Modular synthesis of 5-substituted furan-2-yl C-2'-deoxyribonudeosides and biaryl covalent base-pair analogues

Article abstract of DOI:10.1002/ejoc.201000726

A modular and efficient synthesis of 5-(hetero)arylfuran C2′-deoxyribonucleosides was developed. Friedel-Crafts Cglycosidation of 2-bromofuran with toluoyl-protected methyl 2′-deoxyribofuranoside in the presence of BF₃.Et₂O gave 5bromofuran C-nucleosides, which were used as key intermediates for Stille or Suzuki coupling with (hetero)arylstannanes or boronic acids to afford a series of 5-(hetero)arylfuran C-nucleosides. 5-Boronofuran C-nucleoside was pre-pared by the Suzuki coupling of bromofuran with bis(pinacolatodiboron) or by Ir-catalyzed C-H borylation of furan and was used for cross-coupling with 5-bromoheteroaryl C-nucleosides to furnish novel covalent analogues of nucleoside pairs. The title 5-arylfuran C-nucleosides possess interesting fluorescence properties that may be applicable for fluorescent labeling of biomolecules.

Full text of DOI:10.1002/ejoc.201000726

FULL PAPER
DOI: 10.1002/ejoc.201000726
Modular Synthesis of 5-Substituted Furan-2-yl C-2Ј-Deoxyribonucleosides and
Biaryl Covalent Base-Pair Analogues
[a]
[a]
[a]
[a]
ˇ
ˇ
Jan Bárta, Lenka Slavetínská, Blanka Klepetárová, and Michal Hocek*
Keywords: Alkylation / Cross-coupling / C-glycosides / DNA structures / Nucleosides
A modular and efficient synthesis of 5-(hetero)arylfuran C-
2Ј-deoxyribonucleosides was developed. Friedel–Crafts C-
glycosidation of 2-bromofuran with toluoyl-protected methyl
2Ј-deoxyribofuranoside in the presence of BF3·Et2O gave 5-
bromofuran C-nucleosides, which were used as key interme-
diates for Stille or Suzuki coupling with (hetero)arylstann-
anes or boronic acids to afford a series of 5-(hetero)aryl-
furan C-nucleosides. 5-Boronofuran C-nucleoside was pre-
pared by the Suzuki coupling of bromofuran with bis(pinacol-
atodiboron) or by Ir-catalyzed C–H borylation of furan and
was used for cross-coupling with 5-bromoheteroaryl C-nu-
cleosides to furnish novel covalent analogues of nucleoside
pairs. The title 5-arylfuran C-nucleosides possess interesting
fluorescence properties that may be applicable for fluores-
cent labeling of biomolecules.
ciency and stereoselectivity. Therefore, we have been de-
veloping a modular approach[12,13] based on the synthesis
of halo(hetero)aryl-C-nucleoside intermediates and their
subsequent functionalization by cross-coupling, amination
and other reactions, to afford a series of derivatives from
each intermediate. In our synthesis of aryl-thionyl-C-nu-
cleosides, we found[13] that all of the products were fluores-
cent and that the emission maxima can be finely tuned by
changing the attached aryl group. To further explore this
type of fluorescent nucleoside, we decided to develop the
synthesis and to study the properties of 5-aryl-substituted
furan-C-2Ј-deoxyribonucleosides.
Furan-C-nucleosides of the ribo series were the focus of
most of the previous studies. Furanfurin is an antitumor
compound[14] and many other derivatives have been pre-
pared, usually by Friedel–Crafts glycosidation of furan de-
rivatives by peracetylated ribose in the presence of Lewis
acids,[15,16] where some β-selectivity has been observed due
to neighboring group participation, or alternatively by ad-
dition of lithiofuran to tribenzylribose followed by cycliza-
tion under Mitsunobu conditions.[17] Double arylation of
the ribose moiety was observed as a side reaction in some
Friedel–Crafts glycosidations of furans, causing dramatic
decreases in yields.[16] Furan[18] and 5-methylfuran[19] C-2Ј-
deoxyribonucleosides (the only two known examples in the
2Ј-deoxyribo series) were prepared by addition of lithiated
furans to protected deoxyribose followed by cyclization.
The latter derivative was used as a moderately successful
candidate in an extension of the genetic alphabet.[19]
Introduction
C-Nucleosides are an important nucleoside sub-class that
are characterized by replacement of the nucleosidic bond
by a chemically stable C–C bond.[1] They possess a wide
range of biological activities and are extensively applied in
chemical biology.[1] Some (hetero)aryl-C-2Ј-deoxyribo-
nucleosides are promising candidates for the development
of novel base-pairs in the quest to extend the genetic alpha-
bet[2] due to formation of selective hydrophobic pairs in
DNA duplexes.[3] Some of the artificial base-pairs have al-
ready been efficiently replicated by DNA polymerases[4] and
the most successful pairs[5] were even used in the first suc-
cessful PCR with a 6-letter genetic alphabet.[6] Biaryl C-
nucleosides are of particular interest because of the ex-
tended stacking that occurs, which results in the formation
of very stable duplexes.[7] A donor- and acceptor-modified
biphenyl C-nucleoside-containing oligonucleotide was em-
ployed to recognize a complementary hydrophobic modifi-
cation in the opposite strand or a bulge or single-strand
region.[8] Oligonucleotide arrays of several α-aryl- or α-oli-
goaryl-C-deoxyribonucleoside units in a DNA-like chain
were developed as “oligodeoxyfluorosides” (ODFs)[9] to
tune the emission maxima of fluorescence depending on the
sequence, and were successfully employed for fluorescence
staining of cells and zebra fish embryos.[10]
Most of the current approaches[1,11] to the synthesis of
C-nucleosides are not general and some suffer from low effi-
[a] Institute of Organic Chemistry and Biochemistry, Academy of
Sciences of the Czech Republic, Gilead Sciences & IOCB
Research Center,
Flemingovo nam. 2, 16610 Prague 6, Czech Republic
Fax: +420-220183559
Results and Discussion
E-mail: hocek@uochb.cas.cz
Our selected approach to the synthesis of a series of 5-
substituted furan-2-yl-C-nucleosides was based on the syn-
Supporting information for this article is available on the
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Eur. J. Org. Chem. 2010, 5432–5443

Deoxyribonucleoside Analogues
thesis of protected or unprotected 5-bromothiophen-2-yl-C-
Finally, BF3·Et2O was found to be the best Lewis acid
nucleoside key intermediates, followed by further synthetic for this reaction. When the reaction was performed for 3 h,
transformations. Our previous synthesis[13] of a related 5- an encouraging increase in the yield of 3 to 13% (Table 1,
bromothiophen-2-yl-C-nucleoside intermediate involved the entry 6) was observed; these conditions also somewhat sup-
use of Friedel–Crafts type C-glycosidation of 2-bromothio- pressed formation of the α-anomer 4 (6%). Shortening of
phene with toluoyl-protected 2Ј-deoxyribose O-Me-glyco- the reaction time to 15 min. (Table 1, entry 7) resulted in a
side (1), which gave the desired C-nucleoside very efficiently dramatic increase in the yield, and gave the desired β-anom-
and with good β-selectivity (despite the use of an anomeric eric nucleoside 3 in 39% yield accompanied by only 17%
mixture of 1). Therefore, we focused on analogous Friedel– formation of 4. The use of AgOCOCF3 as co-activator
Crafts reactions of 2-bromofuran (2) and applied the most (Table 1, entry 7) did not bring about any improvement
efficient conditions developed from the previous work.[13] and, moreover, complicated the separation (Table 1, entry
The reactions of toluoyl-protected glycoside 1 with bro- 8). Use of the pure β-anomer of 1 gave almost the same
mofuran (2) were performed in the presence of a range of yield and selectivity as those obtained with the anomeric
Lewis acids under different conditions (Scheme 1, Table 1). mixture (Table 1, entry 9), indicating that the configuration
Reactions in the presence of SnCl4 did not give any C-gly- of the starting glycoside does not have any influence on the
cosidation, whereas when the same reaction was performed outcome of the reaction. The best procedure (Table 1, entry
in the presence of AgOCOCF3 as co-activator, complex 10) involved the use of BF3·Et2O and a very short reaction
mixtures of products with very low yields of the desired β- time (5 min.), to afford the desired β-C-nucleoside 3 in good
(3) and undesired α- (4) C-nucleoside anomers was gener- yield (45%) even when the reaction was performed on a
ated (Table 1, entries 1–4). The use of TMSOTf gave simi- multigram scale. When stored under argon at –10 °C, the
larly low yields (Table 1, entry 5). Furthermore, isolation compound was stable for several months. The undesired α-
of C-nucleosides and the separation of 3 and 4 by column anomer 4 was epimerized by reaction with BF3·Et2O in
chromatography was extremely difficult (large silica gel col- dichloromethane at room temp. for 30 min, to give a mix-
umn and very slow elution with slow gradient of ethyl acet- ture of 3 (70%) and 4 (30%). In this way, the total yield of
ate in hexanes was necessary for efficient separation). Both the intermediate 3 can be increased to an acceptable 58%.
bromofuran nucleosides 3 and 4 were found to be of limited
Deprotection of the toluoylated bromofuran-C-nucleo-
stability in air and when exposed to light (both turned dark side intermediate 3 under Zemplén conditions (NaOMe/
over several days) and therefore must be stored in a freezer MeOH) gave the free 2Ј-deoxyribonucleoside 5, which is a
under argon. We screened a wide range of Lewis acids potential intermediate for aqueous-phase cross-coupling re-
(ZnCl2, AlCl3, TiCl4, SnCl2–AgClO4, Cp2ZrCl2–AgClO4, actions, in 93% yield (Scheme 2).
and Cp2HfCl2–AgClO4) without any improvement in reac-
tivity (data not shown).
Scheme 2. Deprotection of the nucleoside intermediate.
Having the optimized multigram-scale procedures for the
synthesis of 5-bromofuran-2-yl-C-nucleosides 3 and 5 at
hand, we then studied further functional group transforma-
tions. Initially, we introduced aryl and heteroaryl groups by
using the Stille cross-coupling reactions of toluoyl-pro-
Scheme 1. Preparation of the key intermediate by C-glycosidation
of 2-bromofuran.
Table 1. Friedel–Crafts alkylation of methylglycoside 1 with 2-bromofuran (2).[a]
Entry
Lewis acid [equiv.]
Temp. [°C]
Time [min]
3 [%]
4 [%]
1
2
SnCl4 (1)
SnCl4 (1)
SnCl4 (1.5), AgOCOCF3 (0.6)
SnCl4 (1.5), AgOCOCF3 (0.6)
TMSOTf (1)
BF3·Et2O (3.8)
BF3·Et2O (3.8)
BF3·Et2O (3.8), AgOCOCF3 (0.6)
BF3·Et2O (3.8)
BF3·Et2O (3.8)
room temp.
0
–20
18
13
30
10
10
3 h
15
15
15
5
0
0
2
9
3
13
39
40
42
45
0
0
2
4
2
3[b]
4[b]
5
–20
room temp.
–30 to room temp.
room temp.
room temp.
room temp.
room temp.
6
7
6
17
18
20
18
8
9[c]
10
[a] Unless otherwise stated, 2 (2 equiv.) and an anomeric mixture (ca. 1:1) of 1 were used in all experiments. [b] 2-Bromofuran (2; 3 equiv.)
was used. [c] Pure β-anomer of methyl glycoside 1 was used.
Eur. J. Org. Chem. 2010, 5432–5443
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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5433

J. Bárta, L. Slaveˇtínská, B. Klepetárˇová, M. Hocek
FULL PAPER
tected β-C-deoxribonucleoside 3 with aryl stannanes. The
reactions were performed in the presence of [PdCl2dppf] in
N,N-dimethylformamide (DMF) at 105–115 °C for 21 h.
(Scheme 3). In all cases, the reactions proceeded smoothly
to give the target protected biaryl β-C-nucleosides 6a–e in
acceptable yields of 54–69% (accompanied by some degra-
dation products). Only the reaction of strongly chelating
bipyridyl-stannane gave a lower yield of 44%, which was
probably due to coordination of the Pd-catalyst. Deprotec-
tion of toluoylated nucleosides 6a–e by using sodium meth-
oxide in methanol gave the free β-biaryl C-deoxyribonu-
cleosides 7a–e in good yields (Scheme 3).
Scheme 4. The Suzuki–Miyaura reaction of nucleoside 5.
(Scheme 5). As an alternative, the boronate 8 was also pre-
pared by an Ir-catalyzed C–H borylation[21] of the furan C-
nucleoside 9 with [B2pin2] in the presence of [IrCl(COD)]2
and 4,4Ј-di-tert-butyl-2,2Ј-bipyridyl (dtbpy) in 39% yield af-
ter two days reaction time. The conversion of this reaction
was only ca. 80%, probably due to the limited solubility of
the reaction components in toluene.
Scheme 3. The Stille cross-coupling and deprotection of 5-bro-
mofuran-C-nucleoside.
The unprotected 5-bromofuran-C-nucleoside 5 was used
in aqueous-phase cross-coupling reactions. The Suzuki–
Miyaura cross-coupling reactions of 5 with a variety of ar-
ylboronic acids were performed in the presence of Pd-
(OAc)2, sodium triphenylphosphane trisulfonate (TPPTS)
ligand, and Cs2CO3 as base in a mixture of acetonitrile/
water (2:1) for 4 h at 120 °C, to give biaryl β-C-nucleosides
7f–l in moderate yields (Scheme 4). The yields were lowered
by partial decomposition of the unstable starting com-
pound 3 under the elevated temperature of the reaction.
Despite the lower yields, this approach afforded the desired
biaryl C-nucleosides in one step from the intermediate 5,
thus saving time and avoiding the need for an additional
reaction and separation of the Stille coupling/deprotection
products.
Further efforts focused on the transformation of bro-
mofuran nucleoside 3 into the corresponding furylboronate
derivative 8, which could be a useful nucleophilic compo-
nent for other cross-coupling reactions. The standard Mi-
yaura reaction[20] of bromofuran with bis(pinacolato)di-
boron in the presence of [PdCl2dppf] [dppf: 1,1Ј-bis(diphen-
ylphosphanyl)ferrocene] and potassium acetate gave the de-
sired boronate 8 in 68% yield, accompanied by minor side-
products: debrominated nucleoside 9 (17%) and bis(furan)
Scheme 5. Reagents and conditions: (i)
3 (1 equiv.), B2pin2
(4 equiv.), AcOK (6 equiv.), [PdCl2dppf] (15%), dioxane, 105 °C,
70 min; yield of 8: 68%. (ii) 9 (1 equiv.), B2pin2 (1.2 equiv.),
[IrCl(COD)]2 (5%), dtbpy (15%), toluene, 2 d, 105 °C; yield 8:
39%. (iii) 1-bromopyrene (1.1 equiv.), [Pd(PPh3)4] (5%), K2CO3
(4 equiv.), DMF, 19 h, 105 °C. (iv) 3 or 10 (1.1 equiv.), 8 (1 equiv.),
[PdCl2dppf] (5%), K2CO3 (4 equiv.), DMF, 17 h, 105 °C. (v)
MeONa (1  in MeOH, 2 equiv.), room temp., 15 h. Yields: 6m,
11a (traces) as a product of cross-coupling of 8 with 3 78%; 11a, 90%; 11b, 76%; 7m, 53%; 12a, 91%; 12b, 71%.
5434 Eur. J. Org. Chem. 2010, 5432–5443
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Deoxyribonucleoside Analogues
The Suzuki–Miyaura reaction of boronofuran C-nucleo- Table 2. UV/Vis and fluorescence spectroscopic data.
side 8 with 1-bromopyrene under the standard conditions in
DMF in the presence of [Pd(PPh3)4] and K2CO3 proceeded
smoothly to give the pyrenyl-furan C-nucleoside in 78%
yield. Its deprotection under the standard Zemplén condi-
tions gave the free nucleoside 7m in 53%. The reaction of 7c
boronate 8 with bromofuran C-nucleoside 3 was performed
Absorption λmax [nm] (ε, Lmol–1 cm–1) Emission
λmax [nm]
φ
7a
7b
308 (20380)
280 (21000), 286 (22200), 301 (13200)
302 (19800)
362
324
351
360
410
337
341
345
0.03
0.18
0.06
0.55
0.15
0.24
0.03
0.01
7d
277 (14000), 304(18000)
237 (22000), 279 (28000)
290 (25600)
229 (8200), 282 (11000)
259 (12200), 264 (12400)
307 (15400), 324 (11800)
254 (21200), 286 (18800), 328 (10200)
273 (16000), 287 (16600)
227 (9800), 288 (7600)
232 (24400), 277 (15400), 360 (17000)
7e
in DMF in the presence of [PdCl2dppf] and K2CO3 to give
the 2,2Ј-bifuran bis-nucleoside 11a in an excellent yield of
7f
7g
90%. Its standard deprotection gave the biaryl bis-nucleo-
side 12a in 91% yield. An analogous hetero-cross-coupling
of 8 with 5-bromothiophene C-nucleoside 10 also pro-
ceeded smoothly with almost quantitative conversion but
gave the desired thienylfuran bis-nucleoside 11b as a com-
7h
7i
330, 347 0.61
7j
356
342
399
411
334
362
0.96
0.01
0.04
0.73
0.20
0.14
7k
7l
7m
plex mixture with the corresponding bifuran 11a (8%) and 12a 286 (27000), 293 (28000), 308 (17800)
12b
310 (18800)
bithiophene 11c (13%), resulting from homo-coupling of 8
and 10. The composition of this inseparable mixture was
determined from NMR analysis to be a 10:1:1.8 ratio of
11b/11a/11c (yield of 11b: 76%). The whole mixture was
deprotected under standard conditions and the free nucleo-
sides were successfully separated by column chromatog-
raphy to give the desired thienylfuran bis-nucleoside 12b in
54% overall yield (ca. 71% yield for deprotection and sepa-
ration) from 8 (the minor bis-nucleoside byproducts were
not isolated). The novel biaryl bis-nucleosides 12 are an
interesting new type of covalently linked nucleoside-pair an-
alogues[22] that could be used for construction of permanent
cross-links in DNA duplexes. The crystal structure of sym-
metrical dimer 12a was determined by X-ray diffraction
analysis (Figure 1).
Conclusions
An efficient procedure for the synthesis of toluoyl-pro-
tected 5-bromofuran C-nucleoside 3 was developed based
on Friedel–Crafts type C-glycosidation of 2-bromofuran
with methyl glycoside 1 in the presence of BF3·Et2O. A very
short reaction time of 5 min was crucial to avoid side reac-
tions. The separation of anomers 3 and 4 was quite difficult
and required careful column chromatography using a very
slow gradient of ethyl acetate in hexanes. The protected bro-
mofuran nucleoside 3 was used directly for the Stille cross-
couplings with (hetero)arylstannanes, whereas the unpro-
tected nucleoside 5 was efficiently used for the Suzuki cou-
plings with (hetero)arylboronic acids to afford a series of 5-
(hetero)arylfuran C-nucleoside 7. 5-Boronofuran C-nucleo-
side 8 was prepared for the first time either by the Suzuki
coupling of bromofuran 3 with bis(pinacolatodiboron) or
by Ir-catalyzed C–H borylation of furan 9. The boronate 8
was used either for cross-coupling with aryl halides to make
other arylfuran C-nucleosides, or with 5-bromoheteroaryl
C-nucleosides to afford novel, interesting covalent ana-
logues of nucleoside pairs 12a and 12b. Final 5-arylfuran
C-nucleosides possess interesting fluorescence properties
that may be applicable in the construction of ODF arrays
for fluorescent labeling.
Figure 1. ORTEP drawing of 12a with the atom numbering scheme.
Thermal ellipsoids are drawn at the 50% probability level.
UV/Vis and fluorescence spectroscopy was used to study
all the title 5-arylfuran C-nucleosides 7a–m and biaryl C-
nucleoside dyads 12a and 12b (Table 2). The absorption
maxima varied from 279 to 324 nm for most of the com-
pounds, with the exception of the pyrenyl derivative 7m,
which exerted the longest wavelength maximum at 360 nm.
All the compounds showed luminescence, with emission
Experimental Section
General Methods: Melting points were determined with a Kofler
block. Optical rotations, [α]D were measured at 20 °C, values are
maxima varying from 324 to 411 nm. Similar to previous given in units of 10–1 cm2 g–1. NMR spectra were measured at
500 MHz for 1H and 125.8 MHz for 13C; samples were recorded in
[D6]acetone for protected nucleosides and [D6]DMSO for depro-
tected products (TMS was used as internal standard, referenced to
the residual solvent signal). Chemical shifts are given in ppm (δ
scale) and coupling constants (J) in Hz. Complete assignment of
all NMR signals was performed by using a combination of H,H-
COSY, H,H-ROESY, H,C-HSQC, and H,C-HMBC experiments.
Mass spectra were measured by using ESI or EI (electron energy
70 eV). All solvents used for reactions were anhydrous, degassed in
vacuo and stored over molecular sieves under an atmosphere of
argon.
studies on substituted thiophene C-nucleosides,[13,23] the
emission maxima could be finely tuned by changing the at-
tached aryl groups. Pyridyl, benzofuryl and pyrenyl deriva-
tives 7d, 7i, and 7m showed high quantum yields of over
0.5, whereas the dibenzofuryl derivative 7j exerted the
brightest fluorescence, with a quantum yield of 0.96. In
combination with other types of fluorescent nucleo-
sides,[9,10,13,23] the title furan C-nucleosides clearly have the
potential for applications in ODF arrays for fluorescent la-
beling of biomolecules.[9,10]
Eur. J. Org. Chem. 2010, 5432–5443
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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J. Bárta, L. Slaveˇtínská, B. Klepetárˇová, M. Hocek
FULL PAPER
1β-(5-Bromofuran-2-yl)-1,2-dideoxy-3,5-di-O-toluoyl-
(3): BF3·Et2O (3.7 mL, 29.7 mmol) was added dropwise by syringe
to a dried flask covered with an aluminum foil containing methyl
D
-ribofuranose
HRMS (ESI): calcd. for C28H25O6NSNa [M + Na] 526.1295; found
526.1293. 1H NMR (500 MHz, [D6]acetone): δ = 2.40 and 2.42
(2ϫs, 2 ϫ3 H, CH3-Tol), 2.60 (ddd, Jgem = 13.7, J2Јa,1Ј = 5.4, J2Јa,3Ј
= 1.4 Hz, 1 H, 2Јa-H), 2.76 (ddd, Jgem = 13.7, J2Јb,1Ј = 10.6, J2Јb,3Ј
glycoside
1 (3 g, 7.8 mmol) and 2-bromofuran (2; 1.4 mL,
15.6 mmol) in anhydrous dichloromethane (50 mL) and the mix-
ture was stirred for 5 min at room temp. The reaction was quenched
by addition of satd. aqueous NaHCO3 (40 mL) and the mixture
was diluted with a satd. aqueous NaHCO3 (100 mL), extracted
with EtOAc (3ϫ40 mL) and washed with satd. aqueous NaCl
(100 mL). The collected organic layers were dried with Na2SO4 and
the solvents were evaporated. Products were isolated by slow col-
umn chromatography on silica gel, eluent gradient from hexane to
hexane/EtOAc (19.7:0.3) to give the desired product 3 (1.75 g, 45%)
followed by the α-anomer 4 (0.7 g, 18%) as colorless oils. Com-
= 6.0 Hz, 1 H, 2Јb-H), 4.53 (ddd, J4Ј,5Јb = 4.7, J4Ј,5Јa = 4.2, J4Ј,3Ј =
2.1 Hz, 1 H, 4Ј-H), 4.57 (dd, Jgem = 11.6, J5Јa,4Ј = 4.1 Hz, 1 H, 5Јa-
H), 4.60 (dd, Jgem = 11.6, J5Јb,4Ј = 4.8 Hz, 1 H, 5Јb-H), 5.37 (dd,
J1Ј,2b = 10.6, J1Ј,2Јa = 5.4 Hz, 1 H, 1Ј-H), 5.72 (dddd, J3Ј,2Јb = 6.0,
J3Ј,4Ј = 2.0, J3Ј,2Јa = 1.4, J3Ј,1Ј = 0.5 Hz, 1 H, 3Ј-H), 6.67 (br. d, J3,4
= 3.4 Hz, 1 H, 3-H), 6.99 (d, J4,3 = 3.4 Hz, 1 H, 4-H), 7.32 and
7.35 (2ϫm, 2ϫ2 H, o-Tol-H), 7.59 (d, J5,4 = 3.2 Hz, 1 H, thiazyl-
5-H), 7.85 (d, J4,5 = 3.2 Hz, 1 H, thiazyl-4-H), 7.98 and 8.00 (2ϫm,
2ϫ2 H, oTol-H) ppm. 13C NMR (125.7 MHz, [D6]acetone): δ =
21.58 (CH3-Tol), 37.83 (CH2-2Ј), 65.22 (CH2-5Ј), 74.43 (CH-1Ј),
pound 3: HRMS (ESI): calcd. for C25H23BrO6Na [M + Na] 77.60 (CH-3Ј), 83.69 (CH-4Ј), 109.96 (CH-4), 111.38 (CH-3),
1
521.0570; found 521.0571. H NMR (500 MHz, [D6]acetone): δ =
2.41 and 2.42 (2ϫs, 2 ϫ3 H, CH3-Tol), 2.68 (ddd, Jgem = 13.8,
J2Јa,1Ј = 5.4, J2Јa,3Ј = 1.4 Hz, 1 H, 2Јa-H), 2.68 (ddd, Jgem = 13.8,
119.66 (CH-5-thiazyl), 128.15 and 128.25 (C-i-Tol), 130.06 and
130.09 (CH-o-Tol), 130.44 and 130.47 (CH-o-Tol), 144.66 (CH-4-
thiazyl), 144.70 and 144.95 (C-p-Tol), 150.01 (C-5), 155.38 (C-2),
J2Јb,1Ј = 10.7, J2Јb,3Ј = 6.1 Hz, 1 H, 2Јb-H), 4.48 (br. td, J4Ј,5Јa
=
158.22 (C-2-thiazyl), 166.43 and 166.56 (CO) ppm. IR (CCl ): ν =
˜
4
J4Ј,5Јb = 4.2, J4Ј,3Ј = 2.0 Hz, 1 H, 4Ј-H), 4.51 (dd, Jgem = 11.4, J5Јa,4Ј
= 4.3 Hz, 1 H, 5Јa-H), 4.57 (dd, Jgem = 11.4, J5Јb,4Ј = 4.0 Hz, 1 H,
5Јb-H), 5.26 (dd, J1Ј,2b = 10.7, J1Ј,2Јa = 5.4 Hz, 1 H, 1Ј-H), 5.65 (br.
dtd, J3Ј,2Јb = 6.1, J3Ј,4Ј = J3Ј,2Јa = 1.7, J3Ј,1Ј = 0.4 Hz, 1 H, 3Ј-H),
3039, 2982, 2925, 1726, 1613, 1443, 1268, 1178, 1103, 715 cm–1.
1β-[5-(Furan-2-yl)furan-2-yl]-1,2-dideoxy-3,5-di-O-toluoyl-D-ribo-
furanose (6b): Compound 6b was prepared from 3 (434 mg,
0.87 mmol) and 2-(tributylstannyl)furan (330 µL, 1.04 mmol), by
the general procedure (115 °C, 21 h). 6b was obtained (290 mg,
69%) as a colorless oil. HRMS (ESI): calcd. for C29H26O7Na [M
6.44 (dd, J4,3 = 3.3 Hz, 1 H, 4-H), 6.53 (dd, J3,4 = 3.3, J3,1Ј
=
0.4 Hz, 1 H, 3-H), 7.30–7.33 (m, 4 H, o-Tol-H), 7.96–8.02 (m, 4 H,
o-Tol-H) ppm. 13C NMR (125.7 MHz, [D6]acetone): δ = 21.58
(CH3-Tol), 37.55 (CH2-2Ј), 65.26 (CH2-5Ј), 74.39 (CH-1Ј), 77.66
(CH-3Ј), 83.65 (CH-4Ј), 112.03 (CH-3), 113.17 (CH-4), 122.44 (C-
5), 128.19 and 128.30 (C-i-Tol), 130.06 and 130.10 (CH-o-Tol),
130.47 (CH-o-Tol), 144.69 and 144.96 (C-p-Tol), 156.26 (C-2),
1
+ Na] 509.1571; found 509.1568. H NMR (500 MHz, [D6]ace-
tone): δ = 2.41, 2.42 (2ϫs, 2 ϫ3 H, CH3), 2.53 (ddd, Jgem = 13.8,
J2Јa,1Ј = 5.4, J2Јa,3Ј = 1.3 Hz, 1 H, 2Јa-H), 2.75 (ddd, Jgem = 13.8,
J2Јb,1Ј = 10.7, J2Јb,3Ј = 6.0 Hz, 1 H, 2Јb-H), 4.50 (td, J4Ј,5Јa = J4Ј,5Јb
= 4.4, J4Ј,3Ј = 2.0 Hz, 1 H, 4Ј-H), 4.54 (dd, Jgem = 11.6, J5Јa,4Ј
=
166.42 and 166.59 (CO) ppm. IR (KBr): ν = 3390, 3304, 2893,
˜
4.3 Hz, 1 H, 5Јa-H), 4.60 (dd, Jgem = 11.6, J5Јb,4Ј = 4.5 Hz, 1 H,
5Јb-H), 5.32 (ddd, J1Ј,2b = 10.7, J1Ј,2Јa = 5.4, J1Ј,3Ј = 0.6 Hz, 1 H,
1501, 1131, 1045, 1032, 997, 792, 782 cm–1. Compound 4: HRMS
(ESI): calcd. for C25H23BrO6Na [M + Na]: 521.0570; found
521.0572. 1H NMR (500 MHz, [D6]acetone): δ = 2.40 and 2.41
(2ϫs, 2 ϫ3 H, CH3-Tol), 2.51 (ddd, Jgem = 14.0, J2Јa,1Ј = 5.2, J2Јa,3Ј
= 3.4 Hz, 1 H, 2Јa-H), 2.94 (ddd, Jgem = 14.0, J2Јb,1Ј = 8.0, J2Јb,3Ј
= 7.1 Hz, 1 H, 2Јb-H), 4.50–4.60 (m, 3 H, 4Ј,5Ј-H), 5.36 (ddd, J1Ј,2b
1Ј-H), 5.71 (dddd, J3Ј,2Јb = 6.0, J3Ј,4Ј = 2.0, J3Ј,2Јa = 1.3, J3Ј,1Ј
=
0.6 Hz, 1 H, 3Ј-H), 6.46 (dd, J6,7 = 3.4, J6,8 = 0.8 Hz, 1 H, 6-H),
6.51 (dd, J7,6 = 3.4, J7,8 = 1.9 Hz, 1 H, 7-H), 6.57 (s, 2 H, 2-H, 3-
H), 7.31–7.37 (m, 4 H, 4ϫ3ЈЈ-H), 7.58 (dd, J8,7 = 1.8, J8,6 = 0.8 Hz,
1 H, 8-H), 7.97–8.01 (m, 4 H, 4 ϫ 2ЈЈ-H) ppm. 13C NMR
(125.7 MHz, [D6]acetone): δ = 21.57 (2 ϫCH3), 37.72 (CH2-2Ј),
65.26 (CH2-5Ј), 74.50 (CH-1Ј), 77.72 (CH-3Ј), 83.55 (CH-4Ј),
106.29 (CH-6), 106.56 (CH-3), 110.87 (CH-2), 112.28 (CH-7),
128.18, 128.29 (2ϫ C-1ЈЈ), 130.06, 130.09 (2 ϫCH-3ЈЈ), 130.43,
130.46 (2 ϫ CH-2ЈЈ), 143.27 (CH-8), 144.72, 144.94 (2 ϫC-4ЈЈ),
147.04 (C-4, C-5), 153.37 (C-1), 166.44, 166.54 (2ϫCO) ppm. IR
= 8.0, J1Ј,2Јa = 5.2, J1Ј,3 = 0.7 Hz, 1 H 1Ј-H), 5.64 (br. dt, J3Ј,2Јb
=
7.0, J3Ј,4Ј = J3Ј,2Јa = 3.3 Hz, 1 H, 3Ј-H), 6.45 (d, J4,3 = 3.3 Hz, 1 H,
4-H), 6.52 (dd, J3,4 = 3.3, J3,1Ј = 0.7 Hz, 1 H, 3-H), 7.32 and 7.33
(2ϫm, 2ϫ2 H, o-Tol-H), 7.91 and 7.93 (2ϫm, 2ϫ2 H, o-Tol-H)
ppm. 13C NMR (125.7 MHz, [D6]acetone): δ = 21.57 and 21.58
(CH3-Tol), 37.10 (CH2-2Ј), 65.19 (CH2-5Ј), 74.41 (CH-1Ј), 76.83
(CH-3Ј), 82.87 (CH-4Ј), 111.22 (CH-3), 113.13 (CH-4), 122.03 (C-
5), 128.12 and 128.24 (C-i-Tol), 130.04 and 130.09 (CH-o-Tol),
130.39 and 130.49 (CH-o-Tol), 144.75 and 144.90 (C-p-Tol), 157.87
(CCl ): ν = 2925, 1725, 1613, 1269, 1178, 1103, 730 cm–1.
˜
4
1β-[5-(Thiophen-2-yl)furan-2-yl]-1,2-dideoxy-3,5-di-O-toluoyl-D-
ribofuranose (6c): Prepared from 3 (358 mg, 0.72 mmol) and 2-(tri-
butylstannyl)thiophene (270 µL, 0.86 mmol), by the general pro-
cedure (110 °C, 21 h). Compound 6c (220 mg, 61%) was obtained
as a colorless oil. HRMS (ESI): calcd. for C29H26O6SNa [M + Na]
(C-2), 166.49 and 166.59 (CO) ppm. IR (CCl ): ν = 2925, 1726,
˜
4
1613, 1268, 1178, 1106, 800 cm–1.
General Procedure for the Stille Cross-Coupling Reaction: Hetero-
aryl(tributyl)stannane (1.2 equiv.) was added dropwise under argon
to a stirred solution of 3 (1 equiv.) and [PdCl2dppf] (10 mol.%) in
DMF (10 mL). The mixture was stirred at 105–115 °C for 21 h. The
crude reaction mixture was diluted with EtOAc (15 mL), filtered
through Celite, and washed with 2  HCl and brine. The aqueous
layers were extracted with EtOAc (3ϫ20 mL), the collected organic
layers were dried with MgSO4, and the solvents were evaporated
under vacuum. The crude product was purified by chromatography
on silica gel, eluent gradient from hexane to hexane/EtOAc
(9.7:0.3).
1
525.1342; found 525.1340. H NMR (500 MHz, [D6]acetone): δ =
2.41 and 2.42 (2ϫs, 2 ϫ3 H, CH3-Tol), 2.54 (ddd, Jgem = 13.7,
J2Јa,1Ј = 5.4, J2Јa,3Ј = 1.3 Hz, 1 H, 2Јa-H), 2.76 (ddd, Jgem = 13.7,
J2Јb,1Ј = 10.7, J2Јb,3Ј = 6.0 Hz, 1 H, 2Јb-H), 4.50 (td, J4Ј,5Јa = J4Ј,5Јb
= 4.4, J4Ј,3Ј = 2.0 Hz, 1 H, 4Ј-H), 4.54 (dd, Jgem = 11.6, J5Јa,4Ј
=
4.3 Hz, 1 H, 5Јa-H), 4.61 (dd, Jgem = 11.6, J5Јb,4Ј = 4.6 Hz, 1 H,
5Јb-H), 5.32 (dd, J1Ј,2b = 10.7, J1Ј,2Јa = 5.4 Hz, 1 H, 1Ј-H), 5.72
(dddd, J3Ј,2Јb = 6.0, J3Ј,4Ј = 2.0, J3Ј,2Јa = 1.3, J3Ј,1Ј = 0.6 Hz, 1 H,
3Ј-H), 6.55 (dd, J3,4 = 3.4, J3,1Ј = 0.4 Hz, 1 H, 3-H), 6.60 (d, J4,3
=
3.4 Hz, 1 H, 4-H), 7.05 (dd, J4,5 = 5.1, J4,3 = 3.6 Hz, 1 H, thienyl-
4-H), 7.22 (br. dd, J3,4 = 3.6, J3,5 = 1.2 Hz, 1 H, thienyl-3-H), 7.33
1β-[5-(Thiazol-2-yl)furan-2-yl]-1,2-dideoxy-3,5-di-O-toluoyl-D-ribo-
furanose (6a): Prepared from 3 (271 mg, 0.54 mmol) and 2-(tri- and 7.36 (2 ϫ m, 2 ϫ 2 H, o-Tol-H), 7.41 (dd, J5,4 = 5.1, J5,3
butylstannyl)thiazole (210 µL, 0.65 mmol) by the general procedure
(105 °C, 21 h). 6a (273 mg, 54%) was obtained as a yellow oil.
=
1.2 Hz, 1 H, thienyl-5-H), 7.97–8.01 (m, 4 H, o-Tol-H) ppm. 13C
NMR (125.7 MHz, [D6]acetone): δ = 21.58 (CH3-Tol), 37.71 (CH2-
5436
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 5432–5443

Deoxyribonucleoside Analogues
2Ј), 65.25 (CH2-5Ј), 74.50 (CH-1Ј), 77.69 (CH-3Ј), 83.54 (CH-4Ј),
1.1 Hz, 1 H, bipy-3Ј-H), 8.68 (ddd, J6Ј,5Ј = 4.7, J6Ј,4Ј = 1.8, J6Ј,3Ј =
106.55 (CH-4), 111.23 (CH-3), 123.81 (CH-3-thienyl), 125.55 (CH- 0.9 Hz, 1 H, bipy-6Ј-ЈH) ppm. 13C NMR (125.7 MHz, [D6]ace-
5-thienyl), 128.20 and 128.30 (C-i-Tol), 128.63 (CH-4-thienyl), tone): δ = 21.59 (CH3-Tol), 37.86 (CH2-2Ј), 65.26 (CH2-5Ј), 74.68
130.06 and 130.10 (CH-o-Tol), 130.44 and 130.47 (CH-o-Tol),
134.11 (C-2-thienyl), 144.70 and 144.94 (C-p-Tol), 150.29 (C-5),
(CH-1Ј), 77.75 (CH-3Ј), 83.61 (CH-4Ј), 110.26 (CH-4), 111.54 (CH-
3), 119.01 (CH-5-bipy), 119.84 (CH-3-bipy), 121.58 (CH-3Ј-bipy),
153.12 (C-2), 166.45 and 166.55 (CO) ppm. IR (CCl ): ν = 2926, 124.97 (CH-5Ј-bipy), 128.21 and 128.30 (C-i-Tol), 130.08 and
˜
4
1725, 1613, 1268, 1178, 1103, 1021, 693 cm–1.
130.14 (CH-o-Tol), 130.45 and 130.48 (CH-o-Tol), 137.81 (CH-4Ј-
bipy), 138.64 (CH-4-bipy), 144.75 and 144.97 (C-p-Tol), 149.35 (C-
6-bipy), 150.06 (CH-6Ј-bipy), 154.71 (C-5), 154.90 (C-2), 156.44
(C-2Ј-bipy), 156.60 (C-2-bipy), 166.48 and 166.55 (CO) ppm. IR
1β-[5-(Pyridin-2-yl)furan-2-yl]-1,2-dideoxy-3,5-di-O-toluoyl-D-ribo-
furanose (6d): Prepared from 3 (409 mg, 0.82 mmol) and 2-(tri-
butylstannyl)pyridine (270 µL, 0.98 mmol), by the general pro-
cedure (115 °C, 21 h). 6d (223 mg, 55%) was obtained as a yellow
oil. HRMS (ESI): calcd. for C30H27NO6Na [M + Na] 520.1731;
found 520.1727. 1H NMR (500 MHz, [D6]acetone): δ = 2.41 and
2.42 (2ϫs, 2 ϫ3 H, CH3-Tol), 2.57 (ddd, Jgem = 13.7, J2Јa,1Ј = 5.4,
J2Јa,3Ј = 1.3 Hz, 1 H, 2Јa-H), 2.82 (ddd, Jgem = 13.7, J2Јb,1Ј = 10.7,
(CCl ): ν = 3039, 2955, 2926, 1725, 1613, 1428, 1268, 1178, 1103,
˜
4
1021, 690 cm–1.
General Procedure for the Zemplén Deprotection: NaOMe (1  in
MeOH, 0.32 mL, 0.32 mmol) was added to a solution of toluoyl-
protected C-nucleoside 3, 6a–e, 6m, or 11a–b (0.16 mmol) in
MeOH (30 mL) and the resulting solution was stirred at r.t. over-
night. The solvent was evaporated and the products were isolated
by column chromatography on silica gel, eluent gradient from chlo-
roform to chloroform/MeOH (19.5:0.5). Compounds were re-puri-
fied by flash chromatography on reverse-phase C18 column (with
linear gradient of H2O to MeOH).
J2Јb,3Ј = 6.0 Hz, 1 H, 2Јb-H), 4.52 (td, J4Ј,5Јa = J4Ј,5Јb = 4.2, J4Ј,3Ј
=
2.0 Hz, 1 H, 4Ј-H), 4.55 (dd, Jgem = 11.5, J5Јa,4Ј = 4.2 Hz, 1 H, 5Јa-
H), 4.65 (dd, Jgem = 11.5, J5Јb,4Ј = 4.3 Hz, 1 H, 5Јb-H), 5.37 (dd,
J1Ј,2b = 10.7, J1Ј,2Јa = 5.4 Hz, 1 H, 1Ј-H), 5.74 (dddd, J3Ј,2Јb = 6.0,
J3Ј,4Ј = 2.0, J3Ј,2Јa = 1.3, J3Ј,1Ј = 0.5 Hz, 1 H, 3Ј-H), 6.63 (dd, J3,4
= 3.4, J3,1Ј = 0.4 Hz, 1 H, 3-H), 7.04 (d, J4,3 = 3.4 Hz, 1 H, 4-H),
7.23 (ddd, J5,4 = 7.5, J5,6 = 4.8, J5,3 = 1.2 Hz, 1 H, py-5-H), 7.34 1β-(5-Bromofuran-2-yl)-1,2-dideoxy-D-ribofuranose (5): Compound
and 7.36 (2ϫm, 2ϫ2 H, o-Tol-H), 7.56 (dt, J3,4 = 8.0, J3,5 = J3,6
= 1.1 Hz, 1 H, py-3-H), 7.71 (ddd, J4,3 = 8.0, J4,5 = 7.6, J4,6
5 was prepared from 3 (1.10 g, 2.22 mmol) according to the general
procedure in 93% yield as a colorless oil. After coevaporation with
=
1.8 Hz, 1 H, py-4-H), 7.98–8.03 (m, 4 H, o-Tol-H), 8.54 (ddd, J6,5 EtOAc the oil furnished a white powder, which was stored under
= 4.8, J6,4 = 1.8, J6,3 = 1.0 Hz, 1 H, py-6-H) ppm. 13C NMR
(125.7 MHz, [D6]acetone): δ = 21.58 (CH3-Tol), 37.84 (CH2-2Ј),
argon in the freezer; m.p. 101–102 °C. HRMS (ESI): calcd. for
C9H11O4BrNa [M + Na] 284.9733; found 284.9734. 1H NMR
65.26 (CH2-5Ј), 74.66 (CH-1Ј), 77.75 (CH-3Ј), 83.61 (CH-4Ј), (500 MHz, [D6]DMSO): δ = 1.95 (ddd, Jgem = 12.8, J2Јa,1Ј = 5.8,
109.96 (CH-4), 111.53 (CH-3), 118.85 (CH-3-py), 123.05 (CH-5- J2Јa,3Ј = 2.0 Hz, 1 H, 2Јa-H), 2.12 (ddd, Jgem = 12.8, J2Јb,1Ј = 10.2,
py), 128.19 and 128.29 (C-i-Tol), 130.07 and 130.12 (CH-o-Tol),
J2Јb,3Ј = 5.7 Hz, 1 H, 2Јb-H), 3.32 (dd, Jgem = 11.4, J5Јa,4Ј = 6.0 Hz,
130.44 and 130.47 (CH-o-Tol), 137.53 (CH-4-py), 144.74 and 1 H, 5Јa-H), 3.36 (dd, Jgem = 11.4, J5Јb,4Ј = 5.4 Hz, 1 H, 5Јb-H),
144.97 (C-p-Tol), 149.92 (C-2-py), 150.53 (CH-6-py), 154.66 and
3.70 (ddd, J4Ј,5Јa = 6.0, J4Ј,5Јb = 5.4, J4Ј,3Ј = 2.5 Hz, 1 H, 4Ј-H), 4.17
(br. dt, J3Ј,2Јb = 5.7, J3Ј,2Јa = J3Ј,4Ј = 2.2 Hz, 1 H, 3Ј-H), 4.94 (dd,
J1Ј,2b = 10.2, J1Ј,2Јa = 5.8 Hz, 1 H, 1Ј-H), 6.49 (br. d, J3,4 = 3.3 Hz,
1 H, 3-H), 6.51 (d, J4,3 = 3.3 Hz, 1 H, 4-H) ppm. 13C NMR
(125.7 MHz, [D6]DMSO): δ = 38.70 (CH2-2Ј), 62.43 (CH2-5Ј),
71.97 (CH-3Ј), 72.12 (CH-1Ј), 87.88 (CH-4Ј), 110.74 (CH-3), 112.47
(CH-4), 121.09 (C-5), 156.64 (C-2) ppm. C9H11BrO4 (263.1): calcd.
C 41.09, H 4.21, Br 30.37; found C 41.30, H 4.26, Br 30.78. IR
154.74 (C-2,5), 166.48 and 166.55 (CO) ppm. IR (CCl ): ν = 2925,
˜
4
1725, 1613, 1269, 1178, 1103, 1021 cm–1.
1β-[5-(2,2Ј-Bipyridin-6-yl)furan-2-yl]-1,2-dideoxy-3,5-di-O-toluoyl-
D-ribofuranose (6e): nBuLi (1.75 mL, 1.6  in hexane, 2.8 mmol)
was added dropwise into a solution of 6-bromo-2,2Ј-bipyridine
(460 mg, 1.96 mmol) in THF (15 mL) under argon at –72 °C during
5 min, and the mixture was stirred for 2 min followed by addition
of Bu3SnCl (530 µL, 1.96 mmol). After stirring for 20 min at
–72 °C, the reaction was warmed to room temp., and the solvent
was carefully evaporated under vacuum. The crude 6-(tributylstan-
nyl)-2,2Ј-bipyridine was dissolved in DMF (5 mL) and added
through septum to a flask containing 3 (700 mg, 1.4 mmol) and
[PdCl2dppf] (103 mg, 0.14 mmol) under argon. The reaction mix-
ture was stirred at 100 °C for 21 h. Chromatography on silica gel,
eluent gradient from hexane to hexane/EtOAc (9.7:0.3) gave 6e
(355 mg, 44%) as a yellow oil. HRMS (ESI): for C35H30N2O6Na
[M + Na] 597.1996; found 597.1993. 1H NMR (500 MHz, [D6]-
acetone): δ = 2.41 and 2.43 (2ϫs, 2 ϫ3 H, CH3-Tol), 2.60 (ddd,
Jgem = 13.7, J2Јa,1Ј = 5.5, J2Јa,3Ј = 1.5 Hz, 1 H, 2Јa-H), 2.85 (ddd,
Jgem = 13.7, J2Јb,1Ј = 10.6, J2Јb,3Ј = 6.0 Hz, 1 H, 2Јb-H), 4.54 (td,
(KBr): ν = 3390, 3304, 1501, 1045, 1032, 792, 782, 605 cm–1. [α]20
˜
D
= +10.9 (c = 0.27, MeOH).
1β-[5-(Thiazol-2-yl)furan-2-yl]-1,2-dideoxy-D-ribofuranose (7a):
Compound 6a was prepared (80 mg, 0.47 mmol) by the general
procedure. 7a (41 mg, 98%) was obtained as a yellow oil, which was
crystallized from 2-propanol/heptane to give gray crystals. HRMS
(ESI): calcd. for C12H13O4NSNa [M + Na] 290.0460; found
1
290.0457. H NMR (500 MHz, [D6]DMSO): δ = 2.05 (ddd, Jgem
12.8, J2Јa,1Ј = 6.0, J2Јa,3Ј = 2.2 Hz, 1 H, 2Јa-H), 2.21 (ddd, Jgem
=
=
12.8, J2Јb,1Ј = 9.9, J2Јb,3Ј = 5.7 Hz, 1 H, 2Јb-H), 3.40 (m, 2 H, 5Ј-
H), 4.76 (td, J4Ј,5Јb = J4Ј,5Јa = 5.7, J4Ј,3Ј = 2.5 Hz, 1 H, 4Ј-H), 4.23
(m, 1 H, 3Ј-H), 4.76 (t, JOH,5Јa = JOH,5Јb = 5.7 Hz, OH-5Ј), 5.06
(dd, J1Ј,2b = 9.9, J1Ј,2Јa = 6.0 Hz, 1 H, 1Ј-H), 5.13 (d, JOH,3Ј
=
4.1 Hz, OH-3Ј), 6.30 (dd, J3,4 = 3.4, J3,1Ј = 0.5 Hz, 1 H, 3-H), 7.01
(d, J4,3 = 3.4 Hz, 1 H, 4-H), 7.75 (d, J5,4 = 3.2 Hz, 1 H, thiazyl-
5-H), 7.88 (d, J4,5 = 3.2 Hz, 1 H, thiazyl-4-H) ppm. 13C NMR
(125.7 MHz, [D6]DMSO): δ = 39.00 (CH2-2Ј), 62.44 (CH2-5Ј),
72.03 (CH-3Ј), 72.21 (CH-1Ј), 87.95 (CH-4Ј), 109.75 (CH-4), 110.14
(CH-3), 119.77 (CH-5-thiazyl), 143.93 (CH-4-thiazyl), 148.03 (C-
J4Ј,5Јa = J4Ј,5Јb = 4.1, J4Ј,3Ј = 2.0 Hz, 1 H, 4Ј-H), 4.57 (dd, Jgem
11.3, J5Јa,4Ј = 4.2 Hz, 1 H, 5Јa-H), 4.68 (dd, Jgem = 11.3, J5Јb,4Ј
=
=
4.1 Hz, 1 H, 5Јb-H), 5.40 (dd, J1Ј,2b = 10.6, J1Ј,2Јa = 5.5 Hz, 1 H,
1Ј-H), 5.78 (br. dt, J3Ј,2Јb = 5.9, J3Ј,2Јa = J3Ј,4Ј = 1.7 Hz, 1 H, 3Ј-H),
6.68 (br. d, J3,4 = 3.4 Hz, 1 H, 3-H), 7.23 (d, J4,3 = 3.3 Hz, 1 H, 4-
H), 7.34 and 7.37 (2ϫm, 2ϫ2 H, o-Tol-H), 7.43 (ddd, J5Ј,4Ј = 7.5,
J5Ј,6Ј = 4.7, J5Ј,3Ј = 1.2 Hz, 1 H, bipy-5Ј-H), 7.61 (dd, J5,4 = 7.8,
J5,3 = 1.0 Hz, 1 H, bipy-5-H), 7.87 (t, J4,3 = J4,5 = 7.9 Hz, 1 H,
bipy-4-H), 7.93 (ddd, J4Ј,3Ј = 7.9, J4Ј,5Ј = 7.5, J4Ј,6Ј = 1.8 Hz, 1 H,
bipy-4Ј-H), 7.99–8.03 (m, 4 H, o-Tol-H), 8.36 (dd, J3,4 = 7.8, J3,5
5), 156.13 (C-2), 157.13 (C-2-thiazyl) ppm. IR (KBr): ν = 3410,
˜
3110, 2913, 1603, 1338, 1255, 1215, 1057, 1033, 998, 793, 652 cm–1.
20
[α] = –15.0 (c = 0.25, MeOH).
D
1β-[5-(Furan-2-yl)furan-2-yl]-1,2-dideoxy-D-ribofuranose (7b): Com-
= 1.0 Hz, 1 H, -bipy-3-H), 8.59 (dt, J3Ј,4Ј = 8.0, J3Ј,5Ј = J3Ј,6Ј
=
pound 7b was prepared from 6b (365 mg, 0.75 mmol) by the general
Eur. J. Org. Chem. 2010, 5432–5443
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5437

J. Bárta, L. Slaveˇtínská, B. Klepetárˇová, M. Hocek
FULL PAPER
procedure. 7b (145 mg, 77%) was obtained as a white powder; m.p. 1β-[5-(2,2Ј-Bipyridin-6-yl)furan-2-yl]-1,2-dideoxy-
D-ribofuranose
102–104 °C. HRMS (ESI): calcd. for C13H14O5Na [M + Na] (7e): Compound 7e was prepared from 6e (240 mg, 0.42 mmol) by
1
273.0734; found 273.0733. H NMR (500 MHz, [D6]DMSO): δ =
2.00 (ddd, Jgem = 12.8, J2Јa,1Ј = 5.9, J2Јa,3Ј = 2.1 Hz, 1 H, 2Јa-H),
the general procedure. 7e (86 mg, 61%) was obtained as a yellow
oil. HRMS (ESI): calcd. for C19H18N2O4Na [M + Na] 361.1161;
1
2.19 (ddd, Jgem = 12.8, J2Јb,1Ј = 10.1, J2Јb,3Ј = 5.8 Hz, 1 H, 2Јb-H), found 361.1159. H NMR (500 MHz, [D6]DMSO): δ = 2.07 (ddd,
3.36 (dd, Jgem = 11.4, J5Јa,4Ј = 6.0 Hz, 1 H, 5Јa-H), 3.39 (dd, Jgem Jgem = 12.8, J2Јa,1Ј = 5.9, J2Јa,3Ј = 2.1 Hz, 1 H, H-2Јa), 2.28 (ddd,
= 11.4, J5Јb,4Ј = 5.4 Hz, 1 H, 5Јb-H), 3.73 (ddd, J4Ј,5Јa = 5.9, J4Ј,5Јb Jgem = 12.8, J2Јb,1Ј = 10.0, J2Јb,3Ј = 5.7 Hz, 1 H, H-2Јb), 3.39–3.47
= 5.5, J4Ј,3Ј = 2.5 Hz, 1 H, 4Ј-H), 4.21 (br. dt, J3Ј,2Јb = 5.8, J3Ј,2Јa
=
(m, 2 H, H-5Јa, H-5Јb), 3.78 (ddd, J4Ј,5Јa = 5.9, J4Ј,5Јb = 5.5, J4Ј,3Ј
J3Ј,4Ј = 2.3 Hz, 1 H, 3Ј-H), 4.73 (br. s, 1 H, OH-5Ј), 5.01 (dd, J1Ј,2b = 2.4 Hz, 1 H, H-4Ј), 4.26 (br. dt, J3Ј,2Јb = 5.6, J3Ј,2Јa = J3Ј,4Ј
=
= 10.0, J1Ј,2Јa = 5.9 Hz, 1 H, 1Ј-H), 5.10 (br. s, 1 H, OH-3Ј), 6.52
(dd, J3,4 = 3.4, J3,1Ј = 0.6 Hz, 1 H, 3-H), 6.59 (dd, J4,3 = 3.4, J4,5
= 1.8 Hz, 1 H, furyl-4-H), 6.61 (d, J4,3 = 3.4 Hz, 1 H, 4-H), 6.66
2.3 Hz, 1 H, H-3Ј), 4.81 (br. s, 1 H, OH-5Ј), 5.10 (dd, J1Ј,2b = 10.0,
J1Ј,2Јa = 5.9 Hz, 1 H, H-1Ј), 5.16 (br. s, 1 H, OH-3Ј), 6.64 (dd, J3,4
= 3.3, J3,1Ј = 0.5 Hz, 1 H, H-3), 7.22 (d, J4,3 = 3.3 Hz, 1 H, H-4),
(dd, J3,4 = 3.4, J3,5 = 0.9 Hz, 1 H, furyl-3-H), 7.72 (dd, J5,4 = 1.8, 7.48 (ddd, J5Ј,4Ј = 7.5, J5Ј,6Ј = 4.7, J5Ј,3Ј = 1.2 Hz, 1 H, H-5Ј-bipy),
J5,3 = 0.8 Hz, 1 H, furyl-5-H) ppm. 13C NMR (125.7 MHz, [D6]-
DMSO): δ = 38.94 (CH2-2Ј), 62.48 (CH2-5Ј), 72.04 (CH-3Ј), 72.24
7.75 (dd, J5,4 = 7.8, J5,3 = 1.0 Hz, 1 H, H-5-bipy), 7.99 (ddd, J4Ј,3Ј
= 7.9, J4Ј,5Ј = 7.5, J4Ј,6Ј = 1.8 Hz, 1 H, H-4Ј-bipy), 8.01 (t, J4,3
=
(CH-1Ј), 87.87 (CH-4Ј), 105.77 (CH-3-furyl), 106.23 (CH-4), J4,5 = 7.9 Hz, 1 H, H-4-bipy), 8.28 (dd, J3,4 = 7.9, J3,5 = 1.0 Hz, 1
109.48 (CH-3), 111.94 (CH-4-furyl), 142.98 (CH-5-furyl), 145.38 H, H-3-bipy), 8.51 (dt, J3Ј,4Ј = 7.9, J3Ј,5Ј = J3Ј,6Ј = 1.1 Hz, 1 H, H-
and 145.67 (C-2-furyl, C-5), 154.07 (C-2) ppm. IR (KBr): ν = 3401, 3Ј-bipy), 8.70 (ddd, J6Ј,5Ј = 4.8, J6Ј,4Ј = 1.8, J6Ј,3Ј = 0.9 Hz, 1 H, H-
˜
3131, 2919, 1337, 1211, 1061, 1008, 790, 747 cm–1. [α]2D0 = –10.7 (c
= 2.52, DMSO).
6Ј-bipy) ppm. 13C NMR (125.7 MHz, [D6]DMSO): δ = 39.07
(CH2-2Ј), 62.56 (CH2-5Ј), 72.16 (CH-3Ј), 72.48 (CH-1Ј), 87.95
(CH-4Ј), 110.01 (CH-4), 110.15 (CH-3), 118.56 (CH-5-bipy),
119.03 (CH-3-bipy), 120.87 (CH-3Ј-bipy), 124.65 (CH-5Ј-bipy),
137.61 (CH-4Ј-bipy), 138.58 (CH-4-bipy), 148.29 (C-6-bipy),
149.51 (CH-6Ј-bipy), 152.70 (C-5), 155.07 and 155.26 (C-2,2Ј-bipy),
1β-[5-(Thiophen-2-yl)furan-2-yl]-1,2-dideoxy-D-ribofuranose (7c):
Compound 7c was prepared from 6c (480 mg, 0.96 mmol) by the
general procedure. 7c (240 mg, 95%) was obtained as a white pow-
der; m.p. 98–102 °C. HRMS (ESI): calcd. for C13H14O4SNa [M +
155.79 (C-2) ppm. IR (KBr): ν = 3421, 2923, 2873, 1699, 1611,
˜
1
1564, 1428, 1085, 1045, 993, 778 cm–1. [α]2D0 = +12.0 (c = 0.27,
Na] 289.0506; found 289.0505. H NMR (500 MHz, [D6]DMSO):
δ = 2.00 (ddd, Jgem = 12.8, J2Јa,1Ј = 5.8, J2Јa,3Ј = 2.1 Hz, 1 H, 2Јa-
H), 2.20 (ddd, Jgem = 12.8, J2Јb,1Ј = 10.1, J2Јb,3Ј = 5.7 Hz, 1 H, 2Јb-
H), 3.34–3.43 (m, 2 H, 5Јa-H, 5Јb-H), 3.76 (ddd, J4Ј,5Јa = 6.1, J4Ј,5Јb
MeOH).
General Procedure for the Suzuki Cross-Coupling: A mixture of
H2O/acetonitrile (2:1, 5 mL) was added to an argon-purged flask
containing TPPTS (76 mg, 0.13 mmol) and [Pd(OAc)2] (12 mg,
0.05 mmol), and the mixture was sonicated for 1 min. This solution
was added into a mixture of 5 (280 mg, 1.06 mmol), boronic acid
(1.6 mmol), and Na2CO3 (340 mg, 3.2 mmol) in H2O/acetonitrile
(2:1, 5 mL). The mixture was then stirred at 110 °C for 4 h. After
evaporation, the crude product was purified by column chromatog-
raphy on silica gel, eluent gradient from CHCl3 to CHCl3/MeOH
(9.5:0.5).
= 5.5, J4Ј,3Ј = 2.4 Hz, 1 H, 4Ј-H), 4.21 (br. dt, J3Ј,2Јb = 5.6, J3Ј,2Јa
=
J3Ј,4Ј = 2.3 Hz, 1 H, 3Ј-H), 4.75 (br. s, 1 H, OH-5Ј), 5.01 (br. dd,
J1Ј,2b = 10.1, J1Ј,2Јa = 5.8 Hz, 1 H, 1Ј-H), 5.12 (br. s, 1 H, OH-3Ј),
6.50 (dd, J3,4 = 3.3, J3,1Ј = 0.6 Hz, 1 H, 3-H), 6.67 (d, J4,3 = 3.4 Hz,
1 H, 4-H), 7.10 (dd, J4,5 = 5.1, J4,3 = 3.6 Hz, 1 H, thienyl-4-H),
7.34 (dd, J3,4 = 3.5, J3,5 = 1.2 Hz, 1 H, thienyl-3-H), 7.52 (dd, J5,4
= 5.1, J5 , 3 = 1.2 Hz, 1 H, Thienyl-5-H) ppm. 1 3 C NMR
(125.7 MHz, [D6]DMSO): δ = 38.87 (CH2-2Ј), 62.53 (CH2-5Ј),
72.08 (CH-3Ј), 72.26 (CH-1Ј), 87.86 (CH-4Ј), 106.16 (CH-4), 109.90
(CH-3), 123.18 (CH-3-thienyl), 125.41 (CH-5-thienyl), 128.31 (CH-
4-thienyl), 132.99 (C-2-thienyl), 148.53 (C-5), 153.76 (C-2) ppm. IR
1β-[5-(4-Chlorophenyl)furan-2-yl]-1,2-dideoxy-D-ribofuranose (7f):
Compound 7f was prepared from 5 and 4-chlorophenylboronic
acid (250 mg, 1.6 mmol) by the general procedure (110 °C, 4 h). 7f
(212 mg, 68%) was obtained as a yellow solid, which was crys-
tallized from 2-propanol/heptane to give yellow crystals; m.p. 120–
124 °C. HRMS (ESI): calcd. for C15H15ClO4Na [M + Na]
317.0551; found 317.0551. H NMR (500 MHz, [D6]DMSO): δ =
2.01 (ddd, Jgem = 12.8, J2Јa,1Ј = 5.9, J2Јa,3Ј = 2.0 Hz, 1 H, H-2Јa),
2.23 (ddd, Jgem = 12.8, J2Јb,1Ј = 10.0, J2Јb,3Ј = 5.7 Hz, 1 H, H-2Јb),
(KBr): ν = 3388, 2919, 1328, 1203, 1068, 1006, 947, 790, 687 cm–1.
˜
[α]2D0 = –13.7 (c = 0.28, DMSO).
1β-[5-(Pyridin-2-yl)furan-2-yl]-1,2-dideoxy-D-ribofuranose (7d):
Compound 7d was prepared from 6d (233 mg, 0.47 mmol) by the
general procedure. 7d (86 mg, 71%) was obtained as a yellow oil.
1
HRMS (ESI): calcd. for C14H15NO4Na [M + Na] 284.0894; found
1
284.0893. H NMR (500 MHz, [D6]DMSO): δ = 2.04 (ddd, Jgem
12.8, J2Јa,1Ј = 5.9, J2Јa,3Ј = 2.1 Hz, 1 H, H-2Јa), 2.25 (ddd, Jgem
=
=
3.34–3.44 (m, 2 H, H-5Јa, H-5Јb), 3.75 (ddd, J4Ј,5Јa = 6.0, J4Ј,5Јb
5.5, J4Ј,3Ј = 2.4 Hz, 1 H, H-4Ј), 4.23 (m, 1 H, H-3Ј), 4.77 (t, JOH,5Ј
= 5.7 Hz, 1 H, OH-5Ј), 5.03 (dd, J1Ј,2b = 10.0, J1Ј,2Јa = 5.9 Hz, 1
=
12.8, J2Јb,1Ј = 10.0, J2Јb,3Ј = 5.7 Hz, 1 H, H-2Јb), 3.36–3.45 (m, 2 H,
H-5Јa, H-5Јb), 3.76 (ddd, J4Ј,5Јa = 6.0, J4Ј,5Јb = 5.5, J4Ј,3Ј = 2.4 Hz, 1
H, H-4Ј), 4.24 (br. dt, J3Ј,2Јb = 5.7, J3Ј,2Јa = J3Ј,4Ј = 2.3 Hz, 1 H, H-
3Ј), 4.78 (br. s, 1 H, OH-5Ј), 5.07 (dd, J1Ј,2b = 10.0, J1Ј,2Јa = 5.9 Hz,
H, H-1Ј), 5.14 (d, JOH,3Ј = 4.0 Hz, 1 H, OH-3Ј), 6.53 (dd, J3,4
=
3.4, J3,1Ј = 0.5 Hz, 1 H, H-3), 6.93 (d, J4,3 = 3.3 Hz, 1 H, H-4),
7.48 (m, 2 H, H-m-C6H4Cl), 7.69 (m, 2 H, H-o-C6H4Cl) ppm. 13C
NMR (125.7 MHz, [D6]DMSO): δ = 38.97 (CH2-2Ј), 62.59 (CH2-
5Ј), 72.18 (CH-3Ј), 72.43 (CH-1Ј), 87.88 (CH-4Ј), 107.44 (CH-4),
110.18 (CH-3), 125.26 (CH-o-C6H4Cl), 129.21 (CH-m-C6H4Cl),
129.36 (C-i-C6H4Cl), 132.04 (C-p-C6H4Cl), 151.68 (C-5), 154.64
1 H, H-1Ј), 5.15 (br. s, 1 H, OH-3Ј), 6.58 (dd, J3,4 = 3.4, J3,1Ј
=
0.4 Hz, 1 H, H-3), 7.03 (d, J4,3 = 3.4 Hz, 1 H, H-4), 7.28 (ddd, J5,4
= 7.6, J5,6 = 4.8, J5,3 = 1.1 Hz, 1 H, H-5-py), 7.69 (dt, J3,4 = 8.0,
J3,5 = J3,6 = 1.1 Hz, 1 H, H-3-py), 7.85 (ddd, J4,3 = 7.9, J4,5 = 7.6,
J4,6 = 1.8 Hz, 1 H, H-4-py), 8.56 (ddd, J6,5 = 4.8, J6,4 = 1.8, J6,3
=
(C-2) ppm. IR (KBr): ν = 3408, 3343, 1483, 1086, 1044, 1035, 839,
˜
1.0 Hz, 1 H, H-6-py) ppm. 13C NMR (125.7 MHz, [D6]DMSO): δ
= 39.04 (CH2-2Ј), 62.54 (CH2-5Ј), 72.14 (CH-3Ј), 72.46 (CH-1Ј),
87.92 (CH-4Ј), 109.57 (CH-4), 110.11 (CH-3), 118.33 (CH-3-py),
122.60 (CH-5-py), 137.36 (CH-4-py), 148.67 (C-2-py), 149.85 (CH-
793 cm–1. Anal. calcd. C15H15ClO4 (294.7): C 61.13, H 5.13, Cl
12.03; found C 61.01, H 4.99, Cl 12.11. [α]2D0 = +8.2 (c = 0.24,
MeOH).
6-py), 152.79 (C-5), 155.57 (C-2) ppm. IR (KBr): ν = 3382, 2924,
1β-[5-(Thiophen-3-yl)furan-2-yl]-1,2-dideoxy-
Prepared from 5 and 3-thienylboronic acid (204 mg, 1.6 mmol) by
D-ribofuranose (7g):
˜
2877, 1588, 1427, 1047, 778 cm–1. [α]2D0 = –8.1 (c = 2.10, DMSO).
5438
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© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 5432–5443

Deoxyribonucleoside Analogues
the general procedure (110 °C, 4 h). 7g (112 mg, 40%) was obtained
as a yellow oil, which was crystallized from 2-propanol/heptane to
give grey crystals; m.p. 132–134 °C. HRMS (ESI): calcd. for
101.51 (CH-3-C8H5O), 109.15 (CH-4), 109.84 (CH-3), 111.26 (CH-
7-C8H5O), 121.46 (CH-4-C8H5O), 123.67 (CH-5-C8H5O), 124.94
(CH-6-C8H5O), 128.44 (C-9-C8H5O), 144.70 (C-5), 147.41 (C-2-
C13H14O4SNa [M + Na] 289.0505; found 289.0506. 1H NMR C H O), 154.11 (C-8-C H O), 155.73 (C-2) ppm. IR (KBr): ν =
˜
8
5
8
5
(500 MHz, [D6]DMSO): δ = 1.99 (ddd, Jgem = 12.8, J2Јa,1Ј = 5.8, 3439, 2924, 1629, 1446, 1253, 1045, 793, 755 cm–1. C17H16O5
J2Јa,3Ј = 2.1 Hz, 1 H, H-2Јa), 2.22 (ddd, Jgem = 12.8, J2Јb,1Ј = 10.1,
J2Јb,3Ј = 5.7 Hz, 1 H, H-2Јb), 3.34–3.43 (m, 2 H, H-5Јa, H-5Јb),
3.73 (ddd, J4Ј,5Јa = 5.9, J4Ј,5Јb = 5.5, J4Ј,3Ј = 2.4 Hz, 1 H, H-4Ј), 4.21
(m, 1 H, H-3Ј), 4.75 (t, JOH,5Ј = 5.7 Hz, 1 H, OH-5Ј), 5.01 (dd,
J1Ј,2b = 10.1, J1Ј,2Јa = 5.8 Hz, 1 H, H-1Ј), 5.11 (d, JOH,3Ј = 4.0 Hz,
1 H, OH-3Ј), 6.47 (dd, J3,4 = 3.3, J3,1Ј = 0.5 Hz, 1 H, H-3), 6.67
(d, J4,3 = 3.3 Hz, 1 H, H-4), 7.40 (dd, J4,5 = 5.0, J4,2 = 1.3 Hz, 1
H, Thienyl-4-H), 7.62 (dd, J5,4 = 5.0, J5,2 = 3.0 Hz, 1 H, Thienyl-
5-H), 7.67 (dd, J2,5 = 3.0, J2,4 = 1.3 Hz, 1 H, H-2-thienyl). 13C
NMR (125.7 MHz, [D6]DMSO): δ = 38.93 (CH2-2Ј), 62.58 (CH2-
5Ј), 72.14 (CH-3Ј), 72.40 (CH-1Ј), 87.85 (CH-4Ј), 106.13 (CH-4),
109.52 (CH-3), 119.48 (CH-2-thienyl), 124.92 (CH-4-thienyl),
127.62 (CH-5-thienyl), 132.24 (C-3-thienyl), 150.20 (C-5), 153.38
(300.3): C 67.99, H 5.37; found C 67.83, H 5.75. [α]2D0 = –2.9 (c =
0.24, DMSO).
1β-[5-(Dibenzo[b,d]furan-4-yl)furan-2-yl]-1,2-dideoxy-D-ribofuranose
(7j): Prepared from 5 and dibenzo[b,d]furan-4-ylboronic acid
(339 mg, 1.6 mmol) by the general procedure (110 °C, 4 h). Com-
pound 7j (175 mg, 47%) was obtained as a yellow oil, which was
crystallized from 2-propanol/heptane to give yellow crystals; m.p.
139–142 °C. HRMS (ESI): calcd. for C21H18O5Na [M + Na]
1
373.1046; found 373.1046. H NMR (500 MHz, [D6]DMSO): δ =
2.08 (ddd, Jgem = 12.8, J2Јa,1Ј = 5.9, J2Јa,3Ј = 2.1 Hz, 1 H, H-2Јa),
2.31 (ddd, Jgem = 12.8, J2Јb,1Ј = 10.0, J2Јb,3Ј = 5.7 Hz, 1 H, H-2Јb),
3.42–3.48 (m, 2 H, H-5Јa, H-5Јb), 3.79 (ddd, J4Ј,5Јa = 6.0, J4Ј,5Јb
5.6, J4Ј,3Ј = 2.4 Hz, 1 H, H-4Ј), 4.29 (br. ddt, J3Ј,2Јb = 5.8, J3Ј,OH
3.8, J3Ј,2Јa = J3Ј,4Ј = 2.2 Hz, 1 H, H-3Ј), 4.79 (t, JOH,5Јa = JOH,5Јb
=
=
=
(C-2) ppm. IR (KBr): ν = 3412, 3350, 2880, 1033, 785, 600 cm–1.
˜
C13H14O4S (266.3): C 58.63, H 5.30, S 12.04; found C 58.37, H
5.37, S 12.51. [α]2D0 = +10.5 (c = 0.23, MeOH).
5.7 Hz, 1 H, OH-5Ј), 5.13 (dd, J1Ј,2b = 9.9, J1Ј,2Јa = 5.9 Hz, 1 H,
H-1Ј), 5.15 (d, JOH,3Ј = 4.0 Hz, 1 H, OH-3Ј), 6.69 (d, J3,4 = 3.4 Hz,
1β-[5-(Furan-3-yl)furan-2-yl]-1,2-dideoxy-D-ribofuranose (7h): Pre-
1 H, H-3), 7.26 (d, J4,3 = 3.3 Hz, 1 H, H-4), 7.45 (td, J8,7 = J8,9
=
pared from 5 and 3-furylboronic acid (179 mg, 1.6 mmol) by the
general procedure (110 °C, 4 h). 7h (120 mg, 44%) was obtained as
a yellow oil and crystallized from 2-propanol/heptane to give
orange crystals; m.p. 120–121 °C. HRMS (ESI): calcd. for
7.5, J8,6 = 1.0 Hz, 1 H, H-8-C12H7O), 7.49 (t, J2,1 = J2,3 = 7.7 Hz,
1 H, H-2-C12H7O), 7.58 (ddd, J7,6 = 8.4, J7,8 = 7.3, J7,9 = 1.4 Hz,
1 H, H-7-C12H7O), 7.82 (dt, J6,7 = 8.3, J6,8 = J6,9 = 0.9 Hz, 1 H,
H-6-C12H7O), 7.85 (dd, J3,2 = 7.7, J3,1 = 1.2 Hz, 1 H, H-3-C12H7O),
8.10 (dd, J1,2 = 7.7, J1,3 = 1.2 Hz, 1 H, H-1-C12H7O), 8.20 (ddd,
J9,8 = 7.7, J9,7 = 1.4, J9,6 = 0.7 Hz, 1 H, H-9-C12H7O) ppm. 13C
NMR (125.7 MHz, [D6]DMSO): δ = 39.05 (CH2-2Ј), 62.62 (CH2-
5Ј), 72.20 (CH-3Ј), 72.43 (CH-1Ј), 87.91 (CH-4Ј), 110.22 (CH-3),
110.89 (CH-4), 112.16 (CH-6-C12H7O), 115.35 (C-4-C12H7O),
120.29 (CH-1-C12H7O), 121.56 (CH-9-C12H7O), 122.23 (CH-3-
C12H7O), 123.46 (C-9a-C12H7O), 123.71 and 123.78 (CH-2,8-
C12H7O), 124.59 (C-9b-C12H7O), 128.14 (CH-7-C12H7O), 147.93
(C-5), 150.51 (C-4a-C12H7O), 154.62 (C-2), 155.73 (C-5a-C12H7O)
C
13H14O5Na [M + Na] 273.0733; found 273.0733. 1H NMR
(500 MHz, [D6]DMSO): δ = 1.98 (ddd, Jgem = 12.8, J2Јa,1Ј = 5.8,
J2Јa,3Ј = 2.0 Hz, 1 H, H-2Јa), 2.19 (ddd, Jgem = 12.8, J2Јb,1Ј = 10.2,
J2Јb,3Ј = 5.8 Hz, 1 H, H-2Јb), 3.32–3.42 (m, 2 H, H-5Јa, H-5Јb),
3.72 (ddd, J4Ј,5Јa = 5.9, J4Ј,5Јb = 5.6, J4Ј,3Ј = 2.4 Hz, 1 H, H-4Ј), 4.20
(ddt, J3Ј,2Јb = 6.0, J3Ј,OH = 3.9, J3Ј,2Јa = J3Ј,4Ј = 2.2 Hz, 1 H, H-3Ј),
4.73 (t, JOH,5Ј = 5.7 Hz, 1 H, OH-5Ј), 4.98 (dd, J1Ј,2b = 10.2, J1Ј,2Јa
= 5.7 Hz, 1 H, H-1Ј), 5.09 (d, JOH,3Ј = 4.1 Hz, 1 H, OH-3Ј), 6.45
(dd, J3,4 = 3.3, J3,1Ј = 0.5 Hz, 1 H, H-3), 6.55 (d, J4,3 = 3.4 Hz, 1
H, H-4), 6.79 (dd, J4,5 = 1.9, J4,2 = 0.8 Hz, 1 H, H-4-furyl), 7.73
(t, J5,4 = J5,2 = 1.7 Hz, 1 H, H-3-furyl), 8.00 (m, 1 H, H-2-furyl).
13C NMR (125.7 MHz, [D6]DMSO): δ = 38.90 (CH2-2Ј), 62.53
(CH2-5Ј), 72.09 (CH-3Ј), 72.32 (CH-1Ј), 87.85 (CH-4Ј), 106.40
(CH-4), 108.05 (CH-4-furyl), 109.30 (CH-3), 117.63 (C-3-furyl),
138.52 (CH-2-furyl), 144.51 (CH-5-furyl), 147.06 (C-5), 153.29 (C-
ppm. IR (KBr): ν = 3399, 3326, 2927, 1450, 1193, 1060, 794, 750
˜
cm–1. C21H18O5 (350.4): C 71.99, H 5.18; found C 71.73, H 5.30.
[α]2D0 = +10.8 (c = 0.24, MeOH).
1β-[5-(3-Nitrophenyl)furan-2-yl]-1,2-dideoxy-D-ribofuranose (7k):
Prepared from 5 and 3-nitrophenylboronic acid (267 mg, 1.6 mmol)
by the general procedure (110 °C, 4 h). Compound 7k (135 mg,
42%) was obtained as a yellow oil, which was crystallized from
toluene/heptane to give yellow crystals; m.p. 146–149 °C. HRMS
2) ppm. IR (KBr): ν = 3406, 3335, 2951, 1157, 1044, 1031, 787,
˜
596 cm–1. [α]2D0 = +3.1 (c = 0.29, MeOH).
1β-[5-(Benzofuran-2-yl)furan-2-yl]-1,2-dideoxy-D-ribofuranose (7i):
Prepared from 5 (120 mg, 0.46 mmol) and 2-benzofurylboronic
acid (111 mg, 1.6 mmol) by the general procedure (110 °C, 4 h).
Compound 7i (137 mg, 37%) was obtained as a yellow oil, which
was crystallized from 2-propanol/heptane to give orange crystals;
m.p. 124–128 °C. HRMS (ESI): calcd. for C17H16O5Na [M + Na]
(ESI): calcd. for C15H15NO6Na [M + Na] 328.0792; found
1
328.0791. H NMR (500 MHz, [D6]DMSO): δ = 2.04 (ddd, Jgem
12.8, J2Јa,1Ј = 5.9, J2Јa,3Ј = 2.1 Hz, 1 H, H-2Јa), 2.25 (ddd, Jgem
=
=
12.8, J2Јb,1Ј = 10.0, J2Јb,3Ј = 5.7 Hz, 1 H, H-2Јb), 3.36–3.45 (m, 2 H,
H-5Јa, H-5Јb), 3.76 (ddd, J4Ј,5Јa = 6.0, J4Ј,5Јb = 5.5, J4Ј,3Ј = 2.4 Hz, 1
H, H-4Ј), 4.25 (ddm, J3Ј,2Јb = 5.8, J3Ј,OH = 3.7 Hz, 1 H, H-3Ј), 4.77
(t, JOH,5Јa = JOH,5Јb = 5.7 Hz, 1 H, OH-5Ј), 5.07 (dd, J1Ј,2b = 10.0,
1
323.0892; found 323.0890. H NMR (500 MHz, [D6]DMSO): δ =
2.05 (ddd, Jgem = 12.8, J2Јa,1Ј = 5.8, J2Јa,3Ј = 2.1 Hz, 1 H, H-2Јa),
2.24 (ddd, Jgem = 12.8, J2Јb,1Ј = 10.0, J2Јb,3Ј = 5.9 Hz, 1 H, H-2Јb), J1Ј,2Јa = 5.9 Hz, 1 H, H-1Ј), 5.14 (d, JOH,3Ј = 4.0 Hz, 1 H, OH-3Ј),
3.38–3.44 (m, 2 H, H-5Јa, H-5Јb), 3.76 (td, J4Ј,5Јa = J4Ј,5Јb = 5.7,
J4Ј,3Ј = 2.5 Hz, 1 H, H-4Ј), 4.24 (m, 1 H, H-3Ј), 4.75 (m, 1 H, OH-
5Ј), 5.07 (dd, J1Ј,2b = 10.0, J1Ј,2Јa = 5.8 Hz, 1 H, H-1Ј), 5.13 (br. s,
1 H, OH-3Ј), 6.63 (dd, J3,4 = 3.4, J3,1Ј = 0.5 Hz, 1 H, H-3), 6.91
6.61 (br. d, J3,4 = 3.4 Hz, 1 H, H-3), 7.20 (d, J4,3 = 3.4 Hz, 1 H,
H-4), 7.72 (t, J5,4 = J5,6 = 8.0 Hz, 1 H, H-5-C6H4NO2), 8.11–8.14
(m, 2 H, H-4,6-C6H4NO2), 8.42 (t, J2,4 = J2,6 = 2.0 Hz, 1 H, H-2-
C6H4NO2) ppm. 13C NMR (125.7 MHz, [D6]DMSO): δ = 38.99
(d, J4,3 = 3.4 Hz, 1 H, H-4), 7.12 (br. d, J3,7 = 1.0 Hz, 1 H, H-3- (CH2-2Ј), 62.50 (CH2-5Ј), 72.11 (CH-3Ј), 72.36 (CH-1Ј), 87.93
C8H5O), 7.29 (td, J5,4 = J5,6 = 7.5, J5,7 = 1.1 Hz, 1 H, H-5-C8H5O),
7.32 (ddd, J6,7 = 8.2, J6,5 = 7.3, J6,4 = 1.4 Hz, 1 H, H-6-C8H5O),
(CH-4Ј), 109.26 (CH-4), 110.30 (CH-3), 117.62 (CH-2-C6H4NO2),
122.04, 129.62 (CH-4,6-C6H4NO2), 130.84 (CH-5-C6H4NO2),
7.61 (dq, J7,6 = 8.2, J7,5 = J7,4 = J7,3 = 1.0 Hz, 1 H, H-7-C8H5O), 131.90 (C-1-C6H4NO2), 148.65 (C-3-C6H4NO2), 150.47 (C-5),
7.66 (ddd, J4,5 = 7.7, J4,6 = 1.4, J4,7 = 0.7 Hz, 1 H, H-4-C8H5O)
155.61 (C-2) ppm. IR (KBr): ν = 3531, 3378, 1525, 1354, 1081,
˜
ppm. 13C NMR (125.7 MHz, [D6]DMSO): δ = 39.03 (CH2-2Ј), 802, 741 cm–1. C15H15NO6 (305.3): C 59.01, H 4.95, N 4.59; found
62.45 (CH2-5Ј), 72.05 (CH-3Ј), 72.27 (CH-1Ј), 87.96 (CH-4Ј), C 58.70, H 4.86, N 4.34. [α]2D0 = +12.2 (c = 0.26, MeOH).
Eur. J. Org. Chem. 2010, 5432–5443
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5439

J. Bárta, L. Slaveˇtínská, B. Klepetárˇová, M. Hocek
FULL PAPER
1β-[5-(Phenoxathiin-4-yl)furan-2-yl]-1,2-dideoxy-
D
-ribofuranose H-o-Tol) ppm. 13C NMR (125.7 MHz, [D6]acetone): δ = 21.57 and
(7l): Prepared from 5 and phenoxathiin-4-ylboronic acid (390 mg,
1.6 mmol) by the general procedure (110 °C, 4 h). Compound 7l
(80 mg, 20%) was obtained as an orange oil, which was crystallized
from 2-propanol/heptane to give orange crystals; m.p. 71–75 °C.
21.59 (CH3-Tol), 25.05 and 25.08 [(CH3)2C], 38.05 (CH2-2Ј), 65.35
(CH2-5Ј), 74.77 (CH-1Ј), 77.68 (CH-3Ј), 83.69 (CH-4Ј), 84.77
[(CH3)2C], 109.30 (CH-3), 125.01 (CH-4), 128.23 and 128.31 (C-i-
Tol), 130.07 and 130.10 (CH-o-Tol), 130.45 and 130.49 (CH-o-Tol),
144.60 and 144.94 (C-p-Tol), 159.16 (C-2), 166.45 and 166.59 (CO)
HRMS (ESI): calcd. for C21H18O5SNa [M + Na] 405.0767; found
1
405.0766. H NMR (500 MHz, [D6]DMSO): δ = 2.04 (ddd, Jgem
12.8, J2Јa,1Ј = 5.9, J2Јa,3Ј = 2.1 Hz, 1 H, H-2Јa), 2.27 (ddd, Jgem
=
=
ppm. IR (KBr): ν = 3429, 2927, 1721, 1613, 1346, 1271, 1106, 754
˜
cm–1. Compound 9: HRMS (ESI): calcd. for C25H24O6Na [M +
1
12.8, J2Јb,1Ј = 10.0, J2Јb,3Ј = 5.7 Hz, 1 H, H-2Јb), 3.36–3.46 (m, 2 H, Na] 443.1465; found 443.1465. H NMR (500 MHz, [D6]acetone):
H-5Јa, H-5Јb), 3.77 (ddd, J4Ј,5Јa = 6.0, J4Ј,5Јb = 5.5, J4Ј,3Ј = 2.4 Hz, 1
H, H-4Ј), 4.25 (ddm, J3Ј,2Јb = 5.8, J3Ј,OH = 3.8 Hz, 1 H, H-3Ј), 4.77
δ = 2.41 and 2.42 (2ϫs, 2 ϫ3 H, CH3-Tol), 2.48 (ddd, Jgem = 13.8,
J2Јa,1Ј = 5.5, J2Јa,3Ј = 1.5 Hz, 1 H, H-2Јa), 2.69 (ddd, Jgem = 13.8,
(t, JOH,5Јa = JOH,5Јb = 5.7 Hz, 1 H, OH-5Ј), 5.09 (dd, J1Ј,2b = 10.0, J2Јb,1Ј = 10.7, J2Јb,3Ј = 6.1 Hz, 1 H, H-2Јb), 4.47 (ddd, J4Ј,5Јb = 5.0,
J1Ј,2Јa = 5.9 Hz, 1 H, H-1Ј), 5.13 (d, JOH,3Ј = 4.0 Hz, 1 H, OH-3Ј),
6.62 (d, J3,4 = 3.3 Hz, 1 H, H-3), 7.16 (td, J8,7 = J8,9 = 7.5, J8,6
J4Ј,5Јa = 4.2, J4Ј,3Ј = 2.1 Hz, 1 H, H-4Ј), 4.49–4.56 (m, 2 H, H-5Ј),
5.29 (br. dd, J1Ј,2b = 10.7, J1Ј,2Јa = 5.5 Hz, 1 H, H-1Ј), 5.66 (dddd,
=
1.5 Hz, 1 H, H-8-C12H7SO), 7.20 (t, J2,1 = J2,3 = 7.6 Hz, 1 H, H- J3Ј,2Јb = 6.1, J3Ј,4Ј = 2.1, J3Ј,2Јa = 1.5, J3Ј,1Ј = 0.6 Hz, 1 H, H-3Ј),
2-C12H7SO), 7.23 (dd, J3,2 = 7.7, J3,1 = 2.0 Hz, 1 H, H-3-C12H7SO),
7.23 (d, J4,3 = 3.3 Hz, 1 H, H-4), 7.27 (ddd, J7,6 = 8.3, J7,8 = 7.3,
J7,9 = 1.5 Hz, 1 H, H-7-C12H7SO), 7.32–7.35 (m, 2 H, H-6,9-
C12H7SO), 7.63 (dd, J1,2 = 7.5, J1,3 = 2.0 Hz, 1 H, H-1-C12H7SO)
6.39 (dd, J4,3 = 3.3, J4,5 = 1.8 Hz, 1 H, H-4), 6.46 (ddd, J3,4 = 3.2,
J3,5 = 0.9, J3,1Ј = 0.5 Hz, 1 H, H-3), 7.33 and 7.35 (2ϫm, 2ϫ2 H,
H-o-Tol), 7.52 (dd, J5,4 = 1.8, J5,3 = 0.9 Hz, 1 H, H-5), 7.96–8.00
(m, 4 H, H-o-Tol) ppm. 13C NMR (125.7 MHz, [D6]acetone): δ =
ppm. 13C NMR (125.7 MHz, [D6]DMSO): δ = 39.04 (CH2-2Ј), 21.57 and 21.58 (CH3-Tol), 37.64 (CH2-2Ј), 65.33 (CH2-5Ј), 74.55
62.56 (CH2-5Ј), 72.16 (CH-3Ј), 72.38 (CH-1Ј), 87.88 (CH-4Ј), (CH-1Ј), 77.73 (CH-3Ј), 83.44 (CH-4Ј), 108.90 (CH-3), 111.16 (CH-
110.31 (CH-3), 112.25 (CH-4), 118.45 (CH-6-C12H7SO), 119.97 (C- 4), 128.25 and 128.36 (C-i-Tol), 130.04 and 130.07 (CH-o-Tol),
9a-C12H7SO), 120.27 (C-10a-C12H7SO), 121.03 (C-4-C12H7SO),
124.49 (CH-1-C12H7SO), 125.31 (CH-2-C12H7SO), 125.79 (CH-8-
130.43 and 130.47 (CH-o-Tol), 143.71 (CH-5), 144.68 and 144.93
(C-p-Tol), 154.00 (C-2), 166.44 and 166.58 (CO) ppm. IR (CCl4):
˜
C
12H7SO), 126.09 (CH-3-C12H7SO), 127.33 (CH-9-C12H7SO),
ν = 2926, 1725, 1613, 1269, 1178, 1104 cm–1.
128.64 (CH-7-C12H7SO), 147.27 (C-4a-C12H7SO), 147.52 (C-5),
1β-[5-(Pyren-1-yl)furan-2-yl]-1,2-dideoxy-3,5-di-O-toluoyl-D-ribofur-
151.62 (C-5a-C H SO), 154.36 (C-2) ppm. IR (KBr): ν = 3401,
˜
12
7
anose (6m): A solution of 8 (350 mg, 0.64 mmol), 1-bromopyrene
(198 mg, 0.7 mmol), K2CO3 (354 mg, 2.56 mmol), and [PdCl2dppf]
(24 mg, 0.03 mmol) in anhydrous DMF (10 mL) under argon was
-ri- stirred at 105 °C for 19 h. The mixture was diluted with satd. aque-
ous NaHCO3 (50 mL) and extracted with EtOAc (3ϫ10 mL) and
washed with satd. aqueous NaCl (50 mL). The collected organic
layers were dried with MgSO4, and solvents were evaporated under
vacuum. Products were isolated by column chromatography on sil-
1715, 1454, 1435, 1223, 1027, 780, 752 cm–1. [α]2D0 = +7.4 (c = 0.20,
MeOH).
1β-[5-(Pinacolatoboryl)furan-2-yl]-1,2-dideoxy-3,5-di-O-toluoyl-
D
bofuranose (8). Method A: A solution of 3 (1.42 g, 2.84 mmol) in
anhydrous dioxane (10 mL) under argon was added dropwise in
five portions (each portion: 2 mL/3.5 min then 2 min pause) to a
stirred solution of bis(pinacolato)diboron (2.9 g, 11.4 mmol),
AcOK (1.67 g, 17 mmol) and [PdCl2dppf] (312 mg, 0.43 mmol) un- ica gel, eluent gradient from hexane to hexane/EtOAc (19.5:0.5) to
der argon in anhydrous dioxane (11 mL) at 105 °C. The mixture
was then stirred at 105 °C for 40 min. The crude reaction mixture
was filtered through Celite, diluted with EtOAc (20 mL) and sol-
vents were evaporated under vacuum. The crude product was puri-
fied by chromatography on silica gel, eluent gradient from hexane
to hexane/EtOAc (9.7:0.3) to give the desired product 8 (1.06 g,
68%), followed by 9 (0.20 g, 17%) as colorless oils.
give 6m (310 mg, 78%) as a yellow oil. HRMS (ESI): calcd. for
C
(500 MHz, [D6]acetone): δ = 2.10 and 2.43 (2ϫs, 2 ϫ3 H, CH3-
Tol), 2.66 (ddd, Jgem = 13.8, J2Јa,1Ј = 5.4, J2Јa,3Ј = 1.4 Hz, 1 H, H-
2Јa), 2.95 (ddd, Jgem = 13.8, J2Јb,1Ј = 10.6, J2Јb,3Ј = 6.0 Hz, 1 H, H-
2Јb), 4.58 (br. ddd, J4Ј,5Јb = 4.4, J4Ј,5Јa = 3.9, J4Ј,3Ј = 2.1 Hz, 1 H,
41H32O6Na [M + Na] 643.2091; found 643.2091. 1H NMR
H-4Ј), 4.63 (m, 2 H, H-5Ј), 5.50 (br. dd, J1Ј,2b = 10.6, J1Ј,2Јa
5.4 Hz, 1 H, H-1Ј), 5.77 (dddd, J3Ј,2Јb = 6.0, J3Ј,4Ј = 2.1, J3Ј,2Јa
=
=
Method B: A solution of 4 (260 mg, 0.62 mmol), bis(pinacolato)-
diboron (188 mg, 0.74 mmol), [IrCl(COD)]2 (21 mg, 0.03 mmol)
and 4,4Ј-di-tert-butyl-2,2Ј-dipyridyl (22 mg, 0.08 mmol) under ar-
gon in anhydrous toluene (7 mL) was stirred at 105 °C for 2 d. The
crude reaction mixture was filtered through Celite, diluted with
EtOAc (20 mL) and the solvents were evaporated under vacuum.
The crude product was purified by chromatography on silica gel,
eluent gradient from hexane to hexane/EtOAc (9.7:0.3) to give the
desired product 8 (130 mg, 39%), followed by 9 (50 mg) as colorless
oils. Compound 8: HRMS (ESI): calcd. for C31H35O8BNa [M +
1.4, J3Ј,1Ј = 0.6 Hz, 1 H, H-3Ј), 6.79 (dd, J3,4 = 3.3, J3,1Ј = 0.4 Hz,
1 H, H-3), 6.96 (m, 2 H, H-o-Tol), 6.99 (d, J4,3 = 3.3 Hz, 1 H, H-
4), 7.37 (m, 2 H, H-o-Tol), 7.89 and 8.03 (2ϫm, 2ϫ2 H, H-o-Tol),
8.09 (t, J7,6 = J7,8 = 7.6 Hz, 1 H, H-7-py), 8.17–8.23 (m, 3 H, H-
4,5,9-py), 8.26–8.28 (m, 2 H, H-2,3-py), 8.27 and 8.31 (2ϫdd, J6,7
= 7.6, J6,8 = 1.2, J8,7 = 7.8, J8,6 = 1.2 Hz, 2 H, H-6,8-py), 8.72 (d,
J10,9 = 9.3 Hz, 1 H, H-10-py) ppm. 13C NMR (125.7 MHz, [D6]-
acetone): δ = 21.30 and 21.61 (CH3-Tol), 37.95 (CH2-2Ј), 65.44
(CH2-5Ј), 74.85 (CH-1Ј), 77.87 (CH-3Ј), 83.65 (CH-4Ј), 119.54 and
111.55 (CH-3, 4), 125.47 (C-10c-py), 125.61 (CH-10-py), 125.87 (C-
10b-py), 125.89, 126.16 and 126.48 (CH-3,6,8-py), 126.49 (C-3a-
py), 127.03 (CH-2-py), 127.29 (CH-7-py), 128.15 (C-i-Tol), 128.29
(CH-4 or 5 or 9-py), 128.29 (C-i-Tol), 128.46 (C-10a-py), 128.75
and 129.23 (CH-4 or 5 or 9-py), 129.80 and 130.10 (CH-o-Tol),
130.29 and 130.51 (CH-o-Tol), 131.82 (C-1-py), 132.05 and 132.44
(C-5a,8a-py), 144.37 and 144.97 (C-p-Tol), 154.45 (C-2), 154.85 (C-
1
Na] 569.2317; found 569.2320. H NMR (500 MHz, [D6]acetone):
δ = 1.31 and 1.32 [2ϫs, 2 ϫ6 H, C(CH3)2], 2.41 and 2.42 (2ϫs,
2ϫ3 H, CH3-Tol), 2.54 (ddd, Jgem = 13.7, J2Јa,1Ј = 5.4, J2Јa,3Ј
1.4 Hz, 1 H, H-2Јa), 2.67 (ddd, Jgem = 13.7, J2Јb,1Ј = 10.7, J2Јb,3Ј
=
=
6.1 Hz, 1 H, H-2Јb), 4.49 (td, J4Ј,5Јa = J4Ј,5Јb = 4.3, J4Ј,3Ј = 2.2 Hz,
1 H, H-4Ј), 4.51 (dd, Jgem = 11.1, J5Јa,4Ј = 4.4 Hz, 1 H, H-5Јa), 4.58
(dd, Jgem = 11.1, J5Јb,4Ј = 4.1 Hz, 1 H, H-5Јb), 5.33 (br. dd, J1Ј,2b
10.8, J1Ј,2Јa = 5.4 Hz, 1 H, H-1Ј), 5.65 (dddd, J3Ј,2Јb = 6.1, J3Ј,4Ј
=
=
5), 166.53 and 166.66 (CO) ppm. IR (KBr): ν = 3430, 1719, 1612,
˜
1271, 1177, 1104, 752 cm–1.
2.1, J3Ј,2Јa = 1.4, J3Ј,1Ј = 0.5 Hz, 1 H, H-3Ј), 6.51 (dd, J3,4 = 3.3,
J3,1Ј = 0.5 Hz, 1 H, H-3), 6.99 (br. d, J4,3 = 3.3 Hz, 1 H, H-4), 7.34
and 7.35 (2ϫm, 2ϫ2 H, H-o-Tol), 7.97 and 7.99 (2ϫm, 2ϫ2 H,
1β-[5-(Pyren-1-yl)furan-2-yl]-1,2-dideoxy-
D-ribofuranose (7m): Pre-
pared from 6m (280 mg, 0.45 mmol) by the general procedure de-
5440
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 5432–5443

Deoxyribonucleoside Analogues
scribed for the Zemplén deprotection. Careful reverse-phase flash
chromatography (H2O/MeOH) afforded 7m (92 mg, 53 %) as an
orange powder; m.p. 166–170 °C. HRMS (ESI): calcd. for
pling products 11a (8%) and 11c (13%). The crude mixture was
used for the next deprotection step. Compound 11b (spectra re-
corded from the mixture): HRMS (ESI): calcd. for C50H46O11NaS
C25H20O4Na [M + Na] 407.1254; found 407.1254. 1H NMR [M + Na] 877.2653; found 877.2655. 1H NMR (500 MHz, [D6]-
(500 MHz, [D6]DMSO): δ = 2.13 (ddd, Jgem = 12.8, J2Јa,1Ј = 5.9, acetone, assignment of sugar signals for furan part A and thio-
J2Јa,3Ј = 2.1 Hz, 1 H, H-2Јa), 2.37 (ddd, Jgem = 12.8, J2Јb,1Ј = 10.0,
phene part B): δ = 2.38, 2.40, 2.42 and 2.43 (4ϫs, 4 ϫ3 H, CH3-
J2Јb,3Ј = 5.7 Hz, 1 H, H-2Јb), 3.48 (m, 2 H, H-5Ј), 3.83 (ddd, J4Ј,5Јa Tol), 2.43 (ddd, Jgem = 13.8, J2Јa,1Ј = 10.7, J2Јa,3Ј = 6.1 Hz, 1 H, B-
= 6.2, J4Ј,5Јb = 5.4, J4Ј,3Ј = 2.4 Hz, 1 H, H-4Ј), 4.31 (m, 1 H, H-3), 2Јa-H), 2.53 (ddd, Jgem = 13.8, J2Јa,1Ј = 5.4, J2Јa,3Ј = 1.4 Hz, 1 H,
4.80 (m, 1 H, OH-5Ј), 5.17 (m, 1 H, OH-3Ј), 5.20 (dd, J1Ј,2b = 10.0, A-2Јa-H), 2.67 (ddd, Jgem = 13.8, J2Јb,1Ј = 5.2, J2Јb,3Ј = 1.4 Hz, 1
J1Ј,2Јa = 5.9 Hz, 1 H, H-1Ј), 6.73 (d, J4,3 = 3.3 Hz, 1 H, H-4), 7.09
(d, J3,4 = 3.3 Hz, 1 H, H-3), 8.11 (t, J7,6 = J7,8 = 7.6 Hz, 1 H, H-
7-py), 8.19–8.24 (m, 2 H, H-4,5-py), 8.26 (d, J9,10 = 9.4 Hz, 1 H,
H, B-2Јb-H), 2.73 (ddd, Jgem = 13.8, J2Јb,1Ј = 10.7, J2Јb,3Ј = 6.0 Hz,
1 H, A-2Јb-H), 4.48–3.54 (m, 2 H, A,B-4Ј-H), 4.54–4.68 (m, 2ϫ2
H, A,B-5Ј-H), 5.30 (dd, J1Ј,2b = 10.7, J1Ј,2Јa = 5.3 Hz, 1 H, A-1Ј-
H-9-py), 8.28–8.37 (m, 4 H, H-2,3,6,8-py), 8.75 (d, J10,9 = 9.4 Hz, H), 5.53 (br. dd, J1Ј,2a = 10.7, J1Ј,2Јb = 5.2 Hz, 1 H, B-1Ј-H), 5.68
1 H, H-10-py) ppm. 13C NMR (125.7 MHz, [D6]DMSO): δ = 39.02 (br. dt, J3Ј,2Јa = 6.1, J3Ј,2Јb = J3Ј,4Ј = 1.8 Hz, 1 H, B-3Ј-H), 5.70 (br.
(CH2-2Ј), 62.66 (CH2-5Ј), 72.23 (CH-3Ј), 72.55 (CH-1Ј), 87.86 dt, J3Ј,2Јb = 6.0, J3Ј,2Јa = J3Ј,4Ј = 1.8 Hz, 1 H, A-3Ј-H), 6.50 (d, J4,3
(CH-4Ј), 110.14 (CH-3), 111.12 (CH-4), 121.14 (C-10c-py), 124.59
(C-10b-py), 124.66 (CH-10-py), 125.14 (C-3a-py), 125.40, 125.42,
= 3.4 Hz, 1 H, furyl-4-H), 6.53 (d, J3,4 = 3.3 Hz, 1 H, furyl-3-H),
7.04 (dd, J3,4 = 3.7, J3,1Ј = 0.8 Hz, 1 H, thienyl-3-H), 7.06 (d, J4,3
125.89 and 125.91 (CH-2,3,6,8-py), 126.61 (C-10a-py), 126.78 (CH- = 3.6 Hz, 1 H, thienyl-4-H), 7.29–7.38 (m, 8 H, H-o-Tol), 7.95–8.01
7-py), 127.53 and 127.93 (CH-4,5-py), 128.51 (CH-9-py), 130.50
(m, 8 H, H-o-Tol) ppm. 13C NMR (125.7 MHz, [D6]acetone): δ =
(C-1-py), 130.64 and 131.20 (C-5a,8a-py), 152.89 (C-5), 155.15 (C- 21.60, 21.61 and 21.63 (CH3-Tol), 37.78 (CH2-2Ј-A), 42.49 (CH2-
2) ppm. IR (KBr): ν = 3427, 1635, 1626, 1079, 1020, 843 cm–1.
2Ј-B), 65.26 (CH2-5Ј-A, B), 74.54 (CH-1Ј-A), 77.57 (CH-1Ј-B),
77.70 (CH-3Ј-A), 77.99 (CH-3Ј-B), 83.58 and 83.94 (CH-4Ј-A, B),
106.62 (CH-4-furyl), 111.13 (CH-3-furyl), 123.23 (CH-4-thienyl),
126.26 (CH-3-thienyl), 128.22, 128.24, 128.32 and 128.33 (C-i-Tol),
130.05, 130.07, 130.08 and 130.10 (CH-o-Tol), 130.44, 130.47 and
130.49 (CH-o-Tol), 133.60 (C-5-thienyl), 144.68, 144.71, 144.90,
144.96 and 144.98 (C-p-Tol, C-2-thienyl), 150.13 (C-5-furyl), 153.33
(C-2-furyl), 166.45, 166.47, 166.55 and 166.59 (CO) ppm. IR
˜
[α]2D0 = –5.0 (c = 0.38, DMSO).
1β,1Јβ-(2,2Ј-Bifuran-5,5Ј-diyl)-bis(1,2-dideoxy-3,5-di-O-toluoyl-D-ri-
bofuranose) (11a): A solution of 8 (330 mg, 0.60 mmol), 3 (332 mg,
0.66 mmol), K2CO3 (334 mg, 2.4 mmol), and [PdCl2dppf] (22 mg,
0.03 mmol) in anhydrous DMF (10 mL) under argon was stirred at
105 °C for 17 h. The mixture was diluted with satd. aqueous
NaHCO3 (50 mL), extracted with EtOAc (3ϫ10 mL) and washed
with satd. aqueous NaCl (50 mL). The collected organic layers were
dried with MgSO4 and solvents were evaporated under vacuum.
Products were isolated by column chromatography on silica gel,
eluent gradient from hexane to hexane/EtOAc (19.5:0.5) to give the
desired product 11a (453 mg, 90%) as a colorless oil. HRMS (ESI):
(KBr): ν = 3429, 1719, 1612, 1271, 1104, 752 cm–1.
˜
1β,1Јβ-(2,2Ј-Bifuran-5,5Ј-diyl)bis(1,2-dideoxy-D-ribofuranose) (12a):
Prepared from 11a (435 mg, 0.52 mmol) by the general procedure
described for Zemplén deprotection. 12a (173 mg, 91%) was ob-
tained as a white powder, which was crystallized from 2-propanol/
calcd. for C50H46O12Na [M + Na] 861.2881; found 861.2887. 1H heptane to give white crystals; m.p. 145–147 °C. HRMS (ESI):
NMR (500 MHz, [D6]acetone): δ = 2.40 and 2.42 (2ϫs, 2 ϫ6 H, calcd. for C18H22O8Na [M + Na] 389.1207; found 389.1205. 1H
CH3-Tol), 2.53 (ddd, Jgem = 13.8, J2Јa,1Ј = 5.5, J2Јa,3Ј = 1.4 Hz, 2 H, NMR (500 MHz, [D6]DMSO): δ = 2.00 (ddd, Jgem = 12.8, J2Јa,1Ј
=
H-2Јa), 2.75 (ddd, Jgem = 13.8, J2Јb,1Ј = 10.6, J2Јb,3Ј = 6.0 Hz, 2 H,
H-2Јb), 4.50 (td, J4Ј,5Јa = J4Ј,5Јb = 4.4, J4Ј,3Ј = 1.9 Hz, 2 H, H-4Ј),
5.8, J2Јa,3Ј = 2.1 Hz, 2ϫ1 H, 2Јa-H), 2.19 (ddd, Jgem = 12.8, J2Јb,1Ј
= 10.1, J2Јb,3Ј = 5.9 Hz, 2ϫ1 H, 2Јb-H), 3.38 (m, 2ϫ2 H, 5Ј-H),
4.52 (dd, Jgem = 11.2, J5Јa,4Ј = 4.4 Hz, 2 H, H-5Јa), 4.60 (dd, Jgem 3.73 (td, J4Ј,5Јa = J4Ј,5Јb = 5.7, J4Ј,3Ј = 2.6 Hz, 2ϫ1 H, 4Ј-H), 4.20
= 11.2, J5Јb,4Ј = 4.3 Hz, 2 H, H-5Јb), 5.31 (br. dd, J1Ј,2b = 10.5,
J1Ј,2Јa = 5.4 Hz, 2 H, H-1Ј), 5.72 (br. dtd, J3Ј,2Јb = 6.0, J3Ј,2Јa = J3Ј,4Ј
= 1.7, J3Ј,1Ј = 0.5 Hz, 2 H, H-3Ј), 6.40 (d, J4,3 = 3.3 Hz, 2 H, H-4),
6.53 (dd, J3,4 = 3.3, J3,1Ј = 0.4 Hz, 2 H, H-3), 7.31 and 7.35 (2ϫm,
2ϫ4 H, H-o-Tol), 7.97 and 7.99 (2ϫm, 2ϫ4 H, H-o-Tol) ppm.
13C NMR (125.7 MHz, [D6]acetone): δ = 21.59 (CH3-Tol), 37.74
(br. dt, J3Ј,2Јb = 5.9, J3Ј,2Јa = J3Ј,4Ј = 2.3 Hz, 2ϫ1 H, 3Ј-H), 4.73
(br. s, 2ϫ1 H, OH-5Ј-H), 5.01 (dd, J1Ј,2b = 10.0, J1Ј,2Јa = 5.9 Hz,
2ϫ1 H, 1Ј-H), 5.10 (br. s, 2ϫ1 H, OH-3Ј-H), 6.51 (br. d, J3,4
=
3.4 Hz, 2ϫ1 H, 3-H), 6.59 (d, J4,3 = 3.3 Hz, 2ϫ1 H, 4-H) ppm.
13C NMR (125.7 MHz, [D6]DMSO): δ = 38.96 (CH2-2Ј), 62.45
(CH2-5Ј), 72.02 (CH-3Ј), 72.23 (CH-1Ј), 87.88 (CH-4Ј), 106.32
(CH2-2Ј), 65.28 (CH2-5Ј), 74.51 (CH-1Ј), 77.73 (CH-3Ј), 83.54 (CH-4), 109.41 (CH-3), 145.23 (C-5), 154.18 (C-2) ppm. IR (KBr):
(CH-4Ј), 106.88 (CH-4), 110.74 (CH-3), 128.25 and 128.32 (C-i- ν = 3392, 2894, 1635, 1335, 1035, 857 cm–1. C H O (366.4): C
˜
18 22
8
Tol), 130.08 and 130.09 (CH-o-Tol), 130.44 and 130.49 (CH-o-Tol),
144.71 and 144.95 (C-p-Tol), 147.02 (C-5), 153.71 (C-2), 166.45 and DMSO).
59.01, H 6.05; found C 59.18, H 6.26. [α]2D0 = –16.7 (c = 0.29,
166.56 (CO) ppm. IR (KBr): ν = 2925, 1725, 1613, 1269, 1178,
˜
1β,1Јβ-(2,2Ј-Thienylfuran-5,5Ј-diyl)bis(1,2-dideoxy-D-ribofuranose)
1103, 840 cm–1.
(12b): Prepared from the crude mixture 11b/11a/11c (240 mg) by
the general procedure described for the Zemplén deprotection.
Careful reverse-phase flash chromatography (H2O/MeOH) af-
forded pure 12b (60 mg, 54% overall yield from 8, ca. 71% yield
for the deprotection step) as a white powder, which was recrys-
tallized from 2-propanol/heptane to give white crystals; m.p. 133–
136 °C. HRMS (ESI): calcd. for C18H22O7SNa [M + Na] 405.0978;
1β,1Јβ-(2,2Ј-Thienylfuran-5,5Ј-diyl)bis(1,2-dideoxy-3,5-di-O-toluoyl-
D
-ribofuranose) (11b): A solution of 8 (170 mg, 0.31 mmol), 10
(176 mg, 0.34 mmol), K2 CO3 (172 mg, 1.24 mmol), and
[PdCl2dppf] (12 mg, 0.02 mmol) in anhydrous DMF (10 mL) under
argon was stirred at 105 °C for 17 h. The mixture was diluted with
satd. aqueous NaHCO3 (50 mL), extracted with EtOAc
(3ϫ10 mL) and washed with satd. aqueous NaCl (50 mL). The found 405.0977. 1H NMR (500 MHz, [D6]DMSO, assignment of
collected organic layers were dried with MgSO4 and the solvents
were evaporated under vacuum. Products were isolated by column
chromatography on silica gel, eluent gradient from hexane to hex-
ane/EtOAc (19.5:0.5) to give an inseparable mixture of the desired
product 11b (76% by NMR analysis) accompanied by homo-cou-
sugar signals for furan part A and thiophene part B): δ = 1.93
(ddd, Jgem = 12.8, J2Јa,1Ј = 10.1, J2Јa,3Ј = 5.6 Hz, 1 H, B-2Јa-H),
2.00 (ddd, Jgem = 12.8, J2Јa,1Ј = 5.9, J2Јa,3Ј = 2.1 Hz, 1 H, A-2Јa-H),
2.13 (ddd, Jgem = 12.8, J2Јb,1Ј = 5.5, J2Јb,3Ј = 1.8 Hz, 1 H, B-2Јb-H),
2.19 (ddd, Jgem = 12.8, J2Јb,1Ј = 10.0, J2Јb,3Ј = 5.8 Hz, 1 H, A-2Јb-
Eur. J. Org. Chem. 2010, 5432–5443
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5441

J. Bárta, L. Slaveˇtínská, B. Klepetárˇová, M. Hocek
FULL PAPER
H), 3.34–3.47 (2ϫm, 2ϫ2 H, A-5Ј-H, B), 3.73 (br. td, J4Ј,5Јa
J4Ј,5Јb = 5.7, J4Ј,3Ј = 2.5 Hz, 1 H, A or B-4Ј-H), 3.76 (ddd, J4Ј,5Јa
=
=
Acknowledgments
6.1, J4Ј,5Јb = 5.0, J4Ј,3Ј = 2.2 Hz, 1 H, A or B-4Ј-H), 4.18–4.22 (m, 2
H, A,B-3Ј-H), 4.76 and 4.77 (2ϫt, JOH,5Јa = JOH,5Јb = 5.7, JOH,5Јa
JOH,5Јb = 5.6 Hz, 2ϫ1 H, A,B-5Ј-OH), 4.99 (dd, J1Ј,2b = 10.0, J1Ј,2Јa
This work was supported by the Academy of Sciences of the Czech
Republic (Z4 055 905), by the Ministry of Education (LC 512), by
the Grant Agency of the ASCR (IAA400550902) and by Gilead
Sciences, Inc.
=
= 5.9 Hz, 1 H, A-1Ј-H), 5.09 and 5.12 (2ϫs, JOH,3Ј = 4.1, JOH,3Ј
3.9 Hz, 2ϫ1 H, A, B-3Ј-OH), 5.23 (br. dd, J1Ј,2a = 10.1, J1Ј,2Јb
=
=
5.5 Hz, 1 H, B-1Ј-H), 6.49 (br. d, J3,4 = 3.3 Hz, 1 H, furyl-3-H),
6.62 (d, J4,3 = 3.3 Hz, 1 H, furyl-4-H), 7.01 (dd, J3,4 = 3.7, J3,1Ј
ˇ
[1] For reviews, see: a) J. Stambaský, M. Hocek, P. Kocˇovský,
=
Chem. Rev. 2009, 109, 6729–6764; b) M. F. A. Adamo, R. Per-
goli, Curr. Org. Chem. 2008, 12, 1544–1569; c) Q. P. Wu, C.
Simons, Synthesis 2004, 1533–1553.
0.9 Hz, 1 H, thienyl-3-H), 7.16 (d, J4,3 = 3.6 Hz, 1 H, thienyl-4-H)
ppm. 13C NMR (125.7 MHz, [D6]DMSO): δ = 38.87 (CH2-2Ј-A),
43.71 (CH2-2Ј-B), 62.49 and 62.62 (CH2-5Ј-A, B), 72.04, 72.24 and
72.51 (CH-1Ј-A, CH-3Ј-A, B), 75.34 (CH-1Ј-B), 87.83 (CH-4Ј-A),
88.03 (CH-4Ј-B), 105.98 (CH-4-furyl), 109.86 (CH-3-furyl), 122.43
(CH-4-thienyl), 125.38 (CH-3-thienyl), 131.89 (C-5-thienyl), 145.56
(C-2-thienyl), 148.48 (C-5-furyl), 153.72 (C-2-furyl) ppm. IR
[2] For reviews, see: a) L. Wang, P. G. Schultz, Chem. Commun.
2002, 1–11; b) A. A. Henry, F. E. Romesberg, Curr. Opin.
Chem. Biol. 2003, 7, 727–733; c) E. T. Kool, J. C. Morales,
K. M. Guckian, Angew. Chem. Int. Ed. 2000, 39, 990–1009; d)
E. T. Kool, Acc. Chem. Res. 2002, 35, 936–943.
[3] a) A. K. Ogawa, O. K. Abou-Zied, V. Tsui, R. Jimenez, D. A.
Case, F. E. Romesberg, J. Am. Chem. Soc. 2000, 122, 9917–
9920; b) Y. Q. Wu, A. K. Ogawa, M. Berger, D. L. Mcminn,
P. G. Schultz, F. E. Romesberg, J. Am. Chem. Soc. 2000, 122,
7621–7632; c) K. M. Guckian, T. R. Krugh, E. T. Kool, J. Am.
Chem. Soc. 2000, 122, 6841–6847; d) J. Parsch, J. W. Engels, J.
Am. Chem. Soc. 2002, 124, 5664–5672; e) J. S. Lai, J. Qu, E. T.
Kool, Angew. Chem. Int. Ed. 2003, 42, 5973–5977; f) J. S. Lai,
E. T. Kool, J. Am. Chem. Soc. 2004, 126, 3040–3041.
[4] a) A. A. Henry, A. G. Olsen, S. Matsuda, C. Yu, B. H. Geier-
stanger, F. E. Romesberg, J. Am. Chem. Soc. 2004, 126, 6923–
6931; b) A. A. Henry, C. Z. Yu, F. E. Romesberg, J. Am. Chem.
Soc. 2003, 125, 9638–9646; c) G. T. Hwang, F. E. Romesberg,
Nucleic Acids Res. 2006, 34, 2037–2045; d) S. Matsuda, A. A.
Henry, F. E. Romesberg, J. Am. Chem. Soc. 2006, 128, 6369–
6375; e) Y. Kim, A. M. Leconte, Y. Hari, F. E. Romesberg, An-
gew. Chem. Int. Ed. 2006, 45, 7809–7812; f) S. Matsuda, J. D.
Fillo, A. A. Henry, P. Rai, S. J. Wilkens, T. J. Dwyer, B. H. Gei-
erstanger, D. E. Wemmer, P. G. Schultz, G. Spraggon, F. E. Ro-
mesberg, J. Am. Chem. Soc. 2007, 129, 10466–10473; g) S. Mat-
suda, A. M. Leconte, F. E. Romesberg, J. Am. Chem. Soc.
2007, 129, 5551–5557; h) Y. Hari, G. T. Hwang, A. M. Leconte,
N. Joubert, M. Hocek, F. E. Romesberg, ChemBioChem 2008,
9, 2796–2799.
(KBr): ν = 3388, 2905, 2505, 1628, 1067, 787 cm–1. C H O S
˜
18 22
7
(382.4): C 56.53, H 5.80, S 8.38; found C 56.84, H 5.96, S 8.78.
[α]2D0 = –15.1 (c = 0.27, DMSO).
UV/Vis and Fluorescence Spectroscopy: UV/Vis spectra were mea-
sured with a Varian CARY 100 Bio Spectrophotometer (ε is the
molar extinction coefficient in Lmol–1 cm–1) in MeOH. The fluo-
rescence measurements (in MeOH) were performed with a spectro-
fluorometer Aminco Bowman series 2 with 220–850 nm range, xe-
non source, excitation and emission wavelength scans, spectral
bandwidth 1–16 nm, PMT detector, scan rate 3–6000 nm/min,
Saya-Namioka grating monochromator. We used the comparative
method of Williams et al.[24] to record the fluorescence quantum
yield of a sample ΦSA [a 10 m solution of quinine sulfate in 0.1 
H2SO4 (in H2O) was chosen as a standard: ΦST = 0.54]. Thus, the
fluorescence quantum yield of a sample ΦSA was calculated by the
formula given in Equation (1), where the subscripts ST and SA
denote standard and sample, respectively, Φ is the fluorescent
quantum yield, IFI the integrated fluorescence intensity, Grad the
gradient from the plot of IFI vs. absorbance A, and η the refractive
index of the solvent.
[5] a) A. M. Leconte, G. T. Hwang, S. Matsuda, P. Capek, Y. Hari,
F. E. Romesberg, J. Am. Chem. Soc. 2008, 130, 2336–2343; b)
Y. J. Seo, F. E. Romesberg, ChemBioChem 2009, 10, 2394–2400.
[6] D. Malyshev, Y. J. Seo, P. Ordoukhanian, F. E. Romesberg, J.
Am. Chem. Soc. 2009, 131, 14620–14621.
[7] a) C. Brotschi, A. Häberli, C. J. Leumann, Angew. Chem. Int.
Ed. 2001, 40, 3012–3014; b) I. Singh, W. Hecker, A. K. Prasad,
V. S. Parmar, O. Seitz, Chem. Commun. 2002, 500–501; c) C.
Beuck, I. Singh, A. Bhattacharya, W. Hecker, V. S. Parmar, O.
Seitz, E. Weinhold, Angew. Chem. Int. Ed. 2003, 42, 3958–3960;
d) C. Brotschi, G. Mathis, C. J. Leumann, Chem. Eur. J. 2005,
11, 1911–1923; e) A. Zahn, C. Brotschi, C. J. Leumann, Chem.
Eur. J. 2005, 11, 2125–2129; f) Z. Johar, A. Zahn, C. J. Leum-
ann, B. Jaun, Chem. Eur. J. 2008, 14, 1080–1086; g) M. Kauf-
mann, M. Gisler, C. J. Leumann, Angew. Chem. Int. Ed. 2009,
48, 3810–3813; h) S. Hainke, O. Seitz, Angew. Chem. Int. Ed.
2009, 48, 8250–8253.
Single-Crystal X-ray Structure Analysis: The diffraction data for
single-crystals of 12a (colorless, 0.04ϫ0.08ϫ0.59 mm) were col-
lected with an Xcalibur X-ray diffractometer with Cu-Kα (λ =
1.54180 Å) at 293 K. The structure was solved by direct methods
with SIR92[25] and refined by full-matrix, least-squares methods
based on F with CRYSTALS.[26] The hydrogen atoms were located
in a difference map; those attached to carbon atoms were reposi-
tioned geometrically and then refined with riding constraints. All
other atoms were refined anisotropically in both cases.
X-ray Crystal Data for 12a: C18H22O8; monoclinic; space group C2;
a = 25.615(5) Å, b = 6.0607(12) Å, c = 5.5592(14) Å, β =
101.12(3)°; V = 846.9(3) Å3; Z = 2; M = 183.18; 5028 reflections
measured, 966 independent reflections. Final R = 0.052, wR =
0.055, GoF = 1.143 for 786 reflections with IϾ2σ(I) and 119 pa-
rameters.
[8] N. A. Grigorenko, C. J. Leumann, Chem. Eur. J. 2009, 15, 639–
645.
[9] a) C. Strässler, N. E. Davis, E. T. Kool, Helv. Chim. Acta 1999,
82, 2160–2171; b) J. Gao, C. Strässler, D. Tahmassebi, E. T.
Kool, J. Am. Chem. Soc. 2002, 124, 11590–11591; c) J. Gao, S.
Watanabe, E. T. Kool, J. Am. Chem. Soc. 2004, 126, 12748–
12749; d) J. N. Wilson, Y. N. Teo, E. T. Kool, J. Am. Chem.
Soc. 2007, 129, 15426–15427; e) A. Cuppoletti, Y. Cho, J. S.
Park, S. Strassler, E. T. Kool, Bioconjugate Chem. 2005, 16,
528–534; f) J. N. Wilson, Y. Cho, S. Tan, A. Cuppoletti, E. T.
Kool, ChemBioChem 2008, 9, 279–285; g) J. N. Wilson, J. Gao,
E. T. Kool, Tetrahedron 2007, 63, 3427–3433.
CCDC-777665 contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_request/cif.
Supporting Information (see also the footnote on the first page of
this article): Copies of NMR spectra.
5442
www.eurjoc.org
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2010, 5432–5443

Deoxyribonucleoside Analogues
[10] a) N. Y. Teo, J. N. Wilson, E. T. Kool, J. Am. Chem. Soc. 2009,
131, 3923–3933; b) N. Dai, Y. N. Teo, E. T. Kool, Chem. Com-
mun. 2010, 46, 1221–1223.
Chem. 1995, 60, 7508–7510; c) J. Takagi, K. Sato, J. F. Hartwig,
T. Ishiyama, N. Miyaura, Tetrahedron Lett. 2002, 43, 5649–
5651; d) T. Ishiyama, K. Ishida, N. Miyaura, Tetrahedron 2001,
57, 9813–9816; e) Y. Deng, C. K. Chang, D. G. Nocera, Angew.
Chem. Int. Ed. 2000, 39, 1066–1068.
[11] For recent examples, see: a) I. Singh, O. Seitz, Org. Lett. 2006,
8, 4319–4322; b) S. Hainke, I. Singh, J. Hemmings, O. Seitz, J.
Org. Chem. 2007, 72, 881–8819; c) P. Redpath, S. Macdonald,
M. E. Migaud, Org. Lett. 2008, 10, 3323–3326; d) M. Spad-
afora, V. Y. Postupalenko, V. V. Shvadchak, A. S. Klymchenko,
Y. Mely, A. Burger, R. Benhida, Tetrahedron 2009, 65, 7809–
7816; e) J. Lu, N.-S. Li, S. C. Koo, J. A. Piccirilli, J. Org. Chem.
2009, 74, 8021–8030.
[21] For reviews, see: a) I. A. I. Mkhalid, J. H. Barnard, T. B.
Marder, J. M. Murphy, J. F. Hartwig, Chem. Rev. 2010, 110,
890–931. Examples: b) J. Y. Cho, M. K. Tse, D. Holmes, R. E.
Maleczka, M. R. Smith III, Science 2002, 295, 305–308; c) T.
Ishiyama, J. Takagi, J. F. Hartwig, N. Miyaura, Angew. Chem.
Int. Ed. 2002, 41, 3056–3058; d) T. Ishiyama, Y. Nobuta, J. F.
Hartwig, N. Miyaura, Chem. Commun. 2003, 2924–2925; e)
T. M. Boller, J. M. Murphy, M. Hapke, T. Ishiyama, N. Mi-
yaura, J. F. Hartwig, J. Am. Chem. Soc. 2005, 127, 14263–
14278; f) G. A. Chotana, M. A. Rak, M. R. Smith III, J. Am.
Chem. Soc. 2005, 127, 10539–10544; g) S. Paul, G. A. Chotana,
D. Holmes, R. C. Reichle, R. E. Maleczka, M. R. Smith III, J.
Am. Chem. Soc. 2006, 128, 15552–15553; h) M. Klecˇka, R.
Pohl, B. Klepetárˇová, M. Hocek, Org. Biomol. Chem. 2009, 7,
866–868.
[22] For previous examples of covalent base-pair and nucleoside-
pair analogues, see: a) B. Bhat, N. J. Leonard, H. Robinson,
A. H. J. Wang, J. Am. Chem. Soc. 1996, 118, 10744–10751; b)
X. Quiao, Y. Kishi, Angew. Chem. Int. Ed. 1999, 38, 928–931;
c) H. Y. Li, Y. L. Qiu, E. Moyroud, Y. Kishi, Angew. Chem.
Int. Ed. 2001, 40, 1471–1475; d) F. Nagatsugi, K. Uemura, S.
Nakashima, M. Maeda, S. Sasaki, Tetrahedron 1997, 53, 3035–
3044; e) F. Nagatsugi, T. Kawasaki, D. Usui, M. Maeda, S.
Sasaki, J. Am. Chem. Soc. 1999, 121, 6753–6754; f) M. Hocek,
H. Dvorˇáková, I. Císarˇová, Collect. Czech. Chem. Commun.
2002, 67, 1560–1578; g) M. Havelková, D. Dvorˇák, M. Hocek,
Tetrahedron 2002, 58, 7431–7435.
[12] a) M. Hocek, R. Pohl, B. Klepetárˇová, Eur. J. Org. Chem. 2005,
ˇ
4525–4528; b) M. Stefko, R. Pohl, B. Klepetárˇová, M. Hocek,
Eur. J. Org. Chem. 2008, 1689–1704; c) N. Joubert, M. Urban,
R. Pohl, M. Hocek, Synthesis 2008, 1918–1932; d) M. Urban,
R. Pohl, B. Klepetárˇová, M. Hocek, J. Org. Chem. 2006, 71,
7322–7328; e) N. Joubert, R. Pohl, B. Klepetárˇová, M. Hocek,
ˇ
J. Org. Chem. 2007, 72, 6797–6805; f) M. Stefko, R. Pohl, M.
ˇ
Hocek, Tetrahedron 2009, 65, 4471–4483; g) M. Stefko, L. Slav-
eˇtínská, B. Klepetárˇová, M. Hocek, J. Org. Chem. 2010, 75,
442–449; h) T. Kubelka, L. Slaveˇtínská, B. Klepetárˇová, M.
Hocek, Eur. J. Org. Chem. 2010, 2666–2669.
[13] J. Bárta, R. Pohl, B. Klepetárˇová, N. P. Ernsting, M. Hocek, J.
Org. Chem. 2008, 73, 3798–3806.
[14] A. Cappellacci, S. Marchetti, C. Martini, B. Costa, K. Varani,
P. A. Borea, M. Grifantini, P. Franchetti, Bioorg. Med. Chem.
2000, 8, 2367–2373.
[15] a) A. Astarita, M. R. Iesce, L. Previtera, F. Cermola, Tetrahe-
dron 2008, 64, 6744–6748; b) M. R. Iesce, G. Buonerba, F. Cer-
mola, J. Org. Chem. 2005, 70, 6503–6505; c) M. Nomura, T.
Tanabe, H. Togo, M. Yokoyama, Heteroat. Chem. 1995, 2, 189–
193.
[16] M. Spadafora, M. Mehiri, A. Burger, R. Benhida, Tetrahedron
Lett. 2008, 49, 3967–3971.
[17] a) T. Tanabe, A. Toyoshima, H. Togo, M. Yokoyama, Synthesis
1993, 517–520; b) A. Toyoshima, T. Akiba, H. Togo, M.
Yokoyama, Chem. Lett. 1994, 265–268.
[23] M. Spadafora, V. Y. Postupalenko, V. V. Shvadchak, A. S.
Klymchenko, Y. Mely, A. Burger, R. Benhida, Tetrahedron
2009, 65, 7809–7816.
[24] A. T. R. Williams, S. A. Winfield, J. N. Miller, Analyst 1983,
108, 1067–1071.
[18] a) M. Yokoyama, T. Akiba, H. Togo, Synthesis 1995, 638–640; [25] A. Altomare, G. Cascarano, G. Giacovazzo, A. Guagliardi,
b) M. Spadafora, A. Burger, R. Benhida, Synlett 2008, 1225–
1229.
[19] M. Berger, S. D. Luzzi, A. A. Henry, F. E. Romesberg, J. Am.
Chem. Soc. 2002, 124, 1222–1226.
[20] For reviews, see: a) E. Tyrrell, P. Brookes, Synthesis 2004, 469–
483. Examples: b) T. Ishiyama, M. Murata, N. Miyaura, J. Org.
M. C. Burla, G. Polidori, M. Camalli, J. Appl. Crystallogr.
1994, 27, 435–435.
[26] P. W. Betteridge, J. R. Carruthers, R. I. Cooper, K. Prout, D. J.
Watkin, J. Appl. Crystallogr. 2003, 36, 1487–1487.
Received: May 20, 2010
Published Online: August 16, 2010
Eur. J. Org. Chem. 2010, 5432–5443
© 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
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