Er(OTf)3 as a valuable catalyst in a short synthesis of 2′,3′-dideoxy pyranosyl nucleosides via Ferrier rearrangement

Article abstract of DOI:10.1055/s-2006-942443

Er(OTf)₃ is a useful catalyst for the Ferrier rearrangement furnishing 2′,3′-dideoxy pyranosyl nucleosides easily by means of cleaner reaction profiles, short reaction times, mild reaction conditions, good stereoselectivity, and good recoverability of the commercially available catalyst. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-942443

2608
PAPER
Er(OTf)3 as a Valuable Catalyst in a Short Synthesis of 2¢,3¢-Dideoxy
Pyranosyl Nucleosides via Ferrier Rearrangement
S
hor
t
Synthesis of
n
2¢, 3¢-Dideo
t
xy Pyr
o
anosyl
N
ucle
n
osides by E
r
i
(OTf
)
3ocatalysis Procopio,*a Renato Dalpozzo,b Antonio De Nino,b Monica Nardi,b Manuela Oliverio,a Beatrice Russoa
a
Dipartimento Farmaco-Biologico, Università degli Studi della Magna Grascia Complesso Ninì Barbieri,
Roccelletta di Borgia (CZ) 88021, Italy
Fax +39(0961)391270; E-mail: procopio@unicz.it
Dipartimento di Chimica, Università della Calabria, Ponte Bucci, Arcavacata di Rende (CS), 87030, Italy
b
Received 14 February 2006; revised 23 March 2006
rearrangement using silylated nucleophiles.8 In order to
expand the applicability of Er(OTf)3 as a Lewis acid cata-
lyst in the Ferrier rearrangement we looked at N-glycosi-
dation. We first tested the reaction of 3,4,6-tri-O-acetyl-D-
glucal (1) with transient protected trimethylsilyl thymine
4 generate in situ using HMDS (Scheme 1).9
Abstract: Er(OTf)3 is a useful catalyst for the Ferrier rearrange-
ment furnishing 2¢,3¢-dideoxy pyranosyl nucleosides easily by
means of cleaner reaction profiles, short reaction times, mild reac-
tion conditions, good stereoselectivity, and good recoverability of
the commercially available catalyst.
Key words: Ferrier rearrangement, erbium(III) triflate, Lewis acid
catalyst, nucleosides, glycals
AcO
AcO
O
OTMS
AcO
AcO
O
Over recent decades, there has been considerable interest
in nucleoside analogues as a consequence of their poten-
tial use as antiviral, antineoplastic,1 and antibiotic thera-
peutic agents.2 Therefore, many structural modifications
of natural nucleosides have been made to find molecules
showing enhanced biological activities.1b,d,3 Most nucleo-
side modifications have focused around five-membered
ring systems, but few examples have been published on
the corresponding pyranosides,1b,4 especially regarding
the 2,3-dideoxy pyranoside nucleoside analogues,2,4a,4e,5
which resemble the potent antiviral modified nucleosides
ddNs.
CH3
N
Er(OTf)3
+
N
O
O
H
(NH4)2SO4, solvent
TMSO
N
AcO
1
4
N
H3C
8 α/β = 70:30
Scheme 1
The reaction conditions were explored performing the
process in several solvents at different temperatures with
different amounts of catalyst (Table 1).
Very few methodologies exist to prepare N-glycosides by
means of a Ferrier rearrangement, and often they have
limitations in terms of drastic reaction conditions, work-
up, reaction time, and amount of catalyst; some others
were tested in only limited examples. Herdewijn and co-
workers proposed,6 about ten years ago, a ‘no-acid-added’
Ferrier rearrangement of the glycal 3,4-bis-O-(p-nitroben-
zoyl)-D-xylal and pyridine/pyrimidine derivatives to pro-
vide acceptable yields of a,b-2¢,3¢-unsaturated
pentopyranosyl nucleosides on a preparative scale.
The best result was obtained when the reaction was car-
ried out in anhydrous acetonitrile with 10 mol% Er(OTf)3
at 50 °C (Table 1, entry 3). A similar result was obtained
in anhydrous THF, but the reaction time almost doubled
(Table 1, entry 5). All the other solvents were shown to be
considerably less appropriate for the reported reaction and
in the absence of anhydrous conditions no product was re-
covered.
Table 1 N-Glycosidation of 3,4,6-Tri-O-acetyl-D-glucal (1) in
Herein we report the synthesis of 2¢,3¢-pyranosyl nucleo-
sides via Ferrier rearrangement catalyzed by erbium(III)
triflate.
Various Reaction Conditions
Entry Solvent
Er(OTf)3 Time
(mol%) (h)
Temp
(°C)
Yield
(%)
Over the last few years, we have developed the use of new
catalytic reagents for several strategic steps in organic
synthesis with the aim of lowering the environmental im-
pact.7 More recently, we described the use of erbium(III)
trifluoromethanesulfonate, as a Lewis acid catalyst, for
the synthesis of 2,3-unsaturated C-glycosides via Ferrier
1
2
3
4
5
6
7
CH2Cl2 (anhyd)
5
10
10
10
10
10
10
24
15
7
25
50
50
50
50
50
50
20
30
64
10
40
10
30
CH2Cl2 (anhyd)
CH3CN (anhyd)
CH3NO2 (anhyd)
THF (anhyd)
15
15
15
10
SYNTHESIS 2006, No. 15, pp 2608–2612
x
x.
x
x
.
2
0
0
6
Et2O (anhyd)
Advanced online publication: 28.06.2006
DOI: 10.1055/s-2006-942443; Art ID: Z03806SS
© Georg Thieme Verlag Stuttgart · New York
CHCl3 (anhyd)

PAPER
Short Synthesis of 2¢,3¢-Dideoxy Pyranosyl Nucleosides by Er(OTf)3 catalysis
2609
a
Table 2 N-Glycosidation of Glycal Derivatives Using Er(OTf)3
Entry
1
Glycal
Silyl nucleobase
Product
Time (h)
7b
Yield (%)
64
a/b ratio
70:30
65:35
27:73
OTMS
OAc
AcO
AcO
O
CH3
O
Thy
N
TMSO
N
AcO
8
AcO
4
1
2
3
4
16
14
43
51
OAc
AcO
AcO
O
O
O
Thy
Thy
AcO
AcO
2
9
4
H3C
H3C
O
AcO
AcO
AcO
10
3
1
4
5
10b
55
42
75:25
65:35
OTMS
N
OAc
O
Ura
N
TMSO
AcO
11
5
5
2
8
OAc
O
O
Ura
Ura
AcO
12
H3C
6
7
3
1
5
12
10
70
45
37:63
71:29
AcO
13
NHTMS
N
OAc
O
Cyt
N
TMSO
AcO
14
6
8
2
6
6
N
15
42
73:27
OAc
O
O
Cyt
Cyt
AcO
15
9
3
1
16
8
36
60
38:62
65:35
H3C
AcO
16
10
NHTMS
OAc
O
O
Ade
Ade
N
AcO
TMS
17
7
7
11
2
13
45
72:28
OAc
AcO
18
Synthesis 2006, No. 15, 2608–2612 © Thieme Stuttgart · New York

2610
A. Procopio et al.
PAPER
a
Table 2 N-Glycosidation of Glycal Derivatives Using Er(OTf)3 (continued)
Entry
12
Glycal
Silyl nucleobase
Product
Time (h)
15
Yield (%)
46
a/b ratio
40:60
3
7
H3C
O
Ade
AcO
19
a Er(OTf)3 (10 mol%) in anhyd MeCN at reflux.
b The reaction was carried out at 50 °C.
H4
In addition, the yield of the reaction did not exceed 64%;
nevertheless, it is much higher than the yields in the pre-
viously reported examples.2,6
O
H4
O
H1
R
AcO
AcO
AcO
R
H1
AcO
H5
H5
Noteworthy, after work-up, the aqueous phase can be con-
centrated under reduced pressure to furnish the Er(III)
salt10 as a pale pink solid (85–90% recovered), which can
be recycled after drying overnight over P2O5. The recov-
ered catalyst was used five times in the above reported re-
action without significant loss of activity.
NOE
H1
NOE
α-D-gluco series
OAc
β-D-gluco series
OAc
O
O
R
H4
H4
R
H1
AcO
AcO
Based on the results reported in Table 1, we adopted a
simple experimental procedure and tested the four nucleo-
bases 4–7 with glucal 1, galactal 2, and 6-deoxyglucal 3.
A solution of the substrate in anhydrous acetonitrile was
stirred in the presence of 10 mol% catalyst for about five
minutes, then the silyl nucleic base (2.0 equiv) was added
under reflux and the course of reaction was followed by
TLC (Table 2).
H5
H5
NOE
NOE
α-D-galacto series
β-D-galactoseries
H4
O
H4
O
H1
R
AcO
AcO
H5
R
H5
H1
CH3
CH3
All reactions gave satisfactory yields, comparable or high-
er than reported examples. Particularly, the tri-O-acetyl-
D-glucal 1 always gave higher yields than the galactal an-
alogue 2 as previously reported.8,11d,13
NOE
NOE
NOE
NOE
H5
In every case, the anomeric ratio was determined from the
crude mixture by means of 1H and 13C NMR spectroscopy
in accordance with earlier studies.8,11 Then the major ano-
mer was fully characterized by 1H and 13C NMR after pu-
rification by flash column chromatography. The
configuration was assigned on the basis of NOE experi-
ments (Figure 1) and on the assertion that, in the 13C NMR
spectra, the C-5 chemical shift is always less than 75 ppm
as reported for the g-gauche effect on 1,5-trans isomers (a
for D-gluco and galacto-series and b for L-deoxygluco se-
ries).12
H5
R
H3C
H4
H1
H3C
H4
H1
OAc
O
R
OAc
O
α-deoxy-L-gluco series
β-deoxy-L-gluco series
Figure 1 NOE interactions in glycals
In conclusion, the use of Er(OTf)3 presents several advan-
tages which include acceptable yields of products, cleaner
reaction profiles, mild reaction conditions [a solution 0.1
M of Er(OTf)3 in water is only weakly acidic with pH ca.
5.9], good stereoselectivity, wide applicability, and recov-
erability of the catalyst, which is also commercially avail-
able.
The stereoselectivity of this reaction is good, giving most-
ly the a-anomers for the glucal- and galactal-derivatives.
It is easily explained considering the key step of the reac-
tion where all cationic intermediates should take a confor-
mation with C-6 in a pseudo-equatorial orientation,
independently from the 4-AcO-group position as was re-
ported in our previous publications.8 Then the less hin-
dered face of the C1–O p-orbital of the D-gluco and
galacto series orients the incoming nucleophile to form a
bond always in the a-axial position. On the other hand, in
L-deoxy glucal, the less hindered face of the p-orbital al-
lows the nucleophile to find a major orbital overlapping,
approaching from the b-side of the ion, so that the b-ano-
mer was the predominant product.
1H and 13C NMR spectra were recorded with a Bruker WM 300 in-
strument, at 300 MHz and 75 MHz respectively. in CDCl3 solution,
with TMS as the internal standard. Elemental analyses were per-
formed on a Perkin Elmer 2400 analyzer.
Preparation of Silylated Nucleobases
The appropriate nucleobase (4.4 mmol) was heated at 140–150 °C
with HMDS (2.62 g, 16.2 mmol), TMSCl (217 mg, 2.0 mmol), and
a trace of (NH4)2SO4 until a clear solution formed. Then, the solu-
tion was concentrated in vacuo giving the product as a white solid
which is pure enough to be used in the next step.
Synthesis 2006, No. 15, 2608–2612 © Thieme Stuttgart · New York

PAPER
Short Synthesis of 2¢,3¢-Dideoxy Pyranosyl Nucleosides by Er(OTf)3 catalysis
1-(4¢,6¢-O-Diacetyl-2¢,3¢-dideoxy-a-D-threo-hex-2-eno-
2611
N-Glycosidation; Typical Procedure
The 3,4,6-tri-O-acetyl-D-glucal (1; 0.5 g, 1.84 mmol) was added to
a solution of Er(OTf)3 (0.11 g, 0.184 mmol, 10 mol%) in dry MeCN
(3.0 mL) and the resulting solution was stirred at r.t. for 5 min.
Then, silylated thymine 4 (0.13 g, 1.103 mmol) was added and the
reaction was stirred under reflux for 7 h, until almost complete con-
version of substrate 1 was achieved (TLC, CHCl3–MeOH, 9:1). The
organic solution was washed with H2O (5.0 mL), dried, and concen-
trated to give the crude product, which was purified by flash chro-
matography (CHCl3–MeOH, 9:1); yield: 0.398 g (1.18 mmol).
pyranosyl)uracil (12)
Pale yellow oil.
1H NMR (CDCl3): d = 2.09 (s, 3 H, CH3COO), 2.13 (s, 3 H,
CH3COO), 4.09–4.13 (m, 1 H, H-5¢), 4.14–4.29 (m, 2 H, H-6¢),
4.70–4.79 (m, 1 H, H-2¢), 4.90–4.98 (m, 1 H, H-4¢), 5.27–5.34 (m,
1 H, H-3¢), 5.75 (d, J = 8.13 Hz, 1 H, H-5), 6.82 (dd, J = 6.14, 1.34
Hz, 1 H, H-1¢), 7.52 (d, J = 8.13 Hz, 1 H, H-6).
13C NMR (CDCl3): d = 20.7, 50.6, 62.1, 66.4, 70.9, 94.4, 102.3,
140.8, 149.3, 150.6, 163.3, 169.2, 170.4.
1-(4¢,6¢-O-Diacetyl-2¢,3¢-dideoxy-a-D-erythro-hex-2-eno-
pyranosyl)thymidine (8)
Pale yellow oil.
Anal. Calcd for C14H16N2O7: C, 51.85; H, 4.97; N, 8.64. Found: C,
51.93; H, 4.90; N, 8.74.
1H NMR (CDCl3): d = 1.94 (d, J = 1.24 Hz, 3 H, CH3), 2.09 (s, 3 H,
CH3COO), 2.14 (s, 3 H, CH3COO), 3.98–4.09 (m, 1 H, H-5¢), 4.18
(dd, J = 12.21, 3.46 Hz, 1 H, H-6¢), 4.29 (dd, J = 12.21, 5.63 Hz, 1
H, H-6¢), 5.21–5.32 (m, 1 H, H-4¢), 5.86–5.96 (m, 1 H, H-2¢), 6.28–
6.37 (m, 1 H, H-3¢), 6.44 (dd, J = 4.40, 2.06 Hz, 1 H, H-1¢), 7.28 (d,
J = 1.24 Hz, 1 H, H-6), 9.92 (br s, 1 H, NH).
1-(4¢-O-Acetyl-2¢,3¢,6¢-trideoxy-b-L-erythro-hex-2-eno-
pyranosyl)uracil (13)
Pale yellow oil.
1H NMR (CDCl3): d = 1.29 (d, 3 H, CH3, J = 6.27 Hz), 2.10 (s, 3 H,
CH3COO), 4.05–4.21 (m, 1 H, H-5¢), 4.53–4.62 (m, 1 H, H-4¢),
4.76–4.90 (m, 1 H, H-2¢), 5.57–5.70 (m, 1 H, H-3¢), 5.80 (d, J = 8.13
Hz, 1 H, H-5), 6.65 (dd, J = 5.87, 2.1 Hz, 1 H, H-1¢), 7.25 (d, J =
8.13 Hz, 1 H, H-6), 9.76 (br s, 1 H, NH).
13C NMR (CDCl3): d = 12.4, 20.6, 62.2, 64.00, 70.0, 110.7, 126.1,
131.1, 136.2, 150.8, 164.0, 170.0, 170.5.
13C NMR (CDCl3): d = 20.2, 20.4, 69.3, 78.0, 102.9, 126.9, 131.9,
139.9, 150.2, 163.4, 169.7, 170.2.
Anal. Calcd for C15H18N2O7: C, 53.25; H, 5.36; N, 8.28. Found: C,
53.21; H, 5.39; N, 8.11.
Anal. Calcd for C12H14N2O5: C, 54.13; H, 5.30; N, 10.52. Found: C,
53.08; H, 5.39; N, 10.41.
1-(4¢,6¢-O-Diacetyl-2¢,3¢-dideoxy-a-D-threo-hex-2-eno-
pyranosyl)thymidine (9)
Pale yellow oil.
1-(4¢,6¢-O-Diacetyl-2¢,3¢-dideoxy-a-D-erythro-hex-2-eno-
pyranosyl)cytosine (14)
Pale yellow oil.
1H NMR (CDCl3): d = 1.73 (br s, 2 H, NH2), 2.08 (s, 3 H, CH3COO),
2.11 (s, 3 H, CH3COO), 3.98–4.06 (m, 1 H, H-5¢), 4.17–4.26 (m, 2
H, H-6¢), 5.33–5.41 (m, 1 H, H-4¢), 5.73–5.85 (m, 2 H, H-2¢, H-5),
6.06–6.13 (m, 1 H, H-3¢), 6.72 (dd, J = 4.0, 2.54 Hz, 1 H, H-1¢), 7.30
(d, J = 7.47 Hz, 1 H, H-6).
1H NMR (CDCl3): d = 1.93 (d, J = 1.32 Hz, 3 H, CH3), 2.10 (s, 3 H,
CH3COO), 2.13 (s, 3 H, CH3COO), 3.95–4.26 (m, 3 H, H-5¢, H-6¢),
4.60–4.70 (m, 1 H, H-2¢), 4.80–4.90 (m, 1 H, H-4¢), 5.10–5.25 (m,
1 H, H-3¢), 6.85 (dd, J = 6.27, 1.62 Hz, 1 H, H-1¢), 7.29 (d, J = 1.32
Hz, 1 H, H-6), 9.10 (br s, 1 H, NH).
13C NMR (CDCl3): d = 12.4, 20.7, 50.3, 62.0, 66.6, 71.0, 95.1,
110.7, 136.4, 150.7, 163.8, 169.1, 170.3.
13C NMR (CDCl3): d = 20.7, 21.1, 60.1, 66.4, 68.3, 79.9, 95.8,
124.2, 126.1, 140.1, 152.3, 168.3, 171.3, 172.4.
Anal. Calcd for C15H18N2O7: C, 53.25; H, 5.36; N, 8.28. Found: C,
53.18; H, 5.30; N, 8.21.
Anal. Calcd for C14H17N3O6: C, 52.01; H, 5.30; N, 13.00. Found: C,
51.93; H, 5.39; N, 12.91.
1-(4¢-O-Acetyl-2¢,3¢,6¢-trideoxy-b-L-erythro-hex-2-eno-
pyranosyl)thymidine (10)
Pale yellow oil.
1-(4¢,6¢-O-Diacetyl-2¢,3¢-dideoxy-a-D-thero-hex-2-eno-
pyranosyl)cytosine (15)
Pale yellow oil.
1H NMR (CDCl3): d = 1.70 (br s, 2 H, NH2), 2.10 (s, 3 H, CH3COO),
2.14 (s, 3 H, CH3COO), 4.08–4.16 (m, 1 H, H-5¢), 4.18–4.40 (m, 2
H, H-6¢), 5.32–5.43 (m, 1 H, H-4¢), 5.63–5.78 (m, 2 H, H-2¢, H-5),
6.01–6.10 (m, 1 H, H-3¢), 6.77 (dd, J = 1.74, 6.27 Hz, 1 H, H-1¢),
7.28 (d, J = 7.33 Hz, 1 H, H-6).
1H NMR (CDCl3): d = 1.20 (d, J = 6.13 Hz, 3 H, CH3), 1.95 (d, J =
1.07 Hz, 3 H, CH3), 2.12 (s, 3 H, CH3COO), 4.02–4.19 (m, 1 H, H-
5¢), 4.60–4.67 (m, 1 H, H-4¢), 4.77–4.88 (m, 1 H, H-2¢), 5.38–5.57
(m, 1 H, H-3¢), 6.65 (dd, J = 6.01, 2.27 Hz, 1 H, H-1¢), 7.29 (d, J =
1.07 Hz, 1 H, H-6), 9.76 (br s, 1 H, NH).
13C NMR (CDCl3): d = 13.2, 21.4, 23.6, 68.8, 71.1, 110.9, 123.1,
132.9, 134.3, 149.8, 164.0, 169.6, 170.1.
13C NMR (CDCl3): d = 20.4, 20.7, 58.3, 66.1, 65.3, 77.4, 100.0,
123.2, 125.2, 139.1, 150.2, 167.3, 169.8, 171.2.
Anal. Calcd for C13H16N2O5: C, 55.71; H, 5.75; N, 9.99. Found: C,
55.61; H, 5.69; N, 9.85.
Anal. Calcd for C14H17N3O6: C, 52.01; H, 5.30; N, 13.00. Found: C,
52.11; H, 5.23; N, 12.89.
1-(4¢,6¢-O-Diacetyl-2¢,3¢-dideoxy-a-D-erythro-hex-2-eno-
pyranosyl)uracil (11)
Pale yellow oil.
1-(4¢-O-Acetyl-2¢,3¢,6¢-trideoxy-b-L-erythro-hex-2-eno-
pyranosyl)cytosine (16)
Pale yellow oil.
1H NMR (CDCl3): d = 1.21–1.30 (m, 3 H, CH3), 2.04 (m, 3 H,
CH3COO), 3.98–4.18 (m, 1 H, H-5¢), 5.15–5.27 (m, 1 H, H-4¢),
5.60–5.90 (m, 2 H, H-5, H-2¢), 6.00–6.12 (m, 1 H, H-3¢), 6.65–6.76
(m, 1 H, H-1¢), 7.17 (d, J = 7.35 Hz, 1 H, H-6).
1H NMR (CDCl3): d = 2.12 (s, 3 H, CH3COO), 2.14 (s, 3 H,
CH3COO), 4.07–3.98 (m, 1 H, H-5¢), 4.13–4.34 (m, 2 H, H-6¢),
5.23–5.30 (m, 1 H, H-4¢), 5.86–5.93 (m, 1 H, H-2¢), 6.35–6.28 (m,
1 H, H-3¢), 6.46 (dd, J = 4.40, 2.05 Hz, 1 H, H-1¢), 7.21 (d, J = 8.07
Hz, 1 H, H-5), 7.47 (d, J = 8.07 Hz, 1 H, H-6), 9.68 (br s, 1 H, NH).
13C NMR (CDCl3): d = 16.9, 18.5, 66.9, 73.2, 74.3, 79.7, 101.5,
127.7, 143.6, 130.2, 151.9, 163.8, 170.8, 171.0.
13C NMR (CDCl3): d = 14.2, 20.3, 68.8, 74.8, 78.3, 95.4, 127.8,
128.5, 140.7, 155.9, 165.3, 169.2.
Anal. Calcd for C14H16N2O7: C, 51.85; H, 4.97; N, 8.64; O, 34.54.
Found: C, 51.78; H, 4.89; N, 8.51.
Synthesis 2006, No. 15, 2608–2612 © Thieme Stuttgart · New York

2612
A. Procopio et al.
PAPER
Anal. Calcd for C12H15N3O4: C, 54.33; H, 5.70; N, 15.84. Found: C,
54.46; H, 5.59; N, 15.91.
G. Nucleosides Nucleotides 1999, 18, 581. (e) Piperno, A.;
Procopio, A.; Rescifina, A.; Romeo, G.; Romeo, R. Eur. J.
Org. Chem. 2001, 1893. (f) Chiacchio, U.; Corsaro, A.;
Iannazzo, D.; Piperno, A.; Pistarà, V.; Procopio, A.;
Rescifina, A.; Romeo, G.; Romeo, R.; Siciliano, M. C. R.;
Valveri, E. Arkivoc 2002, (xi), 159. (g) Chiacchio, U.;
Genovese, F.; Iannazzo, D.; Librando, V.; Merino, P.;
Rescifina, A.; Romeo, R.; Procopio, A.; Romeo, G.
Tetrahedron 2004, 60, 441. (h) Procopio, A.; Alcaro, S.; De
Nino, A.; Maiuolo, L.; Ortuso, F.; Sindona, G. Bioorg. Med.
Chem. Lett. 2005, 15, 545.
7-(4¢,6¢-O-Diacetyl-2¢,3¢-dideoxy-a-D-erythro-hex-2-eno-
pyranosyl)adenine (17)
Pale yellow oil.
1H NMR (CDCl3): d = 2.38 (s, 3 H, CH3COO), 2.46 (s, 3 H,
CH3COO), 4.41–4.48 (m, 1 H, H-5¢), 4.55–4.58 (m, 2 H, H-6¢),
5.77–5.87 (m, 1 H, H-4¢), 6.32–6.39 (m, 1 H, H-2¢), 6.52–6.58 (m,
1 H, H-3¢), 6.97 (dd, J = 4.0, 2.4 Hz, 1 H, H-1¢), 8.01 (s, 1 H, H-2),
8.38 (s, 1 H, H-8).
(4) (a) Bowles, W. A.; Robins, R. K. J. Am. Chem. Soc. 1964,
86, 1252. (b) Niedballa, U.; Vorbrüggen, H. J. Org. Chem.
1974, 39, 3654. (c) Chow, K.; Danishefsky, S. J. Org.
Chem. 1990, 55, 4211. (d) Augustyns, K.; Rezenski, J.; Van
Aerschot, A.; Janssen, G.; Herdewijn, P. J. Org. Chem.
1993, 58, 2977. (e) Biörsne, M.; Classon, B.; Kvarnström,
I.; Samuelsson, B. Tetrahedron 1993, 49, 8637.
(5) Perez-Perez, M. J.; Doboszewski, B.; Rozenski, J.;
Herdewijn, P. Tetrahedron: Asymmetry 1995, 6, 973.
(6) Doboszewski, B.; Blaton, N.; Herdewijn, P. J. Org. Chem.
1995, 60, 7909.
(7) (a) Bartoli, G.; Cupone, G.; Dalpozzo, R.; De Nino, A.;
Maiuolo, L.; Marcantoni, E.; Procopio, A. Synlett 2001,
1897. (b) Bartoli, G.; Cupone, G.; Dalpozzo, R.; De Nino,
A.; Maiuolo, L.; Procopio, A.; Sambri, L.; Tagarelli, A.
Tetrahedron Lett. 2002, 43, 5945. (c) Dalpozzo, R.; De
Nino, A.; Maiuolo, L.; Procopio, A.; Tagarelli, A.; Sindona,
G.; Bartoli, G. J. Org. Chem. 2002, 67, 9093. (d) Dalpozzo,
R.; De Nino, A.; Maiuolo, L.; Procopio, A.; Nardi, M.;
Bartoli, G.; Romeo, R. Tetrahedron Lett. 2003, 44, 5621.
(e) Bartoli, G.; Bosco, M.; Dalpozzo, R.; Macantoni, E.;
Massaccesi, M.; Rinaldi, S.; Sambri, L. Synlett 2003, 39.
(f) Dalpozzo, R.; De Nino, A.; Maiuolo, L.; Nardi, M.;
Procopio, A.; Tagarelli, A. Synthesis 2004, 496.
13C NMR (CDCl3): d = 17.5, 17.9, 67.0, 71.1, 75.8, 83.9, 132.2,
143.6, 149.1, 153.6, 156.2, 170.9, 171.3.
Anal. Calcd for C15H17N5O5: C, 51.87; H, 4.93; N, 20.16. Found: C,
51.95; H, 4.89; N, 20.09.
7-(4¢,6¢-O-Diacetyl-2¢,3¢-dideoxy-a-D-thero-hex-2-eno-
pyranosyl)adenine (18)
Pale yellow oil.
1H NMR (CDCl3): d = 1.68 (br s, 2 H, NH2), 2.09 (s, 3 H, CH3COO),
2.13 (s, 3 H, CH3COO), 4.18–4.34 (m, 3 H, H-5¢, H-6¢), 4.70–4.76
(m, 1 H, H-2¢), 5.40–5.45 (m, 1 H, H-4¢), 5.53–5.60 (m, 1 H, H-3¢),
6.43–6.50 (dd, J = 6.27, 1.74 Hz, 1 H, H-1¢), 7.94 (s, 1 H, H-2), 8.40
(s, 1 H, H-8).
13C NMR (CDCl3): d = 20.9, 21.7, 62.9, 68.9, 69.7, 82.0, 120.1,
127.3, 140.8, 150.3, 152.7, 156.6, 170.3, 171.0.
Anal. Calcd for C15H17N5O5: C, 51.87; H, 4.93; N, 20.16. Found: C,
51.75; H, 4.99; N, 20.29.
7-(4¢-O-Acetyl-2¢,3¢,6¢-trideoxy-b-L-erythro-hex-2-eno-
pyranosyl)adenine (19)
Pale yellow oil.
1H NMR (CDCl3): d = 1.36 (s, 3 H, CH3), 2.22 (s, 3 H, CH3COO),
4.16–4.22 (m, 1 H, H-5¢), 4.57–4.68 (m, 1 H, H-4¢), 5.07–5.18 (m,
1 H, H-2¢), 5.54–5.70 (m, 1 H, H-3¢), 6.62–6.75 (m, 1 H, H-1¢), 7.83
(s, 1 H, H-2), 8.43 (s, 1 H, H-8).
(g) Procopio, A.; Dalpozzo, R.; De Nino, A.; Nardi, M.;
Sindona, G.; Tagarelli, A. Synlett 2004, 2633.
(h) Dalpozzo, R.; De Nino, A.; Maiuolo, L.; Nardi, M.;
Procopio, A.; Tagarelli, A. Adv. Synth. Catal. 2004, 346,
1465.
13C NMR (CDCl3): d = 13.4, 20.5, 67.4, 72.3, 80.9, 119.4, 125.3,
127.9, 139.3, 148.3, 152.8, 156.1, 170.3.
(8) Procopio, A.; Dalpozzo, R.; De Nino, A.; Nardi, M.; Russo,
B.; Tagarelli, A. Synthesis 2006, 332.
(9) Ho, T. L. Tetrahedron 1985, 41, 1.
Anal. Calcd for C13H15N5O3: C, 53.97; H, 5.23; N, 24.21. Found: C,
53.83; H, 5.32; N, 24.11.
(10) The purity of recovered Er(OTf)3 was confirmed by
comparison with the IR spectrum of the commercial product.
(11) (a) Ghosh, R.; De, D.; Shown, B.; Maiti, S. B. Carbohydr.
Res. 1999, 321, 1. (b) Yadav, J. S.; Reddy, B. V. S.
Synthesis 2002, 511. (c) Yadav, J. S.; Reddy, B. V. S.; Raju,
A. K.; Rao, C. V. Tetrahedron Lett. 2002, 43, 5437.
(d) Yadav, J. S.; Reddy, B. V. S.; Rao, C. V.; Chand, P. K.;
Prasad, A. R. Synlett 2001, 1638. (e) Saeeng, R.; Sirion, U.;
Sahakitpichan, P.; Isobe, M. Tetrahedron Lett. 2003, 44,
6211. (f) Yadav, J. S.; Reddy, B. V. S.; Reddy, K. S.;
Chandraiah, L. Synthesis 2004, 2523.
(12) Günter, H. NMR Spectroscopy: Basic Principles Concepts
and Applications in Chemistry; J. Wiley & Sons: New York,
1998, 501–504.
(13) (a) Das, S. K.; Reddy, K. A.; Abbineni, C.; Roy, J.; Rao, K.
V. L. N.; Sachwani, R.; Iqbal, J. Tetrahedron Lett. 2003, 44,
4507. (b) Yadav, J. S.; Reddy, B. V. S.; Chand, P. K.
Tetrahedron Lett. 2001, 42, 4057.
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Synthesis 2006, No. 15, 2608–2612 © Thieme Stuttgart · New York