A New Entry to 2-Substituted Purine Nucleosides Based on Lithiation-Mediated Stanny Transfer of 6-Chloropurine Nucleosides

Article abstract of DOI:10.1021/jo970398q

In spite of exclusive lithiation at the 8-position of 9-(2,3,5-tris-O-TBDMS-β-D-ribofuranosyl)-6-chloropurine (2) with LDA, subsequent quenching of its lithiated species with Bu3SnCl (or TMSCl) results in the formation of 2-substituted products.Under optimized reaction conditions, where LTMP was used as a lithiating agent, 9-(2,3,5-tris-O-TBDMS-β-D-ribofuranosyl)-6-chloro-2-(tributylstannyl)purine (11) was formed in quantitative yield.Several experiments carried out to verify the reaction mechanism suggested that an anionic stannyl (or silyl) transfer from the 8- to the 2-position had been involved.Manipulation of the 2-tributylstannyl group in 11 and its adenine counterpart (22) has disclosed a new entry to 2-substituted purine nucleosides.This chemistry was briefly applied to the synthesis of the 2-fluoro analogue of neplanocin A.

Full text of DOI:10.1021/jo970398q

J . Org. Chem. 1997, 62, 6833-6841
6833
A New En tr y to 2-Su bstitu ted P u r in e Nu cleosid es Ba sed on
Lith ia tion -Med ia ted Sta n n yl Tr a n sfer of 6-Ch lor op u r in e
Nu cleosid es
Keisuke Kato,†,‡ Hiroyuki Hayakawa, Hiromichi Tanaka,* Hiroki Kumamoto,
†,|
,†
†
†
§
†
Satoru Shindoh, Satoshi Shuto, and Tadashi Miyasaka
School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku,
Tokyo 142, J apan, and Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12 Nishi-6,
Kita-ku, Sapporo 060, J apan
Received March 3, 1997X
In spite of exclusive lithiation at the 8-position of 9-(2,3,5-tris-O-TBDMS-â-D-ribofuranosyl)-6-
chloropurine (2) with LDA, subsequent quenching of its lithiated species with Bu SnCl (or TMSCl)
3
results in the formation of 2-substituted products. Under optimized reaction conditions, where
LTMP was used as a lithiating agent, 9-(2,3,5-tris-O-TBDMS-â-D-ribofuranosyl)-6-chloro-2-(tribu-
tylstannyl)purine (11) was formed in quantitative yield. Several experiments carried out to verify
the reaction mechanism suggested that an anionic stannyl (or silyl) transfer from the 8- to the
2
-position had been involved. Manipulation of the 2-tributylstannyl group in 11 and in its adenine
counterpart (22) has disclosed a new entry to 2-substituted purine nucleosides. This chemistry
was briefly applied to the synthesis of the 2-fluoro analogue of neplanocin A.
In tr od u ction
has provided a general entry to various types of 8-carbon-
substituted purine nucleosides.5
Lithiation (hydrogen-lithium exchange) of purine
nucleosides started with the finding by Barton et al. that
8
-alkylation of N-methyl derivatives of 2′,3′-O-isopropyl-
ideneadenosine can be achieved by way of lithiation with
butyllithium followed by alkylation.1 Later, in 1983, we
reported an improved method for the synthesis of 8-carbon-
substituted purine nucleosides in which 6-chloro-9-(2,3-
O-isopropylidene-â-D-ribofuranosyl)purine (1) was used
as a substrate for lithiation.3 In this instance, the use
of butyllithium as a lithiating agent appeared to be
unsatisfactory due to the intervention of halogen-lithium
exchange.4 The use of LDA for the lithiation of 1, on the
other hand, enabled a clean conversion to the 8-lithiated
species to give a yield of more than 80%. Its reaction
with carbon electrophiles (such as MeI, PhCHO, EtCHO,
,2
Ph
2 2
CO, and Et CO), combined with the feasibility of
subsequent nucleophilic substitution at the 6-position,
*
Corresponding author. Phone: 81-3-3784-8187. Fax: 81-3-3784-
8
252.
†
Showa University.
Hokkaido University.
Current address: School of Pharmaceutical Sciences, Toho Uni-
§
‡
It is well known that, unlike 8-substituted purine
nucleosides, the 2-substituted derivatives adopt an anti-
versity, 2-2-1 Miyama, Funabashi, Chiba 274, J apan.
|
Currrent address: Tsumura Central Research Laboratories, 3586
Yoshiwara, Ami-machi, Inashiki-gun, Ibaraki 300-11, J apan.
glycosidic conformation due to the absence of a substitu-
X
ent ortho to the glycosyl bond.6 Therefore, the 2-substi-
Abstract published in Advance ACS Abstracts, September 15, 1997.
(1) Barton, D. H. R.; Hedgecock, C. J . R.; Lederer, E.; Motherwell,
tuted purine nucleosides are considered to serve as
mimics of naturally occurring purine nucleosides. Syn-
thesis of these analogues has previously mostly been
accomplished by either the classical condensation method
W. B. Tetrahedron Lett. 1979, 279.
(
2) The halogen-lithium exchange of trimethylsilylated 8-bromopu-
rine nucleosides has also been reported: C oˆ ng-Danh, N.; Beaucourt,
J .-P.; Pichat, L. Tetrahedron Lett. 1979, 2385.
(
3) Tanaka, H.; Uchida, Y.; Shinozaki, M.; Hayakawa, H.; Matsuda,
A.; Miyasaka, T. Chem. Pharm. Bull. 1983, 31, 787.
4) There can be seen an inconsistency between our result and the
7
or the ring closure of imidazole nucleoside precursors.
(
Consequently, there have only been a limited number of
approaches available for constructing C-C bonds at the
2-position of purine nucleosides. These involve a ho-
following report, in which 6-chloro-9-(tetrahydropyran-2-yl)purine
underwent 8-lithiation with butyllithium and, upon treatment with
carbon electrophiles, gave the 8-carbon-substituted derivatives in
good yields: Leonard, N. J .; Bryant, J . D. J . Org. Chem. 1979, 44,
8
molytic methylation and nucleophilic substitution with
4
612.
5) For the LDA lithiation of naturally occurring purine nucleosides,
(
see: (a) Hayakawa, H.; Haraguchi, K.; Tanaka, H.; Miyasaka, T. Chem.
Pharm. Bull. 1987, 35, 72. (b) Hayakawa, H.; Tanaka, H.; Haraguchi,
K.; Mayumi, M.; Nakajima, M.; Sakamaki, T.; Miyasaka, T. Nucleosides
Nucleotides 1988, 7, 121. (c) Hayakawa, H.; Tanaka, H.; Sasaki, K.;
Haraguchi, K.; Saitoh, T.; Takai, F.; Miyasaka, T. J . Heterocycl. Chem.
(6) Saenger, W. Principles of Nucleic Acid Structure; Springer-
Verlag: New York, 1984.
(7) For a review article, see: Srivastava, P. C.; Robins, R. K.; Meyer,
R. B., J r. In Chemistry of Nucleosides and Nucleotides; Townsend, L.
B., Ed.; Plenum Press: New York, 1988; Vol. 1, pp 113-281.
(8) Maeda, M.; Nushi, K.; Kawazoe, Y. Tetrahedron 1974, 30, 2677.
1
989, 26, 189.
S0022-3263(97)00398-8 CCC: $14.00 © 1997 American Chemical Society

6
834 J . Org. Chem., Vol. 62, No. 20, 1997
Ta ble 1. Lith ia tion of 2 w ith LTMP a n d Su bsequ en t Rea ction s w ith Electr op h ilesa
Kato et al.
entry
LTMP (equiv)
electrophile (equiv)
HMPA (equiv)
products (% yield by isolation)
1
2
3
4
5
6
7
8
9
1.2
1.2
1.2
5.0
5.0
5.0
5.0
5.0
5.0
TMSCl (1.2)
2 (40), 4 (49), and 5 plus 6 (10, ca. 1:2)
2 (29), 9, (8), and 10 plus 11 (57, ca. 3:2)
8-deuterated 2 (98)b
2 (43), 4 (23), and 6 (23)
2 (59), 9 (7), and 11 (32)
deuterated 2 (90)c
Bu3SnCl (1.2)
CH3OD (excess)
TMSCl (1.2)
Bu3SnCl (1.2)
CH3OD (excess)
TMSCl (1.2)
10
10
2 (5) and 6 (83)
Bu3SnCl (1.2)
Bu3SnCl (5.0)
11 (90)
11 (100)d
a
b
Purification of the products was carried out by Florisil column chromatography, except for entry 9. Deuterium was incorporated
1
c
exclusively into the C8-position to the extent of 100% (calculated by H NMR spectroscopy). A mixture consisting of 2 (5%), 8-deuterated
2
(84%), and 2,8-dideuterated 2 (11%) (calculated by 1H NMR spectroscopy). d Purification of the product was performed by silica gel
column chromatography.
cyanide.9 An apparent drawback of these methods lies
Sch em e 1
in their narrow scope. An alternative and frequently
used approach starts with the use of 6-chloro-2-iodo-
purine nucleosides,10,11 the preparation of which neces-
sitates guanine precursors for generating the 6-chloro-
purin-2-yl radical.12
During our continuing studies on lithiation chemistry
of nucleosides, we found that quenching of the 8-lithiated
species of 9-(2,3,5-tris-O-TBDMS-â-D-ribofuranosyl)-6-
chloropurine (2) with TMSCl (or Bu
corresponding 2-substituted product, as a result of silyl
or stannyl) transfer from the 8- to the 2-position. The
3
SnCl) gave the
(
present paper describes the details of this reaction as well
as the use of the resulting 2-tributylstannyl derivative
for the synthesis of 2-substituted purine nucleosides.13
presumably due to protonolysis of the silyl group during
the chromatography.
Resu lts a n d Discu ssion
Apart from the question of why the 2-silylated deriva-
tives 4 and 6 were produced, it is apparent that 7 and 8
resulted from nucleophilic displacement with LDA. The
fact that such undesired displacement was not observed
during the formation of the 8-iodo derivative 3 suggests
that the TMSCl was acting as a Lewis acid to coordinate
with the purine ring, for example, at the N1-position. One
would readily anticipate that the presence of a more
bulky lithium dialkylamide could not allow such a
reaction pathway. When LTMP (1.2 equiv) was employed
in the above lithiation-based silylation of 2, only the
Lith ia tion -Ba sed Silyl a n d Sta n n yl Tr a n sfer fr om
th e 8- to th e 2-P osition . When lithiation of 2 was
carried out with LDA (1.2 equiv) in THF below -70 °C
and the resulting lithiated species quenched by adding
CH
-position to the extent of 89% (98% recovery). This is
fully in accord with the previous result obtained by using
3
OD, deuterium was incorporated solely into the
8
3
1
. Additional evidence to support the exclusive 8-lithia-
tion of 2 came from the fact that quenching with iodine
gave the 8-iodo derivative 3 in 93% yield. The structure
6
-chloropurine derivatives 4-6 were formed (entry 1 in
1
of 3 was readily deduced by H NMR spectroscopy:
Table 1). As shown in entry 2, the use of Bu
3
SnCl as an
anisotropic deshielding by the nitrogen atom at the
electrophile gave basically the same result, forming the
bis-stannylated (9) and monostannylated (10 and 11)
products. That the initial lithiation had taken place
exclusively at the 8-position in entries 1 and 2 was
confirmed again by deuterium incorporation (entry 3).
It is interesting to see that, with an increased amount
of LTMP (5.0 equiv), recovery of 2 remained much the
same (entry 4) or became even higher (entry 5). Also,
there can be seen in common in entries 4 and 5 that a
higher yield of the 2-substituted product (6 or 11)
resulted at the expense of the 8-substituted derivative
3
-position, due to the syn-glycosidic conformation of 3,
was observed in its H-2′ (δ 5.50) as compared with that
of 2 (δ 4.58).
In contrast to this, when the same lithiated species of
was treated with TMSCl (1.2 equiv), several products
2
(4-8) were obtained after Florisil column chromatogra-
phy along with recovered 2 (33%) (Scheme 1): the 2,8-
bis-TMS derivative 4 (15%), an inseparable mixture
consisting of 5 plus 6 (ca. 4:1, combined yield 10%), 7
(28%), and 8 (14%). The ratio of the products varied
significantly when silica gel was used as an adsorbent,
(5 or 10). Since the yield of 4 plus 6 (entry 4, 46%) or 9
plus 11 (entry 5, 39%) exceeds the extent of the 2,8-
dilithiated species of 2 (entry 6, 11%, see footnote), it
would be reasonable to assume that initial introduction
(
9) Matsuda, A.; Nomoto, Y.; Ueda, T. Chem. Pharm. Bull. 1979,
7, 183.
10) (a) Nair, V.; Lyons, A. G. Tetrahedron 1990, 46, 7677. (b) Nair,
2
(
V.; Purdy, D. F. Tetrahedron 1991,47, 365. (c) Adah, S. A.; Nair, V.
Tetrahedron Lett. 1995, 36, 6371.
of the 8-TMS or 8-SnBu
3
groups facilitated further
(
11) (a) Matsuda, A.; Shonozaki, M.; Miyasaka, T.; Machida, H.;
lithiation at the 2-position and that the subsequent
reaction leading to the 2-substituted products involves
lithiation-based transfer of the silyl or stannyl group from
the 8- to the 2-position. We found that a high-yield
formation of the 2-substituted derivative (6 or 11) can
be accomplished either by adding HMPA (10 equiv) as
an additive (entries 7 and 8) or by using an increased
Abiru, T. Chem. Pharm. Bull. 1985, 33, 1766. (b) Matsuda, A.;
Shinozaki, M.; Yamaguchi, T.; Homma, H.; Nomoto, R.; Miyasaka, T.;
Watanabe, Y.; Abiru, T. J . Med. Chem. 1992, 35, 241.
(
12) (a) Nair, V.; Richardson, S. G. Synthesis 1982, 670. (b) Nair,
V.; Young, D. A. J . Org. Chem. 1985, 50, 406.
13) A preliminary communication of the present study has been
(
reported: Kato, K.; Hayakawa, H.; Tanaka, H.; Kumamoto, H.;
Miyasaka, T. Tetrahedron Lett. 1995, 36, 6507.

A New Entry to 2-Substituted Purine Nucleosides
J . Org. Chem., Vol. 62, No. 20, 1997 6835
presence of the electronegative 6-chlorine atom plays an
important role in this transfer, since the reaction of
2
′,3′,5′-tris-O-TBDMS-N,N-dimethyladenosine under the
conditions in entry 8 gave the corresponding 8-stannyl
derivative as the sole product.17
Since stannylated organic molecules undergo further
functionalization, for example, through the Stille reac-
tion,18 the present 2-stannylation method will find wider
use for the synthesis of 2-substituted purine derivatives
in general, if the sugar moiety has no effect on the
reaction.19 When 6-chloro-9-methylpurine (12) was used
as a substrate, although concomitant stannylation of the
9
-methyl substituent occurred in this instance as shown
3
amount of Bu SnCl and then subjecting the reaction
in Scheme 4, the combined yield of the 2-stannylated
products (13, 48%; 14, 44%) suggests that the present
method would provide an efficient entry to the synthesis
of 2-substituted purine derivatives.
mixture to silica gel column chromatography (entry 9)
which effects protonolysis of the 8-stannyl group.14
Sch em e 2
Syn th esis of 2-Su bstitu ted P u r in e Ribon u cleo-
sid es b y Ma n ip u la t ion of t h e 2-Tr ib u t ylst a n n yl
Gr ou p . To show the usefulness of the present chemistry
for the synthesis of purine nucleosides variously substi-
tuted at the 2-position, several transformations were
carried out by using the 2-stannyl derivative 11 as shown
in Scheme 5. Compound 11 readily undergoes halogena-
tion in THF when treated with iodine or N-halosuccin-
imides to give 15-17.
Regiochemical assignment of these 2-substituted prod-
ucts was confirmed by 13C- H COLOC (correlation via
long-range coupling) spectroscopy. Since carbon atoms
other than C-5 in the 6-chloropurine ring (and also in
the adenine ring) are bound to two electronegative atoms,
1
Several experiments were carried out to verify the
assumption regarding silyl transfer from the 8- to the
the 1 C resonance of 2 which appeared at the highest field
3
1
(
δ 132.1) is assignable to C-5. When 13C- H COLOC was
2
4
-position (Scheme 2). When the 2,8-bis-TMS derivative
(1.0 equiv) was employed as an electrophile in the
seen between a ring proton and C-5, the compounds are
determined to be 2-substituted derivatives. In the 2-iodo
derivative 15, correlation of a ring proton (δ 8.47) was
seen in both C-5 (δ 132.3) and C-4 (δ 151.9), and C-2
appeared at δ 116.3. On the other hand, in the 8-iodo
derivative 3, such a correlation of a ring proton (δ 8.65)
was not observed with C-5 (δ 134.8) but with both C-4
and C-6 (δ 151.9 or 149.8), and C-8 appeared at a
significantly higher field of δ 109.8 due to the presence
of the iodine atom.
reaction with the lithiated 2, the 2-TMS derivative 6 was
formed in 72% yield (based on the combined amount of 2
plus 4). This fact indicates that 6 resulted not only from
4
through direct removal of the 8-TMS group but also
from silyl transfer from 4 to 2. That the 2-TMS group
once introduced is stable under these lithiation conditions
was confirmed by treating 6 with LTMP. More direct
evidence was obtained upon LTMP lithiation of the
isolated 8-TMS derivative 5, resulting in the formation
of not only the desilylated product 2 but also the
It was also possible to prepare the 2-fluoro derivative
1
2
8 by using XeF in the presence of AgOTf and 2,6-di(tert-
2
-silylated products 4 and 6. These experimental results
2
0
butyl)-4-methylpyridine. For C-C bond formation, the
Stille reaction was applied. Thus, compounds 19 and 20
were prepared in refluxing THF in the presence of
enabled us to propose a possible reaction mechanism
depicted in Scheme 3,15 which can be summarized as
follows: the inital lithiation occurs at the 8-position
Pd(PPh
3 4
) /CuI by using BnBr and PhI, respectively.
(
2
exclusively with LDA, dominantly with LTMP) to give
a ; the 8-TMS derivative 5 formed upon silylation of 2a
promptly undergoes lithiation at the 2-position with 2a
or with the lithiating agent) to give 5a ; the reaction
Introduction of a benzoyl group could be performed with
(16) Rearrangement of a stannyl group has been reported recently
(
in the lithiation of a stannylated heterocycle: Kelly, T. R.; Lang, F.
Tetrahedron Lett. 1995, 36, 9293.
between 5a and 5 gave the 2,8-bis-TMS derivative 4 and
regenerated 2a simultaneously; finally, silyl transfer
from 4 to 2a furnishes 6a which is stable under the
lithiation conditions and thus is accumulated. A high-
yield formation of 6 observed in the presence of HMPA
would be explicable as a consequence of increased sila-
philicity of the lithiated species such as 2a and 5a . We
(17) Although almost quantitative formation of the 8-tributylstannyl
derivative was apparent from TLC analysis (basic alumina plate,
hexane/EtOAc ) 10/1) of the reaction mixture, the product was isolated
only in 35% yield after Florisil column chromatography, resulting in
the formation of the starting material in 50% yield (see the Experi-
mental Section).
(18) For a review concerning the Stille reaction, see: Mitchell, T.
N. Synthesis 1992, 803.
believe that the stannylation reaction of 2 follows a
(19) It has been reported that the extent of lithiation at the
6-position of uridine (or acyclouridine) derivatives is affected by the
structure of the sugar (or acyclic) moiety: (a) Hayakawa, H.; Tanaka,
H.; Maruyama, Y.; Miyasaka, T. Chem. Lett. 1985, 1401. (b) Hayakawa,
H.; Tanaka, H.; Obi, K.; Itoh, M.; Miyasaka, T. Tetrahedron Lett. 1987,
28, 87. (c) Tanaka, H.; Miyasaka, T.; Sekiya, K.; Takashima, H.;
Ubasawa, M.; Nitta, I.; Baba, M.; Walker, R. T.; De Clercq, E.
Nucleosides Nucleotides 1992, 11, 447.
similar pathway.16 It is worth mentioning that the
(14) Protonolysis of stannylated heterocycles with silica gel has been
reported: Sakamoto, T.; Uchiyama, D.; Kondo, Y.; Yamanaka, H.
Chem. Pharm. Bull. 1993, 41, 478.
(
15) For an example of anionic C-C silyl rearrangement, see:
Daney, M.; Lapouyade, R.; Bouas-Laurent, H. J . Org. Chem. 1983, 48,
055.
(20) (a) Tius, M. A.; Kawakami, J . K. Synth. Commun. 1992, 22,
1461. (b) Tius, M. A. Tetrahedron 1995, 51, 6605.
5

6
836 J . Org. Chem., Vol. 62, No. 20, 1997
Kato et al.
Sch em e 3
Sch em e 4
Sch em e 6
Sch em e 5a
Sch em e 7a
a
Reagents (isolated yields are shown in parentheses): (a)
iodine, THF (97%); (b) NBS, THF (92%); (c) NCS, THF (95%); (d)
XeF2, AgOTf, 2,6-di-tert-butyl-4-methylpyridine, CH2Cl2 (85%); (e)
BnBr, Pd(PPh3)4, CuI, THF (55%); (f) PhI, Pd(PPh3)4, CuI, THF
a
Reagents (isolated yields are shown in parentheses): (a)
iodine, THF (100%); (b) NBS, THF (90%); (c) NCS, THF (70%);
(
(41%); (g) PhCOCl, pyridine, toluene (60%).
d) XeF2, AgOTf, 2,6-di-tert-butyl-4-methylpyridine, CH2Cl2 (80%);
(e) BnBr, Pd(PPh3)4, CuI, THF (83%); (f) PhI, Pd(PPh3)4, CuI, THF
PhCOCl/pyridine in refluxing toluene to give the 2-ben-
zoyl derivative 21 without using palladium catalysis.
(89%); (g) allyl bromide, Pd(Ph3)4, CuI, THF (63%); (h) PhCtCI,
Pd(PPh3)4, CuI, THF (72%); (i) PhCHdCHBr, Pd(PPh3)4, CuI, THF
2
1
(40%).
These C-C bond-forming reactions required a longer
reaction time (for 20-24 h), and in some cases, formation
of the destannylated product (2) was observed.
The above series of reactions were also examined after
converting 11 to the 2-stannylated adenosine derivative
3
by heating with NH /MeOH in a sealed tube at 100 °C,
22 was obtained only in moderate yield (50-60%) with
concomitant formation of 2′,3′,5′-tris-O-TBDMS-adeno-
sine (23).5
a,22
Since 11 gave mainly the destannylated
CO /MeOH, it was
conceivable that methoxide formed in the NH /MeOH
was responsible for the formation of 23. When NH /2-
2
2. When this conversion (Scheme 6) was carried out
product upon treatment with K
2
3
3
(21) Yamamoto, Y.; Yanagi, A. Chem. Pharm. Bull. 1982, 30, 2003.
3

A New Entry to 2-Substituted Purine Nucleosides
J . Org. Chem., Vol. 62, No. 20, 1997 6837
Sch em e 8a
a
Reagents (isolated yields are shown in parentheses): (a) TBDMSCl, imidazole, DMF (82%); (b) LTMP, THF, and then Bu3SnCl (100%);
(c) NH3, 2-propanol (78%); (d) XeF2, AgOTf, 2,6-di-tert-butyl-4-methylpyridine, CH2Cl2 (53%).
propanol (ca. 5%, saturated at 0 °C) was used for the
adenine derivatives 36. The 2-fluoroneplanocin A (37)
above ammonolysis of 11, 22 was obtained in 92% yield
with only a small amount (6%) of 23.
was prepared from 36 by using XeF
preparation of 18.
2
as mentioned in the
Compounds 24-32 were synthesized by using 22 under
similar conditions to those employed in the reactions of
Con clu sion
1
1, as shown in Scheme 7. Compounds 29-32 were
prepared by the procedure described for the preparation
of the 2-benzyl-6-chloropurine derivative 19. The 2-ben-
zyl (28) and 2-phenyl (29) derivatives were isolated in
slightly higher yields than those obtained from 11. The
preparations of 30 and 31 were carried out by using allyl
bromide and iodophenylacetylene, respectively. Com-
pound 32 was obtained as a mixture of two geometrical
isomers (E/Z ) 6/1) by the use of â-bromostyrene (a
mixture of isomers).
Syn th esis of th e 2-F lu or o Der iva tive of Nu cleo-
sid e An tibiotic Nep la n ocin A. Among the vast num-
ber of nucleoside antibiotics, including carbocyclic nu-
cleosides, compounds having adenine as a nucleobase
constitute the largest family.23 Their 2-substituted ana-
logues have mostly been synthesized by condensation of
the base and sugar (or carbocyclic) moiety,24 due to the
lack of an appropriate method for functionalizing the
Although the initial lithiation of 6-chloropurine nucleo-
side with lithium dialkylamides takes place at the
8
-position, it was found in the present study that reaction
of the 8-lithiated species with tin and silicon electrophiles
furnished 2-functionalized products. Several experi-
ments were carried out to verify that the mechanism
involved an anionic transfer of a stannyl or silyl group
from the 8- to the 2-position. The resulting 2-stannylated
product obtained in quantitative yield can be used for
further transformations. This constitutes a new entry
into 2-substituted purine nucleosides which previously
have been difficult to synthesize starting from naturally
occurring nucleosides. An application of this approach
to the synthesis of the 2-fluoro analogue of neplanocin A
was also accomplished.
2
-position of intact purine nucleosides. We briefly ap-
Exp er im en ta l Section
plied the present method to the synthesis of the 2-fluoro
analogue of neplanocin A (Scheme 8).
Melting points are uncorrected. 1H and 13C NMR spectra
were measured at 23 °C (internal standard, Me
4
Si) at either
The preparation of 6-chloro-9-[(1R,2S,3R)-4-(hydroxy-
methyl)-2,3-dihydroxy-4-cyclopenten-1-yl]purine (33) from
neplanocin A has a precedent.25 Protection of the hy-
droxyl groups of 33 with TBDMS gave 34. Lithiation-
based stannylation of 34 was carried out under the
reaction conditions shown in entry 9 in Table 1 to give
the corresponding 2-tributylstannylated product 35 in
quantitative yield. Ammonolysis of 35 furnished the
4
00 or 500 MHz. 13C NMR chemical shifts are shown only for
purine ring carbons. Mass spectra (MS) were taken in the
FAB mode (m-nitrobenzyl alcohol as a matrix). For compounds
3
5
containing Cl and/or Sn, ion peaks corresponding to Cl and/
1
20
or Sn are shown. Column chromatography was carried out
on Florisil (Merck) or silica gel (silica gel 60, Merck). Thin
layer chromatography (TLC) was performed on basic alumina
(
precoated plate, aluminum oxide 60 F254, type E, Merck) or
silica gel (precoated silica gel plate F254, Merck).
-(2,3,5-Tr is-O-TBDMS-â-D-r ibofu r a n osyl)-6-ch lor op u -
r in e (2). A mixture of 6-chloro-9-(â-D-ribofuranosyl)purine
14.3 g, 49 mmol), TBDMSCl (40.2 g, 250 mmol), and imidazole
9
(22) Destannylation with aqueous ammonia has been reported in
the reaction of a stannylated heterocycle: Uchiyama, D.; Yabe, M.;
Kameyama, H.; Sakamoto, T.; Kondo, Y.; Yamanaka, H. Heterocycles
(
1
996, 43, 1301.
23) For a review article concerning nucleoside antibiotics, see:
Isono, K. J . Antibiot. 1988, 41, 1711.
24) For a recent example, see: Obara, T.; Shuto, S.; Saito, Y.;
(25.4 g, 340 mmol) in DMF (200 mL) was stirred at room
temperature for 15 h. The reaction mixture was partitioned
(
between EtOAc and saturated aqueous NaHCO
layer was dried (Na SO ), evaporated, and chromatographed
on a silica gel column (hexane/EtOAc ) 30/1). This gave 2
30.1 g, 98%) as a foam. Crystallization from hexane gave an
analytical sample (mp 138 °C): UV (MeOH) λmax 265 nm (ꢀ
3
. The organic
(
2
4
Snoeck, R.; Andrei, G.; Balzarini, J .; De Clercq, E.; Matsuda, A. J . Med.
Chem. 1996, 39, 3847.
(
(25) Shuto, S.; Obara, T.; Toriya, M.; Hosoya, M.; Snoeck, R.; Andrei,
G.; Balzarini, J .; De Clercq, E. J . Med. Chem. 1992, 35, 324.

6
838 J . Org. Chem., Vol. 62, No. 20, 1997
Kato et al.
9
-
0
400), λmin 227 nm (ꢀ 3100); 1H NMR (400 MHz, CDCl
3
) δ
for C24
C, 55.92; H, 9.80; N, 9.59.
H
67
N
5
O
4
Si
3
‚2H
2
O: C, 55.65; H, 9.81; N, 9.59. Found:
0.03, -0.02, 0.09, 0.10, 0.15, and 0.16 (18H, each as s), 0.79,
.93, and 0.96 (27H, each as s), 3.80 (1H, dd, J ) 11.6, 2.6
Lith ia tion of 2 w ith LTMP (1.2 equ iv) a n d Su bsequ en t
Sta n n yla tion : F or m a tion of 9-11 (Ta ble 1, en tr y 2). To
a THF (10 mL) solution of LTMP (0.6 mmol) was added 2 (315
mg, 0.5 mmol) in THF (5 mL) dropwise under a positive
pressure of dry Ar, while maintaining the reaction temperature
below -70 °C. After the mixture was stirred for 5 min,
Hz), 4.02 (1H, dd, J ) 11.6, 3.6 Hz), 4.15-4.17 (1H, m), 4.30
(
1H, dd, J ) 4.5, 3.7 Hz), 4.58 (1H, dd, J ) 5.1, 4.5 Hz), 6.13
13
(
1H, d, J ) 5.1 Hz), 8.55 (1H, s), 8.74 (1H, s); C NMR (400
) δ 132.1, 144.1, 151.0, 151.5, 151.9; FAB-MS m/z
29 (M + H). Anal. Calcd for C28 Si : C, 53.42; H,
.48; N, 8.90. Found: C, 53.58; H, 8.75; N, 8.89.
-(2,3,5-Tr is-O-TBDMS-â-D-r ibofu r a n osyl)-6-ch lor o-8-
MHz, CDCl
3
+
6
8
H
53ClN
4
O
4
3
Bu
further continued for 0.5 h. The reaction mixture was
2
partitioned between saturated aqueous NaHCO and CH Cl .
3
SnCl (400 µL, 0.6 mmol) was added, and stirring was
9
iod op u r in e (3). To a THF (5 mL) solution of LDA (0.6 mmol)
was added 2 (314 mg, 0.5 mmol) in THF (3 mL) dropwise under
a positive pressure of dry Ar, while maintaining the reaction
temperature below -70 °C. The mixture was stirred for 5 min
and then treated with iodine (152.4 mg, 0.6 mmol as I
THF (3 mL). After being stirred at below -70 °C for 0.5 h,
the reaction mixture was diluted with 5% aqueous Na
and extracted with EtOAc. The extract was washed with
brine, dried (MgSO ), and chromatographed on a silica gel
3
2
Florisil column chromatography (hexane/EtOAc ) 100/1) of the
organic layer gave 9 (syrup, 48 mg, 8%) and a mixture of 10
plus 11 (syrup, 261 mg, ca. 3:2, 57%). The starting material
2
) in
2
)
(91 mg, 29%) was recovered by elution with hexane/EtOAc
30/1.
2
2 3
S O
Compounds 9 and 10 were unstable, and their pure samples
could not be obtained. For physical data of 11, see the
corresponding part given below.
Partial 1H NMR data of 9 are as follows: 1H NMR (400
4
column (hexane/EtOAc ) 50/1). This afforded 3 (351 mg, 93%)
as a syrup: UV (MeOH) λmax 276 nm (ꢀ 14 200), λmin 240 nm
1
MHz, CDCl
each as s), 0.86-0.97, 1.17-1.21, 1.29-1.42, and 1.50-1.57
54H, each as m), 3.70-3.74 (1H, m), 3.90 (1H, t, J ) 10.2
3
) δ -0.47, -0.19, -0.18, 0.15, 0.17, and 0.18 (18H,
(ꢀ 7700); H NMR (400 MHz, CDCl
3
) δ -0.37, -0.05, -0.02,
0
.04, 0.18, and 0.19 (18H, each as s), 0.81, 0.84, and 0.99 (27H,
each as s), 3.74 (1H, dd, J ) 11.0, 4.0 Hz), 4.03 (1H, dd, J )
1.0, 8.0 Hz), 4.09-4.11 (1H, m), 4.59 (1H, dd, J ) 4.4, 3.0
(
Hz), 3.97-4.01 (1H, m), 4.28 (1H, t, J ) 3.3 Hz), 5.74-5.82
1
(
2H, m).
Hz), 5.50 (1H, dd, J ) 6.0, 4.4 Hz), 5.98 (1H, d, J ) 6.0 Hz),
Physical data of 10 are as follows: 1H NMR (500 MHz,
1
3
8
.65 (1H, s); C NMR (400 MHz, CDCl
3
) δ 109.8, 134.8, 149.8,
51.2, 151.9; FAB-MS m/z 755 (M + H). Anal. Calcd for
52ClIN Si : C, 44.52; H, 6.94; N, 7.42. Found: C, 44.86;
H, 7.15; N, 7.06.
+
3
CDCl ) δ -0.41, -0.19, 0.07, 0.08, 0.15, and 0.17 (18H, each
as s), 0.69, 0.91, and 0.98 (27H, each as s), 0.88-0.90, 1.26-
1
C
28
H
4
O
4
3
1
3
.50, and 1.59-1.65 (27H, each as m), 3.71 (1H, dd, J ) 9.2,
.2 Hz), 4.02 (1H, t, J ) 9.2 Hz), 4.04-4.07 (1H, m), 4.38 (1H,
Lith ia tion of 2 w ith LDA a n d Su bsequ en t Silyla tion :
F or m a tion of 4-8. To a THF (10 mL) solution of LDA (0.6
mmol) was added 2 (315 mg, 0.5 mmol) in THF (5 mL)
dropwise under a positive pressure of dry Ar, while maintain-
ing the reaction temperature below -70 °C. After the mixture
was stirrred for 5 min, TMSCl (140 µL, 0.6 mmol) was added,
and stirring was further continued for 0.5 h. The reaction
mixture was partitioned between saturated aqueous NaHCO
and CH Cl . Florisil column chromatography of the organic
layer gave 4 (elution with hexane/EtOAc ) 100/1, syrup, 58
mg, 15%), a mixture of 5 plus 6 (elution with hexane/EtOAc
1
3
t, J ) 4.0 Hz), 5.74-5.80 (2H, m), 8.60 (1H, s); C NMR (500
MHz, CDCl
9
3
) δ 134.8, 149.7, 150.2, 153.0, 171.4; FAB-MS m/z
19 (M + H).
P r ep a r a tion of 9-(2,3,5-Tr is-O-TBDMS-â-D-r ibofu r a n o-
+
syl)-6-ch lor o-8-(tr im eth ylsilyl)p u r in e (5). To a THF (10
mL) solution of 2,2,6,6-tetramethylpiperidine (250 µL, 1.5
mmol) kept below -70 °C were added 2 (315 mg, 0.5 mmol) in
THF (5 mL) and TMSCl (130 µL, 0.6 mmol) successively under
a positive pressure of dry Ar. To this mixture was added BuLi
(800 µL, 0.6 mmol, hexane solution) dropwise, while maintain-
ing the reaction temperature below -70 °C. After stirring for
3
2
2
)
50/1, syrup, 35 mg, ca. 4:1, 10%), and 2 (elution with hexane/
EtOAc ) 30/1, 104 mg, 33%). Further elution with hexane/
5 min, saturated aqueous NaHCO
mixture. Extraction with CH Cl
3
was added to the reaction
2
followed by Florisil column
EtOAc ) 10/1 gave 7 (syrup, 107 mg, 28%) and then 8 (foam,
4
2
9 mg, 14%).
chromatography (hexane/EtOAc ) 100/1) gave 5 (213 mg, 61%)
as an oil. Due to the instability of 5 under chromatographic
conditions, its analytically pure sample could not be ob-
Physical data of 4 are as follows: UV (MeOH) λmax 275 nm
1
(
-
ꢀ 11 000), λmin 239 nm (ꢀ 4000); H NMR (400 MHz, CDCl
3
) δ
tained: 1H NMR (400 MHz, CDCl
) δ -0.43, -0.16, 0.09, 0.10,
0.51, -0.21, 0.08, 0.09, 0.14, and 0.18 (18H, each as s), 0.40
3
and 0.53 (18H, each as s), 0.66, 0.92, and 0.96 (27H, each as
0.16, and 0.18 (18H, each as s), 0.55 (9H, s), 0.70, 0.92, and
s), 3.70 (1H, dd, J ) 10.5, 4.4 Hz), 3.98 (1H, t, J ) 10.5 Hz),
4
0.98 (27H, each as s), 3.72-3.76 (1H, m), 4.01-4.10 (2H, m),
.06 (1H, dd, J ) 10.5, 4.2 Hz), 4.31 (1H, d, J ) 4.0 Hz), 5.77
4.39 (1H, d, J ) 4.0 Hz), 5.74 (1H, dd, J ) 7.7, 4.0 Hz), 6.09
1
3
13
(
(
1H, dd, J ) 8.4, 4.0 Hz), 6.11 (1H, d, J ) 8.4 Hz); C NMR
400 MHz, CDCl ) δ 132.7, 150.0, 152.6, 164.9, 173.7; FAB-
(1H, d), 8.67 (1H, s); C NMR (400 MHz, CDCl
3
) δ 133.4, 150.6,
+
150.7, 153.8, 165.4; FAB-MS m/z 701 (M + H).
3
+
MS m/z 773 (M + H). Anal. Calcd for C34
H
69ClN
4
O
4
Si
5
‚H
2
O:
9-(2,3,5-Tr is-O-TBDMS-â-D-r ibofu r a n osyl)-6-ch lor o-2-
(tr im eth ylsilyl)p u r in e (6). As a typical example for the
preparation of this compound, the procedure used in entry 7
in Table 1 is shown below. To a mixture of LTMP (2.5 mmol)
and HMPA (900 µL, 5.0 mmol) in THF (5 mL) was added 2
(315 mg, 0.5 mmol) in THF (3 mL) dropwise under a positive
pressure of dry Ar, while maintaining the reaction temperature
below -70 °C. After stirring for 5 min, TMSCl (77 µL, 0.6
mmol) was added to the lithiated mixture, and stirring was
continued for 0.5 h below -70 °C. The reaction was quenched
C, 51.57; H, 9.04; N, 7.08. Found: C, 51.86; H, 9.04; N, 6.90.
For physical data of 5 and 6, see the individual part given
below.
Due to the instability of 7 under chromatographic condi-
tions, its analytically pure sample could not be obtained.
Physical data of 7 are as follows: H NMR (400 MHz, CDCl
δ -0.18, -0.06, 0.05, 0.12, and 0.14 (18H, each as s), 0.38 (9H,
s), 0.80, 0.90, and 0.94 (27H, each as s), 1.24, 1.26, 1.33, and
1
3
)
7
8
1
3
)
.36 (each as d, J ) 7.0 Hz), 3.55 (1H, t, J ) 10.5 Hz), 3.64-
.70 (1H, m), 3.69 (1H, dd, J ) 10.3, 4.4 Hz), 3.89 (1H, dd, J
by adding aqueous NH
between saturated aqueous NaHCO
4
Cl, and the mixture was partitioned
and EtOAc. Florisil
10.3, 4.4 Hz), 4.16 (1H, d, J ) 4.4 Hz), 4.83 (1H, sept, J )
3
.0 Hz), 5.35 (1H, dd, J ) 8.8 Hz), 5.82 (1H, d, J ) 8.8 Hz),
column chromatography (hexane/EtOAc ) 50/1) of the organic
layer gave 6 (290 mg, 83%) as a syrup. Compound 2 (16 mg,
5%) was recovered by elution with hexane/EtOAc ) 10/1.
Physical data of 6: UV (MeOH) λmax 267 nm (ꢀ 9000), λmin 234
nm (ꢀ 3700); H NMR (400 MHz, CDCl
.17 (1H, s); FAB-MS m/z 767 (M+ + H).
1
Physical data of 8 are as follows: H NMR (400 MHz, CDCl
3
)
δ -0.20, -0.05, 0.08, 0.11, and 0.12 (18H, each as s), 0.80,
0
1
.91, and 0.94 (27H, each as s), 1.24, 1.25, 1.31, and 1.32 (12H,
3
) δ -0.20, -0.03, 0.09,
each as d, J ) 7.0 Hz), 3.63 (1H, sept, J ) 7.0 Hz), 3.73 (1H,
0.11, 0.14, and 0.16 (18H, each as s), 0.39 (9H, s), 0.79, 0.93,
and 0.96 (27H, each as s), 3.82 (1H, dd, J ) 11.4, 2.5 Hz), 4.03
(1H, dd, J ) 11.4, 4.4 Hz), 4.12-4.15 (1H, m), 4.32 (1H, t, J )
dd, J ) 11.3, 2.2 Hz), 3.83 (1H, dd, J ) 11.3, 3.2 Hz), 3.99-
4
.02 (1H, m), 4.16-4.19 (1H, m), 4.20 (1H, dd, J ) 10.2, 4.4
Hz), 4.67 (1H, sept, J ) 7.0 Hz), 5.86 (1H, d, J ) 6.2 Hz), 7.55
4.4 Hz), 4.64 (1H, t, J ) 4.4 Hz), 6.14 (1H, d, J ) 4.4 Hz), 8.49
1
3
13
(1H, s), 8.27 (1H, s); C NMR (400 MHz, CDCl
3
) δ 94.8, 118.4,
3
(1H, s); C NMR (400 MHz, CDCl ) δ 131.0, 143.7, 150.0,
+
+
1
31.9, 151.3, 152.8; FAB-MS m/z 695 (M + H). Anal. Calcd
150.7, 174.8; FAB-MS m/z 701 (M + H). Anal. Calcd for

A New Entry to 2-Substituted Purine Nucleosides
J . Org. Chem., Vol. 62, No. 20, 1997 6839
C
5
31
H
61ClN
4
O
4
Si
0.14; H, 8.65; N, 7.22.
-(2,3,5-Tr is-O-TBDMS-â-D-r ibofu r a n osyl)-6-ch lor o-2-
tr ibu tylsta n n yl)p u r in e (11). As a typical example for the
4
‚2H
2
O: C, 50.48; H, 8.88; N, 7.59. Found: C,
C
30
H
57ClN
4
Sn
2
: C, 48.26; H, 7.70; N, 7.50. Found: C, 48.40;
H, 7.83; N, 7.40.
9
9-(2,3,5-Tr is-O-TBDMS-â-D-r ibofu r a n osyl)-6-ch lor o-2-
(
iod op u r in e (15). A solution of 11 (450 mg, 0.49 mmol) and
preparation of this compound, the procedure used in entry 9
in Table 1 is shown below. To a THF (5 mL) solution of LTMP
iodine (190.5 mg, 0.75 mmol as I
at room temperature for 4 h. The reaction mixture was diluted
with 5% aqueous Na and extracted with CH Cl . The
extract was washed with brine, dried (MgSO ), and chromato-
2
) in THF (5 mL) was stirred
(2.5 mmol) was added 2 (315 mg, 0.5 mmol) in THF (3 mL)
2
S
2
O
3
2
2
dropwise under a positive pressure of dry Ar, while maintain-
4
ing the reaction temperature below -70 °C. After stirring for
graphed on a silica gel column (hexane/EtOAc ) 50/1). This
5
min, Bu
3
SnCl (670 µL, 2.5 mmol) was added to the lithiated
afforded 15 (370 mg, 97%) as a syrup: UV (MeOH) λmax 282
1
mixture, and stirring was continued for 0.5 h below -70 °C.
The reaction was quenched by adding aqueous NH Cl, and the
mixture was partitioned between saturated aqueous NaHCO
and EtOAc. Silica gel column chromatography (hexane/EtOAc
80/1) of the organic layer gave 11 (457 mg, 100%), which
was crystallized from MeOH (mp 66-68 °C): UV (MeOH) λmax
nm (ꢀ 9700), λmin 249 nm (ꢀ 7300); H NMR (400 MHz, CDCl
3
)
4
δ -0.16, 0.01, 0.09, 0.10, 0.15, and 0.17 (18H, each as s), 0.84,
0.93, and 0.96 (27H, each as s), 3.80 (1H, dd, J ) 11.5, 2.2
Hz), 4.04 (1H, dd, J )11.5, 4.0 Hz), 4.15-4.17 (1H, m), 4.29
(1H, dd, J ) 4.0, 4.4 Hz), 4.54 (1H, dd, J ) 4.0, 4.4 Hz), 6.02
3
)
(1H, d, J ) 4.4 Hz), 8.47 (1H, s); 13C NMR (400 MHz, CDCl
)
+
3
1
+
2
70 nm (ꢀ 9200), λmin 236 nm (ꢀ 7700); H NMR (500 MHz,
δ 116.3, 132.3, 144.2, 150.4, 151.9; FAB-MS m/z 755 (M
CDCl
3
) δ -0.20, -0.02, 0.09, 0.10, 0.15, and 0.17 (18H, each
H). Anal. Calcd for C28
4 4 3
H52ClIN O Si : C, 44.52; H, 6.94; N,
as s), 0.88 (9H, t, J ) 7.3 Hz), 0.90, 0.93, and 0.97 (27H, each
as s), 1.19-1.21, 1.29-1.38, and 1.54-1.64 (18H, each as m),
7.41. Found: C, 44.92; H, 7.01; N, 7.29.
2-Br om o-9-(2,3,5-t r is-O-TBDMS-â-D-r ib ofu r a n osyl)-6-
ch lor op u r in e (16). A solution of 11 (102 mg, 0.11 mmol) and
NBS (61 mg, 0.33 mmol) in THF (5 mL) was stirred for 0.5 h
at room temperature. The reaction mixture was diluted with
3
.82 (1H, dd, J ) 11.3, 1.9 Hz), 4.01 (1H, dd, J ) 11.3, 3.3
Hz), 4.14-4.16 (1H, m), 4.30 (1H, t, J ) 4.4 Hz), 4.50 (1H, t,
1
3
J ) 4.4 Hz), 6.19 (1H, d, J ) 4.4 Hz), 8.47 (1H, s); C NMR
400 MHz, CDCl ) δ 130.6, 142.4, 149.2, 150.7, 181.9; FAB-
(
3
3 2 2
saturated aqueous NaHCO and extracted with CH Cl . Silica
+
MS m/z 919 (M + H). Anal. Calcd for C40
C, 52.30; H, 8.67; N, 6.10. Found: C, 52.27; H, 8.82; N, 5.95.
H
79ClN
4
O
4
Si
3
Sn:
gel column chromatography (hexane/EtOAc ) 50/1) of the
extract gave 16 (67 mg, 92%) as a solid (mp 59-61 °C): UV
1
P r ep a r a tion of 2′,3′,5′-Tr is-O-TBDMS-N,N-d im eth yl-8-
(MeOH) λmax 276 nm (ꢀ 11 300), λmin 239 nm (ꢀ 6800); H NMR
(
tr ibu tylsta n n yl)a d en osin e. To a THF (4 mL) solution of
3
(400 MHz, CDCl ) δ -0.19, -0.01, 0.09, 0.10, 0.15, and 0.16
LTMP (4.85 mmol) was added 2′,3′,5′-tris-O-TBDMS-N,N-
dimethyladenosine (620 mg, 0.97 mmol) in THF (4 mL)
dropwise under a positive pressure of dry Ar, while maintain-
ing the reaction temperature below -70 °C. After stirring for
(18H, each as s), 0.82, 0.92, and 0.95 (27H, each as s), 3.79
(1H, dd, J ) 11.9, 2.6 Hz), 4.03 (1H, dd, J ) 11.9, 3.8 Hz),
4.15-4.17 (1H, m), 4.29 (1H, t, J ) 4.4 Hz), 4.55 (1H, t, J )
1
3
4.4 Hz), 6.03 (1H, d, J ) 4.4 Hz), 8.52 (1H, s); C NMR (400
MHz, CDCl ) δ 131.7, 143.0, 144.5, 151.4, 152.4; FAB-MS m/z
4 4 3
707 and 709 (M + H). Anal. Calcd for C28 52BrClN O Si :
5
min, Bu
lithiated mixture, and stirring was continued for 0.5 h below
70 °C. The reaction mixture was partitioned between
saturated aqueous NaHCO and CH Cl Florisil column
3
SnCl (1.25 mL, 4.85 mmol) was added to the
3
+
H
-
C, 47.48; H, 7.40; N, 7.91. Found: C, 47.68; H, 7.55; N, 7.89.
9-(2,3,5-Tr is-O-TBDMS-â-D-r ibofu r a n osyl)-2,6-d ich lor o-
p u r in e (17). A mixture of 11 (102 mg, 0.11 mmol) and NCS
(50 mg, 0.33 mmol) in THF (5 mL) was stirred at room
temperature for 23 h. The reaction mixture was partitioned
3
2
2
.
chromatography of the organic layer gave 2′,3′,5′-tris-O-
TBDMS-N,N-dimethyl-8-(tributylstannyl)adenosine (elution
with hexane, 329 mg, 35%) as a syrup and the starting
material (elution with hexane/EtOAc ) 60/1, 310 mg, 50%).
Due to the instability of the product under chromatographic
3 2 2
between saturated aqueous NaHCO and CH Cl . Silica gel
column chromatography (hexane/EtOAc ) 50/1) of the organic
conditions, its analytically pure sample could not be ob-
layer gave 17 (69 mg, 95%) as a solid (mp 121-122 °C): UV
1
1
tained: H NMR (500 MHz, CDCl
3
) δ -0.40, -0.18, 0.06, 0.08,
(MeOH) λmax 274 nm (ꢀ 10 700), λmin 237 nm (ꢀ 5700); H NMR
0
0
1
4
1
5
.14, and 0.15 (18H, each as s), 0.88 (9H, t, J ) 7.3 Hz), 0.72,
3
(400 MHz, CDCl ) δ -0.02, 0.00, 0.09, 0.10, 0.14, and 0.16
.90, and 0.97 (27H, each as s), 1.23-1.27, 1.30-1.38, and
.59-1.65 (18H, each as m), 3.53 (6H, s), 3.68 (1H, dd, J )
.9, 10.3 Hz), 4.00 (1H, dd, J ) 4.9, 10.3 Hz), 4.16 (1H, t, J )
0.3 Hz), 4.34 (1H, d, J ) 4.2 Hz), 5.68 (1H, d, J ) 7.2 Hz),
(18H, each as s), 0.82, 0.93, and 0.95 (27H, each as s), 3.79
(1H, dd, J ) 11.3, 2.6 Hz), 4.03 (1H, dd, J ) 11.3, 3.7 Hz),
4.15-4.17 (1H, m), 4.29 (1H, t, J ) 4.6 Hz), 4.56 (1H, t, J )
1
3
4.6 Hz), 6.04 (1H, d, J ) 4.6 Hz), 8.53 (1H, s); C NMR (400
MHz, CDCl ) δ 131.5, 144.8, 151.7, 152.6, 153.0; FAB-MS m/z
Si : C, 50.66;
.91 (1H, dd, J ) 7.2, 4.2 Hz), 8.19 (1H, s); FAB-MS m/z 928
3
+
+
(M
+ H).
663 (M + H). Anal. Calcd for C28
H, 7.90; N, 8.44. Found: C, 50.81; H, 8.09; N, 8.40.
H
52Cl
2
N
4
O
4
3
6
-Ch lor o-9-m eth yl-2-(tr ibu tylsta n n yl)p u r in e (13) a n d
6
-Ch lor o-2-(t r ib u t ylst a n n yl)-9-[(t r ib u t ylst a n n yl)m et h -
9-(2,3,5-Tr is-O-TBDMS-â-D-r ibofu r a n osyl)-6-ch lor o-2-
yl]p u r in e (14). These compounds were prepared from 12 (170
mg, 1.0 mmol) by the procedure described for the preparation
of 11. The following amounts of reagents were used: LTMP
2 2
flu or op u r in e (18). A CH Cl (5 mL) solution containing 11
(102 mg, 0.11 mmol), 2,6-di-tert-butyl-4-methylpyridine (23 mg,
0.11 mmol), XeF (51 mg, 0.30 mmol), and silver triflate (50
2
(
5.0 mmol) in THF (5 mL) and Bu
After addition of Bu SnCl, the reaction was continued for 1 h.
Compounds 13 (220 mg, 48%) and 14 (327 mg, 44%) were
isolated after extractive workup (aqueous NaHCO /CH Cl
followed by Florisil column chromatography (hexane/EtOAc
3
SnCl (1.3 mL, 5.0 mmol).
mg, 0.30 mmol) was stirred for 5 min under a positive pressure
of dry Ar. Usual workup (see that for 16) followed by silica
gel column chromatography (hexane/EtOAc ) 60/1) gave 18
(61 mg, 85%) as a solid (mp 121-124 °C): UV (MeOH) λmax
3
3
2
2
)
1
269 nm (ꢀ 9700), λmin 237 nm (ꢀ 4800); H NMR (500 MHz,
)
20/1 for 14, hexane/EtOAc ) 10/1 for 13).
3
CDCl ) δ -0.23, -0.01, 0.09, 0.10, 0.15, and 0.16 (18H, each
Physical data of 13 obtained as a syrup are as follows: UV
as s), 0.80, 0.93, and 0.96 (27H, each as s), 3.79 (1H, dd, J )
11.0, 3.3 Hz), 4.01 (1H, dd, J ) 11.0, 4.2 Hz), 4.15-4.17 (1H,
m), 4.29 (1H, t, J ) 4.4 Hz), 4.54 (1H, t, J ) 4.4 Hz), 6.02 (1H,
1
(
MeOH) λmax 270 nm (ꢀ 6400), λmin 243 nm (ꢀ 5200); H NMR
(500 MHz, CDCl
3
) δ 0.88 (9H, t, J ) 7.3 Hz), 1.19-1.22, 1.31-
1
(
1
C
.38, and 1.58-1.70 (18H, each as m), 3.91 (3H, s), 7.98
d, J ) 4.4 Hz), 8.52 (1H, s); 13C NMR (500 Hz, CDCl
) δ 130.8
3
1
3
1H, s); C NMR (500 MHz, CDCl
51.2, 181.6; FAB-MS m/z 459 (M + H). Anal. Calcd for
3
+
) δ 129.5, 144.0, 149.0,
(J ) 5.2 Hz), 144.7 (J ) 3.1 Hz), 152.7 (J ) 16.8 Hz), 153.2 (J
+
) 16.8 Hz), 157.1 (J ) 221.2 Hz); FAB-MS m/z 647 (M + H).
18
H
31ClN
4
Sn: C, 47.24; H, 6.83; N, 12.24. Found: C, 47.39;
4 4 3
Anal. Calcd for C28H52ClFN O Si : C, 51.94; H, 8.10; N, 8.65.
H, 6.96; N, 12.22.
Found: C, 51.77; H, 8.25; N, 8.57.
Physical data of 14 obtained as a syrup are as follows: UV
MeOH) λmax 270 nm (ꢀ 5700), λmin 255 nm (ꢀ 4900); H NMR
2-Ben zyl-9-(2,3,5-t r is-O-TBDMS-â-D-r ib ofu r a n osyl)-6-
1
(
(
7
1
(
ch lor op u r in e (19). A THF (2 mL) solution containing 11 (102
500 MHz, CDCl
3
) δ 0.83 (9H, t, J ) 7.3 Hz), 0.89 (9H, t, J )
.3 Hz), 0.87-0.93, 1.23-1.40, 1.28-1.37, 1.38-1.44, and
.58-1.68 (36H, each as m), 3.99 (2H, t, J ) 11.3 Hz), 7.90
3 4
mg, 0.11 mmol), Pd(PPh ) (6.5 mg, 5.5 µmol, 5 mol %), CuI (4.4
mg, 22 µmol, 20 mol %), and benzyl bromide (16 µL, 0.13 mmol)
was refluxed for 9 h under a positive pressure of dry Ar. The
1
3
1H, s); C NMR (500 MHz, CDCl
3
+
) δ 130.0, 144.1, 148.9,
reaction mixture was diluted with saturated aqueous NaHCO
and extracted with CH Cl . Silica gel column chromatography
3
1
51.0, 180.8; FAB-MS m/z 747 (M + H). Anal. Calcd for
2
2

6
840 J . Org. Chem., Vol. 62, No. 20, 1997
Kato et al.
(
hexane/EtOAc ) 20/1) of the extract gave 19 (43 mg, 55%) as
5.1 Hz), 4.10-4.13 (1H, m), 4.29 (1H, t, J ) 4.4 Hz), 4.66 (1H,
an oil: UV (MeOH) λmax 269 nm (ꢀ 11 100), λmin 234 nm (ꢀ
5
0
as s), 3.80 (1H, dd, J ) 11.0, 2.6 Hz), 4.04 (1H, dd, J ) 11.0,
4
4
t, J ) 4.4 Hz), 5.89 (1H, d, J ) 4.4 Hz), 6.03 (2H, br), 8.06
1
13
600); H NMR (400 MHz, CDCl
3
) δ -0.20, -0.04, 0.09, 0.10,
3
(1H, s); C NMR (400 MHz, CDCl ) δ 119.5, 120.0, 139.7,
+
.14, and 0.16 (18H, each as s), 0.80, 0.93, and 0.96 (27H, each
149.8, 155.1; FAB-MS m/z 736 (M + H). Anal. Calcd for
C
28
H
54IN
5
O
4
3
Si : C, 45.70; H, 7.40; N, 9.52. Found: C, 45.71;
.0 Hz), 4.12-4.15 (1H, m), 4.29 (2H, s), 4.29-4.31 (1H, m),
.54 (1H, t, J ) 4.4 Hz), 6.06 (1H, d, J ) 4.4 Hz), 7.18-7.39
H, 7.39; N, 9.24.
2-Br om o-2′,3′,5′-tr is-O-TBDMS-a d en osin e (25). The bro-
mination of 22 (102 mg, 0.11 mmol) was carried out for 0.5 h
by the procedure described for the preparation of 16. After
workup of the reaction mixture, silica gel column chromatog-
raphy (hexane/EtOAc ) 3/1) gave 25 (68 mg, 90%) as an oil:
(
1
5H, m), 8.47 (1H, s); 13C NMR (400 MHz, CDCl
3
) δ 130.2,
+
43.7, 150.7, 151.9, 164.0; FAB-MS m/z 719 (M + H). Anal.
1
Calcd for C35
Found: C, 57.80; H, 8.37; N, 7.55.
-(2,3,5-Tr is-O-TBDMS-â-D-r ibofu r a n osyl)-6-ch lor o-2-
p h en ylp u r in e (20). This compound was prepared from 11
102 mg, 0.11 mmol) and iodobenzene (45 µL, 0.33 mmol) by
H
59ClN
4
O
4
Si
3
‚ /
2 2
H O: C, 57.70; H, 8.30; N, 7.69.
1
9
UV (MeOH) λmax 263 nm (ꢀ 12 000), λmin 235 nm (ꢀ 6200); H
NMR (400 MHz, CDCl ) δ -0.16, -0.01, 0.09, 0.10, 0.13, and
3
(
0.15 (18H, each as s), 0.83, 0.92, and 0.95 (27H, each as s),
3.78 (1H, dd, J ) 11.4, 2.9 Hz), 4.04 (1H, dd, J ) 11.4, 4.8
Hz), 4.10-4.13 (1H, m), 4.30 (1H, t, J ) 4.4 Hz), 4.66 (1H,
t,J ) 4.4 Hz), 5.92 (1H, d, J ) 4.4 Hz), 6.18 (2H, br), 8.11 (1H,
the procedure described for the preparation of 19. The reaction
was continued for 24 h at refluxing temperature. After workup
of the reaction mixture, silica gel column chromatography
(
5
1
-
0
hexane/EtOAc ) 60/1) gave 20 (32 mg, 41%) as a solid (mp
s); 13C NMR (400 MHz, CDCl
155.9; FAB-MS m/z 690 (M
3
) δ 119.3, 139.9, 144.7, 150.4,
+
5-59 °C): UV (MeOH) λmax 285 (ꢀ 16 300) and 243 nm (ꢀ
+ H). Anal. Calcd for
1
7 300), λmin 219 nm (ꢀ 8600); H NMR (400 MHz, CDCl
0.18, -0.02, 0.11, 0.14, 0.15, and 0.17 (18H, each as s), 0.80,
.95, and 0.96 (27H, each as s), 3.84 (1H, dd, J ) 12.0, 2.6
Hz), 4.05 (1H, dd, J ) 12.0, 4.0 Hz), 4.17-4.18 (1H, m), 4.36
1H, t, J ) 4.4 Hz), 4.65 (1H, t, J ) 4.4 Hz), 6.20 (1H, d, J )
.4 Hz), 7.47-7.50 (3H, m), 8.48-8.49 (2H, m), 8.54 (1H, s);
3
) δ
C
28
H
54BrN
5
O
4
3
Si : C, 48.82; H, 7.90; N, 10.17. Found: C,
49.06; H, 8.01; N, 9.99.
2′,3′,5′-Tr is-O-TBDMS-2-ch lor oaden osin e (26). The chlo-
rination of 22 (50 mg, 0.056 mmol) was carried out for 6 h by
the procedure described for the preparation of 17. After
workup of the reaction mixture, silica gel column chromatog-
raphy (hexane/EtOAc ) 3/1) gave 26 (26 mg, 70%) as a solid
(
4
1
3
C NMR (400 MHz, CDCl
3
) δ 130.6, 144.2, 151.0, 152.3, 159.3;
FAB MS m/z 705 (M + H). Anal. Calcd for C34 Si
O: C, 56.44; H, 8.22; N, 7.74. Found: C, 56.52; H, 8.17; N,
.51.
-Ben zoyl-9-(2,3,5-tr is-O-TBDMS-â-D-r ibofu r a n osyl)-6-
ch lor op u r in e (21). A toluene (10 mL) solution containing
1 (102 mg, 0.11 mmol) and benzoyl chloride (22 µL, 0.15
+
H
57ClN
4
O
4
3
‚
(mp 125-127 °C): UV (MeOH) λmax 261 nm (ꢀ 9700), λmin 229
1
H
7
2
nm (ꢀ 1300); H NMR (400 MHz, CDCl
3
) δ -0.17, -0.02, 0.09,
0.10, 0.13, and 0.14 (18H, each as s), 0.82, 0.92, and 0.95 (27H,
each as s), 3.37 (1H, dd, J ) 11.4, 2.9 Hz), 4.04 (1H, dd, J )
11.4, 4.4 Hz), 4.11-4.14 (1H, m), 4.30 (1H, t, J ) 4.4 Hz), 4.66
(1H, t, J ) 4.4 Hz), 5.93 (1H, d, J ) 4.4 Hz), 6.09 (2H, br),
2
1
8.16 (1H, s); 13C NMR (400 MHz, CDCl
154.1, 155.8; FAB-MS m/z 644 (M + H). Anal. Calcd for
28 5 4 3
C H54ClN O Si : C, 52.18; H, 8.45; N, 10.87. Found: C, 52.10;
) δ 119.0, 140.3, 150.8,
mmol) was refluxed for 0.5 h under a positive pressure of dry
Ar. After addition of pyridine (10 µL, 0.20 mmol) to this
solution, the reaction mixture was further refluxed for 20 h.
Usual workup (see that for 16) followed by silica gel column
chromatography (hexane/EtOAc ) 40/1) gave 21 (44 mg, 60%)
3
+
H, 8.72; N, 10.79.
2′,3′,5′-Tr is-O-TBDMS-2-flu or oa d en osin e (27). The fluo-
rination of 22 (164 mg, 0.18 mmol) was carried out for 15 min
by the procedure described for the preparation of 18. After
workup of the reaction mixture, silica gel column chromatog-
raphy (hexane/EtOAc ) 5/1) gave 27 (90 mg, 80%) as a solid
as a syrup: UV (MeOH) λmax 263 nm (ꢀ 13 600), λmin 238 nm
(
1
ꢀ 10 600); H NMR (400 MHz, CDCl
3
) δ -0.27, -0.06, 0.06,
0
.08, 0.14, and 0.15 (18H, each as s), 0.75, 0.91, and 0.96 (27H,
each as s), 3.79 (1H, dd, J ) 13.0, 3.2 Hz), 4.03 (1H, dd, J )
3.0, 3.3 Hz), 4.12-4.14 (1H, m), 4.29 (1H, t, J ) 4.8 Hz), 4.54
1H, t, J ) 4.8 Hz), 6.14 (1H, d, J ) 4.8 Hz), 7.50 (2H, t, J )
.3 Hz), 7.64 (1H, t, J ) 7.3 Hz), 8.01 (2H, d, J ) 7.3 Hz), 8.75
1
(
7
(mp 210-211 °C): UV (MeOH) λmax 261 nm (ꢀ 12 700), λmin
1
223 nm (ꢀ 2700); H NMR (500 MHz, CDCl
3
) δ -0.20, -0.03,
0.09, 0.10, 0.12, and 0.13 (18H, each as s), 0.81, 0.92, and 0.95
(27H, each as s), 3.77 (1H, dd, J ) 11.3, 2.9 Hz), 4.02 (1H,
dd,J ) 11.3, 4.4 Hz), 4.10-4.13 (1H, m), 4.30 (1H, t, J ) 4.4
Hz), 4.63 (1H, t, J ) 4.4 Hz), 5.91 (1H, d, J ) 4.4 Hz), 6.27
1
3
(
1
3
1H, s); C NMR (400 MHz, CDCl ) δ 132.5, 145.8, 151.0,
+
51.2, 156.2; FAB-MS m/z 734 (M + H). Anal. Calcd for
1
C
35
H
57ClN
4
O
5
Si
3
2 2
‚ / H O: C, 56.61; H, 7.87; N, 7.55. Found:
(2H, br), 8.11 (1H, s); 13C NMR (500 Hz, CDCl
) δ 119.0 (J )
C, 56.96; H, 8.27; N, 7.53.
′,3′,5′-Tr is-O-TBDMS-2-(tr ibu tylstan n yl)aden osin e (22).
Compound 11 (500 mg, 0.54 mmol) in THF (5 mL) was reacted
with NH /2-propanol (45 mL, saturated at 0 °C, containing ca.
% NH ) in a sealed tube at 105 °C for 60 h. After being
3
2
4.2 Hz), 139.6 (J ) 3.1 Hz), 151.2 (J ) 19.6 Hz), 157.1 (J )
+
19.8 Hz), 159.0 (J ) 211.0 Hz); FAB-MS m/ z 628 (M + H).
3
Anal. Calcd for C28
10.84. Found: C, 52.31; H, 9.00; N, 10.79.
H
54FN
5
O
4
Si
3
2
‚H O: C, 52.06; H, 8.74; N,
5
3
evaporated, the reaction mixture was purified by silica gel
2-Ben zyl-2′,3′,5′-tr is-O-TBDMS-aden osin e (28). This com-
pound was prepared from 22 (102 mg, 0.11 mmol) and benzyl
bromide (16 µL, 0.13 mmol) by the procedure described for the
preparation of 19. The reaction was continued for 9 h at
refluxing temperature. After workup of the reaction mixture,
silica gel column chromatography (hexane/EtOAc ) 5/1) gave
column chromatography. Elution with hexane/EtOAc ) 10/1
5
a
gave 22 (454 mg, 92%) as a syrup. Compound 23 (20 mg,
6
%) was also isolated by elution with hexane/EtOAc ) 5/1.
Physical data for 22: UV (MeOH) λmax 263 nm (ꢀ 11 600), λmin
2
0
1
41 nm (ꢀ 8800); H NMR (400 MHz, CDCl
3
) δ -0.13, -0.02,
.08, 0.09, 0.13, and 0.15 (18H, each as s), 0.81, 0.93, and 0.96
28 (65 mg, 83%) as a syrup: UV (MeOH) λmax 261 nm (ꢀ
1
(
27H, each as s), 0.88 (9H, t, J ) 7.7 Hz), 1.12 (6H, t, J ) 9.5
Hz), 1.32-1.35 (6H, m), 1.54-1.58 (6H, m), 3.79 (1H, dd, J )
1.3, 4.3 Hz), 4.01 (1H, dd, J ) 11.3, 4.3 Hz), 4.10-4.13 (1H,
m), 4.30 (1H, t, J ) 4.4 Hz), 4.60 (1H, t, J ) 4.4 Hz), 5.44 (2H,
10 200), λmin 233 nm (ꢀ 3500); H NMR (400 MHz, CDCl
3
) δ
-0.08, -0.04, 0.09, 0.10, 0.12, and 0.13 (18H, each as s), 0.80,
0.92, and 0.94 (27H, each as s), 3.80 (1H, dd, J ) 11.0, 3.1
Hz), 4.07 (1H, dd, J ) 11.0, 4.8 Hz), 4.11-4.15 (1H, m), 4.10
(2H, s), 4.31 (1H, t, J ) 4.0 Hz), 4.68 (1H, t, J ) 4.0 Hz), 5.57
1
1
3
br), 6.06 (1H, d, J ) 4.4 Hz), 8.13 (1H, s); C NMR (400 MHz,
CDCl ) δ 119.2, 138.6, 149.2, 153.4, 180.6; FAB-MS m/z 900
M + H). Anal. Calcd for C40 Si Sn: C, 53.44; H, 9.08;
N, 7.79. Found: C, 53.73; H, 9.27; N, 7.68.
′,3′,5′-Tr is-O-TBDMS-2-iod oa d en osin e (24). The iodi-
3
(2H, br), 5.96 (1H, d, J ) 4.0 Hz), 7.19-7.35 (5H, m), 8.11
+
13
(
H
81
N
5
O
4
3
3
(1H, s); C NMR (400 MHz, CDCl ) δ 118.5, 139.5, 150.1,
+
155.3, 163.9; FAB-MS m/z 700 (M + H). Anal. Calcd for
3
2
C
35
H
61
N
5
O
4
Si
3
2 2
‚ / H O: C, 57.81; H, 8.87; N, 9.63. Found: C,
nation of 22 (102 mg, 0.11 mmol) was carried out for 0.5 h by
the procedure described for the preparation of 15. After
workup of the reaction mixture, silica gel column chromatog-
raphy (hexane/EtOAc ) 4/1) gave 24 (98 mg, 100%) as a
57.51; H, 8.59; N, 9.41.
2′,3′,5′-Tr is-O-TBDMS-2-ph en yladen osin e (29). This com-
pound was prepared from 22 (80 mg, 0.09 mmol) and iodo-
benzene (10 µL, 0.1 mmol) by the procedure described for the
preparation of 19. The reaction was continued for 15 h at
refluxing temperature. After workup of the reaction mixture,
silica gel column chromatography (hexane/EtOAc ) 5/1) gave
29 (55.1 mg, 89%) as crystals (mp 199 °C): UV (MeOH) λmax
syrup: UV (MeOH) λmax 267 nm (ꢀ 15 200), λmin 237 nm (ꢀ
1
6
0
000); H NMR (400 MHz, CDCl
3
) δ -0.13, 0.00, 0.09, 0.10,
.14, and 0.15 (18H, each as s), 0.93, 0.94, and 0.95 (27H, each
as s), 3.78 (1H, dd, J ) 11.4, 2.9 Hz), 4.03 (1H, dd, J ) 11.4,

A New Entry to 2-Substituted Purine Nucleosides
J . Org. Chem., Vol. 62, No. 20, 1997 6841
1
2
40 nm (ꢀ 17 000), λmin 235 nm (ꢀ 11 700); H NMR (400 MHz,
(Na
2
SO
4
), evaporated, and chromatographed on a silica gel
CDCl
3
) δ -0.13, -0.03, 0.11, 0.12, and 0.14 (18H, each as s),
.82, 0.94, and 0.95 (27H, each as s), 3.83 (1H, dd, J ) 11.0,
.0 Hz), 4.07 (1H, dd, J ) 11.0, 5.1 Hz), 4.14-4.16 (1H, m),
.37 (1H, t, J ) 4.6 Hz), 4.88 (1H, t, J ) 4.6 Hz), 5.58 (2H, br),
.08 (1H, d, J ) 4.6 Hz), 7.42-7.43 (3H, m), 8.18 (1H, s), 8.39-
) δ 119.2, 140.3, 150.9,
55.1, 159.4; FAB-MS m/z 686 (M + H). Anal. Calcd for
Si : C, 59.52; H, 8.67; N, 10.21. Found: C, 59.23;
H, 8.70; N, 9.98.
-Allyl-2′,3′,5′-tr is-O-TBDMS-a d en osin e (30). This com-
column (hexane/EtOAc ) 20/1) to give 34 (130 mg, 82%) as a
0
3
4
6
8
1
solid (mp 120-122 °C): UV (MeOH) λmax 266 nm (ꢀ 6300), λmin
1
232 nm (ꢀ 1100); H NMR (400 MHz, CDCl
3
) δ -0.61, -0.16,
0.10, 0.11, and 0.12 (18H, each as s), 0.74, 0.91, and 0.93 (27H,
each as s), 4.34-4.35 (2H, m), 4.41 (1H, dd, J ) 5.6, 4.4 Hz),
1
3
.40 (2H, m); C NMR (400 MHz, CDCl
3
4.51 (1H, d, J ) 4.4 Hz), 5.51-5.57 (1H, m), 5.79 (1H, d, J )
+
13
3
1.8 Hz), 8.10 (1H, s), 8.72 (1H, s); C NMR (500 MHz, CDCl )
+
C
34
H
59
N
5
O
4
3
δ 132.1, 144.5, 151.1, 151.8, 152.4; FAB-MS m/z 625 (M
H). Anal. Calcd for C29 Si : C, 55.69; H, 8.54; N,
8.96. Found: C, 55.49; H, 8.83; N, 8.83.
+
H
53ClN
4
O
3
3
2
pound was prepared from 22 (102 mg, 0.11 mmol) and allyl
bromide (25 µL, 0.22 mmol) by the procedure described for the
preparation of 19. The reaction was continued for 18 h at
refluxing temperature. After workup of the reaction mixture,
silica gel column chromatography (hexane/EtOAc ) 10/1) gave
9-[(1R,2S,3R)-4-[[(ter t-Bu tyld im eth ylsilyl)oxy]m eth yl]-
2,3-bis[(ter t-bu tyld im eth ylsilyl)oxy]-4-cyclop en ten -1-yl]-
6-ch lor o-2-(tr ibu tylsta n n yl)p u r in e (35). This compound
was prepared from 34 (100 mg) under the reaction conditions
shown in entry 9 of Table 1. The procedure used is similar to
that described for the preparation of 6. After workup of the
reaction mixture, silica gel column chromatography (hexane/
3
0 (42 mg, 59%) as a syrup: UV (MeOH) λmax 263 nm (ꢀ
1
1
-
1 600), λmin 233 nm (ꢀ 7400); H NMR (400 MHz, CDCl
0.14, -0.02, 0.08, 0.10, 0.12 and 0.13 (18H, each as s), 0.81,
.92, and 0.94 (27H, each as s), 3.56 (2H, d, J ) 6.9 Hz), 3.78
1H, dd, J ) 11.0, 3.3 Hz), 4.06 (1H, dd, J ) 11.0, 4.2 Hz),
3
) δ
EtOAc ) 30/1) gave 35 (148 mg, 100%) as a syrup: UV (MeOH)
1
0
(
λ
max 273 nm (ꢀ 7300), λmin 247 nm (ꢀ 4600); H NMR (400 MHz,
3
CDCl ) δ -0.55, -0.18, 0.09, 0.11, and 0.12 (18H, each as s),
4
4
1
.10-4.13 (1H, m), 4.32 (1H, t, J ) 4.4 Hz), 4.73 (1H, t, J )
.4 Hz), 5.09 (1H, dd, J ) 1.7, 9.9 Hz), 5.16 (1H, dd, J ) 1.7,
7.0 Hz), 5.69 (2H, br), 5.95 (1H, d, J ) 4.4 Hz), 6.14 (1H, ddt,
0.71, 0.91, and 0.93 (27H, each as s), 0.88 (9H, t, J ) 7.3 Hz),
1.14-1.23, 1.27-1.39, and 1.56-1.63 (18H, each as m), 4.32
(1H, t, J ) 2.2 Hz), 4.34 (1H, t, J ) 2.2 Hz), 4.40 (1H, dd, J )
1
3
J ) 17.0, 9.9, 6.9 Hz), 8.10 (1H, s); C NMR (400 MHz, CDCl
3
)
4.8, 5.9 Hz), 4.49 (1H, d, J ) 4.8 Hz), 5.63-5.64 (1H, m), 5.77
+
13
δ 118.5, 139.6, 150.4, 155.2, 163.6; FAB-MS m/z 651 (M
H). Anal. Calcd for C31 Si : C, 57.27; H, 9.15; N, 10.77.
Found: C, 57.44; H, 9.43; N, 10.71.
′,3′,5′-Tr is-O-TBDMS-2-(ph en yleth yn yl)aden osin e (31).
+
3
(1H, d, J ) 1.9 Hz), 7.97 (1H, s); C NMR (400 MHz, CDCl )
+
H
59
N
5
O
4
3
δ 132.1, 142.5, 149.3, 151.2, 181.7; FAB-MS m/z 915 (M
H). Anal. Calcd for C41 Si Sn: C, 53.85; H, 8.71; N,
6.13. Found: C, 53.91; H, 8.78; N, 5.99.
+
H
79ClN
4
O
3
3
2
This compound was prepared from 22 (102 mg, 0.11 mmol)
and iodophenylacetylene (30 mg, 0.13 mmol) by the procedure
described for the preparation of 19. The reaction was contin-
ued for 10.5 h at refluxing temperature. After workup of the
reaction mixture, silica gel column chromatography (hexane/
2′,3′,6′-Tr is-O-TBDMS-2-(tr ibu tylsta n n yl)n ep la n ocin A
(36). This compound was prepared from 35 (140 mg) by the
procedure similar to that described for the preparation of 22.
The reaction was carried out at 105 °C for 49 h. After workup
of the reaction mixture, silica gel column chromatography
(hexane/EtOAc ) 5/1) gave 36 (106 mg, 78%) as a syrup
together with the starting material 35 (21 mg, 15%): UV
EtOAc ) 2/1) gave 31 (56.3 mg, 72%) as a syrup: UV (MeOH)
1
λ
max 260 nm (ꢀ 14 600), λmin 238 nm (ꢀ 10 100); H NMR (400
1
MHz, CDCl
3
) δ -0.11, 0.01, 0.10, 0.11, 0.12, and 0.14 (18H,
each as s), 0.85, 0.93, and 0.94 (27H, each as s), 3.80 (1H, dd,
(MeOH) λmax 263 nm (ꢀ 9600), λmin 240 nm (ꢀ 5900); H NMR
(500 MHz, CDCl ) δ -0.48, -0.18, 0.08, 0.11, and 0.12 (18H,
3
J ) 12.5, 2.9 Hz), 4.05 (1H, dd, J ) 12.5, 4.3 Hz), 4.12-4.14
each as s), 0.74, 0.91, and 0.93 (27H, each as s), 0.88 (9H, t, J
) 7.1 Hz), 1.09-1.13, 1.29-1.33, and 1.54-1.59 (18H, each
as m), 4.27-4.30 (1H, m), 4.33-4.37 (1H, m), 4.43 (1H, t, J )
4.9 Hz), 4.50 (1H, d, J ) 4.9 Hz), 5.50 (2H, br), 5.53-5.55 (1H,
(
1H, m), 4.54 (1H, t, J ) 4.8 Hz), 4.70 (1H, t, J ) 4.8 Hz), 5.87
(
2H, br), 6.04 (1H, d, J ) 4.8 Hz), 7.35-7.36 (3H, m), 7.62-
1
3
7
1
3
.63 (2H, m), 8.20 (1H, s); C NMR (400 MHz, CDCl ) δ 119.5,
40.5, 149.9, 155.0, 155.1; FAB-MS m/z 710 (M+ + H). Anal.
Si : C, 60.89; H, 8.37; N, 9.86. Found:
C, 60.64; H, 8.51; N, 9.69.
′,3′,5′-Tr is-O-TBDMS-2-(â-styr yl)a d en osin e (32). This
m), 5.75 (1H, d, J ) 1.8 Hz), 7.67 (1H, s); C NMR (500 MHz,
13
Calcd for C36
H
59
N
5
O
4
3
3
CDCl ) δ 119.3, 138.5, 148.7, 153.4, 180.7; FAB-MS m/z 896
+
(M + H). Anal. Calcd for C41
81 5 3 3
H N O Si Sn: C, 55.02; H, 9.12;
2
N, 7.82. Found: C, 55.17; H, 9.35; N, 7.75.
compound was prepared from 22 (102 mg, 0.11 mmol) and
â-bromostyrene (17 µL, 0.13 mmol) by the procedure described
for the preparation of 19. The reaction was continued for 22
h at refluxing temperature. After workup of the reaction
mixture, silica gel column chromatography (hexane/EtOAc )
2′,3′,6′-Tr is-O-TBDMS-2-flu or on ep la n ocin A (37). The
fluorination of 36 (103 mg, 0.11 mmol) was carried out for 20
min by the procedure described for the preparation of 18. After
workup of the reaction mixture, silica gel column chromatog-
raphy (hexane/EtOAc ) 3/1) gave 37 (28 mg, 53%) as a solid
2
/1) gave 32 (30.3 mg, 40%, E/Z ) ca. 6/1) as a syrup. Further
(mp 245-247 °C): UV (MeOH) λmax 263 nm (ꢀ 10 200), λmin
1
purification by HPLC (hexane/EtOAc ) 2/1) gave an analyti-
227 nm (ꢀ 3000); H NMR (500 MHz, CDCl
3
) δ -0.49, -0.13,
cally pure E-isomer: UV (MeOH) λmax 265 nm (ꢀ 13 800), λmin
0.09, and 0.11 (18H, each as s), 0.78 and 0.91 (27H, each as
s), 4.28-4.32 (2H, m), 4.37 (1H, t, J ) 3.9 Hz), 4.49 (1H,
d, J ) 3.9 Hz), 5.39-5.40 (1H, m), 5.73 (1H, s), 6.11 (2H, br),
1
2
0
41 nm (ꢀ 8100); H NMR (400 MHz, CDCl
3
) δ -0.07, 0.01,
.10, 0.12, 0.14, and 0.16 (18H, each as s), 0.85, 0.94, and 0.96
(
27H, each as s), 3.82 (1H, dd, J ) 11.5, 2.6 Hz), 4.09 (1H, dd,
J ) 11.5, 4.4 Hz), 4.13-4.16 (1H, m), 4.36 (1H, t, J ) 4.4 Hz),
.68 (1H, t, J ) 4.4 Hz), 5.61 (2H, br), 6.06 (1H, d, J ) 4.4
Hz), 7.00 (1H, d, J ) 15.8 Hz), 7.30 (1H, t, J ) 7.4 Hz), 7.38
7.73 (1H, s); 13C NMR (500 Hz, CDCl
3
) δ 118.3 (J ) 4.3 Hz),
149.2, 152.0 (J ) 19.7 Hz), 157.0 (J ) 20.7 Hz), 159.6 (J )
+
4
210.0 Hz); FAB-MS m/z 624 (M + H). Anal. Calcd for
29 5 3 3
C H54FN O Si : C, 55.82; H, 8.72; N, 11.22. Found: C, 56.10;
(
1
1
2H, t, J ) 7.4 Hz), 7.58 (2H, t, J ) 7.4 Hz), 7.87 (1H, d, J )
H, 8.97; N, 10.91.
5.8 Hz), 8.19 (1H, s); 13C NMR (400 MHz, CDCl
) δ 118.9,
3
+
39.8, 150.6, 154.9, 159.4; FAB-MS m/z 712 (M + H). Anal.
Ack n ow led gm en t. Financial support from the Min-
istry of Education, Science and Culture (Grant-in-Aid
No. 08772034 to K.K. and No. 09672159 to H.T.) is
gratefully acknowledged. The authors thank Professor
Takao Sakamoto, Tohoku University, for helpful cor-
respondence about destannylation of stannylated het-
erocycles.
1
Calcd for C36
Found: C, 60.05; H, 8.76; N, 9.32.
-[(1R,2S,3R)-4-[[(ter t-Bu tyld im eth ylsilyl)oxy]m eth yl]-
H
61
N
5
O
4
Si
3
‚ /
2 2
H O: C, 59.96; H, 8.67; N, 9.71.
9
2
6
,3-bis[(ter t-bu tyld im eth ylsilyl)oxy]-4-cyclop en ten -1-yl]-
-ch lor op u r in e (34). A mixture of 33 (70 mg, 0.25 mmol),
TBDMSCl (210 mg, 1.25 mmol), and imidazole (140 mg, 1.75
mmol) in DMF (4 mL) was stirred at room temperature for 18
h. The reaction mixture was partitioned between EtOAc and
saturated aqueous NaHCO
3
.
The organic layer was dried
J O970398Q