Modular Synthesis of 4-aryl- and 4-amino-substituted benzene C-2′-Deoxyribonucleosides

Article abstract of DOI:10.1055/s-2008-1067038

A modular methodology for the syntheses of various 4-substituted-phenyl C-2′-deoxyribonucleosides has been developed. Coupling of toluoylated halogenose 1 with 4-bromophenylmagnesium bromide afforded the desired bis(toluoyl)-protected 1β-(4-bromophenyl)-1

Full text of DOI:10.1055/s-2008-1067038

1918
PAPER
Modular Synthesis of 4-Aryl- and 4-Amino-Substituted Benzene
C-2¢-Deoxyribonucleosides
4
-Aryl- and 4-Ami
i
no-Sub
c
stituted Be
o
nzene
C
-2'-
D
l
eoxyri
a
bonucleosi
s
de
s
Joubert, Milan Urban, Radek Pohl, Michal Hocek*
Gilead & IOCB Research Center, Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic,
Flemingovo nám. 2, 16610 Prague 6, Czech Republic
Fax +420(2)20183559; E-mail: hocek@uochb.cas.cz
Received 7 February 2008; revised 13 March 2008
goaryl C-nucleosides have been used by Kool et al.9 for
Abstract: A modular methodology for the syntheses of various 4-
the construction of fluorescent oligonucleotide probes.
There are several synthetic approaches10 to C-nucleo-
substituted-phenyl C-2¢-deoxyribonucleosides has been developed.
Coupling of toluoylated halogenose 1 with 4-bromophenylmagne-
sium bromide afforded the desired bis(toluoyl)-protected 1b-(4-
bromophenyl)-1,2-dideoxyribofuranose 2a, which was deprotected
under Zemplen conditions to give the unprotected 1b-(4-bromophe-
nyl)-1,2-dideoxyribofuranose 3, and reprotected to give the bis(tert-
butyldimethylsilyl)-protected 1b-(4-bromophenyl)-1,2-dideoxyri-
bofuranose 4. Alternatively, addition of 1-lithio-4-bromobenzene
on tert-butyldimethylsilyl-protected lactone 5, followed by reduc-
tion of the hemiketal 6, also gave bis(tert-butyldimethylsilyl)-pro-
tected bromophenyl nucleoside 4. Intermediates 2a and 4 were then
subjected to a series of palladium-catalyzed cross-coupling reac-
tions, aminations, and C–H activation to give 1b-[4-(aryl-, alkyl-, or
amino)phenyl]-1,2-dideoxyribofuranoses 8a–n after deprotection.
Finally, other types of 4-arylphenyl C-nucleosides 8o–u were pre-
pared directly by aqueous-phase Suzuki cross-coupling reactions of
unprotected 3 with boronic acids under microwave irradiation.
sides: (i) the addition of organometallics to 2-
deoxyribonolactones3,11 or 1,2-anhydro sugars12 (ii) the
coupling of a halogenose with organometallics,13 (iii)
electrophilic substitutions of electron–rich aromatics with
sugars under Lewis acid catalysis14 or (iv) Heck-type cou-
pling of aryl iodides with glycals.15 However, many of
these methods suffer from poor selectivity and low yields
and none of them is truly general. Therefore, the develop-
ment of modular approaches for the synthesis of these im-
portant compounds still remains a challenging target.
We are currently involved in the development of modular
methodologies based on larger scale syntheses of versatile
haloaryl C-nucleoside intermediates and their further use
for the generation of a series of diverse derivatives. In a
previous preliminary communication, we described a
modular approach for the synthesis of few examples of 3-
and 4-substituted-phenyl C-2¢-deoxyribonucleosides by
the preparation of the bromo derivative followed by dis-
placement of the bromine by alkyl or aryl substituents us-
ing cross-coupling reactions.16 Analogous methodology
has been successfully applied in the synthesis of 6-substi-
tuted-2-pyridyl C-2¢-deoxyribonucleosides,17 6-substitut-
ed-3-pyridyl C-2¢-deoxyribonucleosides,18 and 5-
substituted-2-thienyl C-2¢-deoxyribonucleosides,19 and
also for the synthesis of diverse 3- and 4-substituted-phe-
nyl C-ribonucleosides.20 Independently, Leumann21 used
the same strategy to prepare a small series of biaryl C-nu-
cleosides via the synthesis of a silylated bromophenyl C-
nucleoside, de- or reprotection followed by the Suzuki–
Miyaura cross-coupling. Here we wish to report a detailed
full paper that gives many more examples of cross-cou-
plings, extends the methodology to palladium-catalyzed
aminations and C–H activation, compares two different
approaches to the bromophenyl nucleoside intermediates,
and compares cross-couplings of protected versus depro-
tected nucleosides.
Key words: nucleosides, C-nucleosides, cross-coupling reactions,
amination reactions, benzenes
C-Nucleosides bearing hydrophobic aryl groups as an un-
natural nucleobase have attracted great attention due to
their use in the extension of the genetic alphabet.1 In DNA
duplexes, they often form selective pairs due to increased
stacking and favorable desolvation energy compared to
natural hydrophilic nucleobases.2 Triphosphates of some
of C-nucleosides are efficiently incorporated into DNA by
DNA polymerase.3 However, extension of the unnatural
base pairs remains problematic and new analogues that
can improve extension rates are desirable.
Biaryl C-nucleosides are of particular interest because of
their largely extended stacking resulting in the formation
of very stable duplexes.4 Both theoretical calculations5
and experimental (NMR structure) results6 confirmed that
they form a stacked pair within a B-DNA duplex. On the
other hand, incorporation of a bulky biaryl C-nucleoside
into a duplex opposite to a purine or pyrimidine nucleo-
base causes local disruption of the stacking.7 Very
recently, a donor- and acceptor-modified biphenyl C-
nucleoside-containing oligonucleotide was used8 for the
recognition of another hydrophobic modification in the
opposite strand or even of a bulge position. Moreover, oli-
Our selected approach of choice for the synthesis of new
series of 4-substituted-phenyl C-nucleosides was based
on the synthesis of suitably protected or free 4-bromophe-
nyl C-nucleoside intermediates and on their further syn-
thetic transformations (cross-coupling, amination, etc.).
Therefore, our first efforts were devoted to the synthesis
of the corresponding 4-bromophenyl nucleoside interme-
SYNTHESIS 2008, No. 12, pp 1918–1932
x
x.
x
x
.
2
0
0
8
Advanced online publication: 29.04.2008
DOI: 10.1055/s-2008-1067038; Art ID: T02308SS
© Georg Thieme Verlag Stuttgart · New York

PAPER
4-Aryl- and 4-Amino-Substituted Benzene C-2¢-Deoxyribonucleosides
1919
Br
Br
Br
HO
TolO
TolO
MgBr
TolO
NaOMe
O
O
O
Cl
HO
TolO
TolO
TolO
3
2a
1
TFA, PhSO3H
+
O
TBSCl
imidazole
Et3N⋅3HF
or
Tol = toluoyl
2b
Br
Br
Br
Br
TBSO
Et3SiH
BF3⋅OEt2
O
Li
TBSO
TBSO
O
O
O
OH
TBSO
TBSO
TBSO
4
5
6
Scheme 1 Synthesis of the bromo key intermediates 2a, 3, and 4
diates. In our previous communication,16 we described the side 3 in 77% yield (total yield of 18% in three steps from
synthesis of the bis(toluoyl)-protected nucleoside 2a from 5). Although the second strategy afforded 3 in lower yield
the starting halogenose 1,22 which is very easily available in comparison to the first one (32%), both strategies are
in three steps from 2¢-deoxyribose. After optimization, the convenient for a larger scale synthesis of 3. The advantage
coupling with 4-bromophenylmagnesium bromide gave of the former method is the higher yield, but laborious
the desired compound 2a in 12% yield and its anomer 2b repeated epimerizations and separations of epimers are
in 39% yield (Scheme 1). The epimerization of the undes- necessary. On the other hand, the latter method is stereo-
ired a-anomer 2b into the b-anomer 2a was accomplished selective and gives intermediate 4 as the pure b-anomer
by using a mixture of benzenesulfonic acid and trifluoro- after just one chromatographic purification (though in
acetic acid as a reagent in dichloromethane at 40 °C for 24 lower yield).
hours. This gave the b-anomer 2a in a good yield of 56%,
Having practical and scalable procedures for the prepara-
followed by another 22% of the starting a-anomer 2b,
tion of all key intermediates 2a, 3, and 4 in hand, we de-
which was recovered and reused. Thus, the key intermedi-
cided to subject them to various cross-coupling reactions
ate 2a was obtained16 from 1 after coupling and three
and other transformations to prepare a series of new C-
rounds of isomerization with a total yield of 40%. In order
nucleosides.
to test aqueous phase cross-coupling reactions, the unpro-
We first concentrated our efforts on cross-coupling reac-
tions on intermediate 2a with diverse organometallics
(Scheme 2, Table 1). In our previous communication, we
described the reaction of 2a with five different organome-
tected key intermediate 3 was obtained from 2a using
Zemplen conditions in excellent yield (88%, total yield of
35% in two steps from 1). Reprotection of 3 with tert-
butyldimethylsilyl groups was accomplished using tert-
tallics. The Suzuki palladium-catalyzed cross-couplings
butyldimethylsilyl chloride in the presence of imidazole
were performed with 4-fluorophenyl- and 2-naphthyl-
boronic acids (Scheme 2, Table 1, entries 1, 2). Other pal-
ladium-catalyzed cross-couplings involved reactions with
triethylaluminum (entry 3), benzylzinc chloride (entry 4),
and 2-(tributylstannyl)thiophene (entry 5). All these reac-
tions were performed under standard conditions for each
in N,N-dimethylformamide to give 4 in excellent yield
(93%, total yield of 32% in three steps from 1). An alter-
native synthesis was also studied and compared. Recently,
Leumann21 described the synthesis of intermediate 4 in
19% yield by the addition of 1-lithio-4-bromobenzene to
lactone 5 (very easily available in two steps from 2-
type of reaction without any optimization using standard
catalysis of tetrakis(triphenylphosphine)palladium(0). In
all cases the desired 4-substituted-phenyl nucleosides 7a–
e were obtained in good isolated yields of ca. 70%. Now,
we wanted to extend the Stille coupling methodology to
electron-deficient pyridine-type substituents. Therefore,
we performed reactions of 2a with 2-(tributylstannyl)py-
ridine, 2-(tributylstannyl)pyrimidine, and 6-(tributylstan-
nyl)-2,2¢-bipyridine (entries 6–8) in the presence of
deoxyribose23), followed by reduction of the crude
hemiketal 6 in the presence of boron trifluoride–diethyl
ether complex and triethylsilane in dichloromethane at
–78 °C for six hours. Optimization of these conditions
(i.e., reduction at –72 °C for only 2 h, using extra dry sol-
vents, slower addition of the reducing agent and Lewis
acid) allowed us to obtain 4 from 5 in 23% yield.
Desilylation of 4 using triethylamine trihydrofluoride24 in
tetrahydrofuran afforded the free 4-bromophenyl nucleo-
Synthesis 2008, No. 12, 1918–1932 © Thieme Stuttgart · New York

1920
N. Joubert et al.
PAPER
Br
R
R
TolO
TolO
HO
O
O
O
NaOMe
MeOH
see Table 1
TolO
TolO
HO
8a–g
2a
7a–g
Tol = toluoyl
F
N
R
=
S
N
N
a
b
c
d
e
f
g
Scheme 2
dichloro[1,1¢-bis(diphenylphosphino)ferrocene]palladium
basic conditions. Therefore, we have tried the Stille cou-
in N,N-dimethylformamide at 115 °C for 18 hours. In case pling of 4 with 6-(tributylstannyl)-2,2¢-bipyridine under
of the stannylpyridine and stannylpyrimidine, the reac- the conditions used in the unsuccessful reaction of 2a
tions afforded the desired biaryl nucleosides 7f and 7g in (Scheme 3, Table 2, entry 1). Gratifyingly, this reaction
acceptable yield of 58% and 54%, respectively (the isolat- proceeded smoothly without cleavage of protecting
ed yields were lowered by the difficulties in removing groups to give protected bipyridinylphenyl nucleoside 9h
stannane impurities). However, attempts to perform the in a satisfactory yield of 53%.
Stille coupling with 6-(tributylstannyl)-2,2¢-bipyridine
The base stability of the tert-butyldimethylsilyl protecting
groups in intermediate 4 makes it a promising starting
gave only a complex mixture of degradation and reduction
products (entry 8). All toluoylated nucleosides 7a–g were
successfully deprotected using Zemplen conditions to
give the desired final compounds 8a–g with good to ex-
cellent preparative yield after crystallization (72–95%).
compound of choice for the introduction of N-substituents
using Hartwig–Buchwald aminations25,26 (Scheme 3,
Table 2, entries 2–13). At first, lithium hexamethyldisila-
zanide was used as an ammonia equivalent for the intro-
Although the synthesis of the tert-butyldimethylsilyl-pro- duction of the unsubstituted amino group. The reaction of
tected nucleoside 4 was reported by Leumann,21 it was not lithium hexamethyldisilazanide with 4 was performed at
used for cross-coupling reactions itself, but it was only 55 °C in the presence of tris(dibenzylideneacetone)di-
used after deprotection and reprotection with acetyl palladium and (biphenyl-2-yl)dicyclohexylphosphine,
groups. However, at least for certain reactions, the silyl known to be an excellent ligand for the amination of bro-
groups could be of advantage due to their stability under mobenzene,27 to give the desired amino nucleoside 9i in a
Table 1 Cross-Coupling Reactions on Toluoylated Intermediate 2a
Entry
Reagent
Catalyst
Solvent
Temp, time
Product
Yield (%)
Deprotected
product
Yield (%)
1
2
3
4
5
6
7
8
4-FC6H4B(OH)2
2-naphthylB(OH)2
Et3Al
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
PdCl2(dppf)
PdCl2(dppf)
PdCl2(dppf)
toluene
toluene
THF
100 °C, 12 h
100 °C, 12 h
70 °C, 12 h
70 °C, 12 h
100 °C, 12 h
115 °C, 18 h
115 °C, 18 h
115 °C, 18 h
7a
7b
7c
7d
7e
7f
7g
–
67
8a
8b
8c
8d
8e
8f
87
81
95
81
78
72
84
a
71
74
BnZnCl
THF
75
2-(Bu3Sn)thiopheneb
2-(Bu3Sn)pyridinec
DMF
DMF
DMF
DMF
79
58
2-(Bu3Sn)pyrimidined
6-(Bu3Sn)-2,2¢-bipyridinee
54
8g
degradation
a 2-NaphthylB(OH)2 = 2-naphthylboronic acid.
b 2-(Bu3Sn)thiophene = 2-(tributylstannyl)thiophene.
c 2-(Bu3Sn)pyridine = 2-(tributylstannyl)pyridine.
d 2-(Bu3Sn)pyrimidine = 2-(tributylstannyl)pyrimidine.
e 6-(Bu3Sn)-2,2¢-bipyridine = 6-(tributylstannyl)-2,2¢-bipyridine.
Synthesis 2008, No. 12, 1918–1932 © Thieme Stuttgart · New York

PAPER
4-Aryl- and 4-Amino-Substituted Benzene C-2¢-Deoxyribonucleosides
1921
Br
R
R
TBSO
TBSO
HO
O
O
O
see Table 2
Et3N⋅3HF
THF
TBSO
TBSO
9h–n
HO
4
8h–n
F
F
F
F
R
=
N
N
NH2
NHPh
NPh2
H
NMe2
F
h
i
j
k
l
m
n
Scheme 3
good yield of 59% (entry 2). Shortening the reaction time acetate or tris(dibenzylideneacetone)dipalladium, tert-bu-
and performing the reaction at 40 °C gave 9i in an excel- tyl(cyclohexyl)fluorophosphine (Josiphos), or (biphenyl-
lent yield of 78% (entry 3). Hartwig–Buchwald 2-yl)di-tert-butylphosphine (bdtbp)29 ligands and several
reactions28 were also used for the introduction of substi- bases failed (entries 4–7). Further optimizations of cata-
tuted amino groups. We first focused our attention on the lysts, ligands, bases, and solvents revealed an optimum
introduction of the dimethylamino moiety (known to be combination of tris(dibenzylideneacetone)dipalladium,
rather a difficult substituent in the pyridine series17,18). (biphenyl-2-yl)di-tert-butylphosphine, sodium tert-bu-
Our first attempts on dimethylamination of 4 with dimeth- toxide, and toluene. The reaction was then performed at
ylamine hydrochloride in the presence of palladium(II) 40 °C for 18 hours to give the desired dimethylamino nu-
Table 2 Cross-Coupling and Amination Reactions on tert-Butyldimethylsilyl-Protected Intermediate 4
Entry Reagent
Catalyst
Ligand
Base
Solvent
DMF
Temp, time
Product
Yield Deprotect- Yield
(%)
ed Product (%)
1
6-(Bu3Sn)-2,2¢- PdCl2(dppf)
115 °C, 18 h 9h
53
8h
63
bipyridinea
2
3
LiHMDS
LiHMDS
Pd2(dba)3
Pd2(dba)3
bdCypb
bdCypb
t-Bu(Cy)PFc
bdtbpd
toluene
toluene
DME
55 °C, 24 h
40 °C, 20 h
55 °C, 2 d
9i
59
78
8i
80
9i
4
Me2NH·HCl Pd(OAc)2
Me2NH·HCl Pd(OAc)2
Me2NH·HCl Pd(OAc)2
Me2NH·HCl Pd2(dba)3
Me2NH·HCl Pd2(dba)3
Me2NH·HCl Pd2(dba)3
t-BuONa
no reaction
5
K3PO4·3 H2O toluene
K3PO4·3 H2O DME
70 °C, 11 d
70 °C, 11 d
40 °C, 11 d
40 °C, 18 h
35 °C, 22 h
80 °C, 25 h
55 °C, 23 h
55 °C, 24 h
70 °C, 18 h
no reaction
6
bdtbpd
no reaction
7
bdtbpd
LDA
toluene
toluene
toluene
toluene
toluene
DME
no reaction
8
bdtbpd
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
t-BuONa
9j
36
87
52
72
8j
88
83
9
bdtbpd
9j
10
11
12
13
14
15
Ph2NH
Ph2NH
Ph2NH
Ph2NH
HC6F5
H2
Pd2(dba)3
Pd2(dba)3
Pd(OAc)2
Pd2(dba)3
Pd(OAc)2
Pd/C
bdtbpd
9k
8k
bdtbpd
9k
t-Bu(Cy)PFc
bdtbpd
degradation
toluene
DMAe
9l
78
64
70
8l
82
75
84
t-Bu3P·HBF4 K2CO3
115 °C, 20 h 9m
r.t., 7 h 9n
8m
8n
Et3N
THF,
EtOH, H2O
a 6-(Bu3Sn)-2,2¢-bipyridine = 6-(tributylstannyl)-2,2¢-bipyridine.
b bdCyp = (biphenyl-2-yl)dicyclohexylphosphine.
c t-Bu(Cy)PF = Josiphos ligand.
d bdtbp = (biphenyl-2-yl)di-tert-butylphosphine.
e DMA = N,N-dimethylacetamide.
Synthesis 2008, No. 12, 1918–1932 © Thieme Stuttgart · New York

1922
N. Joubert et al.
PAPER
R
Br
HO
HO
see Table 3
O
O
Pd(OAc)2, TPPTS
R-B(OH)2, Na2CO3
H2O–MeCN (2:1)
HO
8o–u
HO
3
CF3 MeO
OMe
OMe
OMe
OMe
OMe
OMe
N
F
R
=
O
o
p
q
r
s
t
u
Scheme 4
cleoside 9j in 36% yield (entry 8). Further decreasing the All the silylated nucleosides 9h–n were deprotected using
temperature to 35 °C gave, after 22 hours, product 9j in triethylamine trihydrofluoride24 in tetrahydrofuran to give
excellent 87% yield (entry 9). Analogous reactions of 4 the free 4-substituted-phenyl C-nucleosides 8h–n in good
with aniline or diphenylamine in toluene in the presence yields (>63%).
of tris(dibenzylideneacetone)dipalladium, (biphenyl-2-
yl)di-tert-butylphosphine, and sodium tert-butoxide gave
the phenylamino derivative 9k or diphenylamino deriva-
tive 9l, in 72% or 78% yield, respectively (entries 11 and
13).
Recently, we became interested in applications of aqueous
phase cross-coupling reactions for the direct and efficient
functionalization of unprotected nucleosides.35 Therefore,
we have tested this approach in phenyl C-nucleosides.
The unprotected 4-bromophenyl C-nucleoside 3 was used
Direct C–H arylation is one of the most efficient and use- for the aqueous phase Suzuki–Miyaura cross-coupling re-
ful methods of C–H activation30 and, as an alternative to actions with a variety of arylboronic acids in the presence
classical cross-coupling reactions, it has been applied to of palladium(II) acetate, tris(3-sulfophenyl)phosphine tri-
many heterocycles31 including purines32 and nucleo- sodium salt (TPPTS) as ligand, and sodium carbonate as
sides.33 Direct C–H arylation of pentafluorobenzene34 base (Scheme 4, Table 3, entries 1–7). The reactions were
with bromobenzene nucleoside 4 in the presence of palla- performed in a mixture of acetonitrile–water (2:1) under
dium(II) acetate, tri-tert-butylphosphine–tetrafluoroboric microwave irradiation at 150 °C for five minutes to give
acid, and potassium carbonate in DMA at 55 °C for 20 biaryl C-nucleosides 8o–t in moderate to good yield (en-
hours gave the desired biaryl nucleoside 9m in 64% yield tries 1–6). In the case of 4-methoxyphenylboronic acid,
(entry 14). Finally, we performed the catalytical hydro- heating at 150 °C gave much degradation in the reaction
genolysis of bromobenzene nucleoside 4 using hydrogen mixture, therefore we tried heating at 80 °C and obtained
over palladium on carbon for seven hours in a mixture of 8u in 38% yield (entry 7). Unfortunately in all cases, the
ethanol, tetrahydrofuran, and water in the presence of tri- desired compound was accompanied by the formation of
ethylamine to give the desired unsubstituted benzene nu- a minor reduced byproduct 8n36 in various amounts (up to
cleoside 9n in 70% yield (entry 15).
20%). It is worthy of note that 8n is not visible under UV
light during TLC monitoring, but can be detected on TLC
Table 3 Aqueous Phase Suzuki Cross-Couplings on Deprotected Nucleoside 3
Entry
Reagent
MW conditions
150 °C, 5 min
150 °C, 5 min
150 °C, 5 min
150 °C, 5 min
150 °C, 5 min
150 °C, 5 min
80 °C, 5 min
Product
8o
Yield (%)
Reduced product
Yield (%)
1
2
3
4
5
6
7
3-pyridylboronic acid
benzofuran-2-ylboronic acid
4-(F3C)C6H4B(OH)2
3,4,5-(MeO)3C6H2PhB(OH)2
3-F-4-MeOC6H3B(OH)2
3,4-(MeO)2C6H3B(OH)2
4-MeOC6H4B(OH)2
39
49
37
47
51
49
38
8n
8n
8n
8n
8n
8n
8n
10
2
8p
8q
15
7
8r
8s
13
13
20
8t
8u
Synthesis 2008, No. 12, 1918–1932 © Thieme Stuttgart · New York

PAPER
4-Aryl- and 4-Amino-Substituted Benzene C-2¢-Deoxyribonucleosides
1923
(CHCl3–MeOH, 9:1) by using phosphomolybdic acid. In conclusion, a modular methodology for the syntheses
The separation of 8o–u from 8n must be performed very of diverse 4-substituted-phenyl C-2¢-deoxyribonucleo-
carefully by column chromatography on silica gel eluting sides has been developed. Key intermediates 4-toluoyl-
no more than 0.5 to 1.0% methanol in chloroform. We at- protected 4-bromophenyl nucleoside 2a and tert-butyl-
tempted to optimize the reaction conditions, by decreasing dimethylsilyl-protected 4-bromophenyl nucleoside 4
the temperature or the reaction time, but no improvement were successfully prepared either via coupling of halo-
was reached, even when the reaction was carried out un- genose with 4-bromophenylmagnesium bromide fol-
der classical heating (results not shown). Despite the lowed by epimerization or via aryllithium addition to the
problem with side reactions, this approach still remains an lactone followed by reduction. Both methods are efficient
efficient alternative for the attachment of an aryl or hetar- and useful. Intermediates 2a and 4 were then subjected to
yl group whenever the corresponding boronic acid is a series of palladium-catalyzed cross-coupling reactions,
available because it saves one step.
aminations, and C–H activation to give protected 1b-[4-
(aryl-, alkyl-, or amino)phenyl]-1,2-dideoxyribofuran-
oses. Toluoyl protection was suitable for most cross-cou-
pling reactions, while tert-butyldimethylsilyl-protection
was suitable for aminations and C–H arylation. Standard
deprotection methods gave a series of 4-substituted-phe-
nyl and anilino C-nucleosides. Alternatively, other types
of 4-arylphenyl C-nucleosides were prepared directly by
aqueous phase Suzuki cross-coupling reactions of unpro-
tected 3 with boronic acids under microwave irradiation.
The title C-nucleosides are interesting building blocks for
the construction of modified nucleic acids and potential
candidates for the extension of the genetic alphabet.
UV-Vis and fluorescence spectra of the final C-nucleo-
sides were studied in methanol to ensure sufficient solu-
bility of all samples. Spectral changes when 1b-(phenyl)-
2-deoxyribose is substituted at the 4-position by different
aryl groups was observed (Table 4).
The electronic coupling of the two chromophores produc-
es pp* absorption bands which peak in the range 242–305
nm. The emission maxima varied from 328 to 480 nm de-
pending on the aryl group attached. Apparently, changing
the aryl substituent can be used for fine-tuning of the ab-
sorption and fluorescent spectral maxima. Benzofuran-2-
yl derivative 8p exerted absorption maxima at 305 nm and
showed a very high value of quantum yield (0.95) which
is in accord with related 2,3-diarylbenzofurans.37 This
compounds seems to be the most promising fluorescent
label for selective excitation within DNA due the highest
absorption wavelength and a very bright emission.
Melting points were determined on a Kofler block. Optical rotations
were measured at 25 °C, [a]D20 values are given in 10–1deg cm2 g–1.
1
NMR spectra were measured at 400 MHz for H, and 100.6 MHz
1
for 13C nuclei, at 500 MHz for H, 470.3 MHz for 19F and 125.7
MHz for 13C, or at 600 MHz for 1H and 151 MHz for 13C in CDCl3
(protected nucleosides) and CD3OD or DMSO-d6 (deprotected).
CDCl3 (TMS internal standard), DMSO-d6 (referenced to the resid-
Table 4 UV-Vis and Fluorescence Spectral Data
1
ual solvent signal: 2.50 for H NMR and 39.7 for 13C NMR),
CD3OD (referenced to the residual solvent signal: 3.31 for 1H NMR
and 49.0 for 13C NMR). Complete assignment of all NMR signals
was performed using a combination of H, H-COSY, H,C-HSQC,
and H,C-HMBC experiments. Mass spectra were measured using
FAB (ionization by Xe, accelerating voltage 8 kV, glycerol +
thioglycerol matrix) or EI (70 eV). DMF was degassed under vacu-
um and stored over molecular sieves under argon. Synthesis and
characterization data of 1b-(4-bromophenyl)-1,2-dideoxy-3,5-di-
O-(4-toluoyl)-D-ribofuranose (2a) (synthesis of 2a, epimerization
of 2b, and characterization data of 2a and 2b), 1,2-dideoxy-1b-[4-
(4-fluorophenyl)phenyl]-3,5-di-O-(4-toluoyl)-D-ribofuranose (7a),
1,2-dideoxy-1b-[4-(2-naphthyl)phenyl]-3,5-di-O-(4-toluoyl)-D-ri-
bofuranose (7b), 1,2-dideoxy-1b-(4-ethylphenyl)-3,5-di-O-(4-tolu-
oyl)-D-ribofuranose (7c), 1b-(4-benzylphenyl)-1,2-dideoxy-3,5-di-
O-(4-toluoyl)-D-ribofuranose (7d), 1,2-dideoxy-1b-[4-(2-thie-
nyl)phenyl]-3,5-di-O-(4-toluoyl)-D-ribofuranose (7e), 1,2-dideoxy-
1b-[4-(4-fluorophenyl)phenyl]-D-ribofuranose (8a), 1,2-dideoxy-
1b-[4-(2-naphthyl)phenyl]-D-ribofuranose (8b), 1,2-dideoxy-1b-
(4-ethylphenyl)-D-ribofuranose (8c), 1b-(4-benzylphenyl)-1,2-
dideoxy-D-ribofuranose (8d), and 1,2-dideoxy-1b-[4-(2-thie-
nyl)phenyl]-D-ribofuranose (8e) are available in the literature.16
Compd Absorption
Emission
max (nm)
l
max (nm) e (L·mol–1·cm–1)
l
f
8a
8b
8e
8f
251
255
286
249
265
264
242
252
305
259
267
263
269
264
2.97 × 104
6.20 × 104
2.53 × 104
1.21 × 104
2.38 × 104
2.27 × 104
1.51 × 104
2.06 × 104
4.50 × 104
1.67 × 104
2.74 × 104
1.70 × 104
0.74 × 104
2.46 × 104
328, 342
480
0.31
0.22
0.10
<0.01
<0.01
0.20
<0.01
0.05
0.95
0.32
0.43
0.74
0.49
0.64
363
402
8g
8h
8m
8o
8p
8q
8r
8s
400
350
347
397
344
317
365
Deprotection of the Toluoyl Group; General Procedure 1
A 1 M soln of NaOMe in MeOH (0.2 mL, 0.2 mmol) was added to
a soln of 2a or 7a–g (0.2 mmol) in MeOH (100 mL) and the result-
ing soln was allowed to stand overnight at r.t. Then it was evaporat-
ed and the residue was chromatographed (silica gel; gradient:
CHCl3 to 10% MeOH–CHCl3) to give 3 or 8a–g.
329
8t
341
8u
335, 345
Synthesis 2008, No. 12, 1918–1932 © Thieme Stuttgart · New York

1924
N. Joubert et al.
PAPER
Deprotection of the tert-Butyldimethylsilyl Group; General
Procedure 2
dropwise and the mixture was stirred at –72 °C for 2 h under argon.
Sat. NaHCO3 soln was added to the mixture, which was extracted
with CH2Cl2 (3 ×). The combined organic layers were dried
(MgSO4), filtered, and concentrated under vacuum to give the crude
product, which was chromatographed (silica gel; gradient: hexane
to 33% hexane–toluene) to give 4 (2.22 g, 23%).
Et3N·3 HF (320 mL, 1.95 mmol) was added to a soln of 9h–n (0.4
mmol) in THF (2 mL), and the mixture was stirred at r.t. for 14 h.
When the reaction was complete (TLC, hexane–EtOAc, 9:1), the
solvent was removed under reduced pressure. The crude product
was dissolved in MeOH (2 mL) and 1 M aq NaOH (8 mL) was add-
ed to neutralize the mixture. The solvent was again removed under
reduced pressure and the crude product was chromatographed (sili-
ca gel; gradient: CHCl3 to 10% MeOH–CHCl3) to give 8h–n.
IR (CHCl3): 2956, 1594, 1587, 1489, 1472, 1463, 1407, 1390, 1362,
1297, 1281, 1172, 1109, 1073, 1011, 939, 838, 815, 683, 633, 585
cm–1.
1H NMR (400 MHz, CDCl3): d = 0.08 and 0.09 (2 s, 2 × 6 H,
CH3Si), 0.907 and 0.913 [2 s, 2 × 9 H, C(CH3)3], 1.84 (ddd,
Jgem = 12.7 Hz, J2¢b,1¢ = 10.4 Hz, J2¢b,3¢ = 5.4 Hz, 1 H, H2¢b), 2.10
(ddd, Jgem = 12.7 Hz, J2¢a,1 = 5.5 Hz, J2¢a,3¢ = 1.7 Hz, 1 H, H2¢a), 3.62
(dd, Jgem = 10.7 Hz, J5¢b,4¢ = 5.6 Hz, 1 H, H5¢b), 3.76 (dd, Jgem = 10.7
Hz, J5¢a,4¢ = 3.7 Hz, 1 H, H5¢a), 3.96 (ddd, J4¢,5¢ = 5.6, 3.7 Hz,
1b-(4-Bromophenyl)-1,2-dideoxy-D-ribofuranose (3)
Pathway 1: Compound 3 was prepared from 2a (1.70 g, 3.35 mmol)
by general procedure 1. Crystallization (EtOAc–heptane) gave 3
(800 mg, 88%) as white crystals.
Pathway 2: Compound 3 was prepared from 4 (2.22 g, 4.43 mmol)
by general procedure 2. Crystallization (EtOAc–heptane) gave 3
(936 mg, 77%) as white crystals.
J
4¢,3¢ = 1.9 Hz, 1 H, H4¢), 4.41 (dt, J3¢,2¢ = 5.4, 1.7 Hz, J3¢,4¢ = 1.9 Hz,
1 H, H3¢), 5.09 (dd, J1¢,2¢ = 10.4, 5.5 Hz, 1 H, H1¢), 7.25 (m, 2 H, H2,
H6), 7.43 (m, 2 H, H3, H5).
Mp 130–131 °C.
[a]D20 +44.1 (c 0.34, MeOH).
13C NMR (100.6 MHz, CDCl3): d = –5.47, –5.38, –4.68, and –4.64
(CH3Si), 18.04 and 18.34 [C(CH3)3], 25.82 and 25.92 [C(CH3)3],
44.41 (2¢-CH2), 63.78 (5¢-CH2), 74.32 (3¢-CH), 79.43 (1¢-CH),
88.15 (4¢-CH), 121.02 (4-C), 127.75 (2-CH, 6-CH; 131.29 (3-CH,
5-CH), 141.55 (1-C).
IR (KBr): 3413, 1632, 1594, 1490, 1412, 1297, 1281, 1212, 1180,
1096, 1072, 1060, 1010, 945, 820, 693, 633, 595, 550, 473 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 1.72 (ddd, Jgem = 12.7 Hz,
J2¢b,1 = 10.4 Hz, J2¢b,3 = 5.6 Hz, 1 H, H2¢b), 2.07 (ddd, Jgem = 12.7
Hz, J2¢a,1 = 5.4 Hz, J2¢a,3¢ = 1.6 Hz, 1 H, H2¢a), 3.41 and 3.48 (2 dt,
Jgem = 11.4 Hz, J5¢,4¢ = 5.6 Hz, J5¢,OH = 5.6 Hz, 2 H, H5¢), 3.78 (td,
MS (EI): m/z = 500 (M).
HRMS (EI): m/z [M] calcd for C23H41BrO3Si2: 500.1778; found:
500.1762.
J4¢,5¢ = 5.6 Hz, J4,3 = 2.1 Hz, 1 H, H4¢), 4.18 (m, J3¢,2¢ = 5.6, 1.6 Hz,
J3¢,OH = 3.8 Hz, J3¢,4¢ = 2.1 Hz, 1 H, H3¢), 4.77 (t, JOH,5¢ = 5.6 Hz, 1 H,
5¢-OH), 4.98 (dd, J1¢,2¢ = 10.4, 5.4 Hz, 1 H, H1¢), 5.07 (d, JOH,3¢ = 3.9
Hz, 1 H, 3¢-OH), 7.32 (m, 2 H, H2, H6), 7.50 (m, 2 H, H3, H5).
13C NMR (100.6 MHz, DMSO-d6): d = 43.80 (2¢-CH2), 62.57 (5¢-
CH2), 72.57 (3¢-CH), 78.71 (1¢-CH), 88.09 (4¢-CH), 120.26 (4-C),
128.39 (2-CH, 6-CH), 131.18 (3-CH, 5-CH), 142.46 (1-C).
1,2-Dideoxy-1b-[4-(pyridin-2-yl)phenyl]-3,5-di-O-(4-toluoyl)-D-
ribofuranose (7f); Typical Procedure
2-(Tributylstannyl)pyridine (390 mL, 1.40 mmol) was added drop-
wise under argon to a stirred soln of 2a (203 mg, 0.40 mmol) and
PdCl2(dppf) (14 mg, 0.02 mmol) in DMF (1.4 mL). The mixture
was stirred at 115 °C for 18 h and then worked up by pouring into
sat. NaCl soln and extracting with EtOAc (3 ×). The combined or-
ganic layers were washed carefully with sat. KF soln, dried
(MgSO4), filtered, and concentrated under vacuum. Crude product
7f was chromatographed (silica gel; gradient: hexane to 70% hex-
ane–EtOAc) to give 7f (146 mg) as a colorless oil, which contained
some inseparable impurities (purity ca. 80% estimated from NMR;
yield calculated on content of pure 7f is ca. 58%). This compound
was directly used in the deprotection step.
MS (EI) m/z = 272 (M).
HRMS (EI): m/z [M] calcd for C11H13BrO3: 272.0048; found:
272.0052.
Anal. Calcd for C11H13BrO3 (272): C, 48.37; H, 4.80. Found: C,
48.57; H, 4.83.
1b-(4-Bromophenyl)-1,2-dideoxy-3,5-di-O-(tert-butyldimethyl-
silyl)-D-ribofuranose (4)
IR (CHCl3): 1718, 1612, 1589, 1579, 1564, 1510, 1469, 1436, 1409,
1378, 1311, 1271, 1249, 1178, 1120, 1106, 1044, 1020, 991, 841,
691, 639, 619 cm–1.
Pathway 1: To a dried flask containing a soln of the nucleoside 3
(611 mg, 2.24 mmol) in anhyd DMF (10.0 mL) at 0 °C under argon,
imidazole (544 mg, 8.00 mmol) and then TBSCl (755 mg, 5.00
mmol) were added and the soln was allowed to warm up to r.t.
stirred for 16 h. The mixture was then poured into sat. NaCl soln
(300 mL) and extracted with EtOAc (3 × 60 mL). The combined or-
ganic fractions were washed with sat. NaCl soln, dried (MgSO4),
and the solvent was evaporated under vacuum. The crude product
was chromatographed (silica gel, hexane–EtOAc, 10:1 to give the
desired nucleoside 4 (1.04 g, 93%) as a colorless oil.
1H NMR (500 MHz, CDCl3): d = 2.27 (ddd, Jgem = 13.8 Hz,
J2¢b,1¢ = 10.9 Hz, J2¢b,3¢ = 6.0 Hz, 1 H, H2¢b), 2.38 and 2.43 (2 s, 2 × 3
H, CH3-Tol), 2.58 (ddd, Jgem = 13.8 Hz, J2¢a,1¢ = 5.1 Hz, J2¢a,3¢ = 1.1
Hz, 1 H, H2¢a), 4.56 (ddd, J4¢,5¢ = 4.2, 3.9 Hz, J4¢,3¢ = 2.1 Hz, 1 H,
H4¢), 4.66 (dd, Jgem = 11.7 Hz, J5¢b,4¢ = 3.9 Hz, 1 H, H5¢b), 4.69 (dd,
Jgem = 11.7 Hz, J5¢a,4¢ = 4.2 Hz, 1 H, H5¢a), 5.32 (dd, J1¢,2¢ = 10.9, 5.1
Hz, 1 H, H1¢), 5.63 (dddd, J3¢,2¢ = 6.0, 1.1 Hz, J3¢,4¢ = 2.0 Hz,
J3¢,1¢ = 0.6 Hz, 1 H, H3¢), 7.21 (ddd, J5,4 = 7.1 Hz, J5,6 = 4.8 Hz,
J5,3 = 1.6 Hz, 1 H, H5py), 7.21 and 7.28 (2 m, 2 × 2 H, m-HTol), 7.50
(m, 2 H, H2, H6), 7.70 (ddd, J3,4 = 8.0 Hz, J3,5 = 1.6 Hz, J3,6 = 0.9
Hz, 1 H, H3py), 7.73 (ddd, J4,3 = 8.0 Hz, J4,5 = 7.1 Hz, J4,6 = 1.8 Hz,
1 H, H4py), 7.95 (m, 2 H, o-HTol), 7.96 (m, 2 H, H3, H5), 7.99 (m, 2
H, o-HTol), 8.68 (ddd, J6,5 = 4.8 Hz, J6,4 = 1.8 Hz, J6,3 = 0.9 Hz, 1 H,
H6py).
13C NMR (125.7 MHz, CDCl3): d = 21.60 and 21.67 (CH3-Tol),
41.75 (2¢-CH2), 64.74 (5¢-CH2), 77.22 (3¢-CH), 80.54 (1¢-CH),
83.03 (4¢-CH), 120.42 (3-CHpy), 122.06 (5-CHpy), 126.20 (2-CH, 6-
CH), 126.98 (i-CTol), 127.01 (3-CH, 5-CH), 127.06 (i-CTol), 129.14
and 129.16 (m-CHTol), 129.65 and 129.70 (o-CHTol), 136.67 (4¢-
Pathway 2: 1.6 M BuLi in hexane (19.5 mL) was added dropwise to
a soln of 1,4-dibromobenzene (7.50 g, 32.0 mmol) in anhyd THF
(75 mL) at –72 °C under argon. The mixture was stirred for 30 min
and then added to a stirred soln of lactone 5 (6.90 g, 19.2 mmol) in
THF (75 mL) cooled at –72 °C. The mixture was worked up after
60 min by pouring onto sat. NH4Cl soln and extracted with EtOAc.
The combined organic layers were dried (MgSO4), filtered, and
concentrated under vacuum to give the unstable crude hemiketal 6,
which was rapidly used for the next step without further purifica-
tion. Et3SiH (9.63 mL, 63.2 mmol) was added dropwise to a soln of
6 in CH2Cl2 (69 mL) at –72 °C under argon. After 10 min, a soln of
BF3·OEt2 (2.63 mL, 23.0 mmol) in CH2Cl2 (0.25 mL) was added
Synthesis 2008, No. 12, 1918–1932 © Thieme Stuttgart · New York

PAPER
4-Aryl- and 4-Amino-Substituted Benzene C-2¢-Deoxyribonucleosides
1925
CHpy), 138.97 (4-C), 141.51 (1-C), 143.77 and 144.09 (p-CTol),
CHpy), 123.66 (5-CHpy), 127.57 (2-CH, 6-CH), 128.08 (3-CH, 5-
149.63 (6-CHpy), 157.05 (C2py), 166.10 and 166.36 (CO).
CH), 138.89 (4-CHpy), 139.60 (4-C), 144.55 (1-C), 150.23 (6-
CHpy), 158.66 (2-Cpy).
MS (FAB): m/z = 508 [M + 1].
MS (FAB): m/z = 272 [M + 1].
HRMS (FAB): m/z [M + H] calcd for C32H30NO5: 508.2123; found:
508.2111.
HRMS (FAB): m/z [M + H] calcd for C16H18NO3: 272.1287; found:
272.1285.
1,2-Dideoxy-1b-[4-(pyrimidin-2-yl)phenyl]-3,5-di-O-(4-tolu-
oyl)-D-ribofuranose (7g)
Anal. Calcd for C16H17NO3 (271): C, 70.83; H, 6.32; N, 5.16.
Found: C, 70.53; H, 6.28; N, 5.00.
2-(Tributylstannyl)pyrimidine (390 mL, 1.40 mmol) was added
dropwise under argon to a stirred soln of 2a (203 mg, 0.40 mmol)
and PdCl2(dppf) (14 mg, 0.02 mmol) in DMF (1.4 mL). The mixture
was stirred at 115 °C for 18 h and then worked up as in the typical
procedure for 7f. Crude product 7g was chromatographed (silica
gel; gradient: hexane to 70% hexane–EtOAc) to give 7g (139 mg)
as a colorless oil, which contained some inseparable impurities (pu-
rity ca. 80% estimated from NMR; yield calculated on content of
pure 7g is ca. 54%). This compound was directly used in the depro-
tection step.
1,2-Dideoxy-1b-[4-(pyrimidin-2-yl)phenyl]-D-ribofuranose (8g)
Compound 8g was prepared from 7g (150 mg, 0.29 mmol) by gen-
eral procedure 1. Crystallization (EtOAc–heptane) gave 8g (66 mg,
84%) as white crystals; mp 132–134 °C.
[a]D20 +35.2 (c 0.27, MeOH).
IR (KBr): 3414, 1632, 1614, 1572, 1557, 1510, 1423, 1313, 1216,
1117, 1090, 1061, 1047, 1017, 981, 812, 794, 645, 566 cm–1.
1H NMR (500 MHz, CD3OD): d = 1.97 (ddd, Jgem = 13.1 Hz,
IR (CHCl3): 1718, 1612, 1581, 1569, 1556, 1510, 1466, 1455, 1419,
1406, 1379, 1311, 1270, 1249, 1178, 1120, 1044, 1020, 946, 841,
802, 691, 641, 565, 476 cm–1.
J
2¢b,1¢ = 10.6 Hz, J2¢b,3¢ = 5.9 Hz, 1 H, H2¢b), 2.25 (ddd, Jgem = 13.1
Hz, J2¢a,1¢ = 5.5 Hz, J2¢a,3¢ = 1.6 Hz, 1 H, H2¢a), 3.69 and 3.72 (2 dd,
Jgem = 11.6 Hz, J5¢,4¢ = 5.2 Hz, 2 H, H5¢), 3.99 (td, J4¢,5¢ = 5.2 Hz,
1H NMR (500 MHz, CDCl3): d = 2.27 (ddd, Jgem = 13.9 Hz,
J4¢,3¢ = 2.4 Hz, 1 H, H4¢), 4.35 (dddd, J3¢,2¢ = 5.9, 1.6 Hz, J3¢,4¢ = 2.4
Hz, J3¢,1¢ = 0.6 Hz, 1 H, H3¢), 5.20 (dd, J1¢,2¢ = 10.6, 5.5 Hz, 1 H,
H1¢), 7.31 (t, J5,4 = J5,6 = 4.9 Hz, 1 H, H5pyrimidine), 7.52 (m, 2 H, H2,
H6), 8.35 (m, 2 H, H3, H5), 8.80 (d, J4,5 = J6,5 = 4.9 Hz, 2 H,
H4pyrimidine, H6pyrimidine).
13C NMR (125.7 MHz, CD3OD): d = 44.95 (2¢-CH2), 64.05 (5¢-
CH2), 74.40 (3¢-CH), 81.21 (1¢-CH), 89.30 (4¢-CH), 120.62 (5-
CHpyrimidine), 127.27 (2-CH, 6-CH), 129.19 (3-CH, 5-CH), 137.94
(4-C), 146.39 (1-C), 158.65 (4-CHpyrimidine, 6-CHpyrimidine ), 165.56
(2-Cpyrimidine).
J2¢b,1¢ = 11.0 Hz, J2¢b,3¢ = 6.1 Hz, 1 H, H2¢b), 2.38 and 2.43 (2 s, 2 × 3
H, CH3-Tol), 2.59 (ddd, Jgem = 13.9 Hz, J2¢a,1¢ = 5.1 Hz, J2¢a,3¢ = 1.1
Hz, 1 H, H2¢a), 4.57 (ddd, J4¢,5¢ = 4.2, 3.9 Hz, J4¢,3¢ = 2.0 Hz, 1 H,
H4¢), 4.67 (dd, Jgem = 11.8 Hz, J5¢b,4¢ = 3.9 Hz, 1 H, H5¢b), 4.69 (dd,
Jgem = 11.8 Hz, J5¢a,4¢ = 4.2 Hz, 1 H, H5¢a), 5.33 (dd, J1¢,2¢ = 11.0, 5.1
Hz, 1 H, H1¢), 5.63 (dddd, J3¢,2¢ = 6.1, 1.1 Hz, J3¢,4¢ = 2.0 Hz,
J
3¢,1¢ = 0.6 Hz, 1 H, H3¢), 7.17 (t, J5,4 = J5,6 = 4.9 Hz, 1 H, H5pyrimidine),
7.21 and 7.28 (2 m, 2 × 2 H, m-HTol), 7.53 (m, 2 H, H2, H6), 7.94
and 7.99 (2 m, 2 × 2 H, o-HTol), 8.41 (m, 2 H, H3, H5), 8.79 (d, J4,5
J6,5= 4.9 Hz, 2 H, H4pyrimidine, H6pyrimidine).
=
MS (FAB): m/z = 273 [M + 1].
13C NMR (125.7 MHz, CDCl3): d = 21.60 and 21.66 (CH3-Tol),
41.75 (2¢-CH2), 64.71 (5¢-CH2), 77.21 (3¢-CH), 80.56 (1¢-CH),
83.12 (4¢-CH), 119.03 (5-CHpyrimidine), 126.02 (2-CH, 6-CH), 127.05
and 127.11 (i-CTol), 128.36 (3-CH, 5-CH), 129.17 (m-CHTol),
129.67 and 129.73 (o-CHTol), 137.19 (4-C), 143.50 (1-C), 143.76
and 144.10 (p-CTol), 157.18 (4-CHpyrimidine, 6-CHpyrimidine), 164.48
(C2pyrimidine), 166.10 and 166.37 (CO).
HRMS (FAB): m/z [M + H] calcd for C15H17N2O3: 273.1239; found:
273.1243.
Anal. Calcd for C15H16N2O3 (272): C, 66.16; H, 5.92; N, 10.29.
Found: C, 65.94; H, 5.85; N, 10.10.
1b-[4-([2,2¢]Bipyridin-6-yl)phenyl]-1,2-dideoxy-3,5-di-O-(tert-
butyldimethylsilyl)-D-ribofuranose (9h)
MS (FAB): m/z = 509 [M + 1].
A 1.6 M soln of BuLi in hexane (1.08 mL) was added to a soln of 6-
bromo-2,2¢-bipyridine (332 mg, 1.41 mmol) in THF (10.8 mL) un-
der argon at –72 °C and the mixture was stirred for 2 min followed
by addition of Bu3SnCl (500 mL, 1.84 mmol). The mixture was
stirred at –72 °C for 20 min and then allowed to warm to r.t. and the
solvent was evaporated under vacuum. The crude 6-(tributylstan-
nyl)-2,2¢-bipyridine was dissolved in DMF (1.9 mL) and added
through septum to a flask containing 4 (286 mg, 0.57 mmol) and
PdCl2(dppf) (20 mg, 0.03 mmol) sealed under argon. The mixture
was stirred at 115 °C for 18 h and then poured into brine (500 mL)
and extracted with EtOAc (3 × 100 mL). The combined organic lay-
ers were evaporated and the crude product 9h was chromatographed
twice (silica gel; gradient: hexane to 90% hexane–EtOAc) to give
9h (249 mg) as a colorless oil, which contained some inseparable
impurities (purity ca. 70% estimated from NMR; yield calculated
on content of pure 9h is ca. 53%). This compound was directly used
in the deprotection step.
HRMS (FAB): m/z [M + H] calcd for C31H29N2O5: 509.2076; found:
509.2069.
1,2-Dideoxy-1b-[4-(pyridin-2-yl)phenyl]-D-ribofuranose (8f)
Compound 8f was prepared from 7f (221 mg, 0.44 mmol) by gener-
al procedure 1. Crystallization (EtOAc–heptane) gave 8f (87 mg,
72%) as white crystals; mp 98–100 °C.
[a]D20 +50.4 (c 0.20, MeOH).
IR (KBr): 3418, 3270, 1615, 1592, 1563, 1516, 1470, 1438, 1300,
1217, 1171, 1117, 1097, 1085, 1055, 1016, 997, 942, 844, 781 cm–1.
1H NMR (500 MHz, CD3OD): d = 1.97 (ddd, Jgem = 13.1 Hz,
J2¢b,1¢ = 10.5 Hz, J2¢b,3¢ = 5.9 Hz, 1 H, H2¢b), 2.24 (ddd, Jgem = 13.1
Hz, J2¢a,1¢ = 5.4 Hz, J2¢a,3¢ = 1.6 Hz, 1 H, H2¢a), 3.68 and 3.72 (2 dd,
Jgem = 11.6 Hz, J5¢,4¢ = 5.2 Hz, 2 H, H5¢), 3.99 (td, J4¢,5¢ = 5.2 Hz,
J4¢,3¢ = 2.5 Hz, 1 H, H4¢), 4.35 (dddd, J3¢,2¢ = 5.9, 1.6 Hz, J3¢,4¢ = 2.5
Hz, J3¢,1¢ = 0.6 Hz, 1 H, H3¢), 5.19 (dd, J1¢,2¢ = 10.5, 5.4 Hz, 1 H,
H1¢), 7.33 (ddd, J5,4 = 7.4 Hz, J5,6 = 4.9 Hz, J5,3 = 1.2 Hz, 1 H,
H5py), 7.52 (m, 2 H, H2, H6), 7.81 (ddd, J3,4 = 8.0 Hz, J3,5 = 1.2 Hz,
J3,6 = 0.9 Hz, 1 H, H3py), 7.86 (ddd, J4,3 = 8.0 Hz, J4,5 = 7.4 Hz,
J4,6 = 1.8 Hz, 1 H, H4py), 7.90 (m, 2 H, H3, H5), 8.59 (ddd, J6,5 = 4.9
Hz, J6,4 = 1.8 Hz, J6,3 = 0.9 Hz, 1 H, H6py).
13C NMR (125.7 MHz, CD3OD): d = 44.97 (2¢-CH2), 64.06 (5¢-
CH2), 74.42 (3¢-CH), 81.21 (1¢-CH), 89.27 (4¢-CH), 122.50 (3-
IR (CHCl3): 3061, 2958, 1614, 1595, 1583, 1564, 1515, 1472, 1463,
1456, 1431, 1390, 1362, 1304, 1258, 1091, 1017, 991, 940, 838,
815, 620 cm–1.
1H NMR (500 MHz, CDCl3): d = 0.106, 0.110 and 0.116 (3 s, 12 H,
CH3Si), 0.931 and 0.935 [2 s, 2 × 9 H, C(CH3)3], 1.94 (ddd,
Jgem = 12.7 Hz, J2¢b,1¢ = 10.4 Hz, J2¢b,3¢ = 5.3 Hz, 1 H, H2¢b), 2.17
(ddd, Jgem = 12.7 Hz, J2¢a,1¢ = 5.4 Hz, J2¢a,3¢ = 1.6 Hz, 1 H, H2¢a), 3.65
(dd, Jgem = 10.6 Hz, J5¢b,4¢ = 6.0 Hz, 1 H, H5¢b), 3.81 (dd, Jgem = 10.6
Synthesis 2008, No. 12, 1918–1932 © Thieme Stuttgart · New York

1926
N. Joubert et al.
PAPER
Hz, J5¢a,4¢ = 3.8 Hz, 1 H, H5¢a), 4.01 (ddd, J4¢,5¢ = 6.0, 3.8 Hz,
4¢,3¢ = 1.9 Hz, 1 H, H4¢), 4.46 (dddd, J3¢,2¢ = 5.3, 1.6 Hz, J3¢,4¢ = 1.9
(silica gel; gradient: hexane to 5% EtOAc–hexane) to give 9j (402
mg, 87%) as a yellow oil.
J
Hz, J3¢,1¢ = 0.5 Hz, 1 H, H3¢), 5.23 (dd, J1¢,2¢ = 10.4, 5.4 Hz, 1 H,
H1¢), 7.32 (ddd, J5¢,4¢ = 7.5 Hz, J5¢,6¢ = 4.8 Hz, J5¢,3¢ = 1.2 Hz, 1 H,
H5¢bipy), 7.51 (m, 2 H, H2, H6), 7.76 (dd, J5,4 = 7.8 Hz, J5,3 = 1.0 Hz,
1 H, H5bipy), 7.85 (ddd, J4¢,3¢ = 7.9 Hz, J4¢,5¢ = 7.5 Hz, J4¢,6¢ = 1.8 Hz,
1 H, H4¢bipy), 7.88 (t, J4,3 = J4,5 = 7.8 Hz, 1 H, H4bipy), 8.10 (m, 2 H,
H3, H5), 8.36 (dd, J3,4 = 7.8 Hz, J3,5 = 1.0 Hz, 1 H, H3bipy), 8.65
(ddd, J3¢,4¢ = 7.9 Hz, J3¢,5¢ = 1.2 Hz, J3¢,6¢ = 0.9 Hz, 1 H, H3¢bipy), 8.69
(ddd, J6¢,5¢ = 4.8 Hz, J6¢,4¢ = 1.8 Hz, J6¢,3¢ = 0.9 Hz, 1 H, H6¢bipy).
13C NMR (125.7 MHz, CDCl3): d = –5.42, –5.33, and –4.65
(CH3Si), 18.07 [C(CH3)3], 25.85 and 25.96 [C(CH3)3], 44.32 (2¢-
CH2), 63.89 (5¢-CH2), 74.39 (3¢-CH), 79.81 (1¢-CH), 88.12 (4¢-CH),
119.19 (3-CHbipy), 120.25 (5-CHbipy), 121.32 (3¢-CHbipy), 123.71
(5¢-CHbipy), 126.34 (2-CH, 6-CH), 126.85 (3-CH, 5-CH), 136.88
(4¢-CHbipy), 137.65 (4-CHbipy), 138.47 (4-C), 143.41 (1-C), 149.00
(6¢-CHbipy), 153.23 (2-Cbipy), 156.35 (2¢-Cbipy), 156.43 (6-Cbipy).
IR (CHCl3): 2896, 2804, 1720, 1616, 1524, 1472, 1463, 1445, 1428,
1389, 1373, 1361, 1350, 1320, 1258, 1173, 1125, 1101, 1092, 1059,
1030, 941, 838, 681 cm–1.
1H NMR (500 MHz, CDCl3): d = 0.078, 0.081, 0.090 and 0.092 (4 s,
4 × 3 H, CH3Si), 0.91 and 0.92 [2 s, 2 × 9 H, C(CH3)3], 1.92 (ddd,
Jgem = 12.9 Hz, J2¢b,1¢ = 10.5 Hz, J2¢b,3¢ = 5.3 Hz, 1 H, H2¢b), 2.03
(ddd, Jgem = 12.9 Hz, J2¢a,1¢ = 5.3 Hz, J2¢a,3¢ = 1.6 Hz, 1 H, H2¢a), 2.92
(s, 6 H, CH3N), 3.58 (dd, Jgem = 10.6 Hz, J5¢b,4¢ = 6.4 Hz, 1 H, H5¢b),
3.76 (dd, Jgem = 10.6 Hz, J5¢a,4¢ = 3.9 Hz, 1 H, H5¢a), 3.92 (ddd,
J
4¢,5¢ = 6.4, 3.9 Hz, J4¢,3¢ = 1.8 Hz, 1 H, H4¢), 4.42 (ddd, J3¢,2¢ = 5.3,
1.6 Hz, J3¢,4¢ = 1.8 Hz, 1 H, H3¢), 5.06 (dd, J1¢,2¢ = 10.5, 5.3 Hz, 1 H,
H1¢), 6.70 (m, 2 H, H3, H5), 7.24 (m, 2 H, H2, H6).
13C NMR (125.7 MHz, CDCl3): d = –5.43, –5.35, –4.66, and –4.64
(CH3Si), 18.05 and 18.37 [C(CH3)3], 25.85 and 25.96 [C(CH3)3],
40.74 (CH3N), 43.71 (2¢-CH2), 64.04 (5¢-CH2), 74.57 (3¢-CH),
79.97 (1¢-CH), 87.71 (4¢-CH), 112.52 (3-CH, 5-CH), 127.23 (2-CH,
6-CH), 129.73 (1-C), 150.27 (4-C).
MS (FAB): m/z = 577 [M + 1].
HRMS (FAB): m/z [M + H] calcd for C33H49N2O3Si2: 577.3282;
found: 577.3290.
MS (FAB): m/z = 466 [M + 1].
HRMS (FAB): m/z [M + H] calcd for C25H48NO3Si2: 466.3172;
found: 466.3177.
1b-(4-Aminophenyl)-1,2-dideoxy-3,5-di-O-(tert-butyldimethyl-
silyl)-D-ribofuranose (9i)
A 1 M soln of LiHMDS in THF (1.44 mL, 1.44 mmol) was added
to a flame-dried argon purged flask containing 4 (360 mg, 0.72
mmol), (biphenyl-2-yl)dicyclohexylphosphine (25 mg, 0.07 mmol),
and Pd2(dba)3 (33 mg, 0.04 mmol ) and the mixture was stirred at
40 °C for 20 h. The reaction was quenched by the addition of Et2O
and 2 M aq HCl (3 drops) and worked up; H2O was added, and the
mixture was extracted with EtOAc (3 ×). The combined organic lay-
ers were dried (MgSO4), filtered, and concentrated under vacuum.
Chromatography (silica gel; gradient: hexane to 5% EtOAc–hex-
ane) gave 9i (245 mg, 78%) as a yellow oil.
1,2-Dideoxy-1b-[4-(phenylamino)phenyl]-3,5-di-O-(tert-butyl-
dimethylsilyl)-D-ribofuranose (9k)
(Biphenyl-2-yl)di-tert-butylphosphine (15 mg, 0.05 mmol),
Pd2(dba)3 (46 mg, 0.05 mmol), t-BuONa (288 mg, 5.00 mmol), and
PhNH2 (270 mL, 5.00 mmol) were added to an argon-purged dry
flask containing 4 (502 mg, 1.00 mmol). Then anhyd toluene was
added (3.0 mL) and the mixture was stirred at 60 °C for 23 h under
argon. The mixture was then worked up given in the typical proce-
dure for 9i to give crude product 9k, which was chromatographed
(silica gel; gradient: hexane to 5% EtOAc–hexane) to give 9k (369
mg, 72%) as a yellow oil.
IR (CHCl3): 3490, 3453, 3398, 3378, 3039, 1623, 1587, 1520, 1472,
1463, 1257, 838 cm–1.
IR (CHCl3): 3431, 2897, 1617, 1599, 1519, 1499, 1472, 1464, 1447,
1390, 1362, 1314, 1258, 1176, 1119, 1091, 1030, 1014, 945, 940,
838, 695, 681, 496 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.08 and 0.09 (2 s, 12 H, CH3Si),
0.910 and 0.913 [2 s, 2 × 9 H, C(CH3)3], 1.89 (ddd, Jgem = 12.7 Hz,
J2¢b,1¢ = 10.5 Hz, J2¢b,3¢ = 5.4 Hz, 1 H, H2¢b), 2.03 (ddd, Jgem = 12.7
1H NMR (500 MHz, CDCl3): d = 0.08 and 0.10 (2 s, 12 H, CH3Si),
0.91 and 0.92 [2 s, 2 × 9 H, C(CH3)3], 1.92 (ddd, Jgem = 12.7 Hz,
Hz, J2¢a,1¢ = 5.2 Hz, J2¢a,3¢ = 1.6 Hz, 1 H, H2¢a), 3.58 (dd, Jgem = 10.6
Hz, J5¢b,4¢ = 6.2 Hz, 1 H, H5¢b), 3.63 (br s, 2 H, NH2), 3.75 (dd,
Jgem = 10.6 Hz, J5¢a,4¢ = 3.8 Hz, 1 H, H5¢a), 3.91 (ddd, J4¢,5¢ = 6.2, 3.8
Hz, J4¢,3¢ = 1.9 Hz, 1 H, H4¢), 4.41 (ddd, J3¢,2¢ = 5.4, 1.6 Hz, J3¢,4¢ = 1.9
Hz, 1 H, H3¢), 5.03 (dd, J1¢,2¢ = 10.5, 5.2 Hz, 1 H, H1¢), 6.64 (m, 2 H,
H3, H5), 7.16 (m, 2 H, H2, H6).
J2¢b,1¢ = 10.5 Hz, J2¢b,3¢ = 5.4 Hz, 1 H, H2¢b), 2.08 (ddd, Jgem = 12.7
Hz, J2¢a,1¢ = 5.2 Hz, J2¢a,3¢ = 1.6 Hz, 1 H, H2¢a), 3.60 (dd, Jgem = 10.7
Hz, J5¢b,4¢ = 6.1 Hz, 1 H, H5¢b), 3.77 (dd, Jgem = 10.7 Hz, J5¢a,4¢ = 3.8
Hz, 1 H, H5¢a), 3.94 (ddd, J4¢,5¢ = 6.1, 3.8 Hz, J4¢,3¢ = 1.9 Hz, 1 H,
H4¢), 4.43 (ddd, J3¢,2¢ = 5.4, 1.6 Hz, J3¢,4¢ = 1.9 Hz, 1 H, H3¢), 5.08
(dd, J1¢,2¢ = 10.5, 5.2 Hz, 1 H, H1¢), 5.72 (br s, 1 H, NH), 6.91 (m, 1
H, p-Hphenyl), 7.03 (m, 2 H, H3, H5), 7.05 (m, 2 H, o-Hphenyl), 7.24
(m, 2 H, m-Hphenyl), 7.27 (m, 2 H, H2, H6).
13C NMR (100.6 MHz, CDCl3): d = –5.45, –5.37, –4.67, and –4.64
(CH3Si), 18.04 and 18.36 [C(CH3)3], 25.84 and 25.95 [C(CH3)3],
43.92 (2¢-CH2), 63.99 (5¢-CH2), 74.52 (3¢-CH), 79.97 (1¢-CH),
87.77 (4¢-CH), 114.95 (3-CH, 5-CH), 127.44 (2-CH, 6-CH), 132.00
(1-C), 145.74 (4-C).
13C NMR (125.7 MHz, CDCl3): d = –5.44, –5.35, –4.66, and –4.63
(CH3Si), 18.06 and 18.37 [C(CH3)3], 25.85 and 25.95 [C(CH3)3],
44.00 (2¢-CH2), 63.96 (5¢-CH2), 74.53 (3¢-CH), 79.89 (1¢-CH),
87.90 (4¢-CH), 117.51 (o-CHphenyl), 117.94 (3-CH, 5-CH), 120.80
(p-CHphenyl), 127.39 (2-CH, 6-CH), 129.31 (m-CHphenyl), 134.73 (1-
C), 142.30 (4-C), 143.37 (i-Cphenyl).
MS (FAB): m/z = 438 [M + 1].
HRMS (FAB): m/z [M + H] calcd for C23H44NO3Si2: 438.2860;
found: 438.2875.
1,2-Dideoxy-1b-[4-(dimethylamino)phenyl]-3,5-di-O-(tert-
butyldimethylsilyl)-D-ribofuranose (9j); Typical Procedure
(Biphenyl-2-yl)di-tert-butylphosphine (32 mg, 0.11 mmol),
Pd2(dba)3 (49 mg, 0.05 mmol), t-BuONa (518 mg, 5.34 mmol), and
Me2NH·HCl (439 mg, 5.34 mmol) were added to an argon-purged
dry flask containing 4 (539 mg, 1.07 mmol). Then anhyd toluene
was added (3.3 mL) and the mixture was stirred at 35 °C for 22 h
under argon. The mixture was then poured into brine (500 mL) and
extracted with EtOAc (3 × 100 mL). The combined organic layers
were evaporated and the crude product 9j was chromatographed
MS (FAB): m/z = 514 [M + 1].
HRMS (FAB): m/z [M + H] calcd for C29H48NO3Si2: 514.3172;
found: 514.3179.
1,2-Dideoxy-1b-[4-(diphenylamino)phenyl]-3,5-di-O-(tert-
butyldimethylsilyl)-D-ribofuranose (9l)
(Biphenyl-2-yl)di-tert-butylphosphine (3 mg, 0.02 mmol),
Pd2(dba)3 (9 mg, 0.01 mmol), t-BuONa (96 mg, 1.00 mmol), and
Ph2NH (169 mg, 1.00 mmol) were added to an argon-purged dry
flask containing 4 (100 mg, 0.20 mmol). Then anhyd toluene was
Synthesis 2008, No. 12, 1918–1932 © Thieme Stuttgart · New York

PAPER
4-Aryl- and 4-Amino-Substituted Benzene C-2¢-Deoxyribonucleosides
1927
added (3.3 mL) and the mixture was stirred at 70 °C for 18 h under
argon. The mixture was then worked up as given in the typical pro-
cedure for 9i to give crude product 9l, which was chromatographed
(silica gel; gradient: 10% toluene–hexane to 50% toluene–hexane)
to give 9l (92 mg, 78%) as a yellow oil.
HRMS (FAB): m/z [M + H] calcd for C29H42F5O3Si2: 589.2593;
found: 589.2708.
1,2-Dideoxy-1b-phenyl-3,5-di-O-(tert-butyldimethylsilyl)-
D-ribofuranose (9n)
To a soln of the nucleoside 4 (387 mg, 0.77 mmol) in a mixture of
THF–EtOH–H2O (10:10:1, 28 mL) at r.t., 10% Pd/C (207 mg, 0.28
mmol) and Et3N (0.80 mL) were added. The flask was evacuated
and then filled with H2 (100 kPa) and stirred at r.t. When the reac-
tion was complete (7 h, TLC, hexane–toluene, 2:1), the Pd was fil-
tered off, the filtrate was poured into H2O and extracted with
EtOAc. The combined organic fractions were dried (MgSO4) and
the solvent was evaporated under vacuum. The crude product was
chromatographed (silica gel; gradient: hexane to 90% hexane–
EtOAc) to give the desired nucleoside 9n (229 mg, 70%) as a col-
orless oil
IR (CHCl3): 3088, 3067, 2897, 1612, 1597, 1590, 1511, 1495, 1487,
1472, 1463, 1390, 13962, 1332, 1326, 1315, 1259, 1176, 1115,
1092, 1030, 1016, 945, 940, 890, 838, 698, 682, 622, 618, 513, 409
cm–1.
1H NMR (500 MHz, CDCl3): d = 0.06, 0.07 and 0.10 (3 s, 12 H,
CH3Si), 0.90 and 0.92 [2 s, 2 × 9 H, C(CH3)3], 1.94 (ddd,
Jgem = 12.7 Hz, J2¢b,1¢ = 10.6 Hz, J2¢b,3¢ = 5.4 Hz, 1 H, H2¢b), 2.08
(ddd, Jgem = 12.7 Hz, J2¢a,1¢ = 5.2 Hz, J2¢a,3¢ = 1.6 Hz, 1 H, H2¢a), 3.60
(dd, Jgem = 10.7 Hz, J5¢b,4¢ = 6.0 Hz, 1 H, H5¢b), 3.76 (dd, Jgem = 10.7
Hz, J5¢a,4¢ = 3.8 Hz, 1 H, H5¢a), 3.94 (ddd, J4¢,5¢ = 6.0, 3.8 Hz,
J
4¢,3¢ = 1.8 Hz, 1 H, H4¢), 4.44 (ddd, J3¢,2¢ = 5.4, 1.6 Hz, J3¢,4¢ = 1.8 Hz,
1 H, H3¢), 5.08 (dd, J1¢,2¢ = 10.6, 5.2 Hz, 1 H, H1¢), 6.98 (m, 2 H, p-
phenyl), 7.03 (m, 2 H, H3, H5), 7.07 (m, 4 H, o-Hphenyl), 7.20–7.26
IR (CHCl3): 3089, 3067, 3035, 2956, 1605, 1494, 1472, 1463, 1455,
1390, 1362, 1306, 1287, 1258, 1173, 1072, 1027, 1006, 940, 906,
838, 700, 526 cm–1.
H
(m, 6 H, m-Hphenyl, H2, H6).
1H NMR (500 MHz, CDCl3): d = 0.08 and 0.10 (2 s, 12 H, CH3Si),
0.91 and 0.92 [2 s, 2 × 9 H, C(CH3)3], 1.90 (ddd, Jgem = 12.7 Hz,
13C NMR (125.7 MHz, CDCl3): d = –5.46, –5.36, –4.66, and –4.63
(CH3Si), 18.06 and 18.35 [C(CH3)3], 25.85 and 25.94 [C(CH3)3],
43.99 (2¢-CH2), 63.92 (5¢-CH2), 74.59 (3¢-CH), 79.92 (1¢-CH),
87.99 (4¢-CH), 122.51 (p-CHphenyl), 123.99 (o-CHphenyl), 124.17 (3-
CH, 5-CH), 127.30 (2-CH, 6-CH), 129.12 (m-CHphenyl), 136.26 (1-
C), 147.12 (4-C), 147.85 (i-Cphenyl).
J2¢b,1¢ = 10.5 Hz, J2¢b,3¢ = 5.4 Hz, 1 H, H2¢b), 2.12 (ddd, Jgem = 12.7
Hz, J2¢a,1¢ = 5.4 Hz, J2¢a,3¢ = 1.7 Hz, 1 H, H2¢a), 3.61 (dd, Jgem = 10.6
Hz, J5¢b,4¢ = 6.0 Hz, 1 H, H5¢b), 3.78 (dd, Jgem = 10.6 Hz, J5¢a,4¢ = 3.8
Hz, 1 H, H5¢a), 3.96 (ddd, J4¢,5¢ = 6.0, 3.8 Hz, J4¢,3¢ = 2.0 Hz, 1 H,
H4¢), 4.43 (dddd, J3¢,2¢ = 5.4, 1.7 Hz, J3¢,4¢ = 2.0 Hz, J3¢,1¢ = 0.6 Hz, 1
H, H3¢), 5.14 (dd, J1¢,2¢ = 10.5, 5.4 Hz, 1 H, H1¢), 7.25 (m, 1 H, H4),
7.31 (m, 2 H, H3, H5), 7.37 (m, 2 H, H2, H6).
MS (FAB): m/z = 590 [M + 1].
HRMS (FAB): m/z [M + H] calcd for C35H52NO3Si2: 590.3486;
13C NMR (125.7 MHz, CDCl3): d = –5.45, –5.38, –4.67, and –4.64
(CH3Si), 18.05 and 18.35 [C(CH3)3], 25.84 and 25.93 [C(CH3)3],
44.26 (2¢-CH2), 63.88 (5¢-CH2), 74.42 (3¢-CH), 80.05 (1¢-CH),
88.02 (4¢-CH), 126.05 (2-CH, 6-CH), 127.34 (4-CH), 128.21 (3-
CH, 5-CH), 142.30 (1-C).
found: 590.3490.
1,2-Dideoxy-1b-[4-(2,3,4,5,6-pentafluorophenyl)phenyl]-3,5-di-
O-(tert-butyldimethylsilyl)-D-ribofuranose (9m)
Pd(OAc)2 (7 mg, 0.03 mmol), t-Bu3P·HBF4 (18 mg, 0.06 mmol),
K2CO3 (91 mg, 0.66 mmol), and pentafluorobenzene (100 mL, 0.90
mmol) were added to an argon-purged dry flask containing 4 (301
mg, 0.60 mmol). Then DMA (150 mL) was added and the mixture
was stirred at 115 °C for 20 h under argon. The mixture was then
worked up as given in the typical procedure for 9i to give crude
product 9m, which was chromatographed (silica gel; gradient: hex-
ane to 90% hexane–EtOAc) to give 9m (226 mg, 64%) as a color-
less oil.
MS (EI): m/z = 445 [M + 23].
HRMS (EI) m/z [M + Na] calcd for C23H42NaO3Si2: 445.2570;
found: 445.2564.
1b-[4-([2,2¢]Bipyridin-6-yl)phenyl]-1,2-dideoxy-D-ribofuranose
(8h)
Compound 8h was prepared from 9h (153 mg, 0.27 mmol) by gen-
eral procedure 2. Crystallization (i-PrOH–heptane) gave 8h (58 mg,
63%) as white crystals; mp 179–180 °C.
IR (CHCl3): 2956, 1653, 1615, 1571, 1529, 1495, 172, 1463, 1411,
1390, 1362, 1307, 1258, 1172, 1115, 1092, 1006, 990, 940, 839
cm–1.
[a]D20 +32.9 (c 0.30, MeOH).
1H NMR (600 MHz, CDCl3): d = 0.090, 0.092 and 0.11 (3 s, 12 H,
CH3Si), 0.91 and 0.93 [2 s, 2 × 9 H, C(CH3)3], 1.94 (ddd,
Jgem = 12.7 Hz, J2¢b,1¢ = 10.5 Hz, J2¢b,3¢ = 5.4 Hz, 1 H, H2¢b), 2.17
(ddd, Jgem = 12.7 Hz, J2¢a,1¢ = 5.4 Hz, J2¢a,3¢ = 1.6 Hz, 1 H, H2¢a), 3.64
(dd, Jgem = 10.7 Hz, J5¢b,4¢ = 5.8 Hz, 1 H, H5¢b), 3.79 (dd, Jgem = 10.7
Hz, J5¢a,4¢ = 3.7 Hz, 1 H, H5¢a), 4.00 (ddd, J4¢,5¢ = 5.8, 3.7 Hz,
IR (KBr): 3400, 1632, 1596, 1584, 1562, 1515, 1478, 1456, 1429,
1303, 1219, 1172, 1107, 1085, 1016, 990, 949, 814, 779, 627 cm–1.
1H NMR (500 MHz, DMSO-d6): d = 1.83 (ddd, Jgem = 12.7 Hz,
J2¢b,1¢ = 10.5 Hz, J2¢b,3¢ = 5.6 Hz, 1 H, H2¢b), 2.14 (ddd, Jgem = 12.7
Hz, J2¢a,1¢ = 5.5 Hz, J2¢a,3¢ = 1.6 Hz, 1 H, H2¢a), 3.46 (dt, Jgem = 11.3
Hz, J5¢b,OH = J5¢b,4¢ = 5.8 Hz, 1 H, H5¢b), 3.53 (ddd, Jgem = 11.3 Hz,
J5¢a,OH = 5.3 Hz, J5¢a,4¢ = 4.9 Hz, 1 H, H5¢a), 3.83 (ddd, J4¢,5¢ = 5.8, 4.9
Hz, J4¢,3¢ = 2.1 Hz, 1 H, H4¢), 4.23 (m, J3¢,2¢ = 5.6, 1.6 Hz, J3¢,OH = 3.8
Hz, J3¢,4¢ = 2.1 Hz, J3¢,1¢ = 0.6 Hz, 1 H, H3¢), 4.81 (dd, JOH,5¢ = 5.8, 5.3
Hz, 1 H, 5¢-OH), 5.10 (dd, J1¢,2¢ = 10.5, 5.5 Hz, 1 H, H1¢), 5.11 (d,
J
4¢,3¢ = 1.9 Hz, 1 H, H4¢), 4.45 (dddd, J3¢,2¢ = 5.4, 1.6 Hz, J3¢,4¢ = 1.9
Hz, J3¢,1¢ = 0.6 Hz, 1 H, H3¢), 5.20 (dd, J1¢,2¢ = 10.5, 5.4 Hz, 1 H,
H1¢), 7.37 (m, 2 H, H3, H5), 7.50 (m, 2 H, H2, H6).
13C NMR (151 MHz, CDCl3): d = –5.47, –5.39, –4.67, and –4.64
(CH3Si), 18.05 and 18.34 [C(CH3)3], 25.83 and 25.91 [C(CH3)3],
44.31 (2¢-CH2), 63.82 (5¢-CH2), 74.41 (3¢-CH), 79.66 (1¢-CH),
JOH,3¢ = 3.8 Hz, 1 H, 3¢-OH), 7.49 (ddd, J5¢,4¢ = 7.5 Hz, J5¢,6¢ = 4.7 Hz,
J5¢,3¢ = 1.2 Hz, 1 H, H5¢bipy), 7.51 (m, 2 H, H2, H6), 8.00 (ddd,
J4¢,3¢ = 7.9 Hz, J4¢,5¢ = 7.5 Hz, J4¢,6¢ = 1.8 Hz, 1 H, H4¢bipy), 8.02 (m, 1
2
88.19 (4¢-CH), 115.81 (t, JC,F = 17 Hz, i-CC6F5), 125.24 (4-C),
126.37 (2-CH, 6-CH), 130.03 (3-CH, 5-CH), 137.79 (m, 1JC,F = 252
H, H5bipy), 8.03 (m, 1 H, H4bipy), 8.19 (m, 2 H, H3, H5), 8.34 (m, 1
H, H3bipy), 8.58 (ddd, J3¢,4¢ = 7.9 Hz, J3¢,5¢ = 1.2 Hz, J3¢,6¢ = 0.9 Hz, 1
H, H3¢bipy), 8.71 (ddd, J6¢,5¢ = 4.7 Hz, J6¢,4¢ = 1.8 Hz, J6¢,3¢ = 0.9 Hz, 1
H, H6¢bipy).
13C NMR (125.7 MHz, DMSO-d6): d = 43.79 (2¢-CH2), 62.67 (5¢-
CH2), 72.64 (3¢-CH), 79.11 (1¢-CH), 88.06 (4¢-CH), 119.14 (5-
CHbipy), 120.53 (3-CHbipy), 120.80 (3¢-CHbipy), 124.46 (5¢-CHbipy),
126.57 (2-CH, 6-CH), 126.67 (3-CH, 5-CH), 137.54 (4¢-CHbipy),
1
Hz, m-CC6F5), 140.24 (m, JC,F = 253 Hz, p-CC6F5), 143.80 (1-C),
144.15 (m, 1JC,F = 248 Hz, o-CC6F5).
19F NMR (470.3 MHz, CDCl3): d = –162.85 (ddd, 3JF,F = 23.0, 21.0
Hz, 5JF,F = 8.1 Hz, 2 F, m-F), –156.34 (t, 3JF,F = 21.0 Hz, 1 F, p-F),
–143.72 (dd, 3JF,F = 23.0 Hz, 5JF,F = 8.1 Hz, 2 F, o-F).
MS (FAB): m/z = 589 [M + 1].
Synthesis 2008, No. 12, 1918–1932 © Thieme Stuttgart · New York

1928
N. Joubert et al.
PAPER
137.60 (4-C), 138.57 (4-CHbipy), 144.16 (1-C), 149.46 (6¢-CHbipy),
153.54 (C2bipy), 156.43 (C2¢bipy), 157.11 (C6bipy).
Hz, J2¢a,1¢ = 5.3 Hz, J2¢a,3¢ = 1.6 Hz, 1 H, H2¢a), 3.42 and 3.47 (2 ddd,
Jgem = 11.3 Hz, J5¢,OH = 5.6 Hz, J5¢,4¢ = 5.4 Hz, 2 H, H5¢), 3.74 (td,
J
4¢,5¢ = 5.4 Hz, J4¢,3¢ = 2.2 Hz, 1 H, H4¢), 4.17 (dddd, J3¢,2¢ = 5.7, 1.6
MS (FAB): m/z = 349 [M + 1].
Hz, J3¢,OH = 3.9 Hz, J3¢,4¢ = 2.2 Hz, 1 H, H3¢), 4.73 (t, JOH,5¢ = 5.6 Hz,
1 H, 5¢-OH), 4.91 (dd, J1¢,2¢ = 10.5, 5.3 Hz, 1 H, H1¢), 5.02 (d,
HRMS (FAB): m/z [M + H] calcd for C21H21N2O3: 349.1552; found:
349.1555.
J
OH,3¢ = 3.9 Hz, 1 H, 3¢-OH), 6.79 (m, 1 H, p-Hphenyl), 7.02 (m, 2 H,
H3, H5), 7.04 (m, 2 H, o-Hphenyl), 7.21 (m, 2 H, m-Hphenyl), 7.22 (m,
Anal. Calcd for C21H20N2O3 (576.3): C, 72.40; H, 5.79; N, 8.04.
Found: C, 72.10; H, 5.71; N, 7.92.
2 H, H2, H6), 8.12 (br s, 1 H, NH).
13C NMR (125.7 MHz, DMSO-d6): d = 43.53 (2¢-CH2), 62.78 (5¢-
CH2), 72.72 (3¢-CH), 79.33 (1¢-CH), 87.77 (4¢-CH), 116.61 and
116.81 (o-CHphenyl, 3-CH, 5-CH), 119.63 (p-CHphenyl), 127.42 (2-
CH, 6-CH), 129.34 (m-CHphenyl), 133.75 (1-C), 142.71 (4-C),
143.78 (i-Cphenyl).
1b-(4-Aminophenyl)-1,2-dideoxy-D-ribofuranose (8i)
Compound 8i was prepared from 9i (245 mg, 0.56 mmol) by general
procedure 2 to give 8i (94 mg, 80%) as a pale yellow oil.
[a]D20 +17.3 (c 0.27, MeOH).
MS (FAB): m/z = 286 [M + 1].
IR (KBr): 3611, 3431, 1617, 1598, 1519, 1499, 1314, 1176, 1155,
1118, 1090, 1079, 1042, 1028, 1016, 943, 877, 696, 493 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 1.72 (ddd, Jgem = 12.7 Hz,
HRMS (FAB): m/z [M + H] calcd for C17H20NO3: 286.1443; found:
286.1437.
J
2¢b,1¢ = 10.4 Hz, J2¢b,3¢ = 5.6 Hz, 1 H, H2¢b), 2.00 (ddd, Jgem = 12.7
1,2-Dideoxy-1b-[4-(diphenylamino)phenyl]-D-ribofuranose (8l)
Compound 8l was prepared from 9l (235 mg, 0.40 mmol) by general
procedure to give 8l (118 mg, 82%) as a colorless oil.
[a]D20 +35.9 (c 0.23, MeOH).
Hz, J2¢a,1¢ = 5.5 Hz, J2¢a,3¢ = 1.7 Hz, 1 H, H2¢a), 3.42 and 3.48 (2 ddd,
Jgem = 11.4 Hz, J5¢,OH = 5.6 Hz, J5¢,4¢ = 5.4 Hz, 2 H, H5¢), 3.78 (td,
J
4¢,5¢ = 5.4 Hz, J4¢,3¢ = 2.1 Hz, 1 H, H4¢), 4.18 (dddd, J3¢,2¢ = 5.6, 1.7
Hz, J3¢,OH = 3.8 Hz, J3¢,4¢ = 2.1 Hz, 1 H, H3¢), 4.77 (t, JOH,5¢ = 5.6 Hz,
1 H, 5¢-OH), 4.98 (dd, J1¢,2¢ = 10.4, 5.5 Hz, 1 H, H1¢), 5.07 (d,
IR (KBr): 3611, 3065, 1611, 1597, 1591, 1511, 1495, 1487, 1459,
1452, 1332, 1326, 1315, 1177, 1155, 1113, 1090, 1077, 1042, 1016,
944, 827, 698, 411 cm–1.
1H NMR (400 MHz, DMSO-d6): d = 1.80 (ddd, Jgem = 12.8 Hz,
J
OH,3¢ = 3.8 Hz, 1 H, 3¢-OH), 7.32 (m, 2 H, H3, H5), 7.50 (m, 2 H,
H2, H6).
13C NMR (100.6 MHz, DMSO-d6): d = 43.80 (2¢-CH2), 62.57 (5¢-
CH2), 72.58 (3¢-CH), 78.72 (1¢-CH), 88.09 (4¢-CH), 120.26 (1-C),
128.39 (3-CH, 5-CH), 131.18 (2-CH, 6-CH), 142.43 (4-C).
J
2¢b,1¢ = 10.5 Hz, J2¢b,3¢ = 5.7 Hz, 1 H, H2¢b), 2.04 (ddd, Jgem = 12.8
Hz, J2¢a,1¢ = 5.4 Hz, J2¢a,3¢ = 1.6 Hz, 1 H, H2¢a), 3.35–3.50 (m, 2 H,
H5¢), 3.76 (td, J4¢,5¢ = 5.1 Hz, J4¢,3¢ = 2.0 Hz, 1 H, H4¢), 4.18 (dddd,
MS (FAB): m/z = 210 [M + 1].
J
J
3¢,2¢ = 5.7, 1.6 Hz, J3¢,OH = 3.9 Hz, J3¢,4¢ = 2.0 Hz, 1 H, H3¢), 4.74 (t,
OH,5¢ = 5.5 Hz, 1 H, 5¢-OH), 4.95 (dd, J1¢,2¢ = 10.5, 5.4 Hz, 1 H, H1¢),
HRMS (FAB): m/z [M + H] calcd for C11H16NO3: 210.1130; found:
210.1126.
5.05 (d, JOH,3¢ = 3.9 Hz, 1 H, 3¢-OH), 6.94 (m, 2 H, H3, H5), 6.97
(m, 4 H, o-Hphenyl), 7.01 (m, 2 H, p-Hphenyl), 7.24–7.30 (m, 6 H, m-
1,2-Dideoxy-1b-[4-(dimethylamino)phenyl]-D-ribofuranose (8j)
Compound 8j was prepared from 9j (269 mg, 0.58 mmol) by gener-
al procedure 2 to give 8j (120 mg, 88%) as a colorless oil.
[a]D20 +9.1 (c 0.24, MeOH).
Hphenyl, H2, H6).
13C NMR (100.6 MHz, DMSO-d6): d = 43.44 (2¢-CH2), 62.71 (5¢-
CH2), 72.70 (3¢-CH), 79.11 (1¢-CH), 87.91 (4¢-CH), 122.95 (p-
CHphenyl), 123.71 (o-CHphenyl), 123.87 (3-CH, 5-CH), 127.66 (2-CH,
6-CH), 129.67 (m-CHphenyl), 137.26 (1-C), 146.52 (4-C), 147.49 (i-
IR (KBr): 3420, 1631, 1616, 1525, 1444, 1435, 1070, 1060, 821,
560 cm–1.
Cphenyl).
1H NMR (500 MHz, CD3OD): d = 1.99 (ddd, Jgem = 13.2 Hz,
MS (FAB): m/z = 362 [M + 1].
J2¢b,1¢ = 10.6 Hz, J2¢b,3¢ = 5.9 Hz, 1 H, H2¢b), 2.09 (ddd, Jgem = 13.2
HRMS (FAB): m/z [M + H] calcd for C23H24NO3: 362.1756; found:
362.1760.
Hz, J2¢a,1¢ = 5.4 Hz, J2¢a,3¢ = 1.6 Hz, 1 H, H2¢a), 2.90 (s, 6 H, CH3N),
3.63 and 3.66 (2 dd, Jgem = 11.6 Hz, J5¢,4¢ = 5.2 Hz, 2 H, H5¢), 3.89
(td, J4¢,5¢ = 5.2 Hz, J4¢,3¢ = 2.4 Hz, 1 H, H4¢), 4.31 (dddd, J3¢,2¢ = 5.9,
1.6 Hz, J3¢,4¢ = 2.4 Hz, J3¢,1¢ = 0.5 Hz, 1 H, H3¢), 5.03 (dd, J1¢,2¢ = 10.6,
5.4 Hz, 1 H, H1¢), 6.75 (m, 2 H, H3, H5), 7.24 (m, 2 H, H2, H6).
1,2-Dideoxy-1b-[4-(2,3,4,5,6-pentafluorophenyl)phenyl]-
D-ribofuranose (8m)
Compound 8m was prepared from 9m (220 mg, 0.37 mmol) by gen-
eral procedure 2. Crystallization (EtOAc–heptane) gave 8m (101
mg, 75%) as white crystals; mp 127–128 °C.
13C NMR (125.7 MHz, CD3OD): d = 41.09 (CH3N), 44.39 (2¢-CH2),
64.11 (5¢-CH2), 74.53 (3¢-CH), 81.76 (1¢-CH), 88.87 (4¢-CH),
113.96 (3-CH, 5-CH), 128.40 (2-CH, 6-CH), 130.62 (1-C), 152.06
(4-C).
[a]D20 +35.4 (c 0.27, MeOH).
IR (KBr): 3401, 1654, 1646, 1632, 1615, 1574, 1531, 1489, 1435,
1412, 1318, 1312, 1221, 1166, 1112, 1097, 1083, 1065, 1055, 1017,
985, 934, 837, 597, 542 cm–1.
MS (FAB): m/z = 238 [M + 1].
HRMS (FAB): m/z [M + H] calcd for C13H20NO3: 238.1443; found:
238.1448.
1H NMR (500 MHz, CD3OD): d = 1.99 (ddd, Jgem = 13.2 Hz,
J2¢b,1¢ = 10.6 Hz, J2¢b,3¢ = 5.9 Hz, 1 H, H2¢b), 2.27 (ddd, Jgem = 13.2
1,2-Dideoxy-1b-[4-(phenylamino)phenyl]-D-ribofuranose (8k)
Compound 8k was prepared from 9k (369 mg, 0.72 mmol) by gen-
eral procedure 2 to give 8k (170 mg, 83%) as a colorless oil.
[a]D20 +24.0 (c 0.41, MeOH).
Hz, J2¢a,1¢ = 5.5 Hz, J2¢a,3¢ = 1.6 Hz, 1 H, H2¢a), 3.68 and 3.71 (2 dd,
Jgem = 11.7 Hz, J5¢,4¢ = 5.1 Hz, 2 H, H5¢), 3.98 (td, J4¢,5¢ = 5.1 Hz,
J
4¢,3¢ = 2.4 Hz, 1 H, H4¢), 4.35 (dddd, J3¢,2¢ = 5.9, 1.6 Hz, J3¢,4¢ = 2.4
Hz, J3¢,1¢ = 0.6 Hz, 1 H, H3¢), 5.20 (dd, J1¢,2¢ = 10.6, 5.5 Hz, 1 H,
H1¢), 7.44 (m, 2 H, H3, H5), 7.57 (m, 2 H, H2, H6).
IR (KBr): 3611, 3065, 1613, 1597, 1591, 1511, 1495, 1487, 1459,
1452, 1332, 1326, 1315, 1177, 1155, 1113, 1077, 1030, 1016, 1002,
944, 887, 835, 827, 698, 623, 618, 511, 411 cm–1.
13C NMR (125.7 MHz, CD3OD): d = 45.04 (2¢-CH2), 64.03 (5¢-
CH2), 74.42 (3¢-CH), 81.12 (1¢-CH), 89.37 (4¢-CH), 117.29 (td,
2JC,F = 19 Hz, 4JC,F = 5 Hz, i-CC6F5), 126.72 (4-C), 127.45 (2-CH, 6-
CH), 131.27 (3-CH, 5-CH), 139.099 (m, 1JC,F = 244 Hz, m-CC6F5),
1H NMR (500 MHz, DMSO-d6): d = 1.80 (ddd, Jgem = 12.8 Hz,
J2¢b,1¢ = 10.5 Hz, J2¢b,3¢ = 5.7 Hz, 1 H, H2¢b), 2.00 (ddd, Jgem = 12.8
Synthesis 2008, No. 12, 1918–1932 © Thieme Stuttgart · New York

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4-Aryl- and 4-Amino-Substituted Benzene C-2¢-Deoxyribonucleosides
1929
1
141.58 (m, JC,F = 254 Hz, p-CC6F5), 145.02 (1-C), 145.56 (m,
1JC,F = 246 Hz, o-CC6F5).
Hz, 1 H, 3¢-OH), 7.48 (ddd, J5,4 = 7.9 Hz, J5,6 = 4.8 Hz, J5,2 = 0.9
Hz, 1 H, H5py), 7.49 (m, 2 H, H2, H6), 7.67 (m, 2 H, H3, H5), 8.06
(ddd, J4,5 = 7.9 Hz, J4,2 = 2.4 Hz, J4,6 = 1.6 Hz, 1 H, H4py), 8.56 (dd,
J6,5 = 4.8 Hz, J6,4 = 1.6 Hz, 1 H, H6py), 8.88 (dd, J2,4 = 2.4 Hz,
J2,5 = 0.9 Hz, 1 H, H2py).
19F NMR (470.3 MHz, CDCl3): d = –163.93 (m, 2 F, m-F), –157.55
(t, 3JF,F = 20.1 Hz, 1 F, p-F), –143.93 (dd, 3JF,F = 22.3 Hz, 5JF,F = 8.2
Hz, 2 F, o-F).
13C NMR (151 MHz, DMSO-d6): d = 43.79 (2¢-CH2), 62.67 (5¢-
CH2), 72.65 (3¢-CH), 79.04 (1¢-CH), 88.04 (4¢-CH), 124.03 (5-
CHpy), 126.86 (2-CH, 6-CH), 126.92 (3-CH, 5-CH), 134.19 (4¢-
CHpy), 135.62 (3-Cpy), 136.13 (4-C), 142.98 (1-C), 147.76 (2-CHpy),
148.54 (6-CHpy).
MS (FAB): m/z = 383 [M + 23].
HRMS (FAB): m/z [M + Na] calcd for C17H13F5NaO3: 383.0683;
found: 383.0673.
Anal. Calcd for C17H13F5O3 (360): C, 56.67; H, 3.64. Found: C,
56.50; H, 3.62.
MS (FAB): m/z = 272 [M + 1].
HRMS (FAB): m/z [M + H] calcd for C16H18NO3: 272.1287; found:
272.1294.
1,2-Dideoxy-1b-phenyl-D-ribofuranose (8n)
Compound 8n was prepared from 9n (210 mg, 0.50 mmol) by gen-
eral procedure 2. Crystallization (EtOAc–heptane) gave 8n (82 mg,
84%) as white crystals; mp 83–84 °C.
Anal. Calcd for C16H17NO3 (271): C, 70.83; H, 6.32; N, 5.16.
Found: C, 70.43; H, 6.28; N, 4.97.
[a]D20 +54.6 (c 0.28, MeOH).
1b-[4-(2-Benzofuran)phenyl]-1,2-dideoxy-D-ribofuranose (8p)
Compound 8p was prepared from 3 by general procedure 3. Crys-
tallization (EtOAc–heptane) gave 8p (56 mg, 49%) as white crys-
tals; mp 195–197 °C.
IR (KBr): 3411, 3284, 1632, 1605, 1490, 1452, 1315, 1285, 1217,
1175, 1155, 1111, 1104, 1081, 1065, 1044, 1029, 916, 840, 755,
700, 618, 545 cm–1.
1H NMR (500 MHz, CD3OD): d = 1.94 (ddd, Jgem = 13.1 Hz,
[a]D20 +49.7 (c 0.31, MeOH).
J2¢b,1¢ = 10.6 Hz, J2¢b,3¢ = 5.9 Hz, 1 H, H2¢b), 2.19 (ddd, Jgem = 13.1
IR (KBr): 3421, 3034, 1632, 1612, 1592, 1567, 1506, 1451, 1420,
1352, 1302, 1274, 1258, 1207, 1171, 1106, 1080, 1047, 1013, 946,
920, 833, 807, 750, 741 cm–1.
Hz, J2¢a,1¢ = 5.4 Hz, J2¢a,3¢ = 1.6 Hz, 1 H, H2¢a), 3.65 and 3.69 (2 dd,
Jgem = 11.7 Hz, J5¢,4¢ = 5.2 Hz, 2 H, H5¢), 3.95 (td, J4¢,5¢ = 5.2 Hz,
J4¢,3¢ = 2.4 Hz, 1 H, H4¢), 4.32 (dddd, J3¢,2¢ = 5.9, 1.6 Hz, J3¢,4¢ = 2.4
Hz, J3¢,1¢ = 0.7 Hz, 1 H, H3¢), 5.12 (dd, J1¢,2¢ = 10.6, 5.4 Hz, 1 H,
H1¢), 7.25 (m, 1 H, H4), 7.32 (m, 2 H, H3, H5), 7.39 (m, 2 H, H2,
H6).
1H NMR (500 MHz, CD3OD): d = 1.96 (ddd, Jgem = 13.1 Hz,
J2¢b,1¢ = 10.6 Hz, J2¢b,3¢ = 5.9 Hz, 1 H, H2¢b), 2.23 (ddd, Jgem = 13.1
Hz, J2¢a,1¢ = 5.4 Hz, J2¢a,3¢ = 1.5 Hz, 1 H, H2¢a), 3.68 and 3.71 (2 dd,
Jgem = 11.7 Hz, J5¢,4¢ = 5.1 Hz, 2 H, H5¢), 3.98 (td, J4¢,5¢ = 5.1 Hz,
13C NMR (125.7 MHz, CD3OD): d = 44.96 (2¢-CH2), 64.06 (5¢-
CH2), 74.44 (3¢-CH), 81.61 (1¢-CH), 89.19 (4¢-CH), 127.15 (2-CH,
6-CH), 128.59 (4-CH), 129.32 (3-CH, 5-CH), 143.19 (1-C).
J4¢,3¢ = 2.3 Hz, 1 H, H4¢), 4.35 (dddd, J3¢,2¢ = 5.9, 1.5 Hz, J3¢,4¢ = 2.3
Hz, J3¢,1¢ = 0.5 Hz, 1 H, H3¢), 5.17 (dd, J1¢,2¢ = 10.6, 5.4 Hz, 1 H,
H1¢), 7.16 (d, J3,7 = 1.0 Hz, 1 H, H3benzofuryl), 7.22 (ddd, J5,4 = 7.7
Hz, J5,6 = 7.3 Hz, J5,7 = 1.1 Hz, 1 H, H5benzofuryl), 7.28 (ddd, J6,7 = 8.5
Hz, J6,5 = 7.3 Hz, J6,4 = 1.3 Hz, 1 H, H6benzofuryl), 7.50 (m, 2 H, H2,
H6), 7.51 (dddd, J7,6 = 8.5 Hz, J7,5 = 1.1 Hz, J7,3 = 1.0 Hz, J7,4 = 0.6
Hz, 1 H, H7benzofuryl), 7.59 (ddd, J4,5 = 7.7 Hz, J4,6 = 1.3 Hz, J4,7 = 0.6
Hz, 1 H, H4benzofuryl), 7.86 (m, 2 H, H3, H5).
MS (EI): m/z = 194 [M].
HRMS (EI) m/z [M] calcd for C11H14O3: 194.0943; found:
194.0948.
Anal. Calcd for C11H14O3 (194): C, 68.02; H, 7.27. Found: C, 67.78;
H, 7.22.
13C NMR (125.7 MHz, CD3OD): d = 44.98 (2¢-CH2), 64.02 (5¢-
CH2), 74.43 (3¢-CH), 81.31 (1¢-CH), 89.28 (4¢-CH), 102.31 (3-
CHbenzofuryl), 111.89 (7-CHbenzofuryl), 122.02 (4-CHbenzofuryl), 124.11
(5-CHbenzofuryl), 125.45 (6-CHbenzofuryl), 125.79 (3-CH, 5-CH),
127.69 (2-CH, 6-CH), 130.62 (3a-Cbenzofuryl), 131.01 (4-C), 143.89
(1-C), 156.20 (7a-Cbenzofuryl), 157.00 (2-Cbenzofuryl).
Suzuki Coupling; General Procedure 3
Pd(OAc)2 (5 mg, 0.02 mmol), TPPTS (57 mg, 0.10 mmol), Na2CO3
(128 mg, 1.20 mmol), and the boronic acid (0.50 mmol) were added
to an argon-purged dry flask containing 3 (100 mg, 0.37 mmol).
Then a soln of H2O–MeCN (2:1, 3 mL) was added under argon and
the mixture was stirred at 150 °C for 5 min under microwave irradi-
ation. The mixture was evaporated and the crude product was chro-
matographed (silica gel; gradient: CHCl3 to 2% MeOH–CHCl3) to
give the products 8o–u.
MS (EI): m/z = 310 [M].
HRMS (EI) m/z [M] calcd for C19H18O4: 310.1205; found:
310.1197.
Anal. Calcd for C19H18O4 (310): C, 73.53; H, 5.85. Found: C, 73.33;
H, 5.83.
1,2-Dideoxy-1b-[4-(pyridin-3-yl)phenyl]-D-ribofuranose (8o)
Compound 8o was prepared from 3 by general procedure 3. Crys-
tallization (EtOAc–heptane) gave 8o (39 mg, 39%) as white crys-
tals; mp 126–127 °C.
1,2-Dideoxy-1b-{4-[4-(trifluoromethyl)phenyl]phenyl}-D-ribo-
furanose (8q)
Compound 8q was prepared from 3 by general procedure 3. Crys-
tallization (EtOAc–heptane) gave 8q (46 mg, 37%) as white crys-
tals; mp 220–222 °C.
[a]D20 +34.2 (c 0.23, MeOH).
[a]D20 +38.8 (c 0.26, MeOH).
IR (KBr): 3401, 3154, 1632, 1615, 1592, 1581, 1519, 1475, 1431,
1317, 1297, 1244, 1224, 1182, 1119, 1110, 1083, 1045, 1007, 799,
832, 708, 630 cm–1.
IR (KBr): 3420, 1632, 1618, 1588, 1566, 1500, 1400, 1329, 1186,
1174, 1142, 1126, 1111, 1019, 1005, 953, 822, 700, 516 cm–1.
1H NMR (600 MHz, DMSO-d6): d = 1.81 (ddd, Jgem = 12.7 Hz,
J
2¢b,1¢ = 10.4 Hz, J2¢b,3¢ = 5.6 Hz, 1 H, H2¢b), 2.12 (ddd, Jgem = 12.7
Hz, J2¢a,1¢ = 5.5 Hz, J2¢a,3¢ = 1.6 Hz, 1 H, H2¢a), 3.45 (dt, Jgem = 11.2
Hz, J5¢b,OH = J5¢b,4¢ = 5.8 Hz, 1 H, H5¢b), 3.52 (dt, Jgem = 11.2 Hz,
J5¢a,OH = J5¢a,4¢ = 5.0 Hz, 1 H, H5¢a), 3.82 (ddd, J4¢,5¢ = 5.8, 5.0 Hz,
1H NMR (500 MHz, CD3OD): d = 1.98 (ddd, Jgem = 13.1 Hz,
J2¢b,1¢ = 10.6 Hz, J2¢b,3¢ = 5.9 Hz, 1 H, H2¢b), 2.24 (ddd, Jgem = 13.1
Hz, J2¢a,1¢ = 5.4 Hz, J2¢a,3¢ = 1.6 Hz, 1 H, H2¢a), 3.68 and 3.71 (2 dd,
Jgem = 11.6 Hz, J5¢,4¢ = 5.1 Hz, 2 H, H5¢), 3.98 (td, J4¢,5¢ = 5.1 Hz,
J
4¢,3¢ = 2.1 Hz, 1 H, H4¢), 4.21 (dddd, J3¢,2¢ = 5.5, 1.6 Hz, J3¢,OH = 3.8
Hz, J3¢,4¢ = 2.1 Hz, 1 H, H3¢), 4.77 (dd, JOH,5¢ = 5.8, 5.0 Hz, 1 H, 5¢-
OH), 5.07 (dd, J1¢,2¢ = 10.4, 5.5 Hz, 1 H, H1¢), 5.08 (d, JOH,3¢ = 3.8
J4¢,3¢ = 2.4 Hz, 1 H, H4¢), 4.35 (dddd, J3¢,2¢ = 5.9, 1.6 Hz, J3¢,4¢ = 2.4
Hz, J3¢,1¢ = 0.6 Hz, 1 H, H3¢), 5.19 (dd, J1¢,2¢ = 10.6, 5.4 Hz, 1 H,
Synthesis 2008, No. 12, 1918–1932 © Thieme Stuttgart · New York

1930
N. Joubert et al.
PAPER
H1¢), 7.53 (m, 2 H, H2, H6), 7.66 (m, 2 H, H3, H5), 7.73 (m, 2 H,
m-H-C6H4CF3), 7.81 (m, 2 H, o-H-C6H4CF3).
13C NMR (151 MHz, CD3OD): d = 44.95 (2¢-CH2), 56.74 [4-
(CH3O)], 64.07 (5¢-CH2), 74.46 (3¢-CH), 81.34 (1¢-CH), 89.24 (4¢-
CH), 114.99 (d, JC,F = 2 Hz, 5-CH-3-F-4-MeOC6H3), 115.24 (d,
JC,F = 19 Hz, 2-CH-3-F-4-MeOC6H3), 123.67 (d, JC,F = 3 Hz, 6-CH-
3-F-4-MeOC6H3), 127.49 (3-CH, 5-CH), 127.74 (2-CH, 6-CH),
135.33 (d, JC,F = 6 Hz, 1-C1-3-F-4-MeOC6H3), 140.25 (4-C),
142.26 (1-C), 148.49 (d, JC,F = 11 Hz, 4-C-3-F-4-MeOC6H3),
153.90 (d, JC,F = 245 Hz, 3-CH-3-F-4-MeOC6H3).
13C NMR (125.7 MHz, CD3OD): d = 44.96 (2¢-CH2), 64.10 (5¢-
CH2), 74.46 (3¢-CH), 81.21 (1¢-CH), 89.31 (4¢-CH), 125.87 (q,
JC,F = 271 Hz, CF3), 126.73 (q, JC,F = 4 Hz, m-CH-C6H4CF3),
127.84 (2-CH, 6-CH), 128.17 (3-CH, 5-CH), 128.47 (o-CH-
C6H4CF3), 130.30 (q, JC,F = 32 Hz, p-C-C6H4CF3), 140.08 (4-C),
143.67 (1-C), 146.03 (i-C-C6H4CF3).
19F NMR (470.3 MHz, CD3OD): d = –138.45.
19F NMR (470.3 MHz, CD3OD): d = –65.26.
MS (FAB): m/z = 319 [M + 1].
MS (FAB): m/z = 361 [M + 23].
HRMS (FAB): m/z [M + H] calcd for C18H20FO4: 319.1346; found:
319.1351.
HRMS (FAB): m/z [M + Na] calcd for C18H17F3NaO3: 361.1028;
found: 361.1044.
Anal. Calcd for C18H19FO4 (318): C, 67.91; H, 6.02. Found: C,
67.80; H, 6.00.
Anal. Calcd for C18H17F3O3 (338): C, 63.90; H, 5.06. Found: C,
63.52; H, 5.04.
1,2-Dideoxy-1b-[4-(3,4-dimethoxyphenyl)phenyl]-D-ribofura-
nose (8t)21
Compound 8t was prepared from 3 by general procedure 3. Crystal-
lization (EtOAc–heptane) gave 8t (61 mg, 49%) as pale yellow
crystals; mp 93–95 °C.
1,2-Dideoxy-1b-[4-(3,4,5-trimethoxyphenyl)phenyl]-D-ribo-
furanose (8r)
Compound 8r was prepared from 3 by general procedure 3. Crystal-
lization (EtOAc–heptane) gave 8r (63 mg, 47%) as white crystals;
mp 110–112 °C.
[a]D20 +30.1 (c 0.22, MeOH).
[a]D20 +27.6 (c 0.31, MeOH).
IR (KBr): 3505, 3417, 2837, 1632, 1601, 1589, 1564, 1527, 1506,
1465, 1449, 1439, 1400, 1300, 1275, 1249, 1186, 1171, 1140, 1087,
1052, 1022, 995, 832, 807, 767, 738, 618, 541 cm–1.
IR (KBr): 3429, 2839, 1632, 1589, 1567, 1523, 1464, 1434, 1425,
1400, 1315, 1275, 1195, 1174, 1154, 1129, 1088, 1078, 1050, 1016,
879, 817, 772, 616, 550, 533 cm–1.
1H NMR (600 MHz, CD3OD): d = 1.98 (ddd, Jgem = 13.1 Hz,
1H NMR (500 MHz, CD3OD): d = 1.98 (ddd, Jgem = 13.1 Hz,
J2¢b,1¢ = 10.5 Hz, J2¢b,3¢ = 5.9 Hz, 1 H, H2¢b), 2.21 (ddd, Jgem = 13.1
J2¢b,1¢ = 10.6 Hz, J2¢b,3¢ = 6.0 Hz, 1 H, H2¢b), 2.22 (ddd, Jgem = 13.1
Hz, J2¢a,1¢ = 5.4 Hz, J2¢a,3¢ = 1.6 Hz, 1 H, H2¢a), 3.67 and 3.70 (2 dd,
Jgem = 11.6 Hz, J5¢,4¢ = 5.1 Hz, 2 H, H5¢), 3.72 (s, 3 H, 4-CH3O), 3.86
(s, 3 H, 3-CH3O), 3.96 (td, J4¢,5¢ = 5.1 Hz, J4¢,3¢ = 2.4 Hz, 1 H, H4¢),
4.34 (dddd, J3¢,2¢ = 5.9, 1.6 Hz, J3¢,4¢ = 2.4 Hz, J3¢,1¢ = 0.5 Hz, 1 H,
H3¢), 5.16 (dd, J1¢,2¢ = 10.5, 5.4 Hz, 1 H, H1¢), 7.01 [d, J5,6 = 8.3 Hz,
1 H, 5-H-3,4-(MeO)2C6H3], 7.16 [d, J6,5 = 8.3 Hz, J6,2 = 2.2 Hz, 1 H,
6-H-3,4-(MeO)2C6H3], 7.18 [d, J2,6 = 2.2 Hz, 1 H, 2-H-3,4-
(MeO)2C6H3], 7.44 (m, 2 H, H2, H6), 7.55 (m, 2 H, H3, H5).
Hz, J2¢a,1¢ = 5.4 Hz, J2¢a,3¢ = 1.6 Hz, 1 H, H2¢a), 3.68 and 3.71 (2 dd,
Jgem = 11.7 Hz, J5¢,4¢ = 5.2 Hz, 2 H, H5¢), 3.79 (s, 3 H, 4-CH3O), 3.90
(s, 6 H, 3,5-CH3O), 3.97 (td, J4¢,5¢ = 5.2 Hz, J4¢,3¢ = 2.4 Hz, 1 H, H4¢),
4.34 (dddd, J3¢,2¢ = 6.0, 1.6 Hz, J3¢,4¢ = 2.4 Hz, J3¢,1¢ = 0.6 Hz, 1 H,
H3¢), 5.17 (dd, J1¢,2¢ = 10.6, 5.4 Hz, 1 H, H1¢), 6.87 [s, 2 H, 2,6-H-
(MeO)3C6H2], 7.46 (m, 2 H, H2, H6), 7.58 (m, 2 H, H3, H5).
13C NMR (125.7 MHz, CD3OD): d = 44.94 (2¢-CH2), 56.77 [3-
(CH3O), 5-(CH3O)], 61.21 [4-(CH3O)], 64.11 (5¢-CH2), 74.47 (3¢-
CH), 81.34 (1¢-CH), 89.26 (4¢-CH), 105.67 [2-CH-(MeO)3C6H2, 6-
CH-(MeO)3C6H2], 127.59 (2-CH, 6-CH), 127.90 (3-CH, 5-CH),
138.47 [1-C-(MeO)3C6H2, 4-C-(MeO)3C6H2], 141.77 (4-C), 142.40
(1-C), 154.82 [3-C-(MeO)3C6H2, 5-C-(MeO)3C6H2].
13C NMR (151 MHz, CD3OD): d = 44.90 (2¢-CH2), 56.48 [4-
(CH3O)], 56.53 [3-(CH3O)], 64.08 (5¢-CH2), 74.47 (3¢-CH), 81.41
(1¢-CH), 89.21 (4¢-CH), 111.83 [2-CH-3,4-(MeO)2C6H3], 113.24
[5-CH-3,4-(MeO)2C6H3], 120.49 [6-CH-3,4-(MeO)2C6H3], 127.59
(3-CH, 5-CH), 127.63 (2-CH, 6-CH), 135.33 [C1-3,4-
(MeO)2C6H3], 141.57 (4-C), 141.74 (1-C), 150.14 [C4-3,4-
(MeO)2C6H3], 150.69 [C3-3,4-(MeO)2C6H3],
MS (FAB): m/z = 361 [M + 1].
HRMS (FAB): m/z [M + H] calcd for C20H25O6: 361.1651; found:
361.1646.
MS (FAB): m/z = 331 [M + 1].
Anal. Calcd for C20H24O6 (360): C, 66.65; H, 6.71. Found: C, 66.56;
H, 6.46.
HRMS (FAB): m/z [M + H] calcd for C19H23O5: 331.1546; found:
331.1536.
Anal. Calcd for C19H22O5 (330): C, 69.07; H, 6.71. Found: C, 68.95;
H, 6.63.
1,2-Dideoxy-1b-[4-(3-fluoro-4-methoxyphenyl)phenyl]-D-ribo-
furanose (8s)
Compound 8s was prepared from 3 by general procedure 3. Crystal-
lization (EtOAc–heptane) gave 8s (62 mg, 51%) as white crystals;
mp 144–145 °C.
[a]D20 +36.9 (c 0.33, MeOH).
1,2-Dideoxy-1b-[4-(4-methoxyphenyl)phenyl]-D-ribofuranose
(8u)21
Pd(OAc)2 (5 mg, 0.02 mmol), TPPTS (57 mg, 0.10 mmol), Na2CO3
(128 mg, 1.20 mmol), and 4-methoxyphenylboronic acid (76 mg,
0.50 mmol) were added to an argon-purged dry flask containing 3
(100 mg, 0.37 mmol). Then a soln of H2O–MeCN (2:1, 3 mL) was
added under argon and the mixture was stirred at 80 °C for 5 min
under microwave irradiation. The mixture was then evaporated, and
the crude product was chromatographed (silica gel; gradient: CHCl3
to 2% MeOH–CHCl3) to give 8u. Crystallization (EtOAc–heptane)
gave 8u (43 mg, 38%) as white crystals; mp 155–158 °C.
IR (KBr): 3421, 2847, 1632, 1620, 1586, 1567, 1534, 1509, 1460,
1447, 1437, 1315, 1296, 1279, 1248, 1194, 1176, 1135, 1088, 1052,
1039, 1016, 947, 834, 807, 765, 702, 617, 545, 454 cm–1.
1H NMR (600 MHz, CD3OD): d = 1.97 (ddd, Jgem = 13.1 Hz,
J2¢b,1¢ = 10.6 Hz, J2¢b,3¢ = 5.9 Hz, 1 H, H2¢b), 2.21 (ddd, Jgem = 13.1
Hz, J2¢a,1¢ = 5.4 Hz, J2¢a,3¢ = 1.6 Hz, 1 H, H2¢a), 3.67 and 3.70 (2 dd,
Jgem = 11.6 Hz, J5¢,4¢ = 5.1 Hz, 2 H, H5¢), 3.90 (s, 3 H, 4-CH3O), 3.96
(td, J4¢,5¢ = 5.1 Hz, J4¢,3¢ = 2.4 Hz, 1 H, H4¢), 4.34 (dddd, J3¢,2¢ = 5.9,
1.6 Hz, J3¢,4¢ = 2.4 Hz, J3¢,1¢ = 0.6 Hz, 1 H, H3¢), 5.16 (dd, J1¢,2¢ = 10.6,
5.4 Hz, 1 H, H1¢), 7.15 (t, J5,6 = JH,F = 8.5 Hz, 1 H, 5-H-3-F-4-
MeOC6H3), 7.35–7.38 (m, 2 H, 2-H-3-F-4-MeOC6H3, 6-H-3-F-4-
MeOC6H3), 7.45 (m, 2 H, H2, H6), 7.54 (m, 2 H, H3, H5).
[a]D20 +37.3 (c 0.29, MeOH).
IR (KBr): d = 3428, 1632, 1607, 1583, 1560, 1528, 1500, 1464,
1444, 1401, 1312, 1270, 1251, 1195, 1189, 1180, 1130, 1113, 1087,
1064, 1013, 1000, 946, 812, 803, 701, 518 cm–1.
Synthesis 2008, No. 12, 1918–1932 © Thieme Stuttgart · New York

PAPER
4-Aryl- and 4-Amino-Substituted Benzene C-2¢-Deoxyribonucleosides
1931
1H NMR (500 MHz, CD3OD): d = 1.98 (ddd, Jgem = 13.1 Hz,
2¢b,1¢ = 10.5 Hz, J2¢b,3¢ = 5.9 Hz, 1 H, H2¢b), 2.21 (ddd, Jgem = 13.1
Hz, J2¢a,1¢ = 5.4 Hz, J2¢a,3¢ = 1.7 Hz, 1 H, H2¢a), 3.67 and 3.70 (2 dd,
Jgem = 11.6 Hz, J5¢,4¢ = 5.1 Hz, 2 H, H5¢), 3.82 (s, 3 H, CH3O), 3.96
(td, J4¢,5¢ = 5.1 Hz, J4¢,3¢ = 2.4 Hz, 1 H, H4¢), 4.34 (dddd, J3¢,2¢ = 5.9,
1.7 Hz, J3¢,4¢ = 2.4 Hz, J3¢,1¢ = 0.7 Hz, 1 H, H3¢), 5.15 (dd, J1¢,2¢ = 10.5,
5.4 Hz, 1 H, H1¢), 6.98 (m, 2 H, 3-H-4-MeOC6H4, 5-H-4-
MeOC6H4), 7.43 (m, 2 H, H2, H6), 7.53 (m, 4 H, 4-MeOC6H4).
13C NMR (125.7 MHz, CD3OD): d = 44.90 (2¢-CH2), 55.74 (CH3O),
64.10 (5¢-CH2), 74.48 (3¢-CH), 81.42 (1¢-CH), 89.21 (4¢-CH),
115.25 (3-CH-4-MeOC6H4, 5-CH-4-MeOC6H4), 127.43 (3-CH, 5-
CH), 127.64 (2-CH, 6-CH), 128.91 (2-CH-4-MeOC6H4, 6-CH-4-
MeOC6H4), 134 (1-C-4-MeOC6H4), 141.48 (4-C), 141.53 (1-C),
160.74 (4-C-4-MeOC6H4).
(2) (a) Ogawa, A. K.; Abou-Zied, O. K.; Tsui, V.; Jimenez, R.;
J
Case, D. A.; Romesberg, F. E. J. Am. Chem. Soc. 2000, 122,
9917. (b) Wu, Y. Q.; Ogawa, A. K.; Berger, M.; Mcminn, D.
L.; Schultz, P. G.; Romesberg, F. E. J. Am. Chem. Soc. 2000,
122, 7621. (c) Guckian, K. M.; Krugh, T. R.; Kool, E. T. J.
Am. Chem. Soc. 2000, 122, 6841. (d) Parsch, J.; Engels, J.
W. J. Am. Chem. Soc. 2002, 124, 5664. (e) Lai, J. S.; Qu, J.;
Kool, E. T. Angew. Chem. Int. Ed. 2003, 42, 5973. (f) Lai,
J. S.; Kool, E. T. J. Am. Chem. Soc. 2004, 126, 3040.
(3) (a) Henry, A. A.; Olsen, A. G.; Matsuda, S.; Yu, C.;
Geierstanger, B. H.; Romesberg, F. E. J. Am. Chem. Soc.
2004, 126, 6923. (b) Henry, A. A.; Yu, C. Z.; Romesberg, F.
E. J. Am. Chem. Soc. 2003, 125, 9638. (c) Hwang, G. T.;
Romesberg, F. E. Nucleic Acids Res. 2006, 34, 2037.
(d) Matsuda, S.; Henry, A. A.; Romesberg, F. E. J. Am.
Chem. Soc. 2006, 128, 6369. (e) Kim, Y.; Leconte, A. M.;
Hari, Y.; Romesberg, F. E. Angew. Chem. Int. Ed. 2006, 45,
7809. (f) Matsuda, S.; Fillo, J. D.; Henry, A. A.; Rai, P.;
Wilkens, S. J.; Dwyer, T. J.; Geierstanger, B. H.; Wemmer,
D. E.; Schultz, P. G.; Spraggon, G.; Romesberg, F. E. J. Am.
Chem. Soc. 2007, 129, 10466. (g) Matsuda, S.; Leconte, A.
M.; Romesberg, F. E. J. Am. Chem. Soc. 2007, 129, 5551.
(4) (a) Brotschi, C.; Häberli, A.; Leumann, C. J. Angew. Chem.
Int. Ed. 2001, 40, 3012. (b) Brotschi, C.; Mathis, G.;
Leumann, C. J. Chem. Eur. J. 2005, 11, 1911. (c) Zahn, A.;
Brotschi, C.; Leumann, C. J. Chem. Eur. J. 2005, 11, 2125.
(5) Řeha, D.; Hocek, M.; Hobza, P. Chem. Eur. J. 2006, 12,
3587.
MS (FAB): m/z = 301 [M + 1].
HRMS (FAB): m/z [M + H] calcd for C18H21O4: 301.1440; found:
301.1435.
Anal. Calcd for C18H20O4 (300): C, 71.98; H, 6.71. Found: C, 71.60;
H, 6.81.
Fluorescence and UV-Vis Spectroscopy
The UV-Vis spectra were measured on Varian CARY 100 Bio
Spectrophotometer (e is the molar extinction coefficient in
L·mol–1·cm–1).
The fluorescence measurements were performed on a spectrofluo-
rometer Aminco Bowman series 2 with 220–850 nm range, xenon
source, excitation and emission wavelength scans, spectral band-
width 1–16 nm, PMT detector, scan rate 3–6000 nm/min, Saya-
Namioka grating monochromator. We used the comparative meth-
od of Williams et al.38 for recording fluorescence quantum yield of
a sample fSA (a 10 mM soln of quinine sulfate in 0.1 M H2SO4 (in
H2O) was chosen as a standard: fST = 0.54).39 Thus, the fluores-
cence quantum yield of a sample fSA is calculated by the formula of
equation 1, where the subscripts ST and SA denote standard and
sample respectively, f is the fluorescent quantum yield, IFI the in-
tegrated fluorescence intensity, Grad the gradient from the plot of
IFI vs absorbance A, and h the refractive index of the solvent.
(6) Johar, Z.; Zahn, A.; Leumann, C. J.; Jaun, B. Chem. Eur. J.
2008, 14, 1080.
(7) (a) Singh, I.; Hecker, W.; Prasad, A. K.; Parmar, V. S.; Seitz,
O. Chem. Commun. 2002, 500. (b) Beuck, C.; Singh, I.;
Bhattacharya, A.; Hecker, W.; Parmar, V. S.; Seitz, O.;
Weinhold, E. Angew. Chem. Int. Ed. 2003, 42, 3958.
(8) Johar, Z.; Zahn, A.; Leumann, C. J.; Jaun, B. Chem. Eur. J.
2008, 14, 1080.
(9) (a) Strässler, C.; Davis, N. E.; Kool, E. T. Helv. Chim. Acta
1999, 82, 2160. (b) Gao, J.; Strässler, C.; Tahmassebi, D.;
Kool, E. T. J. Am. Chem. Soc. 2002, 124, 11590. (c) Gao,
J.; Watanabe, S.; Kool, E. T. J. Am. Chem. Soc. 2004, 126,
12748. (d) Wilson, J. N.; Teo, Y. N.; Kool, E. T. J. Am.
Chem. Soc. 2007, 129, 15426.
Grad
ηSA
ηST
2
IFI
A
SA
φSA = φST
where Grad =
GradST
(10) Wu, Q. P.; Simons, C. Synthesis 2004, 1533.
(11) (a) Matsuda, S.; Romesberg, F. E. J. Am. Chem. Soc. 2004,
126, 14419. (b) Mathis, G.; Hunziker, J. Angew. Chem. Int.
Ed. 2002, 41, 3203. (c) Brotschi, C.; Häberli, A.; Leumann,
C. J. Angew. Chem. Int. Ed. 2001, 40, 3012. (d) Brotschi,
C.; Mathis, G.; Leumann, C. J. Chem. Eur. J. 2005, 11,
1911. (e) Zahn, A.; Brotschi, C.; Leumann, C. J. Chem. Eur.
J. 2005, 11, 2125. (f) Reese, C. B.; Wu, Q. Org. Biomol.
Chem. 2003, 1, 3160.
(12) Singh, I.; Seitz, O. Org. Lett. 2006, 8, 4319.
(13) (a) Chaudhuri, N. C.; Kool, E. T. Tetrahedron Lett. 1995, 36,
1795. (b) Ren, R. X.-FChaudhuriNC.; Paris, P. L.; Rumney,
S. I. V.; Kool, E. T. J. Am. Chem. Soc. 1996, 118, 7671.
(c) Griesang, N.; Richert, C. Tetrahedron Lett. 2002, 43,
8755. (d) Aketani, S.; Tanaka, K.; Yamamoto, K.; Ishihama,
A.; Cao, H.; Tengeiji, A.; Hiraoka, S.; Shiro, M.; Shinoya,
M. J. Med. Chem. 2002, 45, 5594. (e) Hainke, S.; Singh, I.;
Hemmings, J.; Seitz, O. J. Org. Chem. 2007, 72, 881.
(14) (a) Yokoyama, M.; Nomura, M.; Togo, H.; Seki, H. J. Chem.
Soc., Perkin Trans. 1 1996, 2145. (b) He, W.; Togo, H.;
Yokoyama, M. Tetrahedron Lett. 1997, 38, 5541.
(c) Hainke, S.; Arndt, S.; Seitz, O. Org. Biomol. Chem. 2005,
3, 4233.
Equation 1 Fluorescence quantum yield calculation
Acknowledgment
This work is a part of the research project Z04 055 905. It was sup-
ported by the Centre of Biomolecules and Complex Molecular
Systems (LC 512) and by NIH, Fogarty International Center (Grant
1R03TW007372-01).
References
(1) (a) Wang, L.; Schultz, P. G. Chem. Commun. 2002, 1.
(b) Henry, A. A.; Romesberg, F. E. Curr. Opin. Chem. Biol.
2003, 7, 727. (c) Kool, E. T.; Morales, J. C.; Guckian, K. M.
Angew. Chem. Int. Ed. 2000, 39, 990. (d) Kool, E. T. Acc.
Chem. Res. 2002, 35, 936.
Synthesis 2008, No. 12, 1918–1932 © Thieme Stuttgart · New York

1932
N. Joubert et al.
PAPER
(30) Reviews: (a) Labinger, J. A.; Bercaw, J. E. Nature 2002,
(15) (a) Wang, Z. X.; Wiebe, L. I.; De Clercq, E.; Balzarini, J.;
Knaus, E. E. Can. J. Chem. 2000, 78, 1081. (b) Häberli, A.;
Leumann, C. J. Org. Lett. 2001, 3, 489. (c) Sun, Z.; Ahmed,
S.; McLaughlin, L. W. J. Org. Chem. 2006, 71, 2922.
(16) Hocek, M.; Pohl, R.; Klepetářová, B. Eur. J. Org. Chem.
2005, 4525.
(17) Urban, M.; Pohl, R.; Klepetářová, B.; Hocek, M. J. Org.
Chem. 2006, 71, 7322.
(18) Joubert, N.; Pohl, R.; Klepetářová, B.; Hocek, M. J. Org.
417, 507. (b) Godula, K.; Sames, D. Science 2006, 312, 67.
(31) (a) Bellina, F.; Cauteruccio, S.; Mannina, L.; Rossi, R.; Viel,
S. J. Org. Chem. 2005, 70, 3997. (b) Bellina, F.;
Cauteruccio, S.; Mannina, L.; Rossi, R.; Viel, S. Eur. J. Org.
Chem. 2005, 693. (c) Bellina, F.; Cauteruccio, S.; Rossi, R.
Eur. J. Org. Chem. 2006, 1379. (d) Bellina, F.; Calandri, C.;
Cauteruccio, S.; Rossi, R. Tetrahedron 2007, 63, 1970.
(e) Review: Seregin, I. V.; Gevorgyan, V. Chem. Soc. Rev.
2007, 36, 1173.
Chem. 2007, 72, 6797.
(19) Bárta, J.; Pohl, R.; Klepetářová, B.; Ernsting, N. P.; Hocek,
M. J. Org. Chem. 2008, in press; DOI: 10.1021/jo800177y.
(20) Štefko, M.; Pohl, R.; Klepetářová, B.; Hocek, M. Eur. J.
Org. Chem. 2008, 1689.
(21) Zahn, A.; Leumann, C. J. Bioorg. Med. Chem. 2006, 14,
6174.
(32) Čerňa, I.; Pohl, R.; Klepetářová, B.; Hocek, M. Org. Lett.
2006, 8, 5389.
(33) Čerňa, I.; Pohl, R.; Hocek, M. Chem. Commun. 2007, 4729.
(34) For related arylations of pentafluorobenzene, see: Lafrance,
M.; Rowley, C. N.; Woo, T. K.; Fagnou, K. J. Am. Chem.
Soc. 2006, 128, 8754.
(22) Hoffer, M. Chem. Ber. 1960, 93, 2777.
(23) (a) Deriaz, R. E.; Overend, W. G.; Stacey, M.; Teece, E. G.;
Wiggins, L. F. J. Chem. Soc. 1949, 1879. (b) Walker, J. A.
I. I.; Chen, J. J.; Wise, D. S.; Townsend, L. B. J. Org. Chem.
1996, 61, 2219.
(35) (a) Western, E. C.; Daft, J. R.; Johnson, E. M. I. I.; Garnnett,
P. M.; Shoughnessy, K. H. J. Org. Chem. 2003, 68, 6767.
(b) Čapek, P.; Pohl, R.; Hocek, M. Org. Biomol. Chem.
2006, 4, 2278. (c) Vrábel, M.; Pohl, R.; Klepetářová, B.;
Votruba, I.; Hocek, M. Org. Biomol. Chem. 2007, 5, 2849.
(36) Wichai, U.; Woski, S. A. Bioorg. Med. Chem. Lett. 1998, 8,
3465.
(24) Čapek, P.; Pohl, R.; Hocek, M. J. Org. Chem. 2005, 70,
8001.
(25) (a) Lee, S.; Jorgensen, M.; Hartwig, J. F. Org. Lett. 2001, 3,
2729. (b) Lee, D.-Y.; Hartwig, J. F. Org. Lett. 2005, 7, 1169.
(26) Wolfe, J. P.; Tomori, H.; Sadighi, J. P.; Yin, J.; Buchwald,
S. L. J. Org. Chem. 2000, 65, 1158.
(27) Huang, X.; Buchwald, S. L. Org. Lett. 2001, 3, 3417.
(28) Wolfe, J. P.; Tomori, H.; Sadighi, J. P.; Yin, J.; Buchwald,
S. L. J. Org. Chem. 2000, 65, 1158.
(37) Cires, L.; Ofenberg, H.; Nicolaescu, T.; Craita, C.; Pollet, A.
J. Lumin. 1998, 79, 91.
(38) Williams, A. T. R.; Winfield, S. A.; Miller, J. N. Analyst
1983, 108, 1067.
(39) (a) Lakowicz, J. R. Principles of Fluorescence
Spectroscopy, 2nd ed.; Kluwer Academic/Plenum Press:
New York, 1999. (b) Handbook of Organic Photochemistry;
Scaiano, J. C., Ed.; CRC Press: Boca Raton, 1989.
(c) Melhuish, W. H. J. Phys. Chem. 1961, 65, 229.
(29) Shen, Q.; Shekhar, S.; Stambuli, J. P.; Hartwig, J. F. Angew.
Chem. Int. Ed. 2005, 44, 1371.
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