Radical-mediated furanose ring reconstruction from 2′,3′-seco-uridine

Article abstract of DOI:10.1016/S0040-4020(01)00203-4

Starting from 5′-O-trityl-2′,3′-seco-uridine, reconstruction of a furanose structure was carried out by the following sequence of reactions: (1) regioselective introduction of a phenylselenenyl group to the 2′-position of the 2′,3′-seco-uridine, (2) oxidation and subsequent Wittig reaction of the 3′-hydroxyl group and (3) intramolecular radical reaction (5-exo-trig ring closure) leading to 3′-C-carbon-substituted 2′,3′-dideoxyuridine. Also studied is the Pummerer reaction of the 2′-phenylseleno derivative of 2′,3′-seco-uridine. The resulting product, an α-(acyloxy)phenylselenide, also serves as a substrate for the radical cyclization to allow the introduction of a hydroxyl group at the 2′-position of the reconstructed furanose ring.

Full text of DOI:10.1016/S0040-4020(01)00203-4

TETRAHEDRON
Pergamon
Tetrahedron 57 .2001) 3331±3341
Radical-mediated furanose ring reconstruction
from 20,30-seco-uridine
Hiroki Kumamoto,a Junko Ogamino,a Hiromichi Tanaka,a,p Hisaki Suzuki,a Kazuhiro Haraguchi,a
Tadashi Miyasaka,a Tsutomu Yokomatsub and Shiroshi Shibuyab
aSchool of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan
bSchool of Pharmacy, Tokyo University of Pharmacy and Life Science, 1432-1 Horinouchi, Hachioji, Tokyo 192-0392, Japan
Received 25 January 2001; accepted 19 February 2001
AbstractÐStarting from 50-O-trityl-20,30-seco-uridine, reconstruction of a furanose structure was carried out by the following sequence of
reactions: .1) regioselective introduction of a phenylselenenyl group to the 20-position of the 20,30-seco-uridine, .2) oxidation and subsequent
Wittig reaction of the 30-hydroxyl group and .3) intramolecular radical reaction .5-exo-trig ring closure) leading to 30-C-carbon-substituted
20,30-dideoxyuridine. Also studied is the Pummerer reaction of the 20-phenylseleno derivative of 20,30-seco-uridine. The resulting product, an
a-.acyloxy)phenylselenide, also serves as a substrate for the radical cyclization to allow the introduction of a hydroxyl group at the 20-
position of the reconstructed furanose ring. q 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
20-O-silyl derivative 3 was separated from 4 and 5, and
was then converted to the radical precursor 8 which under-
went a highly diastereoselective 5-exo-trig ring closure
leading to 9.
30-C-Branched 20,30-dideoxyribonucleosides of general
structure 1 have attracted much attention due to their struc-
tural similarity to the anti-HIV agent AZT .30-azido-30-
deoxythymidine) as well as their usefulness as building
blocks of nuclease-resistant antisense oligonucleotides.1
Syntheses of 1 have been accomplished by initial construc-
tion of sugar structures which were then condensed with
nucleobases,2 or by radical-mediated 30-C-allylation of 20-
deoxyuridine or thymidine derivatives.3
In 1988, we reported that a phenylselenide anion prepared
by reducing .PhSe)2 with LiAlH4 serves as a highly ef®cient
species for the introduction of a phenylselenenyl group to
the 20-position, through cleavage of the anhydro bond of
O2,20-cyclouridine.6 We anticipated that the regioselective
preparation of the 20-phenylselenenyl-20,30-seco-uridines
would be possible starting with a readily accessible O2,20-
cyclo derivative of 20,30-seco-uridine, and that such
compounds, upon radical cyclization, would give 1 as
reported by Chattopadhyaya et al.
O
X
NH
5'
N
1'
O
HO
O
4'
In the present study, the regioselective introduction of a
phenylselenenyl group to the 20-position of 20,30-seco-
uridine and the radical-mediated reconstruction of the
furanose ring were studied in detail. The choice of phenyl-
selenenyl group is not only as a precursor of a simple 20-
alkyl radical but also due to its possibility to undergo a
Pummerer reaction, the product of which would permit
generation of an a-acyloxyalkyl radical.
1 X = H, Me
Y = CH=CH2, C CH, CN, CO2R, PO(OR)2
3'
2'
CH2Y
The latter method, by further manipulation of the 30-C-allyl
group, allowed the preparations of 30-C-cyanomethyl and
30-C-propargyl derivatives.4 An additional unique approach
to 1 .XˆMe, YˆCO2Et) utilizing 50-O-protected 20,30-seco-
.ribofuranosyl)thymine .2) has been reported by
Chattopadhyaya et al. .Scheme 1).5 In this approach, the
2. Preparation of substrates for radical reaction
The 20,30-seco-uridine 10, prepared from 50-O-trityluridine,
was converted to the O2,20-cyclo derivative 11 according to
the published procedure.7 Preparation of 12 by selective ring
opening of 11 was then examined .Scheme 2).
Keywords: nucleosides; radicals and radical reactions; selenium and
compounds; steric and strain effects.
Corresponding author. Tel.: 181-3-3784-8186; fax: 181-3-3784-8252;
p
e-mail: hirotnk@pharm.showa-u.ac.jp
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020.01)00203-4

3332
H. Kumamoto et al. / Tetrahedron 57 /2001) 3331±3341
O
N
O
Me
O
N
Me
Me
NH
NH
NH
MMTr
MMTr
MMTr
O
O
N
O
O
O
O
TBDMSCl
O
O
O
OH
OTBDMS
OR
HO
HO
TBDMSO
2
3
4 R = H
5 R = TBDMS
MMTr = monomethoxytrityl
TBDMS = tert-butyldimethylsilyl
O
O
Me
Me
NH
NH
N
O
MMTr
O
N
O
RO
O
Bu3SnH
O
OR
CO2Et
CH2CO2Et
9 R = MMTr
1 R = H
6 R = TBDMS
7 R = H
8 R = C(S)OPh
Scheme 1.
O
O
O
N
NH
NH
N
O
TrO
N
O
TrO
TrO
O
N
ref. 7
O
O
O
SePh
MsO
OH
HO
MsO
12
10
11
Scheme 2.
When sodium benzeneselenolate, prepared from Na and
.PhSe)2 in THF in the presence of 18-crown-6,8 was reacted
with 11 .room temperature, for 19 h), several products .13,
3%; 14, 5%; 15, 5%) were formed in addition to 12 .7%) and
the recovered 11 .44%). The formation of 13 and 147 is a
likely consequence of aryl-O-®ssion of the O2,20-anhydro
bond which yields 2-phenylseleno-4-pyrimidone inter-
mediate that could be hydrolyzed during work-up. The
reaction of 11 with a selenide anion generated by reducing
.PhSe)2 with NaBH4 in EtOH±THF9 .room temperature, for
16 h) improved the yield of 12 .49%), but again a consider-
able amount of 11 .26%) was recovered together with a
by-product 16 .6%).
When the Swern oxidation10 was applied, the desired 18
.32%) was accompanied by its 40-epimer 19 .14%), presu-
mably due to Et3N which was used for quenching the oxi-
dation. The use of .i-Pr)2NEt prevented the formation of
19; however, poor reproducibility of the yield of 18 .37±
69%) led us to examine two other oxidation methods, the
O
O
NH
NH
N
O
TrO
N
O
TrO
O
O
X
Y
O
In contrast to these results, when phenylselenide anion
derived from .PhSe)2/LiAlH4/THF6 was used, the desired
12 was obtained exclusively in 94% yield. This reaction is
completed within 15 min at 2208C, which also contrasts
with the above two examples. Compound 12 was converted
to the 30-hydroxyl derivative 17 by treatment with NaOAc
in 5% aqueous DMF .1008C for 3 h, 93%) followed by NH3/
MeOH .room temperature for 42 h, 97%).
13 X = OH, Y = OMs
16 X = Y = SePh
14
O
N
N
TrO
O
O
To introduce radical-acceptors to the 30-position, oxidation
of 17 under several conditions and subsequent Wittig reac-
tion with Ph3PCHCO2Me were examined .Scheme 3).
PhSe
15

H. Kumamoto et al. / Tetrahedron 57 /2001) 3331±3341
3333
O
N
O
O
N
NH
NH
NH
O
N
O
O
TrO
TrO
1) oxidation
O
O
O
TrO
2) Wittig reaction
SePh
HO
SePh
SePh
R
CO2Me
17
18 R = CO2Me
19
20 R = CN (E/Z = 88/12)
21 R = PO(OPh)2
Scheme 3.
P®tzner±Moffatt oxidation11 and the Dess±Martin oxida-
tion.12 Although both methods gave more than 70% yield
of 18 without epimerization at the 40-position, the latter
method appeared to be superior due to its simplicity of
work-up procedure.
Although the reaction time varies signi®cantly depending
on the temperature, no detectable amount of reduced
product was formed in all entries. The highly ef®cient cycli-
zation observed here is certainly due to the nucleophilic
character14 of the 20-alkyl radical, which favors reaction
with electron-de®cient ole®ns.
Thus, when the 30-aldehyde obtained by the Dess±Martin
oxidation of 17 was reacted in CH3CN with
Ph3PCHCO2Me, 18 was obtained in 73% isolated yield.
As pointed out by Chattopadhyaya et al.,5 the observed
dominant formation of the erythro isomer 22 would be
explicable based on the fact that the radical species involved
in this reaction is a `2,4-cis-disubstituted 5-hexenyl radi-
cal'15 and, thus, both substituents .uracil base and 40-
CH2OTr) would favor pseudo-equatorial positions .confor-
mer A in Fig. 1) in the transition state that resembles the
chair form of cyclohexane. An additional factor working
here in disfavor of B may be a 1,3-allylic strain16 between
the vinylic hydrogen alpha to the methoxycarbonyl group
and the 40-CH2OTr substituent. To see which substituent
.uracil base or 40-CH2OTr) is more demanding in the
pseudo-equatorial position, the cyclization of the .40R)-
epimer 19 was also carried out under the conditions of
entry 4 in Table 1.
1
The .E)-con®guration of 18 was con®rmed by H NMR
spectroscopy .J-value of the ole®nic protons: 15.9 Hz).
Occasionally, a small amount .,1±3%) of the .Z)-isomer
.J-value of the ole®nic protons: 11.8 Hz) was observed in
18. The same reaction sequence was applied to the prepara-
tion of 20 .76%, E/Zˆ88:12) and 21 .44%).
3. Reconstruction of furanose ring by radical cyclization
By using 18 as a substrate, reconstruction of the furanose
ring leading to 20,30-dideoxy-30-C-carbon-substituted
uridine was investigated .Scheme 4). The radical-mediated
cyclization, carried out by adding a mixture of Bu3SnH and
AIBN via a motor-driven syringe, proceeded in 5-exo-trig
manner in high yield with a high diastereoselectivity .22/
23), irrespective of the reaction temperature .Table 1).13
As shown in Scheme 5, the reaction of 19 not only gave the
simple furanose-reconstructed products, 24 .51%) and 25
.21%),17 but also the 6,30-methano derivative 26 .7%: as a
O
N
O
N
NH
NH
O
O
TrO
TrO
Bu3SnH / Et3B or AIBN
O
O
18
MeO2C
CO2Me
23
22
Scheme 4.
Table 1. Radical-mediated cyclization of 18
Entry
Reagents .equiv.)
Solvent
Temperature .8C)
Time .h)
68
Yield .%)
84
Ratio of 22/23
1
2
3
4
Bu3SnH .1.5), Et3B .1.2)
Bu3SnH .1.5), Et3B .1.2)
Bu3SnH .2.0), AIBN .0.2)
Bu3SnH .1.5), AIBN .0.1)
Benzene
Benzene
Benzene
Toluene
rt
97:3
5028
80
110
98:2 80
20
1
90
92
97:3
97:3

3334
H. Kumamoto et al. / Tetrahedron 57 /2001) 3331±3341
OTr
H
OTr
O
H
U
O
MeO2C
MeO2C
H2C
U
H2C
H
H
H
A
B
22
23
Figure 1. Transition structures of the radical derived from 18.
O
O
O
N
NH
NH
NH
MeO2C
TrO
N
O
N
O
O
Bu3SnH / AIBN
toluene
O
O
O
19
TrO
TrO
CO2Me
24
CO2Me
26a and 26b
25
Scheme 5.
product 2220 was obtained only in 35% yield after 68 h,
which contrasts with the case of 18 .entry 1 in Table 1).
TLC analysis .hexane/EtOAcˆ2:3) of the reaction mixture
showed that, in addition to 22 .35% yield, Rf 0.19) and the
starting material 27 .29% yield, Rf 0.43), an additional
product .Rf 0.49) was formed in this reaction. The 1H
NMR spectrum of this product con®rmed its structure to
be the .E)-isomer 18 .18% yield). It is conceivable, there-
fore, that the radical-mediated isomerization of 27 to 18 is a
slow process and that the cyclization of 27 takes place at
least in part through 18.21
H
H
H
OTr
O
U
MeO2C
MeO2C
H2C
U
O
H2C
H
H
OTr
C
D
24 and 26
25
O
O
Figure 2. Transition structures of the radical derived from 19.
NH
NH
mixture of two diastereomers).18 One could say that the
transition state conformation C .Fig. 2) is preferred simply
because the 40-CH2OTr group is more bulky than the base
moiety. However, the observed stereochemical outcome
may also be explicable in terms of 1,3-allylic strain: in the
conformer D, an unfavorable disposition of the vinylic
hydrogen and the 40-CH2OTr results, as was seen in the
conformer B in Fig. 1.
N
O
TrO
N
O
TrO
O
O
MeO2C
SePh
TrO
CN
27
28
O
N
NH
O
O
We next examined the in¯uence of the con®guration of the
ole®nic structure. Oxidation of 17 with DMSO±DCC
followed by the Horner±Emmons reaction employing
LHMDS and .CF3CH2O)2P.O)CH2CO2Me19 gave a mixture
of 18 and its .Z)-isomer 27 .total yield 74%, E/Zˆ1.0:4.6).
OPh
OPh
P
O
29
The desired .Z)-isomer 27 was isolated by HPLC puri®ca-
tion of the mixture. When 27 was subjected to the radical
reaction under the conditions of entry 4 in Table 1, almost
the same results as the case of 18 were obtained .93% yield,
ratio of 22/23ˆ99:1). However, when the reaction of 27 was
carried out in benzene at room temperature, the cyclized
The cyclization of other substrates 20 and 21 under the
optimized reaction conditions .entry 4 in Table 1) also
gave the corresponding furanose-reconstructed products
28 .93% yield, erythro/threoˆ97:3) and 29 .95% yield,
erythro/threoˆ99:1), respectively, in a highly diastereo-
selective manner.

H. Kumamoto et al. / Tetrahedron 57 /2001) 3331±3341
3335
O
O
N
NH
NH
N
O
O
TrO
TrO
O
O
Bu3SnH / AIBN or Et3B
31-33
OCOR
MeO2C
MeO2C
OCOR
34a R = Me
34b R = CMe3
34c R = Ph
35a R = Me
35b R = CMe3
35c R = Ph
Scheme 6.
4. Pummerer products derived from 20-phenylseleno-
20,30-seco-uridine and their use as substrates for radical-
mediated reconstruction of furanose ring
uniformly in high yields .78±89%) as a mixture of
two diastereomers.
O
O
N
NH
NH
Although a selenium version of the Pummerer reaction
has been known,22 one concern regarding this reaction is
concomitant formation of elimination products caused by
enhanced reactivity of selenoxides. In our earlier works on
selenoxide elimination using uridine derivatives,6b it was
observed that their phenylselenoxides are stable enough to
be isolated when the b-position is occupied with an electro-
negative atom such as oxygen.23
N
O
O
TrO
TrO
O
O
31 R = Me
32 R = CMe3
33 R = Ph
O
OCOR
SePh
CO2Me
Se Ph
CO2Me
30
Since the b-position to the selenium atom of 20-phenyl-
seleno-20,30-seco-uridines carries an oxygen atom as well
as the base moiety, we reasoned that the selenoxide derived
from these compounds could be stable and that their
Pummerer reaction would give a-.acyloxy)phenylselenides,
that can serve as substrates for the radical cyclization,
without forming 10,20-unsaturated 20,30-seco-uridines. This
appeared to be the case. When 18 was oxidized with
m-CPBA in CH2Cl2, the corresponding selenoxide 30
was isolated in 91% yield as a mixture of two dia-
stereomers. When the seleno-Pummerer reaction using
30 was carried out in CH2Cl2 with acid anhydrides,
the a-.acyloxy)phenylselenides 31±33 were obtained
We next studied the radical reactions of 31±33 to recon-
struct the furanose ring having a hydroxyl group at the
20-position .Scheme 6). The results are summarized in
Table 2. Despite the fact that an acyloxy substituent
decreases the nucleophilicity of carbon-radicals,24 these
substrates uniformly gave high yields of cyclized products.
From Table 2, it can also be seen that, irrespective of the
substrate used, the major product was the isomer 34 having
30-deoxyribofuranosyl con®guration.25 To see the effect of
reaction temperature on the stereoselectivity about the 20-
position .the ratio of 34/35), the reaction of 33 was carried
out at lower temperatures .entries 4±6); however, no
signi®cant change was observed even at 2508C.
Table 2. Radical-mediated cyclization of 31±33
Entry
Substrate
Initiator .equiv.)
Solvent
Temp.
Time .h)
Yield .%)
Ratio of 34/35
1
2
3
4
5
6
31
32
33
33
33
33
AlBN .0.2)
AlBN .0.2)
AlBN .0.2)
Et3B .1.2)
Et3B .1.2)
Et3B .1.2)
toluene
toluene
toluene
benzene
benzene
toluene
1108C
1108C
1108C
r.t.
08C
2508C
1
1
1
24
24
24
9068/32
82
94
91
94
59/41
69/31
74/26
75/25
77/23
76
All reactions were carried out by using 2.0equiv of Bu 3SnH.
Table 3. Radical-mediated cyclization of the two diastereomers of 31
Entry
Substrate
Initiator .equiv.)
Solvent
Temp.
Time .h)
Yield .%)
Ratio of 34/35
1
2
3
4
31a
31a
31b
31b
AlBN .0.2)
Et3B .1.2)
AlBN .0.2)
Et3B .1.2)
toluene
benzene
toluene
benzene
1108C
r.t.
1108C
r.t.
1
24
1
74
93
98
97
66/34
71/29
68/32
71/29
24
All reactions were carried out by using 2.0equiv of Bu 3SnH.

3336
H. Kumamoto et al. / Tetrahedron 57 /2001) 3331±3341
An additional factor, which possibly alters the stereo-
selectivity of these reactions, would be the con®guration
about the 20-position of the substrates 31±33.26 To examine
this possibility, each diastereomer of 31 was isolated by
silica gel column chromatography, and these were sepa-
rately used as substrates for the radical cyclization. In
Table 3, the major isomer and the minor one are referred
to as 31a and 31b, respectively. When a comparison is made
between the yields of entries 1 and 3, it is apparent that the
major diastereomer 31a is less reactive than 31b. In terms of
the stereoselectivity, however, both substrates gave exactly
the same results irrespective of the reaction temperature.
These results suggest that, although accessibility of tin
radical to the 20-phenylseleno group may differ depending
on the con®guration .the steric environment around the
20-position), both diastereomers eventually generate the
same sp2-hybridized radical intermediate.27
between CHCl3 and H2O. Silica gel column chromato-
graphy .10% MeOH in CHCl3) of the organic layer gave
the recovered 11 .219 mg, 44%). Fractions containing 12
and 14 were combined and subjected to HPLC separation
.hexane/EtOAcˆ1:2). This gave 12 .tR 12 min, 47 mg, 7%)
and 14 .tR 15 min, 19 mg, 5%).
Physical data of 12: UV .MeOH) lmax 263 nm .e 11 100),
1
lmin 244 nm .e 7700); H NMR .CDCl3) d 2.94 .3H, s,
SO2Me), 3.12 .1H, dd, Jˆ6.4 and 13.6 Hz, H-50), 3.20±
3.22 .2H, m, H-20), 3.28 .1H, dd, Jˆ6.0and 13.6 Hz,
H-50), 3.63±3.66 .1H, m, H-40), 4.27 .1H, dd, Jˆ2.4 and
11.2 Hz, H-30), 4.40.1H, dd, Jˆ3.2 and 11.2 Hz, H-30),
0
5.42 .1H, d, Jˆ8.0Hz, H-5), 6.02 .1H, t, Jˆ6.0Hz, H-1 ),
7.19 .1H, d, Jˆ8.0Hz, H-6), 7.20±7.35 and 7.49±7.50
.20H, each as m, Ph), 9.01 .1H, br, NH); FAB-MS m/z
707 .M11H). Anal. calcd for C35H34N2O7SSe: C, 59.57;
H, 4.86; N, 3.97. Found: C, 59.47; H, 4.49; N, 3.97.
Physical data of 14: see Ref. 5.
5. Conclusion
Following regioselective preparation of 20,30-seco-uridines
having a phenylselenenyl group at the 20-position, 30-C-
branched 20,30-dideoxyribonucleosides .1) were synthe-
sized based on radical-mediated reconstruction of the fura-
nose ring. The observed dominant formation of the erythro
isomer can be explained in terms of the stability of the chair-
like transition structure, in which 1,3-pseudo-diaxial inter-
action between the base and the 40-CH2OTr as well as 1,3-
allylic strain of the ole®nic portion could be working as
determinants of the stereochemistry.
Fractions containing 13 and 15 were combined and
subjected to HPLC separation .CHCl3/MeOHˆ30:1). This
gave 15 .tR 15 min, 29 mg, 5%) and 13 .tR 16 min, 14 mg,
3%).
Physical data of 13: UV .MeOH) lmax 260nm . e 8600),
1
lmin 243 nm .e 5300); H NMR .CDCl3) d 3.03 .3H, s,
SO2Me), 3.20±3.27 .2H, m, H-2 0), 3.68±3.75 .2H, m,
H-30 and H-40), 3.80.1H, dd, Jˆ5.2 and 12.4 Hz, H-30),
4.34 .1H, dd, Jˆ5.2 and 11.6 Hz, H-50), 4.49 .1H, dd,
Jˆ2.8 and 11.6 Hz, H-50), 5.56 .1H, d, Jˆ8.0Hz, H-5),
5.91 .1H, t, Jˆ5.2 Hz, H-10), 7.21±7.35 .16H, m, Ph and
H-6); FAB-MS m/z 567 .M11H). Anal. calcd for
C29H30N2O8S: C, 61.47; H, 5.34; N, 4.94. Found: C,
61.32; H, 5.28; N, 4.78.
Successful seleno-Pummerer reaction of the selenoxide
derived from 18 exempli®ed the utility of the present
approach by the synthesis of 30-C-branched nucleosides
having a hydroxyl group at the 20-position.
Physical data of 15: UV .MeOH) lshoulder 262 nm .e 8400);
0
1
H NMR .CDCl3) d 2.86 .1H, dd, Jˆ8.0and 13.2 Hz, H-3 ),
6. Experimental
6.1. General
3.03 .1H, dd, Jˆ4.0and 13.2 Hz, H-3 0), 3.27 .1H, dd, Jˆ7.2
0
and 11.2 Hz, H-50), 3.42 .1H, dd, Jˆ4.0and 11.2 Hz, H-5 ),
3.71±3.77 .1H, m, H-40), 4.48 .1H, dd, Jˆ2.8 and 10.4 Hz,
H-20), 4.62 .1H, dd, Jˆ6.4 and 10.4 Hz, H-20), 5.72 .1H, d,
Jˆ7.4 Hz, H-5), 5.78 .1H, dd, Jˆ2.8 and 6.4 Hz, H-10), 7.17
.1H, d, Jˆ7.4 Hz, H-6), 7.25±7.36 and 7.37±7.43 .20H,
each as m, Ph); FAB-MS m/z 611 .M11H). Anal. calcd
for C34H30N2O4Se: C, 66.99; H, 4.96; N, 4.60. Found: C,
66.62; H, 5.07; N, 4.40.
1H NMR spectra were measured at 238C .internal standard,
Me4Si) with JNM-LA500 .500 MHz) or JNM-GX400
.400 MHz) spectrometers. Mass spectra .MS) were taken
in FAB mode .m-nitrobenzyl alcohol as a matrix) with a
JMS-SX 102A spectrometer. For compounds containing
Se, ion peaks corresponding to 80Se are shown. Ultraviolet
.UV) spectra were recorded on a JASCO Ubest-55 spectro-
photometer. Column chromatography was carried out on
silica gel .Silica Gel 60, Merck). Thin layer chromatography
.TLC) was performed on silica gel .precoated silica gel
plate F254, Merck). HPLC was carried out on a Shimadzu
LC-6AD with a Shim-pack PREP-SIL .H) KIT column
.2£25 cm).
6.1.2. Reaction of 11 with 2PhSe)2/NaBH4. Under positive
pressure of dry Ar, an EtOH .5 mL) solution containing
.PhSe)2 .240mg, 0.77 mmol) was treated with NaBH
4
.45 mg, 1.19 mmol) at room temperature for 10min. To
this was added 11 .500 mg, 0.91 mmol) in THF .5 mL),
and the reaction mixture was stirred at room temperature
for 16 h. The mixture was quenched by adding 20% AcOH
in MeOH and evaporated. The resulting residue was chro-
matographed on a silica gel column. Elution with hexane/
EtOAcˆ2:1±1:4 gave 16 .39 mg, 6%, foam) and 12
.315 mg, 49%). Elution with 10% MeOH in CHCl3 gave
the recovered 11 .130mg, 26%).
6.1.1. Reaction of 11 with NaSePh. A mixture of .PhSe)2
.228 mg, 0.73 mmol) and Na .33 mg, 1.43 mmol) in THF
.7 mL) was re¯uxed for 4 h under positive pressure of dry
Ar. To the resulting solution, 11 .500 mg, 0.91 mmol) and
18-crown-6 .12 mg, 0.045 mmol) were added at room
temperature, and stirred for 19 h. The reaction mixture
was treated with 20% AcOH in MeOH and then partitioned
Physical data of 16: UV .MeOH) lmax 265 nm .e 14 700),

H. Kumamoto et al. / Tetrahedron 57 /2001) 3331±3341
3337
1
lmin 245 nm .e 11 200); H NMR .CDCl3) d 3.03±3.13
Compound 17 .711 mg, 1.13 mmol) in CH2Cl2 .7 mL) was
added to the above solution. After stirring for 30min at
2808C, the reaction was quenched by adding Et3N
.1.57 mL, 11.3 mmol), and the mixture was stirred for
30min at room temperature. The reaction mixture was
partitioned between saturated aqueous NH4Cl and CH2Cl2.
The separated organic layer was dried .MgSO4), evaporated,
and taken up into CH3CN .7 mL). The resulting CH3CN
solution was reacted with Ph3PCHCO2Me .568 mg,
1.7 mmol) at room temperature overnight. The reaction
mixture was evaporated and passed through a short column
of silica gel .hexane/EtOAcˆ3:2). HPLC separation
.hexane/EtOAcˆ2:3) of the mixture gave 18 .tR 10min,
247 mg, 32%, foam) and 19 .tR 12 min, 106 mg, 14%,
foam).
.4H, m, H-20 and H-30), 3.19 .1H, dd, Jˆ6.2 and 10.4 Hz,
H-50), 3.26 .1H, dd, Jˆ4.4 and 10.4 Hz, H-50), 3.61±3.63
.1H, m, H-40), 5.36 .1H, d, Jˆ8.0Hz, H-5), 5.92 .1H, t,
Jˆ5.6 Hz, H-10), 7.19±7.32, 7.37±7.40, and 7.44±7.47
.26H, each as m, Ph and H-6), 8.06 .1H, br, NH); FAB-
MS m/z 807 .M11H). Anal. calcd for C40H36N2O4Se2: C,
62.67; H, 4.73; N, 3.65. Found: C, 62.76; H, 4.49; N, 3.66.
6.1.3. Reaction of 11 with 2PhSe)2/LiAlH4. Under positive
pressure of dry Ar, a THF .30mL) solution containing
.PhSe)2 .1.36 g, 4.37 mmol) was treated with LiAlH4
.124 mg, 3.28 mmol) at room temperature for 15 min and
then cooled to 2208C. To this was added 11 .3.0g,
5.47 mmol), and the reaction mixture was stirred at
2208C for 15 min. After being quenched with 10% AcOH
in MeOH, the whole reaction mixture was chromatographed
on a silica gel column .hexane/EtOAcˆ1:4) to give 12
.3.61 g, 94%).
Physical data of 18: UV .MeOH) lmax 263 nm .e 11 900),
1
lmin 244 nm .e 8600); H NMR .CDCl3) d 3.13 .1H, dd,
Jˆ3.2 and 10.9 Hz, H-50), 3.19 .1H, dd, Jˆ5.4 and 13.6 Hz,
H-20), 3.26 .1H, dd, Jˆ5.4 and 13.6 Hz, H-20), 3.36 .1H, dd,
Jˆ7.6 and 10.8 Hz, H-50), 3.72 .3H, s, CO2Me), 3.83±3.87
.1H, m, H-40), 5.47 .1H, dd, Jˆ2.0and 8.0Hz, H-5), 5.79
.1H, t, Jˆ5.4 Hz, H-10), 5.97 .1H, dd, Jˆ1.0and 15.9 Hz,
CHCO2Me), 6.61 .1H, dd, Jˆ3.6 and 15.9 Hz,
CHvCHCO2Me), 7.19±7.31, 7.35±7.38 and 7.46±7.48
.20H, each as m, Ph), 7.58 .1H, d, Jˆ8.0Hz, H-6), 8.80
.1H, br, NH); FAB-MS m/z 683 .M11H). Anal. calcd for
C37H34N2O6Se: C, 65.20; H, 5.03; N, 4.11. Found: C, 64.93;
H, 4.89; N, 4.09.
6.1.4.
20-Deoxy-20-phenylseleno-50-O-trityl-20,30-seco-
uridine 217). A mixture of 12 .2.24 g, 3.17 mmol) and
NaOAc .1.3 g, 15.8 mmol) in 5% aqueous DMF .20mL)
was heated at 1008C for 3 h. The reaction mixture was parti-
tioned between EtOAc and H2O. Silica gel column chroma-
tography .hexane/EtOAcˆ1:1) of the organic layer gave
30-O-acetyl-20-deoxy-20-phenylseleno-50-O-trityl-20,30-seco-
uridine .1.97 g, 93%) as a foam. Physical data of this
compound are as follows: UV .MeOH) lmax 263 nm .e
1
11 400), lmin 244 nm .e 7800); H NMR .CDCl3) d 1.97
.3H, s, Ac), 3.08±3.24 .4H, m, H-20 and H-50), 3.63±3.68
Physical data of 19: UV .MeOH) lmax 263 nm .e 11 600),
1
.1H, m, H-40), 4.08 .1H, dd, Jˆ6.2 and 12.0Hz, H-3 ), 4.30
lmin 244 nm .e 8400); H NMR .CDCl3) d 3.19 .1H, dd,
0
0
.1H, dd, Jˆ3.6 and 12.0Hz, H-3 ), 5.42 .1H, d, Jˆ8.0Hz,
Jˆ6.2 and 13.6 Hz, H-20), 3.24±3.32 .3H, m, H-20 and
H-50), 3.69 .3H, s, CO2Me), 4.06±4.09 .1H, m, H-40),
5.55 .1H, d, Jˆ8.2 Hz, H-5), 5.86 .1H, dd, Jˆ1.4 and
15.8 Hz, CHCO2Me), 6.19 .1H, t, Jˆ6.2 Hz, H-10), 6.61
.1H, dd, Jˆ6.2 and 15.8 Hz, CHvCHCO2Me), 7.16±7.70
.21H, m, Ph and H-6), 8.29 .1H, br, NH); FAB-MS m/z 683
.M11H). Anal. calcd for C37H34N2O6Se´0.5H2O: C, 64.35;
H, 5.11; N, 4.06. Found: C, 64.74; H, 4.82; N, 3.83.
0
H-5), 6.08 .1H, t, Jˆ6.0Hz, H-1 ), 7.21±7.36 and 7.48±
7.50.21H, each as m, Ph and H-6), 8.19 .1H, br, NH);
FAB-MS m/z 671 .M11H). Anal. calcd for
C36H34N2O6Se: C, 64.57; H, 5.12; N, 4.18. Found: C,
64.26; H, 4.72; N, 4.10. The above acetate .1.95 g,
2.91 mmol) in THF .20mL) was treated with saturated
NH3 in MeOH .60mL) in a sealed tube for 42 h. The reac-
tion mixture was evaporated and chromatographed on a
silica gel column .hexane/EtOAcˆ1:4). This gave 17
.1.78 g, 97%) as a foam: UV .MeOH) lmax 263 nm .e
6.1.6. Dess±Martin oxidation of 17 and subsequent reac-
tion with Ph3PCHCO2Me. Under positive pressure of dry
Ar, a mixture of 17 .1.0g, 1.59 mmol) and the Dess±Martin
reagent 1,1,1-triacetoxy-1,1-dihydro-1,2-benziodoxol-3.1H)-
one .810mg, 1.91 mmol) in CH 2Cl2 .10mL) was stirred at
room temperature for 15 min. The reaction mixture was
®ltered, and the ®ltrate was partitioned between saturated
aqueous NH4Cl and CH2Cl2. The organic layer was evapo-
rated and taken up into CH3CN .10mL). The resulting
CH3CN solution was reacted with Ph3PCHCO2Me
.797 mg, 2.39 mmol) at room temperature overnight. After
evaporation of the solvent, the reaction mixture was chro-
matographed on a silica gel column .hexane/EtOAcˆ1:1) to
give 18 .796 mg, 73%).
1
11 300), lmin 245 nm .e 7900); H NMR .CDCl3, after
addition of D2O) d 3.11 .1H, dd, Jˆ7.6 and 13.6 Hz,
H-20), 3.17 .1H, dd, Jˆ4.4 and 13.6 Hz, H-20), 3.21 .1H,
dd, Jˆ4.4 and 10.4 Hz, H-50), 3.30.1H, dd, Jˆ6.4 and
10.4 Hz, H-50), 3.48±3.51 .1H, m, H-40), 3.61 .1H, dd,
Jˆ4.8 and 12.8 Hz, H-30), 3.78 .1H, dd, Jˆ3.6 and
12.8 Hz, H-30), 5.47 .1H, d, Jˆ8.0Hz, H-5), 5.93 .1H, dd,
Jˆ4.4 and 7.6 Hz, H-10), 7.22±7.30, 7.34±7.36, and
7.51±7.54 .20H, each as m, Ph), 7.42 .1H, d, Jˆ8.0Hz,
H-6); FAB-MS m/z 629 .M11H). Anal. calcd for
C34H32N2O5Se´0.5H2O: C, 64.15; H, 5.23; N, 4.40. Found:
C, 64.48; H, 4.94; N, 4.28.
6.1.5. Swern oxidation of 17 and subsequent reaction
with Ph3PCHCO2Me: formation of 30-C-2E)-2carbo-
methoxy)methylene-20,30-dideoxy-20-phenylseleno-50-O-
trityl-20,30-seco-uridine 218) and its 40-epimer 219). Under
positive pressure of dry Ar, .COCl)2 .102 mL, 1.70mmol)
was added to a CH2Cl2 .7 mL) solution of DMSO .200 mL,
2.83 mmol) at 2808C, and the mixture was stirred for 5 min.
6.1.7. 30-C-Cyanomethylene-20,30-dideoxy-20-phenylseleno-
50-O-trityl-20,30-seco-uridine 220). Under positive pressure
of dry Ar, a THF .8 mL) solution of .cyanomethyl)tributyl-
phosphonium chloride .797 mg, 2.87 mmol) was treated
with LHMDS .1 M THF solution, 2.6 mL, 2.58 mmol) for
30min. To this was added a THF .8 mL) solution of the
aldehyde prepared from 17 .600 mg, 0.96 mmol) and the

3338
H. Kumamoto et al. / Tetrahedron 57 /2001) 3331±3341
Dess±Martin reagent .425 mg, 1.05 mmol) as described for
the preparation of 18. The reaction mixture was stirred for
30min at room temperature, and then partitioned between
EtOAc and H2O. Silica gel column chromatography .hex-
ane/EtOAcˆ2:1) of the organic layer gave 20 .471 mg,
76%, foam) as a mixture of two geometrical isomers .E/
Zˆ88:12): UV .MeOH) lmax 263 nm .e 11 400), lmin
Physical data of 22: UV .MeOH) lmax 263 nm .e 9600),
min 242 nm .e 5100); 1H NMR .CDCl3) d 2.13±2.23 .1H,
l
m, H-20), 2.20.1H, dd, Jˆ9.0and 16.0Hz, C H2CO2Me),
2.31 .1H, dd, Jˆ5.1 and 16.0Hz, C H2CO2Me), 2.40.1H,
ddd, Jˆ2.6, 7.6 and 13.9 Hz, H-20), 2.73±2.83 .1H, m,
H-30), 3.34 .1H, dd, Jˆ3.3 and 11.1 Hz, H-50), 3.60.1H,
dd, Jˆ2.6 and 11.1 Hz, H-50), 3.63 .3H, s, CO2Me), 3.77±
3.81 .1H, m, H-40), 5.35 .1H, d, Jˆ8.2 Hz, H-5), 6.11 .1H,
dd, Jˆ2.6 and 6.9 Hz, H-10), 7.25±7.35 and 7.40±7.43
.15H, each as m, Ph), 8.00 .1H, d, Jˆ8.2 Hz, H-6), 8.43
.1H, br, NH); FAB-MS m/z 527 .M11H). Anal. calcd for
C31H30N2O6´0.5H2O: C, 69.52; H, 5.83; N, 5.23. Found: C,
69.33; H, 5.69; N, 5.15.
1
245 nm .e 8200); H NMR .CDCl3) for .E)-isomer d 3.13
.1H, dd, Jˆ5.5 and 13.5 Hz, H-20), 3.15 .1H, dd, Jˆ4.3 and
0
11.0Hz, H-5 ), 3.20.1H, dd, Jˆ6.4 and 13.5 Hz, H-20),
3.32 .1H, dd, Jˆ7.0and 11.0Hz, H-5 0), 3.74±3.77 .1H,
m, H-40), 5.52 .1H, d, Jˆ8.0Hz, H-5), 5.59 .1H, dd, Jˆ
1.5 and 16.5 Hz, CHCN), 5.76 .1H, dd, Jˆ5.5 and 6.4 Hz,
H-10), 6.41 .1H, dd, Jˆ6.1 and 16.5 Hz, CHvCHCN),
7.24±7.31, 7.33±7.36 and 7.48±7.51 .20H, each as m,
Ph), 7.39 .1H, d, Jˆ8.0Hz, H-6); 1H NMR .CDCl3) for
.Z)-isomer d 3.18 .1H, dd, Jˆ5.2 and 13.6 Hz, H-20), 3.18
Physical data of 23: UV .MeOH) lmax 261 nm, lmin
1
241 nm; H NMR .CDCl3) d 1.18 .1H, ddd, Jˆ8.6, 12.0
and 12.2 Hz, H-20), 2.42 .1H, dd, Jˆ7.4 and 16.6 Hz,
0
.1H, dd, Jˆ4.0and 10.4 Hz, H-5 ), 3.28 .1H, dd, Jˆ6.4 and
CH2CO2Me), 2.50.1H, dd,
Jˆ8.2 and 16.6 Hz,
13.6 Hz, H-20), 3.33 .1H, dd, Jˆ6.8 and 10.4 Hz, H-50),
4.37±4.41 .1H, m, H-40), 5.55 .1H, d, Jˆ8.4 Hz, H-5),
5.55 .1H, dd, Jˆ1.2 and 11.2 Hz, CHCN), 5.85 .1H, dd,
Jˆ5.2 and 6.4 Hz, H-10), 6.33 .1H, dd, Jˆ8.4 and 11.2 Hz,
CHvCHCN), 7.20±7.33, 7.35±7.39, and 7.46±7.50 .20H,
each as m, Ph), 7.42 .1H, d, Jˆ8.4 Hz, H-6); FAB-MS m/z
650.M 11H). Anal. calcd for C36H31N3O4Se: C, 66.66; H,
4.82; N, 6.48. Found: C, 66.44; H, 4.69; N, 6.37.
CH2CO2Me), 2.54 .1H, ddd, Jˆ5.5, 6.8 and 12.2 Hz,
H-20), 2.91±2.99 .1H, m, H-30), 3.14 .1H, dd, Jˆ4.0and
10.8 Hz, H-50), 3.52 .1H, dd, Jˆ4.0and 10.8 Hz, H-5 0),
3.56 .3H, s, CO2Me), 4.41 .1H, dt, Jˆ4.0and 8.1 Hz, H-
40), 5.33 .1H, d, Jˆ8.3 Hz, H-5), 6.16 .1H, dd, Jˆ5.5 and
8.6 Hz, H-10), 7.22±7.42 .15H, m, Ph), 7.78 .1H, d,
Jˆ8.3 Hz, H-6), 8.90.1H, br, NH); HRFAB-MS m/z
527.2227 .M11H), calcd for C31H31N2O6 .M11H)
527.2182.
6.1.8. 20,30-Dideoxy-30-C-2E)-2bisphenoxyphosphono)-
methylene-20-phenylseleno-50-O-trityl-20,30-seco-uridine
221). To a CH3CN .10mL) solution containing the alde-
hyde, prepared from 17 .550mg, 0.88 mmol) and the
Dess±Martin reagent .410mg, 0.96 mmol) as described
6.1.10. Radical-mediated cyclization of 19: formation of
24, 25 and 26. To a toluene .4.0mL) solution of 19
.138.9 mg, 0.203 mmol) kept at 1108C, a mixture of
AIBN .6.7 mg, 0.041 mmol) and Bu3SnH .109 mL,
0.406 mmol) in toluene .1.8 mL) was added by a syringe-
pump over 1 h under Ar atmosphere. Evaporation of the
solvent followed by silica gel column chromatography of
the residue gave a mixture of 26a and 26b .elution with
hexane/EtOAcˆ2:1, 7.2 mg, 7% yield, 26a/26bˆ1:1), and
then a mixture of 24 and 25 .elution with hexane/
EtOAcˆ1:1, 77.3 mg, 72% yield, 24/25ˆ2.4:1). Isolation
of pure compounds was carried out by preparative TLC
.hexane/EtOAcˆ1:2) for 26a and 26b, and by HPLC
.hexane/EtOAcˆ2:3) for 24 .tR 30min) and 25 .tR 34 min).
28
for the preparation of 18, was added Ph3PCHP.O).OPh)2
.890mg, 1.75 mmol). The reaction mixture was stirred at
room temperature overnight. Evaporation of the solvent
followed by silica gel column chromatography .hexane/
EtOAcˆ1:1) of the resulting residue gave 21 .327 mg,
44%, foam): UV .MeOH) lmax 262 nm .e 12 700), lmin
1
244 nm .e 8900); H NMR .CDCl3) d 3.09 .1H, dd, Jˆ
3.2 and 11.1 Hz, H-50), 3.09 .1H, dd, Jˆ5.6 and 13.5 Hz,
H-20), 3.18 .1H, dd, Jˆ5.6 and 13.5 Hz, H-20), 3.26 .1H, dd,
Jˆ7.4 and 11.1 Hz, H-50), 3.82±3.85 .1H, m, H-40), 5.41
.1H, d, Jˆ8.0Hz, H-5), 5.72 .1H, t, Jˆ5.6 Hz, H-10), 6.19
.1H, ddd, Jˆ1.0, 17.2 and 23.3 Hz, CHP.O).OPh)2), 6.64
.1H, ddd, Jˆ6.0, 23.3 and 23.3 Hz, CHvCHP.O).OPh)2),
7.12±7.49 .31H, m, Ph and H-6); FAB-MS m/z 857
.M11H). Anal. calcd for C47H41N2O7PSe: C, 65.96; H,
4.83; N, 3.27. Found: C, 66.25; H, 5.05; N, 3.47.
Physical data of 24: UV .MeOH) lmax 261 nm .e 11 000),
1
lmin 242 nm .e 6000); H NMR .CDCl3) d 1.77 .1H, ddd,
Jˆ6.8, 10.0 and 13.4 Hz, H-20), 2.29 .1H, dd, Jˆ8.6 and
15.9 Hz, CH2CO2Me), 2.44 .1H, dd, Jˆ5.2 and 15.9 Hz,
CH2CO2Me), 2.57±2.67 .1H, m, H-30), 2.83 .1H, ddd,
Jˆ6.4, 7.6 and 13.4 Hz, H-20), 3.23 .1H, dd, Jˆ4.8 and
10.6 Hz, H-50), 3.31 .1H, dd, Jˆ4.0and 10.6 Hz, H-5 0),
3.61 .3H, s, CO2Me), 4.05 .1H, ddd, Jˆ4.0, 4.8 and
8.5 Hz, H-40), 5.77 .1H, d, Jˆ8.0Hz, H-5), 6.08 .1H, dd,
Jˆ6.4 and 6.8 Hz, H-10), 7.22±7.32 and 7.43±7.48 .16H, m,
Ph and H-6), 9.15 .1H, br, NH); FAB-MS m/z 527 .M11H).
Anal. calcd for C31H30N2O6´0.25H2O: C, 70.11; H, 5.79; N,
5.27. Found: C, 70.09; H, 5.48; N, 5.23.
6.1.9. Radical-mediated cyclization of 18: formation of
1-[3-C-2carbomethoxy)methyl-2,3-dideoxy-5-O-trityl-b-
d-erythro-pentofuranosyl]uracil 222) and its threo-
isomer 223). To a toluene .8.2 mL) solution of 18
.281 mg, 0.41 mmol) kept at 1108C, a mixture of AIBN
.6.8 mg, 0.04 mmol) and Bu3SnH .166 mL, 0.62 mmol) in
toluene .5.5 mL) was added by a syringe-pump over 1 h
under Ar atmosphere. Evaporation of the solvent followed
by silica gel column chromatography .hexane/EtOAcˆ1:1)
of the residue gave a mixture of 22 and 23 .22/23ˆ97:3
based on integration of H-6, total yield 200 mg, 92%) as
foam. HPLC separation .hexane/EtOAcˆ1:2) of the
mixture gave pure 22 .tR 19.4 min, foam) and 23 .tR
17.3 min, foam).
Physical data of 25: UV .MeOH) lmax 262 nm .e 11 600),
1
lmin 242 nm .e 6100); H NMR .CDCl3) d 2.27 .1H, ddd,
Jˆ1.8, 7.5 and 13.5 Hz, H-20), 2.39 .1H, dd, Jˆ7.0and
17.0Hz, C H2CO2Me), 2.45 .1H, dd, Jˆ7.8 and 17.0Hz,
CH2CO2Me), 2.55 .1H, ddd, Jˆ6.4, 11.5 and 13.5 Hz,
0
H-20), 2.69±2.80.1H, m, H-3 ), 2.87 .1H, dd, Jˆ2.8 and

H. Kumamoto et al. / Tetrahedron 57 /2001) 3331±3341
3339
0
11.0Hz, H-5 ), 3.43 .1H, dd, Jˆ4.0and 11.0Hz, H-5 0),
6.1.12. 1-[3-C-Cyanomethyl-2,3-dideoxy-5-O-trityl-b-d-
erythro-pentofuranosyl]uracil 228). UV .MeOH) lmax
262 nm .e 9500), lmin 243 nm .e 5300); 1H NMR
.CDCl3) d 2.18 .1H, dd, Jˆ7.0and 17.1 Hz, C H2CN),
2.31 .1H, dd, Jˆ4.8 and 17.1 Hz, CH2CN), 2.35±2.39
.2H, m, H-20), 2.61±2.71 .1H, m, H-30), 3.40.1H, dd, Jˆ
0
3.53 .3H, s, CO2Me), 4.60.1H, m, H-4 ), 5.74 .1H, d, Jˆ
8.4 Hz, H-5), 6.30.1H, dd, Jˆ1.8 and 6.4 Hz, H-10), 7.22±
7.34 and 7.42±7.45 .16H, m, Ph and H-6), 8.68 .1H, br,
NH); FAB-MS m/z 527 .M11H). Anal. calcd for
C31H30N2O6: C, 70.71; H, 5.74; N, 5.32. Found: C, 70.67;
H, 5.38; N, 5.28.
0
3.0and 11.4 Hz, H-5 ), 3.73 .1H, dd, Jˆ3.0and 11.4 Hz,
H-50), 3.85 .1H, dt, Jˆ3.0and 9.0Hz, H-4 0), 5.42 .1H, d,
1H NMR and HRFAB-MS data of 26a: 1H NMR .CDCl3)0d
1.89±1.95 .1H, m, H-20), 2.22 .1H, d, Jˆ12.0Hz, H-2 ),
2.53 .1H, dd, Jˆ4.8 and 16.7 Hz, H-5), 2.75±2.79 .2H, m,
H-30 and H-60), 2.97 .1H, dd, Jˆ12.8 and 16.7 Hz, H-5),
3.04 .1H, dd, Jˆ6.4 and 10.2 Hz, H-50), 3.23 .1H, dd, Jˆ5.2
and 10.2 Hz, H-50), 3.74 .3H, s, CO2Me), 3.94 .1H, dt, Jˆ
4.8 and 12.8 Hz, H-6), 4.08 .1H, dd, Jˆ5.2 and 6.4 Hz,
H-40), 6.31 .1H, d, Jˆ4.8 Hz, H-10), 7.22±7.33 and 7.40±
7.43 .15H, m, Ph), 7.67 .1H, br, NH); HRFAB-MS m/z
527.2214 .M11H), calcd for C31H31N2O6 .M11H) 527.2182.
Jˆ8.2 Hz, H-5), 6.11 .1H, dd, Jˆ3.6 and 6.0Hz, H-1 ),
0
7.24±7.43 .15H, m, Ph), 7.95 .1H, d, Jˆ8.2 Hz, H-6),
8.57 .1H, br, NH); FAB-MS m/z 494 .M11H). Anal.
calcd for C30H27N3O4´0.5H2O: C, 71.70; H, 5.62; N, 8.36.
Found: C, 71.80; H, 5.35; N, 8.36.
6.1.13. 1-[2,3-Dideoxy-3-C-2diphenoxy)phosphonomethyl-
5-O-trityl-b-d-erythro-pentofuranosyl]uracil 229). UV
.MeOH) lmax 261 nm .e 10 400), lmin 242 nm .e 5600);
1H NMR .CDCl3) d 1.90.1H, ddd, Jˆ10.4, 15.4 and
18.0Hz, C H2PO), 2.17 .1H, ddd, Jˆ4.0, 15.4 and
20.2 Hz, CH2PO), 2.36 .1H, ddd, Jˆ7.0, 11.0 and
14.1 Hz, H-20), 2.58 .1H, ddd, Jˆ2.0, 7.3 and 14.1 Hz,
H-20), 2.93±3.00 .1H, m, H-30), 3.38 .1H, dd, Jˆ2.8 and
11.2 Hz, H-50), 3.62 .1H, dd, Jˆ2.8 and 11.2 Hz, H-50),
3.82 .1H, ddd, Jˆ2.8 and 9.3 Hz, H-40), 5.38 .1H, d,
Jˆ8.0Hz, H-5), 6.14 .1H, dd, Jˆ2.0and 7.0Hz, H-1 0),
7.09±7.42 .25H, m, Ph), 7.97 .1H, d, Jˆ8.0Hz, H-6),
8.47 .1H, br, NH); FAB-MS m/z 739 .M11K). Anal.
calcd for C41H37N2O7P: C, 70.28; H, 5.32; N, 4.00. Found:
C, 70.20; H, 5.03; N, 4.00.
1H NMR and HRFAB-MS data of 26b: 1H NMR .CDCl3) d
0
1.65 .1H, d, Jˆ12.0Hz, H-2 ), 2.08 .1H, dt, Jˆ5.2 and
0
12.0Hz, H-2 ), 2.38 .1H, dd, Jˆ13.0and 16.7 Hz, H-5),
2.56 .1H, dd, Jˆ2.4 and 10.4 Hz, H-60), 2.90±2.98 .3H,
m, H-50, H-5, and H-30), 3.20.1H, dd, Jˆ4.6 and 9.5 Hz,
H-50), 3.78 .3H, s, CO2Me), 4.06±4.13 .1H, m, H-6), 4.26
.1H, dd, Jˆ4.6 and 7.2 Hz, H-40), 6.25 .1H, d, Jˆ4.4 Hz,
H-10), 7.22±7.32 and 7.36±7.39 .15H, m, Ph), 7.66 .1H, br,
NH); HRFAB-MS m/z 527.2175 .M11H), calcd for
C31H31N2O6 .M11H) 527.2182.
6.1.11. 30-C-2Z)-2Carbomethoxy)methylene-20,30-dideoxy-
20-phenylseleno-50-O-trityl-20,30-seco-uridine 227). To a
DMSO .3 mL) solution of 17 .301.8 mg, 0.48 mmol),
DCC .298 mg, 1.44 mmol) and dichloroacetic acid
.20 mL, 0.24 mmol) were added and the mixture was stirred
for 2 h at room temperature under positive pressure of dry
Ar. Filtration of the oxidation mixture was followed by
participation between EtOAc and H2O. The organic layer
was dried .MgSO4), evaporated to dryness, and dissolved in
THF .3 mL). Under positive pressure of dry Ar, the above
THF solution was added at below 2788C to a mixture of
18-crown-6 .636 mg, 2.41 mmol), .CF3CH2O)2P.O)CH2-
CO2Me .102 mL, 0.48 mmol), and LHMDS .24% THF
solution, 481 mL, 0.48 mmol) in THF .7 mL). After stirring
for 1 h, .CF3CH2O)2P.O)CH2CO2Me .51 mL, 0.24 mmol)
was added, and the mixture was stirred for 15 min. The
reaction mixture was diluted with H2O, and extracted with
EtOAc. Silica gel column chromatography .hexane/
EtOAcˆ3:2) of the extract gave a mixture .242.3 mg,
74%, E/Zˆ1.0:4.6) of 18 and 27. Compound 27 .tR
12 min) was separated from 18 .tR 10min) by HPLC
.hexane/EtOAcˆ2:3): UV .MeOH) lmax 263 nm .e
6.1.14. Oxidation of 18: formation of the selenoxide 30. A
solution of 18 .724.2 mg, 1.06 mmol) in CH2Cl2 .10mL)
was cooled at 08C. To this solution, m-CPBA .275 mg,
1.59 mmol) was added and the reaction mixture was stirred
for 10min. The mixture was neutralized by adding Et 3N,
and then partitioned between saturated aqueous NaHCO3
and CH2Cl2. Silica gel column chromatography .CHCl3/
MeOHˆ50:1) of the organic layer gave 30 .675.1 mg,
91%) as a mixture of two diastereomers .ca. 1.0:0.9):
FAB-MS m/z 737 .M11K). An aliquot of this mixture
1
was puri®ed by HPLC .CHCl3/MeOHˆ10:1) for H NMR
measurement to give the major isomer .tR 8.1 min) and the
minor one .tR 8.6 min).
Physical data of the major isomer: UV .MeOH) lmax
258 nm .e 10 800), lmin 244 nm .e 8800); 1H NMR
.CDCl3) d 3.18±3.24 .3H, m, H-20 and H-50), 3.38 .1H,
dd, Jˆ7.4 and 10.6 Hz, H-50), 3.74 .3H, s, CO2Me), 3.91±
3.95 .1H, m, H-40), 5.59 .1H, d, Jˆ8.4 Hz, H-5), 6.01
.1H, dd, Jˆ0.8 and 15.8 Hz, CHCO2Me), 6.06 .1H, t, Jˆ
7.2 Hz, H-10), 6.66 .1H, dd, Jˆ7.2 and 15.8 Hz,
CHvCHCO2Me), 7.23±7.43, 7.51±7.52 and 7.77±7.79
.21H, each as m, Ph and H-6). Anal. calcd for
C37H34N2O7Se´0.5H2O: C, 62.89; H, 4.85; N, 3.96. Found:
C, 62.79; H, 4.80; N, 3.92.
1
12 100), lmin 244 nm .e 8600); H NMR .CDCl3) d 3.15
.1H dd, Jˆ3.2 and 10.2 Hz, H-50), 3.19 .1H, dd, Jˆ4.4 and
0
13.6 Hz, H-20), 3.24 .1H, dd, Jˆ6.0and 13.6 Hz, H-2 ),
3.26 .1H, dd, Jˆ7.6 and 10.2 Hz, H-50), 3.66 .3H, s,
CO2Me), 5.34±5.38 .1H, m, H-40), 5.57 .1H, dd, Jˆ2.0
Physical data of the minor isomer: UV .MeOH) lmax
258 nm .e 11 200), lmin 244 nm .e 9200); 1H NMR
.CDCl3) d 3.18±3.44 .4H, m, H-20 and H-50), 3.75 .3H, s,
CO2Me), 3.82±3.87 .1H, m, H-40), 5.60.1H, d, Jˆ8.0Hz,
0
and 8.0Hz, H-5), 5.81 .1H, dd, Jˆ4.4 and 6.0Hz, H-1 ),
5.96 .1H, dd, Jˆ0.8 and 11.8 Hz, CHCO2Me), 6.06 .1H, dd,
Jˆ8.4 and 11.8 Hz, CHvCHCO2Me), 7.18±7.40.20H, m,
Ph), 7.67 .1H, d, Jˆ8.0Hz, H-6), 8.03 .1H, br, NH); FAB-
MS m/z 683 .M11H). Anal. calcd for C37H34N2O6Se: C,
65.20; H, 5.03; N, 4.11. Found: C, 65.04; H, 4.75; N, 4.13.
0
H-5), 5.86±5.90.2H, m, H-1 and CHvCHCO2Me), 6.58
.1H, dd, Jˆ7.6 and 15.6 Hz, H-30), 7.23±7.38, 7.50±7.51
and 7.70±7.74 .21H, each as m, Ph and H-6). Anal. calcd for

3340
H. Kumamoto et al. / Tetrahedron 57 /2001) 3331±3341
C37H34N2O7Se´H2O: C, 62.10; H, 4.79; N, 3.91. Found: C,
62.14; H, 4.92; N, 3.73.
7.23±7.32, 7.35±7.39, and 7.57±7.61 .21H, each as m, Ph
and H-6), 8.38 .1H, br, NH).
6.1.15. 20-O-Acetyl-30-C-2E)-2carbomethoxy)methylene-
30-deoxy-20-phenylseleno-50-O-trityl-20,30-seco-uridine
231). A mixture of 30 .373.4 mg, 0.53 mmol) and Ac2O
.151 mL, 1.60mmol) in CH 2Cl2 .6 mL) was stirred for
19.5 h at room temperature. The reaction mixture was
neutralized by adding Et3N, and then partitioned between
saturated aqueous NaHCO3 and CH2Cl2. Silica gel column
chromatography .hexane/EtOAcˆ1:1) of the organic layer
gave 31 .foam, 351.5 mg, 89%) as a mixture of two dia-
stereomers .ca. 1.0:0.6). Further puri®cation of 31 by silica
gel column chromatography .hexane/EtOAcˆ1:1) enabled
the isolation of the major isomer 31a and the minor isomer
31b.
6.1.17. 20-O-Benzoyl-30-C-2E)-2carbomethoxy)methylene-
30-deoxy-20-phenylseleno-50-O-trityl-20,30-seco-uridine
233). This compound .foam, a mixture of two diastereomers,
ca. 1.0:0.7) was prepared in 88% yield from 30 by the
procedure for the preparation of 31: FAB-MS m/z 801
1
.M11H); H NMR .CDCl3) for the major isomer d 3.19
.1H, dd, Jˆ3.2 and 10.8 Hz, H-50), 3.46 .1H, dd, Jˆ7.8 and
10.8 Hz, H-50), 3.70.3H, s, CO Me), 3.94±3.98 .1H, m,
2
H-40), 5.57 .1H, dd, Jˆ2.0and 8.0Hz, H-5), 5.96 .1H, d,
0
Jˆ5.0Hz, H-1 ), 6.10.1H, dd,
Jˆ1.0and 15.8 Hz,
0
CHCO2Me), 6.48 .1H, d, Jˆ5.0Hz, H-2 ), 6.71 .1H, dd,
Jˆ6.8 and 15.8 Hz, CHvCHCO2Me), 7.21±8.13 .26H,
1
m, Ph and H-6), 8.47 .1H, br, NH); H NMR .CDCl3) for
the minor isomer d 3.11 .1H, dd, Jˆ2.8 and 10.8 Hz, H-50),
3.42 .1H, dd, Jˆ8.0and 1.08 Hz, H-5 0), 3.73 .3H, s,
CO2Me), 3.94±3.98 .1H, m, H-40), 5.40.1H, dd, Jˆ2.0
and 8.0Hz, H-5), 6.05 .1H, dd, Jˆ1.4 and 15.8 Hz,
CHCO2Me), 6.09 .1H, d, Jˆ5.6 Hz, H-10), 6.62 .1H, d,
Jˆ5.6 Hz, H-20), 6.63 .1H, dd, Jˆ7.0and 15.8 Hz,
CHvCHCO2Me), 7.21±8.13 .26H, m, Ph and H-6), 8.65
.1H, br, NH).
Physical data of 31a: UV .MeOH) lmax 261 nm .e 11 200),
l
min 244 nm .e 7800); 1H NMR .CDCl3) d 2.07 .3H, s, Ac),
3.18 .1H, dd, Jˆ4.8 and 10.8 Hz, H-50), 3.43 .1H, dd, Jˆ8.4
and 10.8 Hz, H-50), 3.73 .3H, s, CO2Me), 3.97±4.00 .1H, m,
H-40), 5.59 .1H, d, Jˆ8.0Hz, H-5), 5.78 .1H, d, Jˆ4.0Hz,
H-10), 6.15 .1H, dd, Jˆ1.2 and 16.0Hz, C HCO2Me), 6.26
0
.1H, d, Jˆ4.0Hz, H-2 ), 6.64 .1H, dd, Jˆ6.4 and 16.0Hz,
CHvCHCO2Me), 7.24±7.40and 7.51±7.60.20H, each as
m, Ph), 7.91 .1H, d, Jˆ8.0Hz, H-6), 7.95 .1H, br, NH);
FAB-MS m/z 741 .M11H). Anal. calcd for
C39H36N2O8Se: C, 63.33; H, 4.91; N, 3.79. Found: C,
63.23; H, 4.83; N, 3.82.
6.1.18. 20-O-Acetyl-30-deoxy-30-C-2carbomethoxy)methyl-
50-O-trityluridine 234a) and its 20-epimer 235a). These
compounds were obtained as a foam. Separation of 34a
and 35a was carried out by silica gel column chromato-
graphy .hexane/EtOAcˆ2:3).
Physical data of 31b: UV .MeOH) lmax 260nm . e 11 600),
l
min 244 nm .e 8100); 1H NMR .CDCl3) d 2.04 .3H, s, Ac),
Physical data of 34a: UV .MeOH) lmax 260nm . e 9600),
lmin 242 nm .e 5700); H NMR .CDCl3) d 2.08 .1H, dd,
1
3.14 .1H, dd, Jˆ3.1 and 10.9 Hz, H-50), 3.41 .1H, dd, Jˆ7.8
and 10.9 Hz, H-50), 3.74 .3H, s, CO2Me), 3.91±3.94 .1H, m,
H-40), 5.50.1H, dd, Jˆ1.6 and 8.3 Hz, H-5), 5.95 .1H, d,
Jˆ5.2 Hz, H-10), 6.04 .1H, dd, Jˆ1.0and 15.9 Hz,
CHCO2Me), 6.38 .1H, d, Jˆ5.2 Hz, H-20), 6.65 .1H, dd,
Jˆ6.8 and 15.9 Hz, CHvCHCO2Me), 7.24±7.32, 7.36±
7.38 and 7.55±7.59 .21H, each as m, Ph and H-6), 8.68
.1H, br, NH); FAB-MS m/z 741 .M11H). Anal. calcd for
C39H36N2O8Se: C, 63.33; H, 4.91; N, 3.79. Found: C, 63.34;
H, 4.83; N, 3.84.
Jˆ5.4 and 16.7 Hz, CH2CO2Me), 2.11 .3H, s, Ac), 2.35
.1H, dd, Jˆ9.6 and 16.7 Hz, CH2CO2Me), 2.95±3.03 .1H,
m, H-30), 3.34 .1H, dd, Jˆ3.2 and 11.2 Hz, H-50), 3.61 .3H,
s, CO2Me), 3.67 .1H, dd, Jˆ2.4 and 11.2 Hz, H-50), 3.99±
4.03 .1H, m, H-40), 5.38 .1H, dd, Jˆ8.2 Hz, H-5), 5.51 .1H,
0
dd, Jˆ1.6 and 6.0Hz, H-2 ), 5.92 .1H, d, Jˆ1.6 Hz, H-10),
7.25±7.34 and 7.39±7.45 .15H, each as m, Ph), 7.88 .1H, d,
Jˆ8.2 Hz, H-6), 8.83 .1H, br, NH); FAB-MS m/z 585
.M11H). Anal. calcd for C33H32N2O8: C, 67.80; H, 5.52;
N, 4.79. Found: C, 67.59; H, 5.38; N, 4.77.
6.1.16. 30-C-2E)-2Carbomethoxy)methylene-30-deoxy-20-
O-pivaloyl-20-phenylseleno-50-O-trityl-20,30-seco-uridine
232). This compound .foam, a mixture of two diastereomers,
ca. 1.0:0.7) was prepared in 78% yield from 30 by the
procedure described for the preparation of 31: FAB-MS
Physical data of 35a: UV .MeOH) lmax 260nm . e 10100),
l
min 242 nm .e 5900); 1H NMR .CDCl3) d 1.96 .3H, s, Ac),
2.47 .2H, d, Jˆ6.4 Hz, CH2CO2Me), 2.69±2.76 .1H, m, H-
30), 3.33 .1H, dd, Jˆ4.2 and 10.9 Hz, H-50), 3.56 .1H, dd,
Jˆ3.2 and 10.8 Hz, H-50), 3.60.3H, s, CO 2Me), 3.92±3.96
1
m/z 782 .M11H). H NMR .CDCl3) for the major isomer
0
d 1.10.9H, s, CMe ), 3.17 .1H, dd, Jˆ3.0and 10.9 Hz,
.1H, m, H-40), 5.35 .1H, dd, Jˆ5.6 and 6.0Hz, H-2 ), 5.45
3
H-50), 3.42 .1H, dd, Jˆ7.8 and 10.9 Hz, H-50), 3.74 .3H,
s, CO2Me), 3.86±3.90.1H, m, H-4 0), 5.58 .1H, d, Jˆ8.0Hz,
H-5), 5.86 .1H, d, Jˆ5.8 Hz, H-10), 6.04 .1H, dd, Jˆ1.0and
15.9 Hz, CHCO2Me), 6.27 .1H, d, Jˆ5.8 Hz, H-20), 6.66
.1H, dd, Jˆ7.0and 15.9 Hz, C HvCHCO2Me), 7.23±7.32,
7.35±7.39, and 7.57±7.61 .20H, each as m, Ph), 7.67 .1H, d,
Jˆ8.0Hz, H-6), 8.22 .1H, br, NH). 1H NMR .CDCl3) for
the minor isomer d 1.12 .9H, s, CMe3), 3.13 .1H, dd, Jˆ2.8
.1H, d, Jˆ8.2 Hz, H-5), 6.23 .1H, d, Jˆ5.6 Hz, H-10), 7.22±
7.35 and 7.40±7.44 .15H, each as m, Ph), 7.79 .1H, d,
Jˆ8.2 Hz, H-6), 8.12 .1H, br, NH); FAB-MS m/z 585
.M11H). Anal. calcd for C33H32N2O8: C, 67.80; H, 5.52;
N, 4.79. Found: C, 67.75; H, 5.37; N, 4.80.
6.1.19. 30-Deoxy-30-C-2carbomethoxy)methyl-20-O-piva-
loyl-50-O-trityluridine 234b) and its 20-epimer 235b).
These compounds were obtained as a mixture: FAB-MS
m/z 627 .M11H).
0
and 10.8 Hz, H-50), 3.46 .1H, dd, Jˆ8.0and 10.8 Hz, H-5 ),
3.74 .3H, s, CO2Me), 3.90±3.94 .1H, m, H-4 0), 5.48 .1H, d,
Jˆ8.4 Hz, H-5), 5.99 .1H, d, Jˆ5.2 Hz, H-10), 6.04 .1H, dd,
Jˆ1.4 and 15.9 Hz, CHCO2Me), 6.40.1H, d, Jˆ5.2 Hz,
H-20), 6.64 .1H, dd, Jˆ7.0and 15.9 Hz, C HvCHCO2Me),
Compound 34b: 1H NMR .CDCl3) d 1.21 .9H, s, Bu-t), 2.08
.1H, dd, Jˆ5.8 and 16.7 Hz, CH2CO2Me), 2.36 .1H, dd,

H. Kumamoto et al. / Tetrahedron 57 /2001) 3331±3341
3341
0
6. .a) Haraguchi, K.; Tanaka, H.; Hayakawa, H.; Miyasaka, T.
Chem. Lett. 1988, 931±934. .b) Haraguchi, K.; Tanaka, H.;
Maeda, H.; Itoh, Y.; Saito, S.; Miyasaka, T. J. Org. Chem.
1991, 56, 5401±5408.
Jˆ9.2 and 16.7 Hz, CH2CO2Me), 2.96±3.30.1H, m, H-3 ),
3.35 .1H, dd, Jˆ3.2 and 11.4 Hz, H-50), 3.60.3H, s,
CO2Me), 3.65 .1H, dd, Jˆ2.8 and 11.4 Hz, H-50), 3.96±
4.00 .1H, m, H-40), 5.42 .1H, d, Jˆ8.2 Hz, H-5), 5.45
H-10), 7.25±7.34 and 7.40±7.43 .15H, each as m, Ph), 7.82
.1H, d, Jˆ8.2 Hz, H-6), 8.18 .1H, br, NH).
0
7. Jones, A. S.; Walker, R. T.; Wyatt, P. G.; Balzarini, J.; De
Clercq, E. J. Chem. Res. /M) 1985, 3520±3532.
8. Liotta, D.; Santiesteban, H. Tetrahedron Lett. 1977, 4369±
4372.
.1H, dd, Jˆ1.6 and 6.0Hz, H-2 ), 5.85 .1H, d, Jˆ1.6 Hz,
Compound 35b: 1H NMR .CDCl3) d 1.05 .9H, s, Bu-t), 2.49
.2H, d, Jˆ6.4 Hz, CH2CO2Me), 2.63±2.72 .1H, m, H-30),
3.30.1H, dd, Jˆ4.8 and 10.8 Hz, H-50), 3.55 .1H, dd, Jˆ2.8
and 10.8 Hz, H-50), 3.61 .3H, s, CO2Me), 4.00 .1H, ddd,
9. Liotta, D.; Markiewicz, W.; Santiesteban, H. Tetrahedron
Lett. 1977, 4365±4368.
10. For the Swern oxidation, see: Mancuso, A. J.; Swern, D.
Synthesis 1981, 165±185.
0
Jˆ2.8, 4.8 and 8.0Hz, H-4 ), 5.31 .1H, t, Jˆ5.4 Hz, H-20),
11. P®tzner, K. E.; Moffatt, J. G. J. Am. Chem. Soc. 1965, 87,
5661±5670.
5.47 .1H, d, Jˆ8.2 Hz, H-5), 6.25 .1H, d, Jˆ5.4 Hz, H-10),
7.25±7.34 and 7.41±7.44 .15H, each as m, Ph), 7.78 .1H, d,
Jˆ8.2 Hz, H-6), 8.18 .1H, br, NH).
6.1.20. 20-O-Benzoyl-30-deoxy-30-C-2carbomethoxy)methyl-
50-O-trityluridine 234c) and its 20-epimer 235c). These
compounds were obtained as a mixture: FAB-MS m/z 647
.M11H).
12. Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277±
7287.
13. The depicted stereochemistry was con®rmed based on NOE
experiments: 22 .15% between H-30 and H-20b; 2% between
H-10 and H-40), 23 .9% between H-30 and H-40; 1% between
H-10 and H-40).
14. Giese, B. Angew. Chem., Int. Ed. Engl. 1983, 22, 753±764.
15. Beckwith, A. L. J.; Schiesser, C. H. Tetrahedron 1985, 41,
3925±3941.
1
Compound 34c: H NMR .CDCl3) d 2.18 .1H, dd, Jˆ5.8
and 16.6 Hz, CH2CO2Me), 2.98 .1H, dd, Jˆ9.0and
16.6 Hz, CH2CO2Me), 3.09±03.17 .1H, m, H-30), 3.40.1H,
dd, Jˆ3.0and 11.2 Hz, H-5 ), 3.53 .3H, s, CO2Me), 3.69
.1H, dd, Jˆ2.4 and 11.2 Hz, H-50), 4.13±4.17 .1H, m,
H-40), 5.41 .1H, d, Jˆ8.2 Hz, H-5), 5.75 .1H, dd, Jˆ1.6
and 6.2 Hz, H-20), 6.05 .1H, d, Jˆ1.6 Hz, H-10), 7.25±
7.35, 7.42±7.47, 7.57±7.61 and 7.99±8.02 .20H, each as
m, Ph), 7.89 .1H, d, Jˆ8.2 Hz, H-6), 8.60.1H, br, NH).
16. Hoffmann, R. W. Chem. Rev. 1989, 89, 1841±1860.
17. The depicted stereochemistry was con®rmed based on NOE
experiments: 24 .2% between H-40 and H-20b; 3% between
H-50 and H-30; 7% between H-10 and H-30), 25 .7% between
H-30 and H-20b; 9% between H-40 and H-30).
18. The stereochemistry of the two isomeric 20,30-dideoxy-6,30-
methano-5,6-dihydrouridines .26a and 26b) is not known. It
has been reported, however, that the 30-methyl radical derived
from 1-[5-O-benzoyl-2,3-dideoxy-3-C-iodomethyl-b-d-threo-
pentofuranosyl]-5-chlorouracil reacts with the C6 exclusively
at the si-face: Ueda, T.; Shuto, S. Nucleosides Nucleotides
1984, 3, 295±302.
1
Compound 35c: H NMR .CDCl3) d 2.55 .1H, dd, Jˆ6.2
and 16.5 Hz, CH2CO2Me), 2.62 .1H, dd, Jˆ6.4 and
16.5 Hz, CH2CO2Me), 2.82±2.88 .1H, m, H-30), 3.35 .1H,
dd, Jˆ4.4 and 10.8 Hz, H-50), 3.57 .3H, s, CO2Me), 3.60
.1H, dd, Jˆ3.2 and 10.8 Hz, H-50), 4.02±4.06 .1H, m,
H-40), 5.48 .1H, d, Jˆ8.2 Hz, H-5), 5.58 .1H, t, Jˆ5.4 Hz,
H-20), 6.35 .1H, d, Jˆ5.4 Hz, H-10), 7.20±7.30, 7.32±7.46,
7.58±7.60and 7.79±7.81 .20H, each as m, Ph), 7.85 .1H, d,
Jˆ8.2 Hz, H-6), 8.21 .1H, br, NH).
19. Still, W. C.; Gennari, C. Tetrahedron Lett. 1983, 24, 4405±
4408.
20. No trace amount of 23 was detected by 1H NMR spectroscopy.
21. The isomerization would be initiated with attack of tin radical
to the carbonyl oxygen of the methoxycarbonyl group:
Enholm, E. J.; Whitley, P. E. Tetrahedron Lett. 1995, 36,
9157±9160.
22. For an example: Marshall, J. A.; Royce, Jr., R. D. J. Org.
Chem. 1982, 47, 693±698.
References
23. Haraguchi, K.; Saito, S.; Tanaka, H.; Miyasaka, T. Nucleosides
Nucleotides 1992, 11, 483±493.
1. For an example, see: Morr, M.; Ernst, L.; Schomburg, D.
Liebigs Ann. Chem. 1991, 615±631.
Â
2. .a) Lavallee, J.-F.; Just, G. Tetrahedron Lett. 1991, 32, 3469±
24. Giese, B.; Mehl, W. Tetrahedron Lett. 1991, 32, 4275±4278.
25. The depicted stereochemistry was con®rmed based on NOE
experiments, which is exempli®ed by 34a and 35a: 34a .4%
between H-6 and H-30; 3% between H-6 and H-20; 2%
between H-10 and H-40), 35a .5% between H-6 and H-30;
13% between H-10 and H-20; 2% between H-10 and H-40).
26. An enantioselective radical reduction has been reported:
Buckmelter, A. J.; Kim, A. I.; Rychnovsky, S. D. J. Am.
Chem. Soc. 2000, 122, 9386±9390.
3472. .b) Yokomatsu, T.; Shimizu, T.; Yuasa, Y.; Shibuya, S.
Synlett 1995, 1280±1282. .c) Yokomatsu, T.; Sada, T.;
Shimizu, T.; Shibuya, S. Tetrahedron Lett. 1998, 39, 6299±
6302.
3. .a) Chu, C. K.; Doboszewski, B.; Schmidt, W.; Ullas, G. V.;
Roey, P. V. J. Org. Chem. 1989, 54, 2767±2769. .b) De
Mesmaeker, A.; Lebreton, J.; Waldner, A.; Fritsch, V.;
Wolf, R. M.; Freier, S. M. Synlett 1993, 733±736. .c) Lebreton,
J.; Waldner, A.; Lesueur, C.; De Mesmaeker, A. Synlett 1994,
137±140.
27. An alternative possible explanation is that sp3-hybridized
radicals derived from 31a and 31b are at equilibrium with a
low inversion barrier; see Ref. 26.
4. Fiandor, J.; Tam, S. Y. Tetrahedron Lett. 1990, 31, 597±
600.
28. For the preparation of Ph3PvCHP.O).OPh)2, see: Jones,
G. H.; Hamamura, E. K.; Moffatt, J. G. Tetrahedron Lett.
1968, 5731±5734.
5. Papchikhin, A.; Chattopadhyaya, J. Tetrahedron 1994, 50,
5279±5286.