Allylic substitution of 3′,4′-unsaturated nucleosides: Organosilicon-based stereoselective access to 4′-C-branched 2′,3′-didehydro-2′,3′-dideoxyribonucleosides

Article abstract of DOI:10.1021/jo9516190

Reactions of organosilicon reagents (such as allyltrimethylsilane, silyl enol ethers, cyanotrimethylsilane) with 3′,4′-unsaturated nucleosides (of uracil, N⁴-acetylcytosine, and hypoxanthine) having an allyl ester structure were investigated in

Full text of DOI:10.1021/jo9516190

J . Org. Chem. 1996, 61, 851-858
851
Allylic Su bstitu tion of 3′,4′-Un sa tu r a ted Nu cleosid es:
Or ga n osilicon -Ba sed Ster eoselective Access to 4′-C-Br a n ch ed
2′,3′-Did eh yd r o-2′,3′-d id eoxyr ibon u cleosid es
Kazuhiro Haraguchi, Hiromichi Tanaka,* Yoshiharu Itoh, Kentaro Yamaguchi,† and
Tadashi Miyasaka
School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142, J apan
Received September 5, 1995X
Reactions of organosilicon reagents (such as allyltrimethylsilane, silyl enol ethers, cyanotrimethyl-
silane) with 3′,4′-unsaturated nucleosides (of uracil, N4-acetylcytosine, and hypoxanthine) having
an allyl ester structure were investigated in the presence of a Lewis acid in CH2Cl2. In the cases
of uracil and N4-acetylcytosine derivatives, SnCl4 appeared to be suitable, whereas the use of EtAlCl2
was necessary for the hypoxanthine derivatives. The main pathway of these reactions was found
to be R-face-selective SN2′ allylic substitution, irrespective of the configuration of 2′-O-acyl leaving
group. As a result, a new stereoselective operation for C-C bonds formation leading to 4′-carbon-
substituted 2′,3′-didehydro-2′,3′-dideoxyribonucleosides has been disclosed for the first time.
Stereochemistry of these 4′-C-branched products can be assigned on the basis of 1H NMR
spectroscopy in terms of the anisotropic shift of H-5 of the pyrimidine base (or H-8 of the
hypoxanthine), which is caused by the 5′-O-(tert-butyldiphenylsilyl) protecting group.
In tr od u ction
We have demonstrated through a series of publications
that this class of compounds serve as useful substrates
for constructing C-C bonds in the sugar portion.7
In this paper, we describe details of our previous study
concerning Lewis acid-assisted stereoselective reaction
between 3′,4′-unsaturated uracil nucleosides and orga-
nosilicon reagents, which proceeds with SN2′ allylic
substitution to provide an entry to 4′-C-branched 2′,3′-
didehydro-2′,3′-dideoxy derivatives.8 Application of this
method to N4-acetylcytosine and hypoxanthine deriva-
tives is also described. The reaction sequence is general-
ized in Scheme 1.
Although a variety of unsaturated-sugar nucleosides
have long been known,1-5 their use in synthetic chemistry
has attracted scant attention, presumably due to their
anticipated propensity to undergo further elimination to
yield resonance-stabilized furan derivatives.
Consequently, most reactions carried out with regard
to these compounds had been limited to simple electro-
philic additions by which only non-carbon substituents
can be introduced.6
P r ep a r a tion of 3′,4′-Un sa tu r a ted Nu cleosid es of
Ur acil, N4-Acetylcytosin e, an d Hypoxan th in e. Among
methods available for the preparation of unsaturated-
sugar nucleosides, procedures for 3′,4′-unsaturated de-
rivatives are particularly few in number.4 We have
already reported that a phenyl selenide anion generated
from (PhSe)2 and LiAlH4 is highly nucleophilic and, thus,
serves as a useful species for introducing a phenylseleno
group into various positions of the sugar moiety of uracil
nucleosides.9 Since the resulting products readily un-
† Current Address: Chemical Analysis Center, Chiba University,
1-33 Yayoicho, Inage-ku, Chiba 263, J apan.
X Abstract published in Advance ACS Abstracts, J anuary 15, 1996.
(1) For the synthesis of 4′,5′-unsaturated nucleosides: (a) Verhey-
den, J . P. H.; Moffatt, J . G. J . Am. Chem. Soc. 1966, 88, 5684-5685.
(b) Robins, M. J .; McCarthy, J . R., J r.; Robins, R. K. J . Heterocycl.
Chem. 1967, 4, 313-314. (c) Verheyden, J . P. H.; Moffatt, J . G. J . Org.
Chem. 1974, 39, 3573-3579.
(2) For the synthesis of 2′,3′-unsaturated nucleosides: (a) Horwitz,
J . P.; Chua, J .; Klundt, I. L.; Da Rooge, M. A.; Noel, M. J . Am. Chem.
Soc. 1964, 86, 1896-1897. (b) Horwitz, J . P.; Chua, J .; Da Rooge, M.
A.; Noel, M. Tetrahedron Lett. 1964, 2725-2727. (c) Ruyle, W. V.; Shen,
T. Y.; Patchett, A. A. J . Org. Chem. 1965, 30, 4353-4355. (d) Horwitz,
J . P.; Chua, J .; Da Rooge, M. A.; Noel, M.; Klundt, I. L. J . Org. Chem.
1966, 31, 205-211. (e) Khwaja, T. A.; Heidelberger, C. J . Med. Chem.
1967, 10, 1066-1070. (f) Khwaja, T. A.; Heidelberger, C. J . Med. Chem.
1969, 12, 543-545. (g) Kowollik, G.; Gaertner, K.; Etzold, G.; Langen,
P. Carbohydr. Res. 1970, 12, 301-311. (h) Robins, M. J .; Hansske, F.;
Low, N. H.; Park, J . I. Tetrahedron Lett. 1984, 25, 367-370. (i) Cosford,
N. D. P.; Schinazi, R. F. J . Org. Chem. 1991, 56, 2161-2165. (j)
Talekar, R. R.; Coe, P. L.; Walker, R. T. Synthesis 1993, 303-306. (k)
Cosford, N. D. P.; Schinazi, R. F. Nucleosides Nucleotides 1993, 12,
149-155.
(3) For the synthesis of 1′,2′-unsaturated nucleosides: (a) Robins,
M. J .; Trip, E. M. Tetrahedron Lett. 1974, 3369-3372. (b) Ranga-
nathan, R. Tetrahedron Lett. 1977, 1291-1294.
(4) For the synthesis of 3′,4′-unsaturated nucleosides: (a) Zemlicka,
J .; Freisler, J . V.; Gasser, R.; Horwitz, J . P. J . Org. Chem. 1973, 38,
990-999. (b) Lichtenthaler, F. W.; Kitahara, K.; Strobel, K. Synthesis
1974, 860-862. (c) Herdewijn, P.; Ruf, K.; Pfleiderer, W. Helv. Chim.
Acta 1991, 74, 7-23.
(6) For an example of electrophilic additions to 4′,5′-unsaturated
nucleosides: (a) J enkins, I. D.; Verheyden, J . P. H.; Moffatt, J . G. J .
Am. Chem. Soc. 1976, 98, 3346-3357. (b) Maag, H.; Rydzewski, R.
M.; McRoberts, M. J .; Crawford-Ruth, D.; Verheyden, J . P. H.; Prisbe,
E. J . J . Med. Chem. 1992, 35, 1440-1451.
(7) (a) Haraguchi, K.; Tanaka, H.; Miyasaka, T. Tetrahedron Lett.
1990, 31, 227-230. (b) Haraguchi, K.; Tanaka, H.; Itoh, Y.; Miyasaka,
T. Tetrahedron Lett. 1991, 32, 777-780. (c) Haraguchi, K.; Itoh, Y.;
Tanaka, H.; Miyasaka, T. Tetrahedron Lett. 1991, 32, 3391-3394. (d)
Haraguchi, K.; Itoh, Y.; Tanaka, H.; Akita, M.; Miyasaka, T. Tetrahe-
dron 1993, 49, 1371-1390. (e) Haraguchi, K.; Itoh, Y.; Tanaka, H.;
Yamaguchi, K.; Miyasaka, T. Tetrahedron Lett. 1993, 43, 6913-6916.
(f) Kittaka, A.; Tanaka, H.; Odanaka, Y.; Ohnuki, K.; Yamaguchi, K.;
Miyasaka, T. J . Org. Chem. 1994, 59, 3636-3641. (g) Itoh, Y.;
Haraguchi, K.; Tanaka, H.; Gen, E.; Miyasaka, T. J . Org. Chem. 1995,
60, 656-662.
(8) Haraguchi, K.; Tanaka, H.; Itoh, Y.; Saito, S.; Miyasaka, T.
Tetrahedron Lett. 1992, 33, 2841-2844.
(9) (a) Haraguchi, K.; Tanaka, H.; Hayakawa, H.; Miyasaka, T.
Chem. Lett. 1988, 931-934. (b) Haraguchi, K.; Tanaka, H.; Miyasaka,
T. Synthesis 1989, 434-436. (c) Haraguchi, K.; Tanaka, H.; Maeda,
H.; Itoh, Y.; Saito, S.; Miyasaka, T. J . Org. Chem. 1991, 56, 5401-
5408.
(5) Several 3′,4′-unsaturated derivatives have been obtained from
nucleosides having an electron-withdrawing C-5′ (such as CHO, CH2F,
and COOH): (a) Nagpal, K. L.; Horwitz, J . P. J . Org. Chem. 1971, 36,
3743-3745. (b) Kowellik, G.; Gaertner, K.; Langen, P. Tetrahedron
Lett. 1971, 1737-1740. (c) Zemlicka, J .; Gasser, R.; Freisler, J . V.;
Horwitz, J . P. J . Am. Chem. Soc. 1972, 94, 3213-3218.
0022-3263/96/1961-0851$12.00/0 © 1996 American Chemical Society

852 J . Org. Chem., Vol. 61, No. 3, 1996
Haraguchi et al.
Sch em e 1
dergo selenoxide syn-elimination upon oxidative treat-
ment,10 the whole sequence constitutes a general entry
to various types of unsaturated-sugar uracil nucleosides.9c
Compound 1 was prepared from 1-(2,3-anhydro-5-O-
trityl-â-D-lyxofuranosyl)uracil through oxirane ring cleav-
age with (PhSe)2/LiAlH4 and subsequent detritylation.
Selective silylation of 1 gave 2, which was further
acetylated to yield 3. As reported in our previous study,9c
there is a significant difference in regiochemical outcome
of selenoxide elimination between 2a and 3a ,11 both
carrying two syn-â-hydrogens (H-4′ and H-2′): although
two possible elimination pathways occur equally in the
case of the selenoxide derived from 2a , the oxidative
elimination of 3a results in the exclusive formation of
an allyl acetate 4a (88%).
Preparation of the 5′-O-(tert-butyldiphenylsilyl: TB-
DPS) derivative (4b) was carried out by applying the
above procedure for 4a . Thus, when 3b was treated with
m-CPBA in CH2Cl2 and the resulting selenoxide was kept
neat at 30-40 °C, 4b was obtained in 90% yield.
Conventional dehydrohalogenation was applicable to
N4-acetylcytosine and hypoxanthine cases, since intro-
duction of the “3′-up” halogeno substituent can be ac-
complished, starting from cytidine or inosine, according
to the published procedure. Compound 5 has been
synthesized from N4-acetylcytidine by reacting with AcBr
in CH3CN without chromatographic purification.12 When
5 was treated with DBU in CH3CN, the desired 6a was
isolated in 71% yield. Compound 6b was prepared from
6a by a sequential reactions: deacetylation, 5′-O-selective
silylation, and then reacetylation of the 2′-hydroxyl
group. Dehydrohalogenation of the 3′,5′-di-O-acetyl de-
rivative 8a , prepared from 7,4b under similar conditions
gave 9a in 95% yield. Benzoylation of 7 with benzoic
anhydride in CH3CN in the presence of diisopropylethyl-
amine and DMAP directly produced the elimination
product 9b in 40% yield, instead of 8b. Compound 9c
was prepared from 9a in a similar manner to the
conversion of 6a to 6b.
As our 3′,4′-unsaturated nucleosides (4, 6, and 9) have
an allyl ester structure, we reasoned that reaction of
these compounds with organometallic reagents could
provide a route for constructing C-C bonds at the 4′-
position of 2′,3′-didehydro-2′,3′-dideoxyribonucleosides of
potential anti-HIV activity.14,15 There are, however,
several concerns involved in this approach: (1) antici-
pated occurrence of further elimination which leads to
furan derivatives, (2) regioselectivity of organometallic
reagents employed (γ- vs. R-attack to this allyl acetate
system), and (3) stereoselectivity of C-C bond formation
at the 4′-position.
Although Gilman reagents (R2CuLi) are widely used
for γ-selective alkylation of allyl acetates,16 4a underwent
simple deacetylation upon reaction with Me2CuLi (3
(14) Several 2′,3′-didehydro-2′,3′-dideoxynucleosides, such as 3′-
deoxy-2′,3′-didehydrothymidine (D4T), show promising anti-HIV activ-
ity. For a recent review: De Clercq, E. Acquired Immune Defic. Syndr.
1991, 4, 207-218.
(15) There have been only two methods available for constructing
C-C bonds at the 4′-position of nucleosides: (a) Youssefyeh, R.; Tegg,
D.; Verheyden, J . P. H.; J ones, G. H.; Moffatt, J . G. Tetrahedron Lett.
1977, 435-438. (b) Secrist, J . A., III; Winter, W. J ., J r. J . Am. Chem.
Soc. 1978, 100, 2554-2555.
(16) (a) Rona, P.; To¨kes, L.; Tremble, J .; Crabbe´, P. J . Chem. Soc.,
Chem. Commun. 1969, 43-44. (b) Anderson, R. J .; Henrick, C. A.;
Siddall, J . B. J . Am. Chem. Soc. 1970, 92, 735-737. (c) Anderson, R.
J .; Henrick, C. A.; Siddall, J . B.; Zurflu¨h, R. J . Am. Chem. Soc. 1972,
94, 5379-5386. (d) Crabbe´, P.; Dollat, J .-M.; Gallina, J .; Luche, J .-L.;
Velarde, E.; Maddox, M. L.; To¨kes, L. J . Chem. Soc., Perkin Trans. 1
1978, 730-734.
Lew is Acid -Assisted Allylic Su bstitu tion of 3′,4′-
Un sa tu r a ted Ur a cil Nu cleosid es by th e Use of
Or ga n osilicon Rea gen ts. A variety of organometallic
reagents are known to react with allylic substrates.13
(10) For a theoretical study concerning regiochemistry of selenoxide
elimination: Kondo, N.; Fueno, H.; Fujimoto, H.; Makino, M.; Nakaoka,
H.; Aoki, I.; Uemura, S. J . Org. Chem. 1994, 59, 5254-5263.
(11) For physical data of 2a , 3a , and 4a , see ref 9c.
(12) Marumoto, R.; Honjo, M. Chem. Pharm. Bull. 1974, 22, 128-
134.
(13) For a review concerning nucleophilic substitution of allylic
compounds with organometallic reagents: Magid, R. M. Tetrahedron
1980, 36, 1901-1930.

Allylic Substitution of 3′,4′-Unsaturated Nucleosides
J . Org. Chem., Vol. 61, No. 3, 1996 853
Ta ble 1. Rea ction of 4b w ith Or ga n osilicon Rea gen tsa
Sch em e 2
reaction
time (h)
products
(isolated yield, %)
entry
reagent
1
2
3
CH2dCHCH2SiMe3
CH2dC(Me)OSiMe3
CH2C(Ph)OSiMe3
7
1
0.5
12b (74), 13b (5)
14 and 15 (ca. 6:1, 51)
16 and 17 (ca. 6:1, 64),
20 (14)
4
1-[(trimethylsilyl)-
oxy]cyclopentene
NCSiMe3
0.5
1
18 (68), 19 (2), 21 (17)
5
22 and 23 (ca. 2:1, 64)
a
All reactions were carried out at -78 °C in CH2Cl2 by the use
of SnCl4 (5 equiv) and an appropriate silicon reagent (10 equiv).
Stereochemical assignments of 12 and 13 were made
1
on the basis of the following H NMR observations. In
1
the H NMR spectrum of 12b in CDCl3, the resonance
due to H-5 appeared at δ 5.13 ppm, which is significantly
higher than that of its epimer 13b (H-5, δ 5.69 ppm).
Since there was virtually no difference in H-5 chemical
shift between 12a (δ 5.65 ppm) and 13a (δ 5.68 ppm),
both having a 5′-O-TBDMS group, the high-field shift
observed in 12b can be ascribable to the anisotropic effect
of the 5′-O-TBDPS group. This consideration led us to
assume their stereochemistry about C4′ as depicted, and
this was further confirmed by X-ray analysis of 12a .22
It was necessary to search for reaction conditions which
allow a more efficient conversion of 4b to 12b while main-
taining the above regioselectivity. We found that the use
of SnCl4, in place of BF3‚OEt2, brings about several dra-
matic changes, which are in the following order: (1) the
reaction goes to completion at -78 °C (for 7 h), (2) forma-
tion of the furan derivative (11b) can be eliminated com-
pletely, and (3) a high degree of stereoselectivity can be
accomplished with an increased yield of the desired
product (12b, 74%, vs. 13b, 5%, entry 1 in Table 1). With
this promising result in hand, we examined the applica-
bility of other organosilicon reagents to the SnCl4-assisted
reaction of 4b, the results of which are summarized in
Table 1 for the preparation of 14-23. The above result
between allyltrimethylsilane and 4b is also included.
equiv) in THF (0 °C, for 1 h) to give 1017 in 44% yield.
Reaction of 4a with another γ-selective organocopper
reagent BuCu‚BF3 (3 equiv, in Et2O, -78 °C to room
temperature) also failed: 71% of the starting material
was recovered. When Me3Al (3 equiv) was reacted with
4a (in CH2Cl2, -78 °C to room temperature),19 only the
furan derivative 11a was isolated in 29% yield.20
18
On the other hand, when BF3‚OEt2 (5 equiv) was added
to a mixture of allyltrimethylsilane (5 equiv) and 4a in
CH2Cl2 at -78 °C and the mixture was allowed to warm
to -40 °C, the expected γ-attack of the nucleophile took
place to yield 12a (23%) and its 4′-epimer 13a (4%)
(Scheme 2). Although a considerable amount of 11a
(10%) was isolated, no 2′-C-substituted product derived
from R-attack of the nucleophile was formed. When 4b
was used in this reaction, a similar trend was seen: 12b
(33%), 13b (14%), and 11b (30%).20,21 The use of 10 equiv
of allyltrimethylsilane in this reaction of 4b gave an
improved stereoselectivity for the desired 12b (12b: 53%
vs. 13b: 11%), but again 11b was inevitably formed in
34% yield.
(17) In addition to 10, an unknown product was also formed. For
physical data of 10 see ref 9c.
(18) Yamamoto, Y.; Yamamoto, S.; Yatagai, H.; Maruyama, K. J .
Am. Chem. Soc. 1980, 102, 2318-2325.
(19) Reactions between glycals and trialkylaluminum with allylic
substitution have been reported: Maruoka, K.; Nonoshita, K.; Itoh,
T.; Yamamoto, H. Chem. Lett. 1987, 2215-2216.
(20) For physical data of 11a see ref 9c. Physical data of 11b are as
follows: mp 136-137 °C (EtOH); UV (MeOH) λmax 250 nm (ꢀ 9700),
λmin 242 nm (ꢀ 9600); 1H NMR (CDCl3) δ 1.05 (9H, s, SiBu-t), 4.63 (2H,
s, H-5′), 5.79 (1H, dd, J 5,NH ) 2.4, J 5,6 ) 8.1 Hz, H-5), 6.22 and 6.39
(2H, each as d, J 2′,3′ ) 3.4 Hz, H-2′ and H-3′), 7.22-7.45 (7H, m, H-6
and Ph), 7.60-7.71 (4H, m, Ph), 8.82 (1H, br, NH); MS m/ z 389 (M+
- Bu-t). Anal. Calcd for C25H26N2O4Si.1/4H2O: C, 66.57; H, 5.92; N,
6.21. Found: C, 66.76; H, 5.88; N, 6.22.
(21) When the reaction temperature was maintained at -40 °C from
the beginning, 11b was obtained as the main product in 37% yield,
together with 12b (25%) and 13b (5%). Premixing of allyltrimethyl-
silane and BF3‚OEt2 gave a similar result, forming 11b in 25% yield
as well as 12b (24%) and 13b (12%).
It may add merit to the present method that the
organosilicon reagents employed can be extended to silyl
enol ethers, since this class of reagents can be readily

854 J . Org. Chem., Vol. 61, No. 3, 1996
Haraguchi et al.
Ta ble 2. 1H NMR Ch em ica l Sh ift of H-5 in 4′-c-Br a n ch ed
2′,3′-Did eh yd r o-2′,3′-d id eoxyu r id in es a n d Th eir
4′-Ep im er s (in CDCl3, 400 MHz)
detected by TLC (Rf 0.30, hexane/EtOAc ) 1/2). Under
similar reaction conditions, cyanotrimethylsilane also
worked in the SnCl4-assisted reaction of 6a to give a
mixture of 31 and 32 (ca. 10:1.3) in 90% yield. That the
main product has the 4′-configuration depicted as 31 was
unambiguously shown by coverting the mixture to the
corresponding uracil derivatives 24 and 25.
H-5 chemical
H-5 chemical
compd
shift (δ in ppm)
compd
shift (δ in ppm)
∆δ
12a
12b
14
5.65
5.13
5.13
13a
13b
15
5.68
5.69
5.74
0.03
0.56
0.61
In contrast to the above results, allylation of the
hypoxanthine derivative 9a in the presence of SnCl4
turned out to be unsuccessful: the furan 33 was formed
as the main product. This was also the case for other
Lewis acids, such as BF3‚OEt2, TMSOTf, and Et2AlCl.
The use of oxophilic TiCl4 gave a complex mixture of
unknown products. We finally found that EtAlCl2 effects
4′-C-allylation with a moderate yield of products. Thus,
when 9a was reacted with allyltrimethylsilane (5 equiv)
in the presence of EtAlCl2 (3 equiv) in CH2Cl2 at -78 °C
and then the reaction mixture was gradually warmed to
-30 °C, 34 and 35 (ca. 10:1) were formed as an insepa-
rable mixture in 54% yield. Compound 9b can also be
used as a substrate under these conditions, forming an
epimeric mixture of 36 and 37 in 68% combined yield.
On the other hand, the elimination pathway leading to
38 (64%) was the sole observable event when the allyla-
tion was carried out by using 9c. The EtAlCl2-assisted
reaction appeared not to be applicable to 4′-C-cyana-
tion: treatment of 6a with cyanotrimethylsilane (10
equiv) in the presence of EtAlCl2 (5 equiv) under the
identical reaction conditions gave a complex mixture of
at least five products.
16
18
22
5.14
4.99 and 5.15
5.21
17
19
23
not assignable
not assignable
5.84
0.63
prepared either by enolate trapping or by hydrosilyla-
tion.23 As shown in entries 2-4, the silyl enol ethers
react uniformly faster than allyltrimethylsilane, although
the stereoselectivity of their reactions remained only
moderate, except the case of entry 4.24 It should be
mentioned that, in entries 3 and 4, R-attack of the nucleo-
phile to this allylic system was also an observable event
to give 20 (14%) and 21 (17%),25 respectively, as an
additional product. Entry 5 shows that introduction of
a cyano group can be done by using cyanotrimethylsilane.
In Table 2 are listed H-5 chemical shifts of 12-19, 22,
and 23. These data were used as a criterion to distin-
guish the requisite 4′-C-branched product from its 4′-
epimer. In the case of the 4′-C-cyano derivatives (22 and
23), the stereochemistry was unambiguously determined.
Thus, the inseparable mixture containing 22 and 23,
obtained in entry 5 in Table 1, was desilylated and then
acetylated with Ac2O in pyridine. This allowed chro-
matographic separation of 24 and 25. The X-ray crystal-
lographic analysis of 24, derived from the main product
22, gave the confirmation of its stereochemistry.26
4′-C-Allyla tion a n d -Cya n a tion of 3′,4′-Un sa tu r -
a ted Nu cleosid es of N4-Acetylcytosin e a n d Hyp o-
xa n th in e. Application of the SnCl4-assisted C-C bond
formation was first carried out by using N4-acetylcytosine
derivative 6a and allyltrimethylsilane. In contrast to the
case of 4b, no reaction took place at -78 °C even after 6
h. However, by performing the reaction at -30 °C for 3
h, the 4′-C-allylated products 26 (65%) and 27 (15%) were
obtained. These were converted to the respective 5′-O-
TBDPS derivatives (28 and 29) by deacetylation followed
by silylation, and their stereochemistry was assigned by
comparing the chemical shifts of H-5 (28, δ 7.04 ppm,
vs. 29, δ 7.45 ppm). The assignments were also sup-
In an attempt to confirm stereochemistry of the 4′-C-
allylated hypoxanthine nucleosides, protecting group
manipulation leading to 39 and 40 was carried out and
1
ported by the additional H NMR evidence that H-5′ of
29 was observed as a singlet due to the absence of the
bulky base moiety in the same face of the furanose ring
(H-5′ of 28 appeared as two doublets: J gem ) 11.0 Hz).
The observed stereochemical outcome of 6a when com-
bined with that of the aforementioned uracil case sug-
gests that the nucleophile prefers attack from the less
hindered R-face, irrespective of whether it is syn or anti
to the 2′-O-acetyl leaving group. Quite unexpectedly,
when this allylation was reexamined by employing 6b,
a complex mixture of products resulted, in which only
characteristic fluorescent product attributable to 30 was
(22) The author has deposited atomic coordinates for 12a with the
Cambridge Crystallographic Data Centre. The coordinates can be
obtained, on request, from the Director, Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK.
(23) Colvin, E. W. Silicon Reagents in Organic Synthesis; Academic
Press: London, 1988.
(24) Compounds 18 and 19 consist of two isomers about the R-carbon
of the 1-oxocyclopent-2-yl moiety.
(25) The stereochemistry of 20 and 21 about the 2′-position is not
known.
(26) Yamaguchi, K.; Haraguchi, K.; Tanaka, H.; Itoh, Y.; Miyasaka,
T. Acta Crystallogr. 1992, C48, 2277-2278.
these 5′-O-TBDPS derivatives (inseparable mixture) were
analyzed by H NMR spectroscopy. While there was no
1

Allylic Substitution of 3′,4′-Unsaturated Nucleosides
J . Org. Chem., Vol. 61, No. 3, 1996 855
significant change in H-2 and H-8 chemical shifts27
between the minor products 35 (H-2, δ 8.24 ppm; H-8, δ
7.91 ppm) and 40 (H-2, δ 8.20 ppm; H-8, δ 7.93 ppm), an
upfield shift was seen, particularly in the H-8 resonance,
when such comparison was made between 34 (H-2, δ 8.24
ppm; H-8, δ 8.03 ppm) and 39 (H-2, δ 8.13 ppm; H-8, δ
7.67 ppm). These 1H NMR observations are in accord
with their depicted stereochemistry, although the ob-
served difference of H-8 chemical shifts between 39 and
40 is rather small (∆δ ) 0.26) when compared with those
difference of H-5 in uracil series in Table 2 (∆δ ) 0.56-
0.63).
1-[3-O-Acetyl-5-O-(ter t-bu tyld ip h en ylsilyl)-3-d eoxy-3-
(p h en ylselen o)-â-D-a r a bin ofu r a n osyl]u r a cil (3b). A pyr-
idine (10 mL) solution of 1 (683.7 mg, 1.78 mmol) and
TBDPSCl (0.93 mL, 3.57 mmol) was stirred overnight. After
evaporation of the solvent, the whole residue was chromato-
graphed on a silica gel column (2% EtOH in CHCl3). This gave
2b, which was dissolved in a mixture of Ac2O (0.5 mL, 5.34
mmol) and pyridine (10 mL) and stirred overnight. Conven-
tional workup followed by silica gel column chromatography
(hexane/EtOAc ) 3/1) gave 3b (929.3 mg, 79%) as an analyti-
cally pure foam: UV (MeOH) λmax 264 nm (ꢀ 11 900), λmin 235
nm (ꢀ 5500); 1H NMR (CDCl3) δ 1.08 (9H, s), 1.92 (3H, s), 3.76
(1H, dd, J 2′,3′ ) 8.1, J 3′,4′ ) 9.5 Hz), 3.86-3.89 (1H, m), 3.98
and 4.06 (2H, each as dd, J 4′,5′ ) 2.6 and 2.2, J gem ) 11.7 Hz),
5.32 (1H, dd, J 5,NH ) 2.6, J 5,6 ) 8.1 Hz), 5.59 (1H, dd), 6.10
(1H, d, J 1′,2′ ) 5.9 Hz), 7.29-7.67 (10H, m), 7.83 (1H, d), 8.30
(1H, br); MS m/ z 607 (M+ - Bu-t). Anal. Calcd for
C33H36N2O6SeSi: C, 59.73; H, 5.47; N, 4.22. Found: C, 59.71;
H, 5.47; N, 4.10.
Con clu sion
The present work has shown that the 3′,4′-unsaturated
nucleosides, which had been considered to be highly
susceptible to elimination, can act as an ordinary allyl
ester under appropriate reaction conditions. Namely, by
selection of a suitable Lewis acid and by reaction with
organosilicon reagents, these substrates (4, 6, and 9)
undergo SN2′ allylic substitution to effect C-C bond
formation at the 4′-position.28 Although SnCl4 can be
employed for both uracil and N4-acetylcytosine deriva-
tives (4 and 6), the use of EtAlCl2 appeared to be crucial
for hypoxanthine derivatives (9a and 9b). Also, the
presence of a 5′-O-acyl protecting group seems to be
indispensable for the 4′-C-allylation of N4-acetylcytosine
and hypoxanthine derivatives.
1-[2-O-Acetyl-5-O-(ter t-bu tyld ip h en ylsilyl)-â-L-glycer o-
p en t-3-en ofu r a n osyl]u r a cil (4b). A mixture of 3b (1.45 g,
2.19 mmol) and m-CPBA (453.5 mg, 2.6 mmol) in CH2Cl2 was
stirred for 20 min at room temperature. After being quenched
with Et3N, the reaction mixture was partitioned between
CHCl3 and saturated aqueous NaHCO3. Silica gel short-
column chromatography (5% EtOH in CHCl3) of the organic
layer gave the corresponding selenoxide. The selenoxide was
kept standing neat at 30-40 °C overnight. The resulting
mixture containing 4b and benzeneselenenic acid was dis-
solved in benzene and then neutralized with Et3N. Silica gel
column chromatography (hexane/EtOAc ) 2/1) of the mixture
gave 4b (994 mg, 90%) as an analytically pure foam: UV
1
(MeOH) λmax 258 nm (ꢀ 9700), λmin 236 nm (ꢀ 4300); H NMR
The 4′-C-branched 2′,3′-didehydro-2′,3′-dideoxyribo-
nucleosides synthesized in this study constitute a new
class of nucleoside analogues with potential anti-HIV
activity.14 Biological evaluations of these compounds are
in progress, and the results will be published separately.
(CDCl3) δ 1.08 (9H, s), 1.98 (3H, s), 4.28 (2H, s), 5.27-5.28
(1H, m), 5.68 (1H, dd, J 5,NH ) 2.2, J 5,6 ) 8.1 Hz), 5.81-5.84
(1H, m), 6.66 (1H, d, J 1′,2′ ) 6.7 Hz), 7.10 (1H, d), 7.39-7.48
(6H, m), 7.64-7.69 (4H, m), 8.61 (1H, br); MS m/ z 449 (M+
-
Bu-t), 389 (M+ - Bu-t-AcOH). Anal. Calcd for C27H30N2O6-
Si: C, 64.02; H, 5.97; N, 5.53. Found: C, 63.74; H, 6.00; N,
5.30.
Exp er im en ta l Section
1-(2,5-Di-O-a cetyl-â-D-glycer o-p en t-3-en ofu r a n osyl)-N4-
a cetylcytosin e (6a ). A mixture of 5 (864.5 mg, 2.0 mmol)
and DBN (0.49 mL, 4.0 mmol) in CH3CN (20 mL) was stirred
overnight and then treated with AcOH. Conventional workup
followed by silica gel column chromatography (2% EtOH in
CH2Cl2) gave 6a (500.7 mg, 71%) as a powder, which was
crystallized from CH2Cl2-acetone (mp 122-125 °C): UV
(MeOH) λmax 249 nm (ꢀ 13 300), λmin 228 nm (ꢀ 7000); 1H NMR
(CDCl3) δ 2.11, 2.15, and 2.16 (9H, each as s), 2.27 and 2.30
(2H, each as d, J gem ) 12.5 Hz), 5.40 (1H, dd, J 2′,3′ ) 1.1, J 1′,2′
) 2.2 Hz), 5.68-5.70 (1H, m), 6.55 (1H, d), 7.47 and 7.51 (2H,
each as d, J 5,6 ) 7.3 Hz), 9.67 (1H, br); FAB-MS m/ z 374 (M+
+ Na), 352 (M+ + H). Anal. Calcd for C15H17N3O7: C, 51.28;
H, 4.88; N, 11.96. Found: C, 50.97; H, 4.87; N, 11.95.
Melting points are uncorrected. 1H NMR spectra were
measured at 23 °C (internal standard, Me4Si) either at 400 or
100 MHz. Mass spectra (MS) were taken either in the FAB
mode (m-nitrobenzyl alcohol as a matrix) or in the EI mode.
High-resolution mass spectrometry (HRMS) was performed in
the FAB mode (m-nitrobenzyl alcohol plus KI as a matrix).
Column chromatography was carried out on silica gel (silica
gel 60, Merck). Thin layer chromatography (TLC) was per-
formed on silica gel (precoated silica gel plate F254, Merck).
1-(3-Deoxy-3-(p h en ylselen o)-â-D-a r a b in ofu r a n osyl)-
u r a cil (1). A solution of 1-[3-deoxy-3-(phenylseleno)-5-O-
trityl-â-D-arabinofuranosyl]uracil9c (1.37 g, 2.19 mmol) in 80%
aqueous AcOH (40 mL) was heated at 90 °C for 20 min. The
reaction mixture was evaporated and then coevaporated with
EtOH to remove trace amounts of AcOH. Silica gel column
chromatography (3% EtOH in CH2Cl2) of the whole residue
gave 1 (788.1 mg, 94%) as an analytically pure foam: UV
(MeOH) λmax 264 nm (ꢀ 13100), λmin 231 nm (ꢀ 5000); 1H NMR
(DMSO-d6, after addition of D2O) δ 3.51 (1H, dd, J 2′,3′ ) 6.6,
J 3′,4′ ) 8.1 Hz), 3.63 and 3.69 (2H, each as dd, J 4′,5′ ) 4.0 and
3.3, J gem ) 12.3 Hz), 3.82-3.86 (1H, m), 4.27 (1H, t, J 1′,2′ ) 5.5
Hz), 5.55 (1H, d, J 5,6 ) 8.1 Hz), 5.98 (1H, d), 7.33-7.35 and
7.59-7.61 (5H, each as m), 7.81 (1H, d); FAB-MS m/ z 385 (M+
+ H). Anal. Calcd for C15H16N2O5Se‚1/4H2O: C, 46.46; H,
4.29; N, 7.22. Found: C, 46.70; H, 4.29; N, 6.97.
1-[2-O-Acetyl-5-O-(ter t-bu tyld ip h en ylsilyl)-â-D-glycer o-
p en t-3-en ofu r a n osyl]-N4-a cetylcytosin e (6b). Compound
6a (91.8 mg, 0.26 mmol) was dissolved in NH3/MeOH (7 mL)
and kept at room temperature for 7 h. After evaporation,
pyridine (4 mL) and TBDPSCl (81 µL, 0.31 mmol) were added
to the residue and the mixture was stirred overnight. After
workup, the reaction mixture was chromatographed on a silica
gel column (6% EtOH in CH2Cl2), which gave 1-[5-O-(tert-
butyldiphenylsilyl)-â-D-glycero-pent-3-enofuranosyl]cytosine (63.3
mg, 52%) as a foam. This product (59.7 mg, 0.13 mmol) was
acetylated with Ac2O (37 µL, 0.39 mmol) in pyridine (2 mL)
overnight. Conventional workup followed by silica gel column
chromatography (hexane/EtOAc ) 1/2) gave 6b (46.5 mg, 65%)
as a syrup: UV (MeOH) λmax 249 (ꢀ 14 500) and 298 nm (ꢀ
(27) The assignments of these two aromatic protons can be made
by 1H NMR spectroscopy: a slightly broad signal, which becomes sharp
upon D2O addition, is assignable to H-2.
(28) According to a reviewer’s advice, a palladium-catalyzed allylic
substitution was briefly examined by using 9b, dimethyl sodiomalonate
(2.5 equiv), and Pd(PPh3)4 (0.2 equiv) in THF. No reaction took place
at room temperature, and heating of the reaction mixture at 60 °C
overnight gave the corresponding furan derivative (20%) along with
the recovered 9b (32%).
1
6400), λmin 277 nm (ꢀ 4600); H NMR (CDCl3) δ 1.09 (9H, s),
2.08 and 2.29 (6H, each as s), 4.30 and 4.35 (2H, each as d,
J gem ) 14.3 Hz), 5.33-5.34 (1H, m), 5.60-5.61 (1H, m), 6.53
(1H, d, J 1′,2′ ) 1.5 Hz), 7.36-7.52 and 7.66-7.69 (12H, each
as m), 9.97 (1H, br); FAB-MS m/ z 570 (M+ + Na), 548 (M+
+
H). Anal. Calcd for C29H33N3O6Si‚1/4H2O: C, 63.08; H, 6.12;
N, 7.61. Found: C, 63.07; H, 6.28; N, 7.21.

856 J . Org. Chem., Vol. 61, No. 3, 1996
Haraguchi et al.
9-(2,5-Di-O-a cet yl-3-d eoxy-3-iod o-â-D-xylofu r a n osyl)-
h yp oxa n th in e (8a ). A mixture of 9-(3-deoxy-3-iodo-â-D-
xylofuranosyl)hypoxanthine4b (1.04 g, 2.75 mmol) and Ac2O
(1.04 mL, 11.0 mmol) in pyridine (10 mL) was stirred over-
night. Conventional workup followed by silica gel column
chromatography (2% EtOH in CH2Cl2) gave 7a (779.1 mg, 61%)
as a foam: UV (MeOH) λmax 245 nm (ꢀ 11 500), λmin 222 nm (ꢀ
3200); 1H NMR (CDCl3) δ 2.13 and 2.18 (6H, each as s), 4.02-
4.04 (1H, m), 4.32-4.46 (3H, m), 5.85 (1H, t, J 1′,2′ ) J 2′,3′ ) 2.6
Hz), 6.15 (1H, d, J 1′,2′ ) 2.6 Hz), 8.22 and 8.33 (2H, each as s);
and 0.06 (6H, each as s), 0.89 (9H, s), 2.42-2.54 (2H, m), 3.56
and 3.63 (2H, each as d, J gem ) 9.9 Hz), 5.13 (1H, d, J ) 17.2
Hz), 5.14 (1H, d, J ) 9.9 Hz), 5.68 (1H, dd, J 5,NH ) 2.6, J 5,6
)
8.1 Hz), 5.73-5.75 (1H, m), 5.82 (1H, d, J ) 5.9 Hz), 6.29 (1H,
dd, J ) 1.8 and 5.9 Hz), 6.93 (1H, m), 7.33 (1H, d), 8.27 (1H,
br); FAB-MS m/ z (M+ - Bu-t); HRMS (m/ z) calcd for
C18H28N2O4Si.K 403.1455 [MK+], found 403.1453 (σ ) 0.0009).
R ea ct ion of 4b w it h Or ga n osilicon R ea gen t s in t h e
P r esen ce of Sn Cl4. Syn th esis of 12b a n d 13b a s a Typ ica l
Exa m p le. To a mixture of 4b (50.7 mg, 0.1 mmol) and
allyltrimethylsilane (0.16 mL, 1.0 mmol) in CH2Cl2 (2 mL) was
added SnCl4 (1 M CH2Cl2 solution, 0.5 mL, 0.5 mmol) at -78
°C under positive pressure of dry Ar. The reaction mixture
was stirred at -78 °C for 7 h, quenched with saturated
aqueous NaHCO3, and then extracted with CHCl3. Prepara-
tive TLC (hexane/EtOAc ) 2/1) of the extract gave 12b (36
mg, 74%) and a crude 13b that contained an unidentified
product having an acetyl group (confirmed by 1H NMR
spectroscopy). The latter was treated overnight with NH3/
MeOH, from which 13b (2 mg, 5%) was isolated by preparative
TLC (hexane/EtOAc ) 2/1).
FAB-MS m/ z 463 (M+ + H). Anal. Calcd for C14H15
-
IN4O6‚1/4EtOH: C, 37.68; H, 3.51; N, 11.83. Found: C, 37.45;
H, 3.38; N, 11.74.
9-(2,5-Di-O-a cet yl-â-D-glycer o-p en t -3-en ofu r a n osyl)-
h yp oxa n th in e (9a ). This compound was prepared from 8a
in 95% yield by the procedure described for the preparation of
6. Crystallization from MeOH-CH2Cl2 gave an analytical
sample (mp 120-122 °C): UV (MeOH) λmax 244 nm (ꢀ 11 000),
1
λmin 227 nm (ꢀ 6400); H NMR (CDCl3) δ 2.12 and 2.14 (6H,
each as s), 4.74 and 4.77 (2H, each as d, J gem ) 15.4 Hz), 5.47-
5.48 (1H, m), 5.99-6.00 (1H, m), 6.57 (1H, d, J 1′,2′ ) 1.8 Hz),
7.87 and 8.23 (2H, each as s); FAB-MS m/ z 335 (M+ + H).
Anal. Calcd for C14H14N4O6‚3/4H2O: C, 48.34; H, 4.49; N,
16.11. Found: C, 48.23; H, 4.17; N, 15.81.
Physical data of 12b obtained as a syrup are as follows: UV
1
(MeOH) λmax 260 nm (ꢀ 9200), λmin 235 nm (ꢀ 2900); H NMR
(CDCl3) δ 1.07 (9H, s), 2.29-2.36 (2H, m), 3.77 and 3.80 (2H,
each as d, J gem ) 11.4 Hz), 5.05-5.11 (2H, m), 5.13 (1H, dd,
J 5,NH ) 2.2, J 5,6 ) 8.4 Hz), 5.66-5.70 (1H, m), 5.82 (1H, dd, J
) 5.9 and 1.1 Hz), 6.21 (1H, dd, J ) 2.5 and 1.1 Hz), 6.93-
6.94 (1H, m), 7.36-7.47 (6H, m), 7.57-7.64 (5H, m), 8.90 (1H,
9-(2,5-Di-O-ben zoyl-â-D-glycer o-p en t-3-en ofu r a n osyl)-
h yp oxa n th in e (9b). A mixture of 9-(3-deoxy-3-iodo-â-D-
xylofuranosyl)hypoxanthine4b (3.20 g, 8.46 mmol), (PhCO)2O
(7.66 g, 33.5 mmol), DMAP (84.6 mg), and diisopropylethyl-
amine (7.37 mL, 42.3 mmol) in CH3CN (25 mL) was stirred
overnight. The reaction mixture was evaporated and parti-
tioned between CHCl3 and H2O. Silica gel column chroma-
tography (2% EtOH in CH2Cl2) of the organic layer gave 8b
(1.56 g, 40%) as a foam: UV (MeOH) λmax 232 nm (ꢀ 35 800),
λmin 214 nm (ꢀ 19 000); 1H NMR (CDCl3) δ 5.02 and 5.06 (2H,
each as d, J gem ) 14.3 Hz), 5.67-5.68 (1H, m), 6.28-6.29 (1H,
m), 6.75 (1H, d, J 1′,2′ ) 2.2 Hz), 7.44-7.49, 7.57-7.63, and
8.04-8.13 (10H, each as m), 7.98 and 8.18 (2H, each as s);
FAB-MS m/ z 459 (M+ + H). Anal. Calcd for C24H18N4O6‚
1/2H2O: C, 61.67; H, 4.10; N, 11.99. Found: C, 61.38; H, 4.19;
N, 11.71.
br); MS m/ z 431 (M+
-
Bu-t). Anal. Calcd for
C28H32N2O4Si.1/4H2O: C, 68.21; H, 6.64; N, 5.68. Found: C,
68.10; H, 6.83; N, 5.51.
Physical data of 13b obtained as a syrup are as follows: UV
(MeOH) λmax 259 nm, λmin 235 nm; 1H NMR (CDCl3) δ 1.06
(9H, s), 2.39-2.55 (2H, m), 3.61 and 3.65 (2H, each as d, J gem
) 10.3 Hz), 5.11 (1H, d, J ) 15.4 Hz), 5,12 (1H, d, J ) 11.7
Hz), 5.69 (1H, dd, J 5,NH ) 1.8, J 5,6 ) 8.1 Hz), 5.68-5.78 (1H,
m), 5.84 (1H, d, J ) 5.9 Hz), 6.27 (1H, dd, J ) 1.5 and 5.9 Hz),
6.96-6.97 (1H, m), 7.33-7.45 (7H, m), 7.64-7.66 (4H, m), 8.20
(1H, br); MS m/ z 431 (M+ - Bu-t); HRMS (m/ z) calcd for
C28H32N2O4Si‚K 527.1768 [MK+], found 527.1761 (σ ) 0.0020).
4′-C-Aceton yl-5′-O-(ter t-bu tyld ip h en ylsilyl)-2′,3′-d id e-
h yd r o-2′,3′-d id eoxyu r id in e (14) a n d It s 4′-E p im er 15.
These compounds were obtained as an epimeric mixture
(foam): UV (MeOH) λmax 260 nm (ꢀ 8800), λmin 235 nm (ꢀ 3200);
MS m/ z 447 (M+ - Bu-t). Anal. Calcd for C28H32N2O5Si‚
1/2H2O: C, 65.48; H, 6.48; N, 5.45. Found: C, 65.75; H, 6.73;
N, 5.21.
9-[2-O-Ben zoyl-5-(ter t-bu tyld ip h en ylsilyl)-â-D-glycer o-
p en t-3-en ofu r a n osyl]h yp oxa n th in e (9c). This compound
was obtained in 26% overall yield from 9a by the procedure
described for the preparation of 6b from 6a . Physical data of
9c obtained as a foam are as follows: UV (MeOH) λmax 245
1
nm (ꢀ 11 000), λmin 233 nm (ꢀ 8600); H NMR (CDCl3) δ 1.08
(9H, s), 2.14 (3H, s), 4.28 and 4.35 (2H, each as d, J gem ) 13.9
Hz), 5.44-5.45 (1H, m), 5.91-5.92 (1H, m), 6.53 (1H, d, J 1′,2′
) 1.8 Hz), 7.36-7.49 and 7.62-7.68 (10H, each as m), 7.73
and 8.16 (2H, each as s); FAB-MS m/ z 553 (M+ + Na), 531
(M+ + H). Anal. Calcd for C28H30N4O5Si: C, 63.38; H, 5.70;
N, 10.56. Found: C, 63.25; H, 5.82; N, 10.28.
1H NMR data of 14 are as follows: 1H NMR (CDCl3) δ 1.06
(9H, s), 2.17 (3H, s), 2.72 and 3.03 (2H, each as d, J gem ) 16.5
Hz), 3.85 (2H, s), 5.13 (1H, dd, J 5,NH ) 2.2, J 5,6 ) 8.1 Hz), 5.81
(1H, dd, J ) 1.1 and 6.0 Hz), 6.52 (1H, dd, J ) 2.2 and 6.0
Hz), 6.98 (1H, m), 7.30-7.65 (11H, m), 9.16 (1H, br).
Selected 1H NMR data of 15 are as follows: 1H NMR (CDCl3)
δ 1.06 (9H, s), 2.15 (3H, s), 2.86 and 3.02 (2H, each as d, J gem
) 15.7 Hz), 4.05 (2H, s), 5.74 (1H, dd, J 5,NH ) 2.2, J 5,6 ) 8.1
Hz), 5.79 (1H, dd, J ) 1.1 and 6.0 Hz), 6.48 (1H, dd, J ) 2.0
and 6.0 Hz), 6.94 (1H, m).
Rea ction of 4a w ith Allyltr im eth ylsila n e in th e P r es-
en ce of BF 3‚OEt2: F or m a tion of 12a , 13a , a n d 11a . To a
mixture of 4a (86.2 mg, 0.23 mmol) and allyltrimethylsilane
(0.36 mL, 2.25 mmol) in CH2Cl2 (4 mL) was added BF3‚OEt2
(0.14 mL, 1.13 mmol) at -78 °C under positive pressure of
dry Ar. The reaction mixture was allowed to warm gradually
to -40 °C over 1 h with stirring and then further stirred at
-40 °C for 2.5 h. The reaction mixture was quenched with
saturated aqueous NaHCO3 and then extracted with CHCl3.
TLC analysis (hexane/EtOAc ) 1/1) of the extract showed the
presence of three products (Rf values: 12a 0.56; 13a 0.46; 11a
0.52), from which 12a (25 mg, 30%) and 13a (5 mg, 6%) were
isolated by preparative TLC (hexane/EtOAc ) 1/1).
Physical data of 12a are as follows: mp 114-115 °C (Et2O-
hexane); UV (MeOH) λmax 260 nm (ꢀ 9200), λmin 235 nm (ꢀ
2900); 1H NMR (CDCl3) δ 0.07 (6H, s), 0.90 (9H, s), 2.17-2.39
(2H, m), 3.71 and 3.75 (2H, each as d, J gem ) 11.0 Hz), 5.09-
5.14 (2H, m), 5.65 (1H, dd, J 5,NH ) 2.2, J 5,6 ) 8.1 Hz), 5.68-
5.79 (1H, m), 5.81 (1H, dd, J ) 1.1 and 5.9 Hz), 6.14 (1H, dd,
J ) 1.8 and 5.9 Hz), 6.92-6.93 (1H, m), 7.92 (1H, d), 8.60 (1H,
br); MS m/ z 307 (M+ - Bu-t). Anal. Calcd for C18H28N2O4Si:
C, 59.33; H, 7.75; N, 7.69. Found: C, 59.27; H, 7.93; N, 7.74.
Physical data of 13a obtained as a syrup are as follows: UV
(MeOH) λmax 259 nm, λmin 230 nm; 1H NMR (CDCl3) δ 0.05
5′-O-(t er t -Bu t yld ip h e n ylsilyl)-2′,3′-d id e h yd r o-2′,3′-
d id eoxy-4′-C-p h en a cylu r id in e (16), Its 4′-Ep im er 17, a n d
20. Compounds 16 and 17 were obtained as an epimeric
mixture (foam): UV λmax 249 nm (ꢀ 17 400), λmin 232 nm (ꢀ
10 800); MS m/ z 509 (M+
C33H34N2O5Si‚1/4H2O: C, 69.39; H, 6.09; N, 4.90. Found: C,
69.35 ; H, 6.13; N, 4.62.
- Bu-t). Anal. Calcd for
1H NMR data of 16 are as follows: 1H NMR (CDCl3) δ 1.04
(9H, s), 3.28 and 3.59 (2H, each as d, J gem ) 16.5 Hz), 3.97
(2H, s), 5.14 (1H, dd, J 5,NH ) 1.8, J 5,6 ) 8.1 Hz), 5.80 (1H, dd,
J ) 1.5 and 6.0 Hz), 6.66 (1H, dd, J ) 1.8 and 6.0 Hz), 6.89-
6.90 (1H, m), 7.31-7.95 (16H, m), 9.11 (1H, br).
Selected 1H NMR data of 17 are as follows: 1H NMR (CDCl3)
δ 0.96 (9H, s), 3.27 and 3.66 (2H, each as d, J gem ) 16.9 Hz),
5.58 (1H, dd, J 5,NH ) 2.2, J 5,6 ) 8.1 Hz), 5.77 (1H, dd, J ) 1.5
and 6.0 Hz), 6.61 (1H, dd, J ) 1.8 and 6.0 Hz), 6.90-6.91 (1H,
m).
Physical data of 20 obtained as a syrup are as follows: UV
(MeOH) λshoulder 275 nm; 1H NMR (CDCl3) δ 1.07 (9H, s), 3.14-

Allylic Substitution of 3′,4′-Unsaturated Nucleosides
J . Org. Chem., Vol. 61, No. 3, 1996 857
(CDCl3) δ 2.15 (3H, s), 4.27 and 4.48 (2H, each as d, J gem
11.7 Hz), 5.86 (1H, d, J 5,6 ) 8.1 Hz), 6.23 (1H, dd, J ) 1.5 and
5.9 Hz), 6.38 (1H, dd, J ) 1.8 and 5.9 Hz), 7.15 (1H, d), 7.17-
7.18 (1H, m), 9.03 (1H, br); MS m/ z 277 (M+). Anal. Calcd
for C12H11N3O5‚1/3EtOH: C, 52.00; H, 4.48; N, 14.36. Found:
C, 51.65; H, 4.35; N, 14.42.
3.21 (1H, m), 3.39-3.44 (2H, m), 4.25 (2H, d, J 3′,5′ ) 1.5 Hz),
5.16-5.17 (1H, m), 5.68 (1H, dd, J 5,NH ) 2.2, J 5,6 ) 8.2 Hz),
6.32 (1H, d, J 1′,2′ ) 2.9 Hz), 7.36-7.49, 7.58-7.69, and 7.84-
7.94 (15H, each as m), 8.80 (1H, br); MS m/ z 509 (M+ - Bu-
t); HRMS (m/ z) calcd for C33H34N2O5Si‚K 605.1874 [MK+],
found 605.1880 (σ ) 0.0015).
)
5′-O-(ter t-Bu t yld ip h en ylsilyl)-4′-C-(1-oxocyclop en t -2-
yl)-2′,3′-dideh ydr o-2′,3′-dideoxyu r idin e (18), Its 4′-Epim er
19, a n d 21. Physical data of 18 (a mixture of two diastereo-
mers, ca. 10:8.1 about C2 of the cyclopentanone ring) obtained
as a foam are as follows: UV (MeOH) λmax 260 nm (ꢀ 9200),
4′-C-Allyl-N4,O5′-d ia cetyl-2′,3′-d id eh yd r o-2′,3′-d id eoxy-
cytid in e (26) a n d Its 4′-Ep im er 27. Compounds 26 (65%)
and 27 (15%) were obtained from 6a by the procedure
described for the preparation of 12b and 13b from 4b by using
allyltrimethylsilane (5 equiv) and SnCl4 (3 equiv). The reac-
tion was carried out initially at -78 °C, and then the reaction
mixture was allowed to warm gradually to -30 °C overnight.
Physical data of 26 obtained as a syrup are as follows: UV
(MeOH) λmax 247 (ꢀ 14 700) and 298 nm (ꢀ 6600), λmin 227 (ꢀ
1
λmin 236 nm (ꢀ 3100); H NMR (CDCl3) δ 1.07 and 1.09 (9H,
each as s), 1.21-2.55 (7H, m), 3.85 and 4.30 (2H, each as d,
J gem ) 11.4 Hz), 4.99 and 5.15 (1H, each as dd, J 5,NH ) 1.8,
J 5,6 ) 8.1 Hz), 5.83 and 5.90 (1H, each as dd, J ) 1.3 and 5.8
Hz), 6.21 and 6.41 (1H, each as dd, J ) 2.2 and 5.8 Hz), 6.88-
6.89 and 7.01-7.02 (1H, each as m), 7.35-7.66 (11H, m), 9.20
and 9.23 (1H, each as br); MS m/ z 473 (M+ - Bu-t). Anal.
Calcd for C30H34N2O5Si: C, 67.91; H, 6.46; N, 5.28. Found:
C, 67.76; H, 6.57; N, 5.11.
Physical data of 19 (a mixture of two diastereomers, ca. 10:1.4,
about C2 of the cyclopentanone ring) obtained as a syrup
are as follows: UV (MeOH) λmax 255 nm, λmin 235 nm; 1H NMR
(CDCl3) of the major diastereomer δ 1.04 (9H, s), 1.93-2.51
(7H, m), 3.72 and 3.75 (2H, each as d, J gem ) 10.2 Hz), 5.74
(1H, dd, J 5,NH ) 2.2, J 5,6 ) 8.1 Hz), 5.85 (1H, dd, J ) 1.5 and
6.0 Hz), 6.58 (1H, dd, J ) 1.8 and 6.0 Hz), 6.91-6.92 (1H, m),
7.37-7.45 and 7.59-7.68 (10H, each as m), 7.73 (1H, d); MS
m/ z 473 (M+ - Bu-t).
1
6100) and 273 nm (ꢀ 4700); H NMR (CDCl3) δ 2.02 and 2.28
(6H, each as s), 2.37-2.50 (2H, m), 4.04 and 4.49 (2H, each as
d, J gem ) 12.1 Hz), 5.12-5.17 (2H, m), 5.68-5.79 (1H, m), 6.07
(2H, s), 6.85 (1H, s), 7.42 and 8.09 (2H, each as d, J 5,6 ) 7.3
Hz), 9.91 (1H, br); FAB-MS m/ z 356 (M+ + Na), 334 (M+
+
H). Anal. Calcd for C16H19N3O5‚1/2H2O: C, 56.30; H, 5.91;
N, 12.31. Found: C, 56.19; H, 5.80; N, 12.19.
Physical data of 27 obtained as a syrup are as follows: UV
(MeOH) λmax 248 (ꢀ 15 600) and 298 nm (ꢀ 7200), λmin 227 (ꢀ
1
5700) and 273 nm (ꢀ 4600); H NMR (CDCl3) δ 2.08 and 2.28
(6H, each as s), 2.49-2.60 (2H, m), 4.08 and 4.28 (2H, each as
d, J gem ) 11.7 Hz), 5.17-5.21 (2H, m), 5.68-5.79 (1H, m), 6.09
(1H, dd, J ) 1.5 and 6.0 Hz), 6.15 (1H, dd, J ) 1.8 and 6.0
Hz), 6.93-6.94 (1H, m), 7.40 and 7.83 (2H, each as d, J 5,6
)
7.7 Hz), 9.43 (1H, br); FAB-MS m/ z 356 (M+ + Na), 334 (M+
+ H). Anal. Calcd for C16H19N3O5‚2/3MeOH: C, 56.43; H,
6.15; N, 11.85. Found: C, 56.14; H, 6.02; N, 11.72.
Physical data of 21 (a mixture of two diastereomers, ca. 10:8.1)
obtained as a syrup are as follows: UV (MeOH) λmax 254
1
nm, λmin 235 nm; H NMR (CDCl3) δ 1.06 and 1.07 (9H, each
N4-Acetyl-4′-C-a llyl-5′-O-(ter t-bu tyld ip h en ylsilyl)-2′,3′-
d id eh yd r o-2′,3′-d id eoxycytid in e (28) a n d Its 4′-Ep im er
29. These compounds were prepared from 26 or 27. The
as s), 1.65-2.36 (7H, m), 3.05-3.06 and 3.37-3.38 (1H, each
as m), 4.24-4.25 (2H, m), 4.78 and 5.26 (1H, each as d, J 2′,3′
)
2.6 and 1.5 Hz), 5.65 (1H, dd, J 5,NH ) 1.8, J 5,6 ) 8.4 Hz), 6.31
and 6.40 (1H, each as d, J 1′,2′ ) 3.3 Hz), 7.30 and 7.31 (1H,
each as d), 7.35-7.47 and 7.57-7.69 (10H, m), 8.81 (1H, br);
MS m/ z 473 (M+ - Bu-t); HRMS (m/ z) calcd for C30H34N2O5-
Si‚K 569.1874 [MK+], found 569.1863 (σ ) 0.0013).
procedure is given below by the preparation 28 from 26.
A
solution of 26 (103.2 mg, 0.3 mmol) in NH3/MeOH (10 mL)
was kept at room temperature overnight. After evaporation,
pyridine (6 mL) and TBDPSCl (0.36 mL, 1.25 mmol) were
added to the residue. The reaction mixture was stirred
overnight. Conventional workup followed by preparative TLC
(CH2Cl2/EtOH ) 20/1) gave 4′-C-allyl-5′-O-(tert-butyldiphen-
ylsilyl)-2′,3′-didehydro-2′,3′-dideoxycytidine (52.2 mg, 36%) as
a syrup. This product (31.5 mg, 0.065 mmol) was acetylated
with Ac2O (12.3 µL, 0.13 mmol) in pyridine (2 mL) for 3 h.
Preparative TLC (hexane/EtOAc ) 1/2) of the reaction mixture
gave 28 (25.4 mg, 76%) as a solid.
5′-O-(ter t-Bu tyld ip h en ylsilyl)-4′-C-cya n o-2′,3′-d id eh y-
d r o-2′,3′-d id eoxyu r id in e (22) a n d Its 4′-Ep im er 23. These
compounds were obtained as an epimeric mixture (foam): UV
(MeOH) λmax 258 nm (ꢀ 9100), λmin 235 nm (ꢀ 3200); MS m/ z
416 (M+ - Bu-t). Anal. Calcd for C26H27N3O4Si‚1/5EtOAc: C,
65.53; H, 5.89; N, 8.55. Found: C, 65.26; H, 6.02; N, 8.31.
1H NMR data of 22 are as follows: 1H NMR (CDCl3) δ 1.10
(9H, s), 4.01 and 4.05 (2H, each as d, J gem ) 11.0 Hz), 5.21
(1H, dd, J 5,NH ) 1.5, J 5,6 ) 8.1 Hz), 6.14 (1H, dd, J ) 2.6 and
5.9 Hz), 6.31 (1H, dd, J ) 1.8 and 5.9 Hz), 7.23-7.24 (1H, m),
7.22 (1H, d), 7.38-7.67 (10H, m), 9.19 (1H, br).
Physical data of 28 are as follows: UV (MeOH) λmax 247 (ꢀ
14 700) and 298 nm (ꢀ 6600), λmin 227 (ꢀ 6100) and 273 nm (ꢀ
4700); 1H NMR (CDCl3) δ 1.07 (9H, s), 2.25 (3H, s), 2.28-2.43
(2H, m), 3.74 and 3.83 (2H, each as d, J gem ) 11.0 Hz), 5.05-
5.14 (2H, m), 5.63-5.78 (1H, m), 5.98 (1H, dd, J ) 1.1 and 5.9
Hz), 6.07 (1H, dd, J ) 1.8 and 5.9 Hz), 6.91-6.92 (1H, m),
7.32-7.49 and 7.60-7.65 (10H, each as m), 7.04 and 8.05 (2H,
each as d, J 5,6 ) 7.3 Hz), 9.48 (1H, br); FAB-MS m/ z 552 (M+
+ Na), 530 (M+ + H). Anal. Calcd for C30H35N3O4Si‚1/2H2O:
C, 56.30; H, 5.91; N, 12.31. Found: C, 56.14; H, 5.80; N, 12.19.
Physical data of 29 obtained as a syrup are as follows: UV
(MeOH) λmax 248 (ꢀ 15 600) and 298 nm (ꢀ 7200), λmin 227 (ꢀ
1H NMR data of 23 are as follows: 1H NMR (CDCl3) δ 1.09
(9H, s), 3.77 and 3.93 (2H, each as d, J gem ) 10.3 Hz), 5.84
(1H, d, J 5,6 ) 8.1 Hz), 6.14 (1H, dd, J ) 5.7 Hz), 6.40 (1H, dd,
J ) 1.7 and 5.7 Hz), 7.08-7.09 (1H, m), 7.19 (1H, d), 7.38-
7.67 (10H, m), 9.19 (1H, br).
5′-O-Acetyl-4′-C-cya n o-2′,3′-d id eh yd r o-2′,3′-d id eoxyu r i-
d in e (24) a n d Its 4′-Ep im er 25. A mixture of 22 and 23 (78
mg, 0.16 mmol) in THF (3 mL) was reacted with Bu4NF.3H2O
(101 mg, 0.32 mmol) for 2 h. The reaction mixture was treated
with MeOH and then evaporated. Silica gel column chroma-
tography (2% EtOH in CHCl3) of the residue gave the corre-
sponding free nucleoside (37.2 mg, 99%) as a mixture. The
free nucleoside (34.5 mg, 0.15 mmol) was acetylated with Ac2O
(35 µL, 0.38 mmol) in pyridine (2 mL) overnight. Preparative
TLC (CH2Cl2/EtOH ) 50/1) of the reaction mixture gave 24
(21.8 mg, 55%, crystals) and 25 (8.1 mg, 21%, syrup).
Physical data of 24 are as follows: mp 161-164 °C (CH2-
Cl2); UV (MeOH) λmax 257 nm (ꢀ 9800), λmin 229 nm (ꢀ 2900);
1H NMR (CDCl3 containing CD3OD) δ 2.15 (3H, s), 4.36 and
4.54 (2H, each as d, J gem ) 12.1 Hz), 5.75 (1H, d, J 5,6 ) 8.1
Hz), 6.27 (1H, dd, J ) 1.1 and 5.9 Hz), 6.40 (1H, dd, J ) 2.2
and 5.9 Hz), 7.18-7.19 (1H, m), 7.27 (1H, d); MS m/ z 277 (M+).
Anal. Calcd for C12H11N3O5‚1/6H2O: C, 51.43; H, 4.08; N,
14.99. Found: C, 51.68; H, 3.89; N, 14.65.
1
5700) and 273 nm (ꢀ 4600); H NMR (CDCl3) δ 1.06 (9H, s),
2.28 (3H, s), 2.50-2.64 (2H, m), 3.66 (2H, s), 5.12-5.16 (2H,
m), 5.66-5.76 (1H, m), 6.05 (1H, d, J ) 5.9 Hz), 6.21 (1H, dd,
J ) 1.8 and 5.9 Hz), 6.88-6.89 (1H, m), 7.37-7.43 and 7.60-
7.66 (10H, each as m), 7.45 and 7.89 (2H, each as d, J 5,6
) 7.3
Hz), 9.56 (1H, br); FAB-MS m/ z 552 (M+ + Na), 530 (M+
+
H). Anal. Calcd for C30H35N3O4Si.2/3MeOH: C, 56.43; H, 6.15;
N, 11.85. Found: C, 56.14; H, 6.02; N, 11.72.
4′-C-Cya n o-N4,O5′-d ia cetyl-2′,3′-d id eh yd r o-2′,3′-d id eox-
ycytid in e (31) a n d Its 4′-Ep im er 32. These compounds (an
epimeric mixture) were obtained from 6a by the procedure
described for the preparation of 12b and 13b from 4b by using
cyanotrimethylsilane (10 equiv) and SnCl4 (5 equiv). The
reaction was carried out initially at -78 °C (2 h) and then was
allowed to warm gradually to -30 °C over 3 h, and finally the
reaction mixture was stirred at -30 °C overnight. A mixture
of 31 and 32 (ca. 10:1.3, combined yield 90%) was obtained
Physical data of 25 obtained as a syrup are as follows: UV
1
(MeOH) λmax 257 nm (ꢀ 9600), λmin 228 nm (ꢀ 2800); H NMR

858 J . Org. Chem., Vol. 61, No. 3, 1996
Haraguchi et al.
by silica gel column chromatography (2% EtOH in CH2Cl2):
UV (MeOH) λmax 250 (ꢀ 15 900) and 298 nm (ꢀ 6400), λmin 227
(ꢀ 5300) and 276 nm (ꢀ 4600); FAB-MS m/ z 319 (M+ + H).
Anal. Calcd for C14H14N4O5‚2/5EtOH: C, 52.64; H, 4.91; N,
16.64. Found: C, 52.75; H, 4.61; N, 16.46.
as d, J gem ) 12.1 Hz), 5.20-5.24 (2H, m), 5.80-5.90 (1H, m),
6.13 (1H, dd, J ) 1.1 and 6.1 Hz), 6.38 (1H, dd, J ) 1.8 and
6.1 Hz), 6.98-6.99 (1H, m), 7.44-7.57 and 7.92-7.96 (10H,
each as m), 7.88 and 8.20 (2H, each as s).
Selected 1H NMR data of the minor product (37) are as
follows: 1H NMR (CDCl3) δ 4.35 and 4.59 (2H, each as d, J gem
) 11.7 Hz), 5.20-5.24 (2H, m), 5.65-5.75 (1H, m), 7.10-7.11
(1H, m), 7.58-7.61 and 8.04-8.14 (10H, each as m), 7.92 and
8.25 (2H, each as s).
2-(t er t -Bu t yld ip h e n ylsilyl)-5-(h yp oxa n t h in -9-yl)fu -
r a n (38). Physical data of this compound are as follows: mp
265-268 °C (EtOH); UV (MeOH) λmax 220 (ꢀ 18 000) and 240
nm (ꢀ 15 300), λmin 231 nm (ꢀ 14 200); 1H NMR (CDCl3) δ 1.07
(9H, s), 4.70 (2H, s), 6.32 and 6.61 (2H, each as d, J 3,4 ) 3.3
Hz), 7.37-7.45 and 7.58-7.70 (10H, each as m), 7.96 and 8.24
(2H, each as s); FAB-MS m/ z 471 (M+ + H). Anal. Calcd for
C26H25N4O3Si‚1/2H2O: C, 65.25; H, 5.48; N, 11.71. Found: C,
65.23; H, 5.58; N, 11.77.
1H NMR data of the major product 31 are as follows: 1H
NMR (CDCl3) δ 2.12 and 2.30 (6H, each as s), 4.35 and 4.65
(2H, each as d, J gem ) 12.1 Hz), 6.30 (1H, dd, J ) 1.8 and 5.9
Hz), 6.40 (1H, dd, J ) 1.1 and 5.9 Hz), 7.22-7.23 (1H, m),
7.49 (1H, d, J ) 7.3 Hz), 7.73 (1H, d), 10.11 (1H, br).
2-(Acet oxym et h yl)-5-(h yp oxa n t h in -9-yl)fu r a n
(33).
Physical data of this compound are as follows: mp 250-252
°C (MeOH); UV (MeOH) λmax 240 nm (ꢀ 23 700), λmin 204 nm
(ꢀ 8600); 1H NMR (CDCl3) δ 2.06 (3H, s), 5.09 (2H, s), 6.73
and 6.76 (2H, each as d, J 3,4 ) 3.3 Hz), 8.12 (1H, br), 8.39 (1H,
s), 12.59 (1H, br). FAB-MS m/ z 275 (M+ + H). Anal. Calcd
for C12H10N4O4‚1/4H2O: C, 51.71; H, 3.80; N, 20.10. Found:
C, 52.07; H, 3.65; N, 19.97.
5′-O-Ace t yl-4′-C-a llyl-2′,3′-d id e h yd r o-2′,3′-d id e oxy-
in osin e (34) a n d Its 4′-Ep im er 35. These compounds (an
epimeric mixture) were obtained from 9a by the procedure
described for the preparation of 12b and 13b from 4b by using
allyltrimethylsilane (5 equiv) and EtAlCl2 (3 equiv). The
reaction was carried out initially at -78 °C, and then the
reaction mixture was allowed to warm gradually to -30 °C
overnight. Compounds 34 and 35 (combined yield: 44%) were
obtained by preparative TLC (CH2Cl2/EtOH ) 20/1): UV
(MeOH) λmax 248 nm (ꢀ 11 800), λmin 222 nm (ꢀ 3700); FAB-
MS m/ z 339 (M+ + Na), 317 (M+ + H). Anal. Calcd for
C15H16N4O4‚1/2EtOH: C, 56.63; H, 5.64; N, 16.57. Found: C,
56.29; H, 5.38; N, 16.80.
4′-C-Allyl-5′-O-(ter t-bu tyldiph en ylsilyl)-2′,3′-d id eh yd r o-
2′,3′-d id eoxyin osin e (39) a n d Its 4′-Ep im er 40. These
compounds (an epimeric mixture, syrup) were obtained in 41%
overall yield from an inseparable mixture of 36 and 37 by
debenzoylation (NaOMe/MeOH) followed by silylation
(TBDPSCl/imidazole/DMF): UV (MeOH) λmax 247 nm (ꢀ 11 500),
λmin 232 nm (ꢀ 7500); FAB-MS m/ z 535 (M+ + Na), 513 (M+
+
H). Anal. Calcd for C29H32N4O3Si‚2/3EtOH: C, 67.04; H, 6.68;
N, 10.31. Found: C, 67.31; H, 6.57; N, 9.93.
1H NMR data of the major product (39) are as follows: 1H
NMR (CDCl3) δ 1.06 (9H, s), 2.51-2.62 (2H, m), 3.65 and 3.72
(2H, each as d, J gem ) 10.3 Hz), 5.12-5.17 (2H, m), 5.72-5.81
(1H, m), 5.98 (1H, d, J ) 5.9 Hz), 6.37 (1H, dd, J ) 1.8 and
5.9 Hz), 6.94-6.95 (1H, m), 7.31-7.47 and 7.54-7.66 (10H,
each as m), 7.67 and 8.13 (2H, each as s).
Selected 1H NMR data of the minor product (40) are as
follows: 1H NMR (CDCl3) δ 1.08 (9H, s), 5.05-5.09 (2H, m),
5.58-5.67 (1H, m), 7.04-7.05 (1H, m), 7.93 and 8.20 (2H, each
as s).
1H NMR data of the major product (34) are as follows: 1H
NMR (CDCl3) δ 2.06 (3H, s), 2.40-2.53 (2H, m), 4.07 and 4.13
(2H, each as d, J gem ) 12.1 Hz), 5.16-5.20 (2H, m), 5.73-5.81
(1H, m), 6.12 (1H, d, J ) 5.9 Hz), 6.29 (1H, dd, J ) 1.8 and
5.9 Hz), 6.99-7.00 (1H, m), 8.03 and 8.24 (2H, each as s).
Selected 1H NMR data of the minor product (35) are as
follows: 1H NMR (CDCl3) δ 2.10 (3H, s), 5.07-5.15 (1H, m),
5.58-5.68 (1H, m), 7.03-7.04 (1H, m), 7.91 and 8.24 (2H, each
as s).
Ack n ow led gm en t. Financial support from the Min-
istry of Education, Science and Culture (Grant-in-Aid
Nos. 07772108 to K.H. and 07672289 to H.T.) are
gratefully acknowledged. This work has also been
supported by a British Council Collaborative Research
Project (to H.T.).
4′-C-Allyl-5′-O-b en zoyl-2′,3′-d id eh yd r o-2′,3′-d id eoxy-
in osin e (36) a n d Its 4′-Ep im er 37. These compounds (an
epimeric mixture) were obtained from 9b by the procedure
described for the preparation of 12b and 13b from 4b by using
allyltrimethylsilane (5 equiv) and EtAlCl2 (3 equiv). The
reaction was carried out initially at -78 °C, and then the
reaction mixture was allowed to warm gradually to -30 °C
overnight. A mixture of 36 and 37 (ca. 10:3.1, combined yield
68%) was obtained by preparative TLC (CH2Cl2/EtOH ) 30/
1): UV (MeOH) λmax 234 nm (ꢀ 18 100), λmin 216 nm (ꢀ 9800);
FAB-MS m/ z 401 (M+ + Na), 379 (M+ + H). Anal. Calcd for
C20H18N4O4‚1/4EtOH: C, 63.14; H, 5.04; N, 14.37. Found: C,
62.96; H, 4.94; N, 14.06.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
compounds 13a ,b, 20, and 21 (12 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
1H NMR data of the major product (36) are as follows: 1H
NMR (CDCl3) δ 2.53-2.64 (2H, m), 4.31 and 4.69 (2H, each
J O9516190