 1542, 1496, 1480, 1451, 1430, 1317, 1317,
1292, 1219, 1170, 1126, 1079, 1054, 1028, 812, 704, 693 cmꢁ1. [
a]
20
0
0
0
0
3.58 (ddd,1H, Jgem¼11.7, J5 a,OH¼5.6, J5 a,4 ¼4.5, H-5 a), 3.70 (ddd,1H,
D
0
0
0
0
0
0
0
0
J2 ,1 ¼7.1, J2 ,OH¼6.8, J2 ,3 ¼5.4, H-2 ), 3.82 (ddd, 1H, J4 ,5 ¼4.8, 4.05,
ꢁ21.9 (c 3.19, MeOH). Anal. Calcd for C19H21NO5: C, 66.46; H, 6.16; N,
0
0
0
0
0
0
0
0
J4 ,3 ¼3.7, H-4 ), 3.89 (ddd, 1H, J3 ,2 ¼5.4, J3 ,OH¼4.8, J3 0,4 ¼3.7, H-3 ),
4.08. Found: C, 66.13; H, 6.19; N, 3.93.
0
0
0
0
4.59 (d,1H, J1 ,2 ¼7.1, H-1 ), 4.83 (t,1H, JOH,5 ¼5.6, OH-5 ), 4.93 (d,1H,
0
0
0
0
JOH,3 ¼4.8, OH-3 ), 5.01 (d, 1H, JOH,2 ¼6.8, OH-2 ), 7.39 (dd, 1H,
J5,4¼7.8, J5,6¼7.6, H-5), 7.54 (dddd, 1H, J6,5¼7.6, J6,2¼1.7, J6,4¼1.3,
3.7.9. 1
b-[3-(Methylcarbamoyl)phenyl]-1-deoxy-D-
ribofuranose (3i)
0
J6,1 ¼0.6, H-6), 7.68 (ddd, 1H, J4,5¼7.8, J4,2¼1.7, J4,6¼1.3, H-4), 7.78 (t,
Compound 3i was prepared from 2i (250 mg, 0.410 mmol)
according to general procedure, method A, in 93% yield, as a col-
ourless oil, which after lyophylization furnished white hygroscopic
powder. HRMS (ESI) for C13H18NO5: [MþH] calculated, 268.1179;
found, 268.1185. 1H NMR (600.1 MHz, DMSO-d6): 2.78 (d, 3H, J¼4.6,
1H, J2,4¼J2,6¼1.7, H-2), 8.41 (d, 1H, J¼4.0, NH). 13C NMR (125.7 MHz,
DMSO-d6): 5.98 and 6.00 (CH2-cycloprop), 23.28 (CH-cycloprop),
62.23 (CH2-50), 71.58 (CH-30), 77.73 (CH-20), 83.04 (CH-10), 85.42
(CH-40), 125.42 (CH-2), 126.30 (CH-4), 128.16 (CH-5), 129.11 (CH-6),
134.52 (C-3), 141.71 (C-1), 167.91 (CO). IR spectrum (KBr): 3351,
0
0
0
0
CH3), 3.54 (ddd, 1H, Jgem¼11.6, J5 b,OH¼5.6, J5 b,4 ¼4.7, H-5 b), 3.58
0
0
0
0
0
3092, 3012, 1642, 1607, 1584, 1534, 1482, 1424, 1303, 1205, 1113,
(ddd, 1H, Jgem¼11.6, J5 a,4 ¼5.6, J5 0a,4 ¼4.5, H-5 a), 3.69 (ddd, 1H,
20
1072, 1050, 813, 698 cmꢁ1. [
a
]
ꢁ29.1 (c 2.51, MeOH). Anal. Calcd
J2 ,1 ¼7.2, J2 ,OH¼6.9, J2 ,3 ¼5.4, H-2 ), 3.83 (ddd, 1H, J4 ,5 ¼4.7, 4.05,
0
0
0
0
0
0
0
D
0
0
0
0
0
0
0
0
for C15H19NO5$0.5H2O: C, 59.59; H, 6.67; N, 4.63. Found: C, 59.81; H,
J4 ,3 ¼3.5, H-4 ), 3.89 (ddd, 1H, J3 ,2 ¼5.4, J3 ,OH¼4.5, J3 ,4 ¼03.7, H-3 ),
0
0
0
0
6.41; N, 4.29.
4.59 (d, 1H, J1 ,2 ¼7.2, H-1 ), 4.83 (t, 1H, JOH,5 ¼5.6, OH-5 ), 4.94 (d,
0
0
0
0
1H, JOH,3 ¼4.9, OH-3 ), 5.03 (d, 1H, JOH,2 ¼6.9, OH-2 ), 7.41 (t, 1H,
0
3.7.7. 1
b
-[3-(Cyclohexylcarbamoyl)phenyl]-1-deoxy-
D-
J5,4¼J5,6¼7.7, H-5), 7.54 (dddd,1H, J6,5¼7.7, J6,2¼1.8, J6,4¼1.3, J6,1 ¼0.6,
ribofuranose (3g)
H-6), 7.70 (ddd, 1H, J4,5¼7.7, J4,2¼1.8, J4,6¼1.3, H-4), 7.80 (t, 1H,
J2,4¼J2,6¼1.8, H-2), 8.41 (q, 1H, J¼4.6, NH). 13C NMR (150.9 MHz,
DMSO-d6): 26.48 (CH3), 62.25 (CH2-50), 71.62 (CH-30), 77.76 (CH-20),
82.99 (CH-10), 85.45 (CH-40), 125.25 (CH-2), 126.16 (CH-4), 128.22
(CH-5), 129.09 (CH-6), 134.62 (C-3), 141.78 (C-1), 166.97 (CO). IR
Compound 3g was prepared from 2g (190 mg, 0.280 mmol)
according to general procedure, method A, in 91% yield, as a col-
ourless oil, which after crystallization from EA furnished white
cotton-like crystals, mp 189–191 ꢀC. HRMS (ESI) for C18H24NO5:
[MꢁH] calculated, 334.1649; found, 334.1650. 1H NMR (500.0 MHz,
DMSO-d6): 1.07–1.17, 1.23–1.37, 1.57–1.64, 1.57–1.64 and 1.77–1.85
(5ꢂm, 10H, H-2,3,4,5,6-cyclohex), 3.54 (ddd, 1H, Jgem¼11.7,
spectrum (KBr): 3412, 1639, 1607, 1585, 1549, 1484, 1434, 1412,
20
1325, 1307, 1307, 1217, 1158, 1115, 1075, 1052, 814, 698 cmꢁ1. [
a]
D
ꢁ10.9 (c 2.87, MeOH). Anal. Calcd for C13H17NO5$0.5H2O: C, 56.51;
0
0
0
0
0
0
J5 b,OH¼5.6, J5 b,4 ¼4.8, H-5 b), 3.58 (ddd, 1H, Jgem¼11.7, J5 a,4 ¼5.06,
H, 6.57; N, 5.07. Found: C, 56.48; H, 6.64; N, 4.85.
0
0
0
0
0
0
0
0
J5 a,4 ¼4.5, H-5 a), 3.71 (ddd, 1H, J2 ,1 ¼7.0, J2 ,OH¼6.8, J2 ,3 ¼5.4, H-2 ),
0
0
3.71–3.79 (br m, 1H, H-1-cyclohex), 3.83 (ddd, 1H, J4 ,5 ¼4.8, 4.05,
3.7.10. 1b-[3-(Carbamoyl)phenyl]-1-deoxy-D-ribofuranose (3j)
0
0
0
0
0
0
0
0
J4 ,3 ¼3.7, H-4 ), 3.90 (ddd, 1H, J3 ,2 ¼5.4, J3 ,OH¼4.9, J3 ,4 ¼03.7, H-3 ),
Compound 3j was prepared from 2j (350 mg, 0.587 mmol)
according to general procedure, method B, in 90% yield, as a colour-
less oil, which after lyophylization furnished white hygroscopic
powder. HRMS (ESI) for C12H16NO5: [MþH] calculated, 254.1023;
found, 254.1024. 1H NMR (600.1 MHz, DMSO-d6): 3.54 (ddd, 1H,
0
0
0
0
4.60 (d, 1H, J1 ,2 ¼7.00, H-1 ), 4.81 (t, 1H, JOH,5 ¼5.6, O0H-5 ), 4.91 (d,
0
0
1H, JOH,3 ¼4.9, OH-3 ), 5.00 (d, 1H, JOH,2 ¼6.8, OH-2 ), 7.39 (t, 1H,
J5,4¼J5,6¼7.7, H-5), 7.54 (dt, 1H, J6,5¼7.7, J6,2¼J6,4¼1.5, H-6), 7.71 (dt,
1H, J4,5¼7.7, J4,2¼J4,6¼1.5, H-4), 7.79 (t,1H, J2,4¼J2,6¼1.5, H-2), 8.15 (d,
1H, J¼8.0, NH). 13C NMR (125.7 MHz, DMSO-d6): 25.16, 25.47 and
32.63 (CH2-2,3,4,5,6-cyclohex), 48.50 (CH-1-cyclohex), 62.17 (CH2-
50), 71.51 (CH-30), 77.67 (CH-20), 83.07 (CH-10), 85.34 (CH-40), 125.56
(CH-2), 126.36 (CH-4), 128.04 (CH-5), 128.86 (CH-6), 134.94 (C-3),
141.62 (C-1), 165.66 (CO). IR spectrum (KBr): 3410, 3299, 3264,
2935, 2854, 1635, 1612, 1587, 1542, 1486, 1449, 1441, 1369, 1350,
0
0
0
0
Jgem¼12.0, J5 b,OH¼5.7, J5 b,4 ¼4.7, H-5 b), 3.58 (ddd, 1H, Jgem¼12.0,
0
0
0
0
0
0
0
0
J5 a,4 ¼5.7, J5 a0 ,4 ¼4.5, H-5 a), 3.70 (ddd, 1H, J2 ,1 ¼7.2, J2 ,OH¼6.9,
0
0
0
0
0
0
0
J2 ,3 ¼5.4, H-2 ), 3.82(ddd,1H,J4 ,5 ¼4.7,04.5, J4 ,3 ¼3.5, H-4 ), 3.89 (dd0d,
0
0
0
0
0
0
0
1H, J3 ,2 ¼5.4, J3 ,OH¼4.8, J3 ,4 ¼3.5, H-3 ), 4.59 (d, 1H, J1 ,2 ¼07.2, H-1 ),
0
0
0
4.83 (t, 1H, JOH,5 ¼5.7, OH-5 ), 4.94 (d, 1H, JOH,3 ¼4.8, OH-3 ), 5.03 (d,
0
0
1H, JOH,2 ¼6.9, OH-2 ), 7.36 (br s,1H, NHaHb), 7.40 (t,1H, J5,4¼J5,6¼7.7,

ˇ
M. Stefko et al. / Tetrahedron 65 (2009) 4471–4483
4481
0
0
0
0
0
H-5), 7.55 (dddd, 1H, J6,5¼7.7, J6,2¼1.8, J6,4¼1.3, J6,1 ¼0.5, H-6), 7.76
(ddd,1H, J4,5¼7.7, J4,2¼1.8, J4,6¼1.3, H-4), 7.85(t,1H, J2,4¼J2,6¼1.8, H-2),
7.95 (br s, 1H, NHaHb). 13C NMR (150.9 MHz, DMSO-d6): 62.25 (CH2-
50), 71.63 (CH-30), 77.78 (CH-20), 83.01 (CH-10), 85.47 (CH-40), 125.68
(CH-2), 126.61 (CH-4), 128.16 (CH-5), 129.37 (CH-6), 134.32 (C-3),
50), 4.94 (d,1H, JOH,3 ¼4.8, OH-3 ), 5.01 (d,1H, JOH,2 ¼7.1, OH-2 ), 7.35–
7.38 (m, 2H, H-3,5), 7.44–7.48 (m, 2H, H-2,6). 13C NMR (125.7 MHz,
DMSO-d6): 42.50 and 48.00 (CH2N-morph), 62.21 (CH2-50), 66.28
(CH2O-morph), 71.70 (CH-30), 77.89 (CH-20), 82.67 (CH-10), 85.47 (CH-
40),126.31 (CH-2,6),127.02 (CH-3,5),134.63 (C-4),143.26 (C-1),169.27
(CO). IR spectrum (KBr): 3401, 2965, 2921, 2858, 1611, 1569,1513,1463,
141.71 (C-1), 168.21 (CO). IR spectrum (KBr): 3419, 1659, 1617, 1607,
20
1582,1486,1397,1217,1114,1072,1050, 695 cmꢁ1. [
a]
ꢁ25.6 (c 1.29,
1436, 1436, 1407, 1389, 1362, 1331, 1302, 1280, 1260, 1221, 1184, 1158,
D
20
MeOH). Anal. Calcd for C21H15NO5$0.5H2O: C, 54.96; H, 6.15; N, 5.34.
1114,1114,1066,1052,1026,1012, 895, 834, 688, 634 cmꢁ1. [
a]
ꢁ27.5
D
Found: C, 54.56; H, 6.15; N, 5.12.
(c 4.21, MeOH). Anal. Calcd forC16H21NO6$0.5H2O:C, 57.82;H, 6.67; N,
4.21. Found: C, 57.67; H, 6.57; N, 4.17.
3.7.11. 1
b-{4-[(Pyrrolidine-1-yl)carbonyl]phenyl}-1-deoxy-D-
ribofuranose (6a)
3.7.14. 1
b-[4-(Dibutylcarbamoyl)phenyl]-1-deoxy-D-
Compound 6a was prepared from 5a (258 mg, 0.397 mmol)
according to general procedure, method A, in 90% yield, as a colour-
less oil, which after lyophylization furnished white hygroscopic
powder. HRMS (ESI) for C16H20NO5: [MꢁH] calculated, 306.1336;
found, 306.1342. 1H NMR (500.0 MHz, DMSO-d6): 1.76–1.83 and
1.83–1.90 (2ꢂm, 2ꢂ2H, CH2-pyr), 3.38 (t, 2H, J¼6.6, CH2N-pyr), 3.45
(t, 2H, J¼6.9, 0CH2N-pyr), 3.53 and 3.56 (2ꢂbr dd, 2ꢂ1H, Jgem¼12.1,
ribofuranose (6d)
Compound 6d was prepared from 5d (220 mg, 0.310 mmol)
according to general procedure, method A, in 87% yield, as
a colourless oil, which after lyophylization furnished colourless
oil. HRMS (FAB) for C20H32NO5: [MþH] calculated, 366.2280;
found, 366.2275. 1H NMR (500.0 MHz, DMSO-d6): 0.71 and 0.92
(2ꢂbr t, 2ꢂ3H, Jvic¼7.1, CH3CH2CH2CH2N), 1.00–1.10, 1.26–1.38,
1.38–1.49 and 1.49–1.60 (4ꢂbr m, 4ꢂ2H, CH3CH2CH2CH2N), 3.14
and 3.38 (2ꢂbr t, 2ꢂ2H, Jvic¼7.1, CH3CH2CH2CH2N), 3.53 (ddd, 1H,
0
0
0
0
0
0
0
J5 ,4 ¼4.5, H-5 ), 3.68 (dd, 1H, J2 ,1 ¼7.2, J2 ,3 ¼5.3, H-2 ), 3.83 (0td, 1H,
0
0
0
0
0
0
0
0
0
J4 ,5 ¼4.5, J4 ,3 ¼3.4, H-4 ), 3.90 (dd, 1H, J3 ,2 ¼05.3, J3 ,4 ¼3.4, H-3 ), 4.59
0
0
0
0
0
0
0
0
(d, 1H, J1 ,2 ¼7.2, H-1 ), 4.83 (br s, 1H, OH-5 ), 5.01 (br s, 1H, OH-3 ),
5.05 (br s, 1H, OH-20), 7.42–7.46 (m, 2H, H-2,6), 7.46–7.48 (m, 2H, H-
3,5). 13C NMR (125.7 MHz, DMSO-d6): 24.11 and 26.17 (CH2-pyr),
46.10 and 49.13 (CH2N-pyr), 62.23 (CH2-50), 71.70 (CH-30), 77.89 (CH-
20), 82.75 (CH-10), 85.46 (CH-40), 126.07 (CH-2,6), 127.02 (CH-3,5),
136.33 (C-4),143.30 (C-1),168.35 (CO). IR spectrum (KBr): 3341, 2969,
2925, 2877, 1606, 1565, 1516, 1482, 1462, 1444, 1444, 1405, 1340, 1304,
Jgem¼11.7, J5 b,OH¼5.5, J5 b,4 ¼4.9, H-5 b), 3.56 (ddd, 1H, Jgem¼11.7,
0
0
0
0
0
0
0
0
0
0
J5 a,4 ¼5.5, J5 a,4 ¼4.4, H-5 a), 3.67 (td, 1H, J2 ,1 ¼J2 ,OH¼7.1, J2 ,3 ¼5.4,
H-20), 3.82 (ddd, 1H, J4 ,5 ¼4.9, 4.4,0J4 ,3 ¼3.2, H-4 ), 3.89 (ddd, 1H,
0
0
0
0
0
0
0
0
0
0
0
0
0
J3 ,2 ¼5.4, J3 ,OH¼4.8, J3 ,4 ¼3.2, H-3 ), 4.58 (d, 1H, J1 ,2 ¼7.1, H-1 ),
0
0
0
0
4.85 (t, 1H, JOH,5 ¼5.5, OH-5 ), 4.98 (d, 1H, JOH,3 ¼4.8, OH-3 ), 5.04
0
0
(d, 1H, JOH,2 ¼7.1, OH-2 ), 7.17–7.31 (m, 2H, H-3,5), 7.38–7.48 (m,
2H, H-2,6). 13C NMR (125.7 MHz, DMSO-d6): 13.70 and 14.11
1253, 1230, 1209, 1184, 1113, 1113, 1078, 1054, 1018, 835, 687,
(CH3CH2CH2CH2N),
19.45,
19.98,
29.50
and
30.47
20
635 cmꢁ1. [
a
]
ꢁ37.9 (c 2.82, MeOH). Anal. Calcd for C16H21NO5$4/
(CH3CH2CH2CH2N), 43.92 and 48.26 (CH3CH2CH2CH2N), 62.24
(CH2-50), 71.66 (CH-30), 77.97 (CH-20), 82.86 (CH-10), 85.45 (CH-
40), 126.27 and 126.31 (CH-2,3,5,6), 136.51 (C-4), 142.50 (C-1),
170.59 (CO). IR spectrum (KBr): 3399, 3334, 3278, 1619, 1568,
D
5H2O: C, 59.73; H, 7.08; N, 4.35. Found: C, 59.58; H, 6.91; N, 4.26.
3.7.12. 1b-{4-[(Piperidine-1-yl)carbonyl]phenyl}-1-deoxy-D-
ribofuranose (6b)
1512, 1430, 1405, 1381, 1307, 1210, 1179, 1119, 1103, 1080, 1047,
20
Compound 6b was prepared from 5b (308 mg, 0.464 mmol)
according to general procedure, method A, in 91% yield, as a col-
ourless oil, which after lyophylization furnished white hygroscopic
powder. HRMS (ESI) for C17H24NO5: [MþH] calculated, 322.1649;
found, 322.1650. 1H NMR (500.0 MHz, DMSO-d6): 1.41–1.49, 1.49–
1.57 and 1.58–1.64 (3ꢂbr m, 3ꢂ2H, CH2-pip), 3.21–3.31 (br m, 2H,
CH2N-pip), 3.50–3.60 (br m, 4H, H-50 and CH2N-pip), 3.69 (dd, 1H,
1018, 839, 682, 638 cmꢁ1. [
a
]
ꢁ34.2 (c 3.30, MeOH). Anal. Calcd
D
for C20H31NO5: C, 65.73; H, 8.55; N, 3.83. Found: C, 65.35; H, 8.39;
N, 3.72.
3.7.15. 1
b-[4-(Dimethylcarbamoyl)phenyl]-1-deoxy-D-
ribofuranose (6e)
Compound 6e was prepared from 5e (150 mg, 0.240 mmol)
according to general procedure, method A, in 95% yield, as a col-
ourless oil, which after lyophylization furnished white powder, mp
103–105 ꢀC. HRMS (ESI) for C14H18NO5: [MꢁH] calculated,
280.1179; found, 280.1190. 1H NMR (500.0 MHz, DMSO-d6): 2.90
and 2.97 (2ꢂbr s, 2ꢂ3H, CH3N),0 3.53 and 3.56 (2ꢂddd, 2H,
0
0
0
0
0
0
0
0
0
0
0
J2 ,1 ¼7.3, J2 ,3 ¼5.3, H-2 ), 3.83 (td, 1H, J4 ,5 ¼4.5, J4 ,3 ¼3.4, H-4 ), 3.90
0
0
0
0
0
0
0
(dd, 1H, J3 ,2 ¼5.3, J3 ,4 ¼3.4, H-3 ), 4.58 (d, 1H, J1 ,2 ¼7.3, H-1 ), 4.83
(br s, 1H, OH-50), 4.98 (br s, 1H, OH-30), 5.04 (br s, 1H, OH-20), 7.29–
7.33 (m, 2H, H-3,5), 7.43–7.46 (m, 2H, H-2,6). 13C NMR (125.7 MHz,
DMSO-d6): 24.25 and 25.74 (CH2-pip), 42.49 and 48.25 (CH2N-pip),
62.24 (CH2-50), 71.72 (CH-30), 77.88 (CH-20), 82.72 (CH-10), 85.48
(CH-40), 126.31 (CH-2,6), 126.60 (CH-3,5), 135.63 (C-4), 142.84 (C-1),
169.07 (CO). IR spectrum (KBr): 3393, 2935, 2858, 1632, 1606, 1569,
0
0
0
0
Jgem¼11.7, J5 ,OH¼5.6, J5 ,4 ¼4.5, H-5 ), 3.65–3.71 (br m, 1H, H-20),
0
0
0
0
0
3.83 (td, 1H, J4 ,5 ¼4.5, J40,3 ¼3.3, H-4 ), 3.87–3.92 (br m, 1H, H-3 ),
0
0
0
0
4.58 (d, 1H, J1 ,2 ¼7.3, H-1 ), 4.86 (t, 1H, JOH,5 ¼5.6, OH-5 ), 4.99 (br s,
0
1H, OH-30), 5.06 (br d, 1H, JOH,2 ¼7.1, OH-2 ), 7.33–7.37 (m, 2H, H-
3,5), 7.42–7.46 (m, 2H, H-2,6). 13C NMR (125.7 MHz, DMSO-d6):
35.02 and 39.29 (CH3N), 62.27 (CH2-50), 71.76 (CH-30), 77.97 (CH-20),
82.77 (CH-10), 85.51 (CH-40), 126.25 (CH-2,6), 127.01 (CH-3,5),
135.62 (C-4), 142.99 (C-1), 170.36 (CO). IR spectrum (KBr): 3333,
0
1515, 1470,1445, 1407, 1368, 1352,1288, 1277, 1113, 1113, 1075, 1055,
20
1027, 1018, 1004, 888, 854, 835, 684, 634 cmꢁ1. [
a
]
ꢁ28.2 (c 2.87,
D
MeOH). Anal. Calcd for C17H23NO5$2/3H2O: C, 61.14; H, 7.36; N, 4.19.
Found: C, 61.14; H, 7.26; N, 4.07.
3.7.13. 1
ribofuranose (6c)
b
-{4-[(Morpholine-4-yl)carbonyl]phenyl}-1-deoxy-
D
-
1613, 1569, 1520, 1493, 1407, 1401, 1305, 1265, 1218, 1182, 1114, 1087,
1053, 1018, 836, 693 cmꢁ1. [
a
]
ꢁ26.1 (c 3.10, MeOH). Anal. Calcd
20
D
Compound 6c was prepared from 5c (317 mg, 0.480 mmol)
accordingtogeneralprocedure, methodA, in87%yield, asacolourless
oil, which after lyophylization furnished white hygroscopic powder.
HRMS (ESI) for C16H22NO6: [MþH] calculated, 324.1442; found,
324.1442. 1H NMR (500.0 MHz, DMSO-d6): 3.33–3.37 (br m, 2H,
CH2N-morph), 3.50–3.70 (br m, 6H, CH2NþCH2O-morph), 3.53 and
for C14H19NO5$0.5H2O: C, 57.92; H, 6.94; N, 4.82. Found: C, 58.20; H,
6.85; N, 4.57.
3.7.16. 1
b-[4-(Cyclopropylcarbamoyl)phenyl]-1-deoxy-D-
ribofuranose (6f)
Compound 6f was prepared from 5f (140 mg, 0.220 mmol)
according to general procedure, method A, in 89% yield, as a col-
ourless oil, which after lyophylization furnished white powder, mp
94–98 ꢀC. HRMS (ESI) for C15H18NO5: [MꢁH] calculated, 292.1179;
found, 292.1191. 1H NMR (500.0 MHz, DMSO-d6): 0.54–0.58 and
0
0
0
0
3.56 (2ꢂddd, 2ꢂ1H, Jgem¼11.7, J5 ,OH¼5.5, J5 ,4 ¼4.5, H-5 ), 3.69 (ddd,
0
0
0
0
0
0
0
0
1H, J2 ,1 ¼7.3, J2 ,OH¼7.1, J2 ,3 ¼5.3, H-2 ), 3.83 (td, 1H, J4 ,5 ¼4.5,
0
0
0
0
0
0
0
0
J4 ,3 ¼3.4, H-04 ), 3.90 (dddd, 1H, J3 ,2 ¼5.3, J3 ,OH¼4.8, J3 ,4 ¼3.4,
0
0
0
0
0
0
J3 ,1 ¼0.4, H-3 ), 4.59 (d,1H, J1 ,2 ¼7.3, H-1 ), 4.82 (t,1H, JOH,5 ¼5.5, OH-

ˇ
M. Stefko et al. / Tetrahedron 65 (2009) 4471–4483
4482
0.63–0.74 (2ꢂm, 2ꢂ2H, CH2-cycloprop), 2.83 (tq 1H, J¼7.2, 4.2, CH-
3.7.19. 1
ribofuranose (6i)
b-[4-(Methylcarbamoyl)phenyl]-1-deoxy-D-
0
cycloprop), 30.53 and 3.57 (2ꢂddd, 2ꢂ1H, Jgem¼11.7, J5 ,OH¼5.04,
0
0
0
0
0
0
0
J5 ,4 ¼4.6, H-5 ), 3.66 (ddd, 1H, J2 ,1 ¼7.1, J2 ,OH¼7.0, J2 ,3 ¼5.4, H-2 ),
Compound 6i was prepared from 5i (205 mg, 0.336 mmol)
according to general procedure, method A, in 90% yield, as a col-
ourless oil, which after lyophylization furnished white hygroscopic
powder. HRMS (ESI) for C13H18NO5: [MþH] calculated, 268.1179;
found, 268.1181. 1H NMR (499.8 MHz, DMSO-d6): 2.78 (d, 3H, J¼4.6,
0
0
0
0
0
0
0
3.82 (td, 1H, J4 ,5 ¼4.6, J4 ,3 ¼3.6, H-4 ), 3.88 (bddd,01H, J3 ,2 ¼5.4,
0
0
0
0
0
0
J3 ,OH¼4.7, J3 ,4 ¼3.6, H-3 ), 4.60 (d, 1H, J1 ,2 ¼7.1, H-1 ), 4.82 (t, 1H,
0
0
0
0
JOH,5 ¼5.4, OH-5 ), 4.93 (d, 1H, JOH,3 ¼4.7, OH-3 ), 5.01 (d, 1H,
0
0
JOH,2 ¼7.1, OH-2 ), 7.43–7.46 (m, 2H, H-2,6), 7.74–7.78 (m, 2H, H-3,5),
8.42 (d, 1H, J¼4.2, NH). 13C NMR (125.7 MHz, DMSO-d6): 5.95 and
5.96 (CH2-cycloprop), 23.20 (CH-cycloprop), 62.14 (CH2-50), 71.57
(CH-30), 77.91 (CH-20), 82.77 (CH-10), 85.41 (CH-40), 125.99 (CH-2,6),
127.08 (CH-3,5), 133.58 (C-4), 144.80 (C-1), 167.54 (CO). IR spectrum
(KBr): 3452, 3355, 3316, 3262, 3093, 3007, 1733, 1649, 1633, 1614,
0
0
0
CH3), 3.54 and 3.57 (2ꢂddd, 2H, Jgem¼11.07, J5 ,OH¼5.4, J5 ,4 ¼4.5, H-
50), 3.67 (dd, 01H, J2 ,1 ¼7.2, J2 ,3 ¼5.3, H-2 ), 3.83 (td,01H, J4 ,5 ¼4.5,
0
0
0
0
0
0
0
0
0
0
0
0
J4 ,3 ¼3.4, H-4 ), 3.89 (dd, 1H, J3 ,2 ¼5.3, J3 ,4 ¼3.4, H-3 ), 4.60 (d, 1H,
0
0
0
0
0
0
J1 ,2 ¼7.2, H-1 ), 4.83 (t, 1H, JOH,5 ¼5.4, OH-5 ), 4.96 (br s, 1H, OH-3 ),
5.03 (br s, 1H, OH-20), 7.44–7.48 (m, 2H, H-2,6), 7.76–7.80 (m, 2H, H-
3,5), 8.38 (q, 1H, J¼4.6, NH). 13C NMR (125.7 MHz, DMSO-d6): 26.42
(CH3), 62.18 (CH2-50), 71.63 (CH-30), 77.91 (CH-20), 82.75 (CH-10),
85.47 (CH-40), 126.12 (CH-2,6), 126.98 (CH-3,5), 133.69 (C-4), 144.73
(C-1), 166.70 (CO). IR spectrum (KBr): 3415, 3362, 3270, 3195, 1671,
1643, 1619, 1572, 1564, 1545, 1508, 1469, 1412, 1404, 1328, 1316,
1571,1538,1525,1504,1493,1422,1320,1306,1277,1211,1189,1120,
20
1080, 1047, 1016, 841, 809, 697, 640 cmꢁ1. [
a]
ꢁ24.8 (c 3.49,
D
MeOH). Anal. Calcd for C15H19NO5$2/3H2O: C, 59.06; H, 6.71; N,
4.59. Found: C, 59.01; H, 6.71; N, 4.31.
3.7.17. 1
ribofuranose (6g)
b
-[4-(Cyclohexylcarbamoyl)phenyl]-1-deoxy-
D
-
1305, 1217, 1186, 1161, 1129, 1108, 1074, 1052, 1035, 1016, 836,
20
706 cmꢁ1
.
[
a
]
ꢁ26.4 (c 3.46, MeOH). Anal. Calcd for
D
Compound 6g was prepared from 5g (120 mg, 0.177 mmol)
accordingtogeneralprocedure, methodA, in85%yield, asacolourless
oil, which after crystalisation from EA furnished white needles, mp
191–195 ꢀC. HRMS (ESI) for C18H24NO5: [MꢁH] calculated, 334.1649;
found, 334.1657.1H NMR (500.0 MHz, DMSO-d6): 1.06–1.17,1.22–1.36,
1.57–1.64, 1.68–1.76 and 1.78–1.85 (5ꢂm, 10H, H-2,3,4,5,6-cyclohex),
C13H17NO5$1H2O: C, 54.73; H, 6.71; N, 4.91. Found: C, 54.61; H, 6.52;
N, 4.73.
3.7.20. 1b-[4-(Carbamoyl)phenyl]-1-deoxy-D-ribofuranose (6j)
Compound 6j was prepared from 5j (332 mg, 0.557 mmol)
according to general procedure, method B, in 90% yield, as a col-
ourless oil, which after lyophylization furnished white powder, mp
166–172 ꢀC. HRMS (ESI) for C12H16NO5: [MþH] calculated,
254.1023; found, 254.1023. 1H NMR (499.8 MHz, DMSO-d6): 3.54
0
0
0
0
3.54 and 3.57 (2ꢂddd, 2ꢂ1H, Jgem¼11.7, J5 ,OH¼5.6, J5 ,4 ¼4.5, H-5 ),
0
0
0
0
0
0
3.66(ddd,1H, J2 ,1 ¼7.0, J2 ,OH¼6.9, J2 ,3 ¼5.3,H-2 ), 3.70–3.79(brm,1H,
0
0
0
0
0
H-1-cyclohex), 3.83 (td, 1H, J4 ,5 ¼0 4.5, J4 ,3 ¼3.7, H-4 ), 3.88 (ddd, 1H,
0
0
0
0
0
0
0
0
0
0
0
0
0
J3 ,2 ¼5.3, J3 ,OH¼4.9,J3 ,4 ¼3.7, H-3 ), 4.60(d,1H, J1 ,2 ¼7.00, H-1 ), 4.83(t,
(ddd, 1H, Jgem¼11.6, J5 b,OH¼5.6, J5 b,4 ¼4.6, H-5 b), 3.57 (ddd, 1H,
0
0
0
0
0
0
0
0
0
1H, JOH,5 ¼5.6, OH-5 ), 4.94 (d, 1H, JOH,3 ¼4.9, OH-3 ), 5.01 (d, 1H,
Jgem¼11.6, J5 a,4 ¼5.6, J50a,4 ¼4.4, H-5 a), 3.67 (ddd, 1H, J2 ,1 ¼7.2,
0
0
0
0
0
0
0
0
0
JOH,2 ¼6.9, OH-2 ), 7.43–7.47 (m, 2H, H-2,6), 7.77–7.80 (m, 2H, H-3,5),
8.13 (d, 1H, J¼8.0, NH). 13C NMR (125.7 MHz, DMSO-d6): 25.17, 25.48
and 32.65 (CH2-2,3,4,5,6-cyclohex), 48.49 (CH-1-cyclohex), 62.16
(CH2-50), 71.56 (CH-30), 77.95 (CH-20), 82.85 (CH-10), 85.39 (CH-40),
125.93 (CH-2,6), 127.21 (CH-3,5), 134.06 (C-4), 144.67 (C-1), 165.45
(CO). IR spectrum (KBr): 3436, 3366, 3314, 3272, 2935, 2854, 1615,
J2 ,OH¼7.0, J2 ,3 ¼5.3, H-2 ), 3.83 (ddd, 1H, J4 ,5 ¼4.6, 4.4, J4 ,3 ¼3.4, H-
40), 3.89 (ddd, 1H, J3 ,2 ¼5.3, J3 ,OH¼4.8, J3 ,4 ¼3.4, H-3 ), 4.61 (d, 1H,
0
0
0
0
0
0
0
0
0
0
0
0
J1 ,2 ¼7.2, H-1 ), 4.82 (t, 1H, JOH,5 ¼5.6, OH-5 ), 4.93 (d, 1H, JOH,3 ¼4.8,
OH-30), 5.01 (d,1H, JOH,2 ¼7.0, OH-2 ), 7.31 (br s,1H, NHaHb), 7.45 (m,
2H, H-2,6), 7.82 (m, 2H, H-3,5), 7.92 (br s, 1H, NHaHb). 13C NMR
(125.7 MHz, DMSO-d6): 62.17 (CH2-50), 71.63 (CH-30), 77.94 (CH-20),
82.75 (CH-10), 85.45 (CH-40), 126.03 (CH-2,6), 127.41 (CH-3,5),
133.43 (C-4), 144.97 (C-1), 167.98 (CO). IR spectrum (KBr): 3442,
3349, 3288, 3238, 3199, 1649, 1614, 1599, 1568, 1513, 1418, 1394,
0
0
1575, 1540,1508,1449, 1438,1415, 1348, 1335, 1314,1307, 1283,1224,
20
1188, 1131, 1082, 1074, 1050, 1019, 839, 693, 635 cmꢁ1. [
a
]
D
ꢁ27.1 (c
3.51, MeOH). Anal. Calcd for C18H25NO5$1H2O: C, 61.17; H, 7.70; N,
3.96. Found: C, 61.15; H, 7.60; N, 3.94.
1309, 1211, 1189, 1131, 1100, 1080, 1052, 1016, 841, 830, 633 cmꢁ1
.
20
[a
]
ꢁ31.1 (c 2.80, MeOH). Anal. Calcd for C12H15NO5$0.2H2O: C,
D
3.7.18. 1
b
-[4-(Benzylcarbamoyl)phenyl]-1-deoxy-
D
-
56.11; H, 6.04; N, 5.45. Found: C, 56.18; H, 6.01; N, 5.34.
ribofuranose (6h)
Compound 6h was prepared from 5h (334 mg, 0.487 mmol)
according to general procedure, method A, in 93% yield, as a col-
ourless oil, which after lyophylization furnished white powder, mp
151–153 ꢀC. HRMS (ESI) for C19H20NO5: [MꢁH] calculated,
342.1336; found, 342.1343. 1H NMR (500.0 MHz, DMSO-d6): 3.54
Acknowledgements
This work is a part of the research project Z4 055 905. It was
supported by the Ministry of Education (LC 512), by the Grant
Agency of the ASCR (IAA400550902) and by Gilead Sciences, Inc.
Cytostatic activity was studied by Dr. I. Votruba (IOCB) and Dr.
Gabriel Birkus and Dr. Tomas Cihlar (Gilead Sciences, Inc.).
0
0
0
0
(ddd, 1H, Jgem¼11.6, J5 b,OH¼5.5, J5 b,4 ¼4.6, H-5 b), 3.58 (ddd, 1H,
0
0
0
0
0
0
Jgem¼11.6, J5 a,OH¼5.5, J5 a,4 ¼4.4, H-5 a), 3.67 (ddd, 1H, J2 ,1 ¼7.2,
0
0
0
0
0
0
0
0
J2 ,OH¼7.0, J2 ,3 ¼5.3, H-2 ), 3.83 (ddd, 1H, J4 ,5 ¼4.6, 4.4, J4 ,3 ¼3.5, H-
40), 3.89 (ddd, 1H, J3 ,2 ¼5.3, J3 ,OH¼4.9, 0J3 ,4 ¼3.5, H-3 ), 4.48 (d, 2H,
0
0
0
0
0
0
Supplementary data
0
0
0
J¼6.2, CH2Ph), 4.61 (d,1H, J1 ,2 ¼7.2, H-1 ), 4.86 (t,1H, JOH,5 ¼5.5, OH-
50), 4.98 (d, 1H, JOH,3 ¼4.9, OH-3 ), 5.06 (d, 1H, JOH,2 ¼7.0, OH-2 ),
7.21–7.27 (m, 1H, H-p-Ph), 7.29–7.35 (m, 2H, H-o-Ph), 7.29–7.35 (m,
2H, H-m-Ph), 7.46–7.50 (m, 2H, H-2,6), 7.84–7.88 (m, 2H, H-3,5),
9.03 (t, 1H, J¼6.2, NH). 13C NMR (125.7 MHz, DMSO-d6): 42.77
(CH2Ph), 62.19 (CH2-50), 71.64 (CH-30), 78.02 (CH-20), 82.76 (CH-10),
85.49 (CH-40), 126.18 (CH-2,6), 126.96 (CH-p-Ph), 127.24 (CH-3,5),
127.38 (CH-o-Ph), 128.53 (CH-m-Ph), 133.49 (C-4), 139.98 (C-i-Ph),
145.09 (C-1), 166.31 (CO). IR spectrum (KBr): 3440, 3324, 3264,
3088, 3063, 3030, 2938, 2885, 1637, 1614, 1587, 1571, 1535, 1505,
0
0
0
0
Copies of the 1H and 13C NMR spectra of all new compounds.
Supplementary data associated with this article can be found in the
online version, at doi:10.1016/j.tet.2009.04.006.
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