Oligonucleosides with a nucleobase-including backbone. Part 3. Synthesis of acetyleno-linked adenosine dimers

Article abstract of DOI:10.1002/1522-2675(20001108)83:11<2975::AID-HLCA2975>3.0.CO;2-2

The adenosine-derived dimers 14a-d and 15b-d have been prepared by coupling the protected 8-iodoadenosines 3 and 13 with the C(5′)-ethynylated adenosine derivatives 5, 6, 11, and 12 (Scheme 4). Similarly, the 5′-epimeric dimer 16 was prepared by coupling

Full text of DOI:10.1002/1522-2675(20001108)83:11<2975::AID-HLCA2975>3.0.CO;2-2

Helvetica Chimica Acta ± Vol. 83 +2000)
2975
Oligonucleosides with a Nucleobase-Including Backbone
Part 3
Synthesis of Acetyleno-Linked Adenosine Dimers
by Hiroki Gunji and Andrea Vasella*
Laboratorium für Organische Chemie, ETH-Zentrum, Universitätstrasse 16, CH-8092 Zürich
The adenosine-derived dimers 14a ± d and 15b ± d have been prepared by coupling the protected 8-
iodoadenosines 3 and 13 with the C+5')-ethynylated adenosine derivatives 5, 6, 11, and 12 +Scheme 4). Similarly,
the 5'-epimeric dimer 16 was prepared by coupling 3 with the alkyne 8 +Scheme 5). The propargylic alcohol 4
was transformed into the N-benzoylated alkyne 5 and into the amine 6, while the epimeric alcohol 7 was
converted to the epimeric amine 8 and the 5'-deoxy analogues 11 and 12 +Scheme 3). Cross-coupling of the
iodoadenosine 13 with the alkyne 5 to 14a was optimised; it is influenced by the N-benzoyl and the Et3SiO group
of the alkyne, but hardly by the N-benzoyl group of the 8-iodoadenosine. The alkyne is most reactive when it is
O-silylated, but not N-benzoylated. Cross-coupling of the 5'-deoxyalkynes proceeded more slowly. The dimers
14a ± d, 15b ± d, and 16 were obtained in good yields +Table 2). Deprotection of 14d and 16 led to 18 and 20,
respectively +Scheme 5). The diols 17 and 19 and the hexols 18 and 20 prefer the syn-conformation in
+D6)DMSO, completely for unit II and ꢀ80% for unit I; they exhibit partially persistent intramolecular
O+5')ÀH ´´´ N+3) H-bonds. The persistence increases from 18% +unit I of 19), 32% +unit II of 17 and 19), 45%
+unit I of 17), 52% +unit II of 18 and 20), and 55% +unit I of 20) to 82% +unit I of 18).
Introduction. ± We have designed oligonucleotide analogues in which the 3',5'-
phosphodiester moiety between adenosine units is replaced by an 8,5'-acetylene link +I,
Scheme 1) [1]. Calculations predict that such adenosine-derived analogues may form
stable complexes with uridine oligonucleotides and with their 6,5'-acetyleno-linked ana-
logues. We have reported the synthesis of uridine- and adenosine-derived monomers
[1][2] and of uridine-derived dimers [1], and we now describe the synthesis of protected
and unprotected 8,5'-acetyleno-linked adenosine dimers I +n ˆ 0; Scheme 1).
Formation of the 8,5'-ethynylidene link is the key to the synthesis of the projected
oligonucleotide analogues. We have considered to construct the dimers II either by
addition of acetylide anions derived from III to aldehydes IV +path A; Scheme 1), or by
a Sonogashira reaction [3] of 8-iodoadenosines V and terminal heptynofuranosyl
adenines VI +path B). In view of the low diastereoselectivity in the addition of
[+trimethylsilyl)ethynyl]magnesium bromide to aldehydes of type IV, we have followed
path B that takes advantage of working with monomers of established configuration
[2]. Considering the sensitivity of the alkynylated adenosine derivatives to acid and
base +as during deprotection), resulting in elimination of the propargylic OH group and
degradation, we also planned to deoxygenate the alkynylated monomers and subject
the products to cross-coupling with iodoadenosines of type V. In this context, we
examined the dependence of the cross-coupling on the propargylic substituent at C+5')

2976
Helvetica Chimica Acta ± Vol. 83 +2000)
Scheme 1. Acetyleno-Linked Adenosine Oligomers I and Retrosynthesis of the Dimer II
and also on the N-benzoyl group, preparing the eight dimers 14a ± d, 15b ± d, and 16 +the
C+5'/I)1) epimer of 14d) +cf. Schemes 4 and 5).
Results and Discussion. ± We first prepared the required monomeric building block
3. Triethylsilylation of the isopropylidenated adenosine 1 [4] afforded 70% of 2
+Scheme 2). Regioselective lithiation of 2 with LDA [5], followed by treatment with I2
[2][6] yielded 87% of the 8-iodo derivative 3.
The 1H-NMR chemical shifts for the ribofuranosyl unit of the amine 2 +cf. Table 4 in
the Exper. Part) are similar to those of the corresponding N6-benzoyl derivative [2]
+Dd ˆ 0.06 ppm for HÀC+1') and ꢁ0.03 for HÀC+2') to HÀC+5')) and evidence the
1
)
Starting from the downstream end, the units of the oligonucleosides are specified by roman numerals +cf.
[1]).

Helvetica Chimica Acta ± Vol. 83 +2000)
2977
Scheme 2
a) Et3SiCl, imidazole, DMF; 70%. b) LDA, THF, then I2; 87%.
anti-conformation. N-Debenzoylation leads to an upfield shift of 0.46 ppm for HÀC+2)
and of 0.2 ppm for HÀC+8) of 22). The downfield shift of HÀC+2') of the iodide 3
+0.53 ppm relative to d+HÀC+2')) of 2) evidences a preferred syn-conformation, as it is
typical for 8-substituted adenosines +cf. [2] and refs. cited there).
The other monomeric building blocks ± the terminal acetylenes 5, 6, 8, 11, and 12
+Scheme 3) ± were prepared from the epimeric propargylic alcohols 4 and 7 [2][8]3).
The building blocks derived from the +5'R)-configured monomer 4 serve as precursors
for the dimers 14a ± d, and those derived from the +5'S)-configured monomer 7 as
precursors for the dimer 16 and the deoxygenated dimers 15b ± d +cf. Schemes 4 and 5,
and Table 2).
C-Desilylation and O-triethylsilylation of the propargylic alcohol 4 provided 5 in
86% yield. Hydrolysis of 4 and 7 with aqueous NH4OH in MeOH [2], followed by
treatment of the crude alcohols with Et3SiCl in pyridine4) led to the epimeric O-
silylated amines 6 and 8 in 91 and 67%, respectively +Scheme 3). The alcohol 7 was
treated with +thiocarbonyl)diimidazole in CH2Cl2 to afford the thiocarbamate 9 +72%).
Deoxygenation of 9 with Bu3SnH/AIBN gave the 5'-deoxy derivative 10 +53% from 7).
Desilylation of 10 with TBAF in aqueous THF afforded the N-benzoylated [5'-deoxy-
d-ribo-heptynofuranosyl]-adenine 11 quantitatively, while the corresponding deben-
zoylated derivative 12 was obtained in 97% yield by treating 10 with aqueous NH4OH.
The 1H-NMR chemical shifts and the vicinal couplings for the ribofuranosyl unit of
5, 6, and 8 +Table 4 in the Exper. Part) are similar to those of the corresponding N6-
benzoylated and C+7')-silylated analogues [2] +Dd ꢁ 0.12 ppm, DJ ꢁ 0.5 Hz). HÀC+2')
of 5, 6, and 8 resonates at 5.25 ± 5.27 ppm, evidencing the anti-conformation. HÀC+2')
of the carbamate 9, however, resonates at 5.53 ppm. The downfield shift of 0.27 ppm
suggests a ca. 1:1 equilibrium between the anti- and the syn-conformers of 9, as
deduced from the downfield shift of ca. 0.55 ppm for HÀC+2') of corresponding l-talo-
2
)
The assignment of HÀC+2) and HÀC+8) is based on the observation that the less deshielded singlet
between 8.0 and 9.0 ppm disappears upon substitution of HÀC+2) by a RÀCꢂC group +RˆH or
trialkylsilyl), while the more deshielded singlet is hardly influenced +Dd < 0.1 ppm) [7].
Independently of us, Matsuda et al. [8] have described the preparation of 4 and 7; much to our regret, we
noticed their results only after our communication [2] had been in print.
Pyridine was conveniently removed by co-evaporation with toluene +see Exper. Part), while the use of
DMF instead of pyridine complicated the workup, as 4 and 7 were extracted together with traces of DMF
that was not readily removed by chromatography.
3
4
)
)

2978
Helvetica Chimica Acta ± Vol. 83 +2000)
Scheme 3
a) +TBAF) ´ 3 H2O, THF; Et3SiCl, imidazole, DMF; 86%. b) 25% aq. NH4OH, MeOH; Et3SiCl, pyridine; 91%
+6), 67% +8), 97% +12). c) +Thiocarbonyl)diimidazole, CH2Cl2; 72%. d) Bu3SnH, 2,2'-azobis[isobutyronitrile]
+AIBN), toluene; 53% from 7. e) TBAF ´ 3 H2O, THF; 100%.
configured 8-haloadenosines [2], which adopt more or less completely the syn-
conformation.
The syn > anti equilibrium influences the conformation of the propargylic side
chain, as evidenced by J+4',5') of 8.5 Hz for 9 and of 4.5 ± 5.5 Hz for 5, 6, and 8. The
preferred conformer of 9 is characterized by an antiperiplanar arrangement of
HÀC+4') and HÀC+5') bonds and exhibits the weakest steric interaction between the
substituent at C+4) and the nucleobase. HÀC+2') of the d-ribo-heptynofuranosyl
adenines 10 ± 12 appears at 5.42 ± 5.46 ppm, ca. 0.17 ppm downfield to HÀC+2') of 2
and ca. 0.36 ppm upfield to HÀC+2') of 3, evidencing a ca. 2 :1 equilibrium between the
anti- and the syn-conformers of 10 ± 12. Again, the enhanced preference for the syn-
conformer is paralleled by larger J+4',5') couplings of 5.5 ± 6.7 Hz for 10 ± 12 vs. 4.0 Hz

Helvetica Chimica Acta ± Vol. 83 +2000)
2979
for 2. The J+1',2') and J+3',4') values evidence ca. 1:1 +N) > +S)-equilibria for 2, 3, 5, 6,
and 8 ± 12.
Due to the unusually large 1J+1H,13C) and 2J+1H,13C) couplings, the tertiary C-atom
of terminal acetylenes does not lead to a signal in the DEPT spectrum, whereas the
quaternary C-atom gives rise to a weak CH-type signal [9]. This has led to incorrect
assignments of these signals +cf. [2][10] and earlier papers of this series)5).
Monoalkylation of acetylene leads to a downfield shift of the signal for the C+a)-
atom and to an upfield shift for the C+b)-atom [11]. Thus, the ꢀsingletsꢁ of 5, 6, and 8 at
74.6 ± 75.4 ppm are assigned to C+7') and the ꢀdoubletsꢁ at 81.5 ± 81.8 ppm to C+6').
Deoxygenation at C+5') leads to upfield shifts of 2 ppm for C+6') and of 4 ppm for C+7')
of 11 and 12, whereas C-silylation leads to the expected downfield shift +cf. [10][12][13]
and earlier papers of this series) for both C+6') +9: 96.2, 10: 101.5 ppm) and C+7') +9:
91.2, 10: 87.9 ppm).
To establish the best reaction conditions, we investigated the cross-coupling of 13
[2] and 5 +Scheme 4 and Table 1). The conditions for the Sonogashira reaction [3]
between 8-iodoadenosine and +trimethylsilyl)acetylene, providing 63% of the coupling
product [14], led to a slow transformation; considerable amounts of starting material
remaining after 3 h +Table 1, Entry 1). Prolonging the duration of the reaction
+Entry 2) showed that the dimer 14a is degraded under the reaction conditions.
Optimisation of solvents and/or bases showed that DMF [15] is not suitable +Entries 3
and 4). Tertiary amines like Et3N or N-methylpyrrolidine, used as solvents and bases,
were superior to secondary amines [16], as they did not lead to N-debenzoylation
+Entries 1 and 6 vs. Entry 5). However, no cross-coupling occurred in Hünigꢁs base or
N,N,N',N'-tetramethylethylenediamine +TMEDA; Entries 7 and 8). [Pd2+dba)3] in the
presence of Et3N or N-methylpyrrolidine proved the best catalyst +Entries 9 ± 17). We
Scheme 4
5
)
We thank Dr. Bruno Bernet for a critical reassessment and correction of these data.

2980
Helvetica Chimica Acta ± Vol. 83 +2000)
Table 1. Cross-Coupling of 8-Iodoadenosine 13 with Heptynofuranosyl-adenine 5a)
Entry Catalystb)
Ligandb) Solvent
Temperature
+Time)
Products and yields
after separation
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
+Ph3P)2PdCl2
+Ph3P)2PdCl2
+Ph3P)2PdCl2
+Ph3P)2PdCl2
+Ph3P)2PdCl2
+Ph3P)2PdCl2
+Ph3P)2PdCl2
+Ph3P)2PdCl2
+Ph3P)4Pd
Pd2+dba)3
Pd2+dba)3
+dppe)PdCl2
+PhCN)2PdCl2 none
+MeCN)2PdCl2 none
Pd+OAc)2
PdCl2
Pd+acac)2
Pd2+dba)3
Pd2+dba)3
Pd2+dba)3
none
none
none
none
none
none
none
none
none
none
none
none
Et3N
Et3N
r.t. +1 h) ! 808 +3 h) 14a: 37%, 5: 47%, 13: 48%
r.t. +1 h) ! 808 +12 h) 14a: 17%
5 equiv. Et3N in DMF r.t. +1 h) ! 808 +12 h) no reaction
Et3N/DMF 1 : 1
pyrrolidine
r.t. +1 h) ! 808 +12 h) no reaction
r.t. 2 h debenzoylation
N-methylpyrrolidine r.t. +1 h) ! 708 +1 h) 14a: 46%
EtN+i-Pr)2
TMEDA
Et3N
808 +5 h)
no reaction
r.t. +1 h) ! 808 +3 h) 5: 97%, 13: decomposed
r.t. +1 h) ! 808 +4 h) 14a: 25%, 5: 53%, 13: 69%
r.t. +1 h) ! 808 +2 h) 14a: 70%
Et3N
N-methylpyrrolidine r.t. +1 h) ! 708 +1 h) 14a: 44%
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
r.t. +1 h) ! 808 +3 h) no reaction
r.t. +1 h) ! 808 +3 h) 14a: 41%, 5: 24%, 13: 19%
r.t. +1 h) ! 808 +3 h) 14a: 23%, 5: 57%, 13: 69%
r.t. +1 h) ! 808 +1.5 h) 63%
P+fur)3
P+fur)3
P+fur)3
P+fur)3
P+C6F5)3 Et3N
Bu3P Et3N
r.t. +1 h) ! 808 +3 h) 14a: 58%, 5: 13%, 13: 16%
r.t. +1 h) ! 808 +1 h) 14a: 63%
r.t. +1 h) ! 808 +0.6 h) 14a: 89%
r.t. +1 h) ! 808 +1.5 h) 14a: 69%
r.t. +1 h) ! 808 +3 h) 14a: 16%, 5: 79%, 13: 73%
a) Unless indicated otherwise, reactions were performed in the presence of 3 mol-% of the catalyst, 6 mol-% of
the ligand, and 9 mol-% of CuI. b) dba ˆ dibenzylideneacetone, dppe ˆ 1,2-+diphenylphosphino)ethane, acac ˆ
acetylacetonate, furˆ furan-2-yl.
Table 2. Influence of the N-Benzoyl and the Et3SiO Group on the Yield of the Cross-Couplinga)
Entry 8-Iodoadenosine Acetylene Solvent
Conditions
r.t. +1 h) ! 808 +40 min) 14a +89)
r.t. +2 h) 14b +83)
Product +yield [%])
1
2
3
4
5
6
7
8
13
13
3
5
6
5
Et3N
Et3N
Et3N
Et3N
Et3N
Et3N
r.t. +1 h) ! 808 +40 min) 14c +91)
3
6
r.t. +2 h)
14d +84)
no reaction
15b +60)
15c +71)
15d +78)
13
13
3
11b)
12
11b)
12
r.t. +1 h) ! 808 +1 h)
r.t. +5.5 h)
Et3N/toluene 1 : 1 r.t. +1 h) ! 808 +1 h)
3
Et3N r.t. +5 h)
a) In the presence of 3 mol-% of Pd2+dba)3, 6 mol% of P+fur)3, and 9 mol-% of CuI. Progress of the cross-
coupling was monitored by observing the precipitation of triethylammonium hydroiodide. The end of the
precipitation is correlated with the consumption of starting materials according to TLC. b) Compound 11 is
poorly soluble in Et3N.
also tested the influence of tertiary phosphines +Entries 18 ± 20). Addition of 6 mol-%
of tris+furan-2-yl)phosphine [17 ± 21] accelerated the cross-coupling about threefold
+Entries 10 and 18) and led to a rapid reaction that was terminated before any sizeable
degradation of the dimer 14a occurred. Coupling the free amines 3 and 6 under
optimised conditions +cf. Entry 18) proceeded at room temperature over 2 h to yield
84% of 14d +Table 2, Entry 4). Using these conditions, we compared the relation
between the structure of the coupling partners and their reactivity +Scheme 4, Table 2).

Helvetica Chimica Acta ± Vol. 83 +2000)
2981
Inspection of Table 2 shows that three substituents contribute to the reactivity and
yields: the N-benzoyl and the Et3SiO group of the acetylene, and the N-benzoyl group
of the iodoadenosine. The amine 6 is more reactive than its N-benzoylated analogue 5,
as shown by the lower temperature required for the transformation of 13 and 3
+Entries 2 and 4 vs. 1 and 3); here the presence or absence of the N-benzoyl group in the
iodoadenosine is irrelevant. Deoxygenation reduces the reactivity of the acetylene, as
evidenced by comparing Entries 5 and 7 vs. 1 and 3, and 8 and 6 vs. 2 and 4; again, the
amine 12 is more reactive than the benzamide 11. The results in Entries 5 and 7 reflect
the poor solubility of 11 in Et3N; by changing the solvent to Et3N/toluene 1:1 this
problem is avoided for the reaction with the amine 3, but not for the reaction with the
benzamide 13, which led at best to ca. 26% of the dimer +product not isolated). We
assume that the required higher temperature reflects the lower reactivity rather than
the influence of the solvent. Thus, the N-unsubstituted and O-silylated alkyne is the
preferred partner for the cross-coupling.
As the NH2 group in 6 is too far from the alkynyl group for a through-bond
interaction, we rationalise the difference between the amines and benzamides by
postulating that the more strongly basic adenyl residue in 6 co-ordinates at N+3) with
the intermediate resulting from oxidative addition of the catalytically active [PdL2]
species to the iodoadenosine and thereby promotes its interaction with the alkynyl
moiety. The enhanced reactivity of the propargylic silyl ethers presumably correlates
with the stronger acidity of the alkynyl group +cf. [17]), while the oxidative addition
only becomes +marginally) relevant when the alkyne is particularly unreactive, as it is
the case for the deoxygenated benzamide 11. The approximate order of reactivity of the
acetylene derivatives appears to be 6 > 12 > 5 > 11.
The +5'S)-configured acetylene 8 showed the same reactivity as its epimer 6
+Scheme 5). Coupling 3 and 8 under standard conditions at room temperature for 2 h
gave the dimer 16 in 76% yield. Desilylation of the protected dimers 14d and 16 with
aqueous AcOH in THF yielded 82 and 97% of the diols 17 and 19, respectively. Finally,
acidic hydrolysis of 17 and 19 in 80% HCOOH [2] led to the fully deprotected
acetyleno-adenosine dimers 18 and 20 in 87 and 92% yield, respectively.
The assignment of the 1H-NMR signals of the silyl ethers 14a ± d, 15b ± d, and 16 is
based on 2D-COSY spectra of 14c, 15c, 15d, and 16 +Table 5 in the Exper. Part). As
already observed for the monomers, N6-debenzoylation leads to an upfield shift of
HÀC+2) +Dd ˆ 0.4 ± 0.5 ppm) and HÀC+8) +Dd ˆ 0.1 ± 0.2 ppm). HÀC+2/I) and
HÀC+2/II)1) of the dibenzamide 14a, and the diamines 14d and 15d resonate at a
similar field +Dd+HÀC+2/I)/HÀC+2/II) ˆ 0.02 ± 0.06 ppm). HÀC+2'/II) of 14a ± d,
15b ± d, and 16 appears at 5.63 ± 5.73 ppm. These compounds are C+8/II)-substituted
adenosine derivatives and should therefore adopt the syn-conformation in unit II. The
weak upfield shift of ca. 0.1 ppm of the HÀC+2') signal relative to one for HÀC+2') of
the 8-iodoadenosine 3 probably reflects the influence of the different substituents and
not an incomplete preference for the syn-conformation. HÀC+2'/I) of 14a ± d, 15b ± d,
and 16 appears at 5.41 ± 5.64 ppm, 0.01 ± 0.27 ppm upfield to the HÀC+2'/II) signal in
the same spectrum and 0.15 ± 0.38 ppm downfield to HÀC+2') signal of the monomers
2, 5, 6, and 8, preferring the anti-conformation. These values suggest anti > syn
equilibria between 7:3 to 1:3. Again, the anti > syn equilibria are paralleled by
enhanced J+4',5') values of 5.7 ± 7.3 Hz for 14a ± d and 15b ± d vs. 4.0 ± 4.8 Hz for 2, 5,

2982
Helvetica Chimica Acta ± Vol. 83 +2000)
Scheme 5
a) CuI, [Pd2+dba)3], P+fur)3, Et3N; 76%. b) THF/AcOH/H2O 1:2 :1; 97% +17), 82% +19). c) 80% aq. HCO2H;
92% +18), 87% +20).
1
and 6. In the absence of H/13C-COSY spectra, an unambiguous assignment of the
corresponding 13C-NMR signals of unit I and unit II is not feasible. However, the shift
difference for C+1'/I)/C+1'/II), C+2'/I)/C+2'/II), C+3'/I)/C+3'/II), and C+4'/I)/C+4'/II) of
14a ± d, 15b ± d, and 16 is small +Dd < 2 ppm, except for C+1'/I)/C+1'/II) of 16 +2.9 ppm)
and C+4'/I)/C+4'/II) of 15b ± d +2.7 ± 4.0 ppm); see Exper. Part). The doublet of C+5'/I)
of 14a ± d and 16 appears at 63.5 ± 64.4 ppm, the triplet of C+5'/I) of 15b ± d at 24.4 ±
24.6 ppm, and the triplet of C+5'/II) of 14a ± d, 15b ± d, and 16 at 62.9 ± 63.2 ppm.
Ethynylation leads to the expected upfield shift6) of the singlet of C+8/II) of 14a ± d,
15b ± d, and 16 at 133.5 ± 137.1 ppm as compared to the doublet of C+8/I) at 139.2 ±
143.5 ppm. Two singlets of 14a ± d, 15b ± d, and 16 at 93.4 ± 96.3 and at 71.3 ± 75.5 ppm
were assigned to C+6'/I) and C+7'/I), respectively, in agreement with the assignments
for alkylated arylacetylenes [23].
The 1H-NMR spectra of the diols 17 and 19 were recorded in +D6)DMSO +Table 5
in Exper. Part). The desilylation and the change of the solvent lead to an increase of
J+1',2') +DJ ꢃ 1.5 Hz), indicating a stronger preference of the ꢀsouthernꢁ conformation
by the diols in +D6)DMSO than by the disilyl ethers in CDCl3. As already observed for
adenosine +23a) in DMSO [24][25], HÀC+8/I) of 17 and 19 appears at lower field than
6
)
Ethynylation of benzene leads to an upfield shift of 6.2 ppm for the quaternary aromatic C-atom [22].

Helvetica Chimica Acta ± Vol. 83 +2000)
2983
HÀC+2/I) and HÀC+2/II). This assignment is ascertained by the disappearance of the
signal of 17 at 8.29 ppm upon iodination at C+8/I) [26]. A discussion of the syn/anti-
conformation and the H-bonding of 17 and 19 in +D6)DMSO requires reference data
for the corresponding 8-unsubstituted and 8-substituted adenosines in the same solvent,
as provided by 21a ± c. The 8-substituted adenosines 21b [27] and 21c [28] are expected
to completely adopt a syn-conformation, whereas a 65 :35 syn > anti equilibrium of the
8-unsubstituted 21a in +D6)DMSO has been deduced from NOE data [29]. The
chemical shifts for HÀC+2') of 21a +5.21 ppm [30]), 21b +5.57 ppm [27]), and 21c
+5.68 ppm [7]) agree with this assignment. The presence of the 8-Br substituent leads to
a stronger downfield shift similarly as observed for the iodide 3. HÀC+2'/II) of 17
+5.49 ppm) and 19 +5.40 ppm) resonate downfield to HÀC+2'/I) at 5.32 and 5.36 ppm,
respectively. A preference +> 75%) for the syn-conformation of all units of 17 and 19 is
deduced from the d+HÀC+2')) values of 21a ± c. The preference for the syn-
conformation may be even more pronounced since the d+HÀC+2')) values are also
influenced by the intramolecular H-bond between HOÀC+5') and N+3). O+5')-
Unprotected 2',3'-O-isopropylidene-adenosines form completely persistent intramo-
lecular O+5')ÀH ´´´ N+3) H-bonds in CDCl3 solution +see [2][31] and refs. cit. therein).
This H-bond leads to an upfield shift of 0.5 ± 0.6 ppm for HOÀC+2') [2]. The change of
the solvent from CDCl3 to +D6)DMSO reduces the persistence of the intramolecular H-
bond in 21c; the persistence is ca. 22%, as deduced from the J+4',5') values of 5.8 Hz
[31]. The smaller J+4',5'/II) values of 5.5 Hz of 17 and 19 suggest a ca. 32% persistence
for the O+5'/II)ÀH ´´´ N+3/II) H-bond and, hence, probably a complete preference of
the syn-conformation for unit II. The J+4',5'/I) values of 17 and 19 are 5.5 and 6.5 Hz,
respectively. An analogous analysis7) suggests a ca. 18% persistence for the O+5'/
II)ÀH ´´´ N+3/II) H-bond of 19 and a ca. 45% persistence for the O+5'/II)ÀH ´´´ N+3/
II) H-bond of 17 and, hence, a more or less complete preference for the syn-
conformation also for unit I. The partially persistent OÀH ´´´ N H-bonds are evidenced
by the downfield shift of the OH signals: the primary HOÀC+5'/II) resonates at 5.23
+17) and 5.15 ppm +19), and the secondary HOÀC+5'/I) at 6.73 +17) and 6.65 ppm +19).
The data have to be compared to d+HOÀC+5)) of pentofuranoses +4.55 ± 4.69 ppm
[32]) and hexofuranoses +4.43 ± 4.69 ppm [32]). The persistence is also evidenced by
the relatively large J+5'/I,OH) of 17 +6.8 vs. 11.0 Hz for a completely intramolecularly
The limiting values for J+4',5'/I) were taken from the 1H-NMR spectra of O+5')-unprotected and O+5')-
silylated 8-chloro-heptynofuranosyl-adenines +2.5 and 8.0 Hz for 17, 2.0 and 7.5 Hz for 19 [2]).
7
)

2984
Helvetica Chimica Acta ± Vol. 83 +2000)
H-bonded OH group [2], and vs. 3.5 ± 5.5 Hz for a completely solvated secondary OH
group [33]). A too rapid H,H-exchange leading to broad signals of the OH groups
prevents a similar analysis of 19.
1
The H-NMR data of the fully deprotected dimers 18 and 20 in +D6)DMSO/D2O
are compiled in Table 3 together with the data of the related monomers: the propargyl
alcohol 22 [2][8], adenosine +23a) [24][25], 8-ethyladenosine +23b) [27], and 8-
bromoadenosine +23c) [34]. Adenosine +23a; J+1',2') ˆ 5.6, J+3',4') ˆ 4.1 Hz) slightly
2
prefers a +S)-conformation, and the other compounds adopt a T3 conformation, as
evidenced by J+1',2') ˆ 6.5 ± 7.8 and J+3',4') ꢁ 2.0 Hz. Adenosine +23a) prefers to 60%
the syn-conformation as determined by NOE measurements [29]. The 8-substituted
derivatives 23b and 23c are expected to adopt completely the syn-conformation.
Smaller J+4',5') values are observed for 18, 20, 22, and 23a ± c than for 17 and 19, and
indicate a stronger persistence of the intramolecular O+5')ÀH ´´´ N+3) H-bond. The
persistence calculated according to [31] increases from 50 ± 52% +23a, 23c, and unit II
of 18 and 20) to 55% +unit I of 20), 72% +22), and 82% +unit I of 18). HÀC+2'/II) of 18
and 20 resonates at 4.91 ± 4.93 ppm at a similar position as HÀC+2) of 8-methyladen-
osine +23b), 0.1 ppm upfield to HÀC+2) of 8-bromoadenosine +23c), and 0.3 ppm
downfield to HÀC+2) of adenosine +23a), evidencing a complete preference for the
syn-conformation of unit II. Since unit I of 20 exhibits a similarly persistent H-bond as
23a and 23c, the d+HÀC+2'/I)) value of 4.72 ppm evidences a 80% preference for the
syn-conformation. However, the persistence of the H-bond of 22 and unit I of 18 is
higher by ca. 20 ± 30% than that for 23a and 23c, leading to a significant upfield shift of
the HÀC+2') signal8). Thus, the upfield shifts +4.63 and 4.68 ppm) still indicate a more
1
Table 3. Selected H-NMR Chemical Shifts [ppm] and Coupling Constants [Hz] of the Deprotected Dimers 18
and 20, and the Related Monomers 22 and 23a ± c in 9D6)DMSO/D2O Solution
18
20
22 [2]
18
20
23a [24]
23b [27]
23c [7]
Unit I
Unit I
Unit II
Unit II
HÀC+2)
HÀC+8)
HÀC+1')
HÀC+2')
HÀC+3')
HÀC+4')
HaÀC+5')
HbÀC+5')
J+1',2')
8.13a)
8.34
5.95
4.68
4.23
4.13 ± 4.20
4.89
±
8.15a)
8.33
5.94
4.72
4.32
4.13
4.87
±
8.14
8.30
5.89
4.63
4.22
3.99
4.47
±
8.15a)
±
8.16a)
±
8.15
8.37
5.87
4.60
4.14
3.96
3.56
3.67
5.6
8.07
±
8.12
±
5.91
4.91
4.13 ± 4.20
3.95
3.51
3.65
6.5
5.94
4.93
4.18
3.99
3.53
3.67
6.5
5.78
4.90
4.18
4.03
3.64
3.64
7.1
5.85
5.03
4.20
4.01
3.55
3.69
7.0
7.0
7.5
7.8
J+2',3')
J+3',4')
J+4'a,5')
J+4'b,5')
J+5'a,5'b)
5.0
2.0
3.5
±
5.0
1.0
4.5
±
5.0
< 1
3.5
±
±
5.0
2.0
3.5
4.0
5.0
2.0
3.5
4.0
5.4
4.1
3.6
3.6
5.4
5.2
2.0
3.5
4.0
b
)
)
)
b
b
b
±
±
12.5
12.5
12.2
)
12.5
a) Assignments may be interchanged. b) Not determined.
8
)
A 70% persistence of the intramolecular C+5')ÀO ´´´ N+3) H-bond of 22 is also evidenced by the relatively
small J+5',OH) ˆ 3.5 Hz +ca. 1.5 Hz is expected for a completely persistent H-bond [2]) and by the
downfield shift of HOÀC+5') resonating at 6.57 ppm [33]. No J+H,OH) and d+OH) values are available for
18 and 20.

Helvetica Chimica Acta ± Vol. 83 +2000)
2985
or less complete preference for the syn-conformation. C+6'/I) and C+7'/I) of 18 and 20
appear at expected positions +94.5 ± 95.4 and 70.4 ± 70.7 ppm, resp.).
We thank the Swiss National Science Foundation, and F. Hoffmann-La-Roche AG, Basel for generous
support.
Experimental Part
General. See [2]. 2',3'-O-Isopropylidene-5'-O-9triethylsilyl)adenosine +2). At 258, a soln. of 1 +Fluka, puriss.;
51.0 mg, 0.167 mmol) and imidazole +34.4 mg, 0.51 mmol) in dry DMF +1.5 ml) was treated dropwise with
Et3SiCl +84 ml, 0.50 mmol), stirred for 14 h, poured into ice-water +ca. 6 ml), and extracted with Et2O/AcOEt
1:1 +3 Â 3.0 ml). The combined org. layers were washed with brine, dried +Na2SO4), and evaporated. FC +2.5 g
of silica gel; CHCl3/acetone 1:1) gave 2 +48.7 mg, 70%). White solid. Rf +CHCl3/acetone 1:1) 0.46. M.p. 1108.
[a]2D5 ˆ À49.7 +c ˆ 1.00, CHCl3). UV +CHCl3): 260.0 +14000). IR +CHCl3): 3413m, 2992m, 2959s, 2913m, 2878m,
1632s, 1589s, 1498w, 1416m, 1384m, 1376m, 1329m, 1295m, 1248m, 1156m, 1131m, 1089s, 1004m, 969m, 859m,
818w. 1H-NMR +300 MHz, CDCl3): see Table 4; additionally, 0.55 +q, J ˆ 7.9, +MeCH2)3Si); 0.89 +t, J ˆ 7.9,
+MeCH2)3Si); 1.39, 1.63 +2s, Me2C); 5.86 +br. s, NH2). 13C-NMR +75 MHz, CDCl3): 155.5 +s, C+6)); 153.1
+d, C+2)); 149.5 +s, C+4)); 139.3 +d, C+8)); 120.0 +s, C+5)); 114.0 +s, Me2C); 91.4 +d, C+1')); 87.5 +d, C+4')); 85.1
+d, C+2')); 81.6 +d, C+3')); 63.1 +t, C+5')); 27.2, 25.4 +2q, Me2C); 6.6 +q, +MeCH2)3Si); 4.1 +t, +MeCH2)3Si). FAB-
‡
MS: 422 +[M ‡ 1] ). Anal. calc. for C19H31N5O4Si +421.57): C 54.13, H 7.41, N 16.61; found: C 54.17, H 7.31,
N 16.67.
Table 4. Selected 1H-NMR Chemical Shifts [ppm] and Coupling Constants [Hz] of the Monomers 2, 3, 5, 6, and
8 ± 12 in CDCl3 Solution
2
3
10
8.86
11
8.79
12
8.36
5
6
8
9
HÀC+2)
HÀC+8)
HÀC+1')
HÀC+2')
HÀC+3')
HÀC+4')
HaÀC+5')
HbÀC+5')
HÀC+7')
J+1',2')
8.37
8.07
6.19
5.27
4.96
4.42
3.75
3.87
±
8.22
±
8.84
8.21
6.25
5.27
5.12
4.43
4.64
±
2.48
3.0
6.5
2.5
4.5
±
8.36
8.00
6.18
5.25
5.12
4.39
4.63
±
2.48
3.0
6.5
2.5
4.8
±
8.37
8.13
6.20
5.27
5.04
4.41
4.59
±
2.53
2.3
6.5
2.0
5.5
±
8.88
8.07
6.20
5.53
5.41
4.66
6.35
±
8.25
6.19
5.42
5.01
4.47
2.63
2.77
±
2.8
6.5
2.8
5.5
8.21
6.17
5.44
5.04
4.44
2.58
2.71
2.05
2.8
6.5
3.0
5.8
6.7
7.96
6.10
5.46
5.06
4.41
2.56
2.72
2.05
2.5
6.3
3.0
6.0
7.0
6.09
5.80
5.13
4.30
3.63
3.74
±
2.0
6.5
3.5
6.5
±
2.5
6.5
2.5
4.0
2.0
6.5
3.0
8.5
±
J+2',3')
J+3',4')
J+4',5'a)
J+4',5'b)
J+5'a,5'b)
J+5',7')
4.0
6.5
6.0
11.5
±
10.8
±
17.0
±
17.0
2.7, 2.7
17.0
2.7, 2.7
±
2.0
±
2.2
±
2.3
±
±
8-Iodo-2',3'-O-isopropylidene-5'-O-9triethylsilyl)adenosine +3). A soln. of iPr2NH +1.2 ml, 8.56 mmol) in dry
THF +10.7 ml) was cooled to 08, treated dropwise with 1.6m BuLi in hexane +5.3 ml, 8.48 mmol), stirred for
25 min, cooled to À788, treated dropwise with a soln. of 2 +713.2 mg, 1.69 mmol) in dry THF +10.7 ml), stirred
for 4 h, treated with I2 +1.35 g, 5.32 mmol), stirred for 1 h, without cooling, and treated with sat. aq. NH4Cl soln.
and sat. aq. Na2S2O3 soln. +10 ml each). The layers were separated, and the aq. layer was extracted with AcOEt
+2 Â 10 ml). The combined org. layers were washed with brine, dried +Na2SO4), and evaporated. FC +25 g of
silica gel; CHCl3/acetone 5 :2) gave 3 +809.4 mg, 87%). Yellow solid. Rf +CHCl3/acetone 5 :2) 0.48. M.p. 688.
[a]2D5 ˆ À11.9 +c ˆ 1.00, CHCl3). UV +CHCl3): 266.0 +15000). IR +CHCl3): 3411w, 2993w, 2958m, 2913w, 2876m,
1631s, 1584m, 1476w, 1456w, 1442m, 1415w, 1376m, 1317w, 1288m, 1157m, 1082s, 1005m, 972w, 915w, 873w, 818w.
1H-NMR +300 MHz, CDCl3): see Table 4 ; additionally, 0.48 +q, J ˆ 8.0, +MeCH2)3Si); 0.85 +t, J ˆ 8.0,

2986
Helvetica Chimica Acta ± Vol. 83 +2000)
+MeCH2)3Si); 1.39, 1.61 +2s, Me2C); 5.92 +br. s, NH2). 13C-NMR +75 MHz, CDCl3): 154.4 +s, C+6)); 153.0
+d, C+2)); 150.8 +s, C+4)); 123.1 +s, C+5)); 114.2 +s, Me2C); 100.8 +s, C+8)); 93.8 +d, C+1')); 88.5 +d, C+4')); 83.1
+d, C+2')); 82.5 +d, C+3')); 63.0 +t, C+5')); 27.3, 25.5 +2q, Me2C); 6.6 +q, +MeCH2)3Si); 4.2 +t, +MeCH2)3Si). FAB-
‡
MS: 548 +[M ‡ 1] ). Anal. calc. for C19H30IN5O4Si +547.47): C 41.68, H 5.52, N 12.79; found: C 41.82, H 5.68,
N 12.71.
N6-Benzoyl-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-9triethylsilyl)-b-d-allo-hept-6-ynofuranosyl]adenine
+5). At 258, a soln. of 4 [2][8] +662.7 mg, 1.31 mmol) in dry THF +20 ml) was treated with a 1.0m soln. of Bu4NF
+TBAF) in THF +2.0 ml, 2.0 mmol), stirred for 3 h, and evaporated. FC +25 g of silica gel; CHCl3/acetone 3 :1)
gave the propargylic alcohol +540.0 mg, 95%). At 258, a soln. of this alcohol +1.1877 g, 2.73 mmol) and imidazole
+550.8 mg, 8.09 mmol) in dry DMF +36 ml) was treated dropwise with Et3SiCl +1.4 ml, 8.34 mmol), stirred for
12 h, poured into ice-water +ca. 60 ml), and extracted with hexane/AcOEt 1:1 +3 Â 40 ml). The combined org.
layers were washed with brine, dried +Na2SO4), and evaporated. FC +60 g of silica gel; hexane/AcOEt 1:2) gave
5 +1.3441 g, 90%). Light yellow solid. Rf +hexane/AcOEt 1 :2) 0.46. M.p. 58 ± 598. [a]2D5 ˆ ‡36.4 +c ˆ 1.02,
CHCl3). UV +CHCl3): 278.0 +18000). IR +CHCl3): 3408w, 3305w, 2998w, 2958w, 2914w, 2878w, 2100w, 1709m,
1612s, 1585s, 1504w, 1479m, 1456s, 1404w, 1385w, 1356w, 1330w, 1295w, 1248m, 1156w, 1090s, 1003w, 972w, 948w,
1
867w. H-NMR +300 MHz, CDCl3): see Table 4; additionally, 0.64, 0.65 +2q, J ˆ 8.0, +MeCH2)3Si); 0.93 +t, J ˆ
8.0, +MeCH2)3Si); 1.42, 1.65 +2s, Me2C); 7.51 +t, J ˆ 7.8, 2 arom. H); 7.60 +t, J ˆ 7.8, 1 arom. H); 8.01 +d, J ˆ 7.8,
2 arom. H); 9.08 +br. s, NH). 13C-NMR +75 MHz, CDCl3): 164.9 +s, CˆO); 153.2 +d, C+2)); 151.6 +s, C+6)); 149.9
+s, C+4)); 141.9 +d, C+8)); 134.0 +s); 133.0 +d); 129.1 +2d); 128.1 +2d); 123.5 +s, C+5)); 114.7 +s, Me2C); 91.7
+d, C+1')); 89.5 +s, C+4')); 84.6 +d, C+2')); 81.5 +s, C+6')); 81.3 +d, C+3')); 75.4 +s, C+7')); 63.1 +d, C+5')); 27.3, 25.5
‡
+2q, Me2C); 6.7 +q, +MeCH2)3Si); 4.7 +t, +MeCH2)3Si). FAB-MS: 550 +[M ‡ 1] ). Anal. calc. for C28H35N5O5Si ´
0.5 H2O +558.71): C 60.19, H 6.49, N 12.53; found: C 60.04, H 6.42, N 12.32.
9-[6,7-Dideoxy-2,3-O-isopropylidene-5-O-9triethylsilyl)-b-d-allo-hept-6-ynofuranosyl]adenine +6). At 258,
a soln. of 4 +674.9 mg, 1.33 mmol) in MeOH +17 ml) was treated with 25% aq. NH4OH +17 ml), stirred at 608 for
2 h, and evaporated. At 258, a soln. of the crude residue in dry pyridine +22 ml) was treated dropwise with
Et3SiCl +0.67 ml, 3.99 mmol), stirred for 12 h, evaporated, and co-evaporated several times with PhMe. A soln.
of the residue in CHCl3 +40 ml) was washed with sat. aq. NaHCO3 soln. +20 ml) and brine +10 ml), dried
+Na2SO4), and evaporated. FC +20 g of silica gel; CHCl3/acetone 1:1) gave 6 +536.5 mg, 91%). Light yellow
solid. Rf +CHCl3/acetone 2 :3) 0.52. M.p. 578. [a]2D5 ˆ À66.7 +c ˆ 1.04, CHCl3). UV +CHCl3): 260.0 +130000). IR
+CHCl3): 3413w, 3305m, 2994m, 2959m, 2914w, 2878w, 2100w, 1632s, 1588m, 1506w, 1472m, 1417w, 1384w,
1375m, 1330w, 1296w, 1248m, 1156w, 1094s, 1004w, 972w, 904w, 863w. 1H-NMR +300 MHz, CDCl3): see Table 4;
additionally, 0.64, 0.65 +2q, J ꢃ 8.0, +MeCH2)3Si); 0.94 +t, J ˆ 8.0, +MeCH2)3Si); 1.41, 1.63 +2s, Me2C); 5.91 +br. s,
NH2). 13C-NMR +75 MHz, CDCl3): 155.5 +s, C+6)); 153.2 +d, C+2)); 149.5 +s, C+4)); 139.3 +d, C+8)); 120.0
+s, C+5)); 114.3 +s, Me2C); 91.2 +d, C+1')); 89.3 +d, C+4')); 84.4 +d, C+2')); 81.7 +s, C+6')); 81.2 +d, C+3')); 75.0
+s, C+7')); 63.0 +d, C+5')); 27.2, 25.4 +2q, Me2C); 6.7 +q, +MeCH2)3Si); 4.7 +t, +MeCH2)3Si). FAB-MS: 446 +[M ‡
‡
1] ). Anal. calc. for C21H31N5O4Si +445.59): C 56.61, H 7.01, N 15.72; found: C 56.45, H 7.09, N 15.48.
9-[6,7-Dideoxy-2,3-O-isopropylidene-5-O-9triethylsilyl)-a-l-talo-hept-6-ynofuranosyl]adenine +8). At 258,
a soln. of 7 [2][8] +314.7 mg, 0.620 mmol) in MeOH +8.0 ml) was treated with 25% aq. NH4OH +8.0 ml), stirred
at 608 for 80 min, and evaporated. A soln. of the residue in dry pyridine +10 ml) was treated dropwise with
Et3SiCl +0.31 ml, 1.85 mmol) at 258, stirred for 12 h, evaporated, and co-evaporated several times with PhMe. A
soln. of the residue in CHCl3 +35 ml) was washed with sat. aq. NaHCO3 soln. +10 ml) and brine +7 ml), dried
+Na2SO4), and evaporated. FC +15 g of silica gel; CHCl3/acetone 1:2) gave 8 +184.1 mg, 67%). Light yellow
solid. Rf +CHCl3/acetone 1:2) 0.58. M.p. 1428 +acetone/hexane). [a]2D5 ˆ À10.0 +c ˆ 1.01, CHCl3). UV +CHCl3):
260.0 +13000). IR +CHCl3): 3413w, 3304w, 2994w, 2958m, 2914w, 2878w, 2250w, 1632s, 1587m, 1498w, 1471m,
1415w, 1376w, 1330w, 1294w, 1248w, 1156w, 1131m, 1095s, 1004m, 908w, 867w. 1H-NMR +300 MHz, CDCl3): see
Table 4; additionally, 0.48, 0.49 +2q, J ꢃ 8.0, +MeCH2)3Si); 0.84 +t, J ˆ 8.0, +MeCH2)3Si); 1.40, 1.62 +2s, Me2C);
5.92 +br. s, NH2).13C-NMR +75 MHz, CDCl3): 155.5 +s, C+6)); 153.2 +d, C+2)); 149.4 +s, C+4)); 139.6 +d, C+8));
120.1 +s, C+5)); 114.2 +s, Me2C); 91.8 +d, C+1')); 89.7 +d, C+4')); 84.9 +d, C+2')); 81.9 +d, C+3')); 81.8 +s, C+6')); 74.6
+s, C+7')); 63.6 +d, C+5')); 27.2, 25.4 +2q, Me2C); 6.5 +q, +MeCH2)3Si); 4.4 +t, +MeCH2)3Si). FAB-MS: 446 +[M ‡
‡
1] ). Anal. calc. for C21H31N5O4Si +445.59): C 56.61, H 7.01, N 15.72; found: C 56.52, H 7.04, N 15.63.
N6-Benzoyl-9-{6,7-dideoxy-5-O-[9imidazol-1-yl)thiocarbonyl]-2,3-O-isopropylidene-7-C-9trimethylsilyl)-
a-l-talo-hept-6-ynofuranosyl}adenine +9). At 258, a soln. of 7 +421.1 mg, 0.83 mmol) in dry CH2Cl2 +12.6 ml) was
treated with +thiocarbonyl)diimidazole +289.2 mg, 1.62 mmol), stirred for 17 h, and evaporated. FC +25 g of
silica gel; CHCl3/acetone 2 :1) gave 9, which contained traces of impurities +369.5 mg, 72%). Yellow solid. Rf
+CHCl3/acetone 2 :1) 0.46. 1H-NMR +200 MHz, CDCl3): see Table 4; additionally, 0.24 +s, Me3Si); 1.42, 1.63 +2s,
Me2C); 6.98 ± 7.00 +m, 1 arom. H); 7.46 ± 7.66 +m, 4 arom. H); 7.98 ± 8.06 +m, 2 arom. H); 8.24 +br. s, 1 arom. H);

Helvetica Chimica Acta ± Vol. 83 +2000)
2987
9.12 +br. s, NH). 13C-NMR +50 MHz, CDCl3): 181.7 +s, CˆS); 164.2 +s, CˆO); 152.6 +d, C+2)); 150.6 +s, C+6));
149.5 +s, C+4)); 142.0 +d, C+8)); 136.5 +d, C+2) of imidazolyl); 133.2 +s); 132.5 +d); 130.5 +d, C+5) of imidazolyl);
128.5 +2d); 127.5 +2d); 123.3 +s, C+5)); 117.7 +d, C+4) of imidazolyl); 114.4 +s, Me2C); 96.2 +s, C+6')); 95.8
+d, C+1')); 91.2 +s, C+7')); 87.5 +d, C+4')); 83.6 +d, C+2')); 81.8 +d, C+3')); 72.4 +d, C+5')); 26.6, 24.9 +2q, Me2C);
À0.8 +s, Me3Si).
N6-Benzoyl-9-[5,6,7-trideoxy-2,3-O-isopropylidene-7-C-9trimethylsilyl)-b-d-ribo-hept-6-ynofuranosyl]ade-
nine +10). At 258, a soln. of 9 containing traces of impurities +86.8 mg) in dry PhMe +2.6 ml) was treated with
AIBN +2.8 mg, 17.1 mmol) and Bu3SnH +74 ml, 0.28 mmol), stirred for 1 h at 808, and evaporated. A soln. of the
residue in MeCN +2 ml) was washed with hexane +2 Â 2 ml) and evaporated. FC +4.5 g of silica gel; CHCl3/
AcOEt 1:1) and crystallization from AcOEt/hexane gave 10 +50.4 mg, 53% from 7). White needles. Rf +CHCl3/
AcOEt 1 :1) 0.47. M.p. 1628. [a]2D5 ˆ À81.1 +c ˆ 1.02, CHCl3). UV +CHCl3): 274.0 +17000). IR +CHCl3): 3407w,
3007m, 2962w, 2176w, 1709s, 1612s, 1585s, 1504w, 1479m, 1456s, 1404w, 1385m, 1357w, 1328m, 1294m, 1252s,
1
1156m, 1087s, 1028w, 951w, 846s. H-NMR +300 MHz, CDCl3): see Table 4; additionally, 0.14 +s, Me3Si); 1.42,
1.65 +2s, Me2C); 7.54 +t, J ꢃ 7.8, 2 arom. H); 7.63 +t, J ꢃ 7.8, 1 arom. H); 8.03 +d, J ˆ 7.8, 2 arom. H); 8.99 +br. s,
NH). 13C-NMR +75 MHz, CDCl3): 164.5 +s, CˆO); 152.9 +d, C+2)); 151.2 +s, C+6)); 149.6 +s, C+4)); 141.8
+d, C+8)); 133.7 +s); 132.8 +d); 128.9 +2d); 127.9 +2d); 123.5 +s, C+5)); 114.7 +s, Me2C); 101.5 +s, C+6')); 91.4
+s, C+1')); 87.9 +s, C+7')); 84.6, 84.5 +2d, C+2'), C+4')); 83.4 +d, C+3')); 27.2, 25.4 +2q, Me2C); 24.8 +t, C+5')); 0.0
‡
+q, Me3Si). FAB-MS: 492 +[M ‡ 1] ). Anal. calc. for C25H29N5O4Si +491.62): C 61.08, H 5.95, N 14.25; found:
C 61.14, H 5.91, N 14.08.
N6-Benzoyl-9-[5,6,7-trideoxy-2,3-O-isopropylidene-b-d-ribo-hept-6-ynofuranosyl]adenine +11). At 258, a
soln. of 10 +55.3 mg, 0.112 mmol) in dry THF +1.7 ml) was treated with 1.0m soln. of TBAF in THF +0.17 ml,
0.17 mmol), stirred for 3 h, and evaporated. FC +2.0 g of silica gel; CHCl3/AcOEt 3 :4) gave 11 +47.1 mg, 100%).
White solid. Rf +CHCl3/AcOEt 1 :2) 0.47. M.p. 78 ± 798. [a]2D5 ˆ ‡52.3 +c ˆ 1.02, CHCl3). 276.0 +15000). IR
+CHCl3): 3407w, 3307m, 3007m, 2940w, 2110w, 1708s, 1612s, 1585s, 1558w, 1540w, 1506m, 1480m, 1456s, 1419w,
1385m, 1359w, 1329m, 1248s, 1157m, 1089s, 1029w, 870m. 1H-NMR +300 MHz, CDCl3): see Table 4; additionally,
1.40, 1.63 +2s, Me2C); 7.46 ± 7.54 +m, 2 arom. H); 7.56 ± 7.63 +m, 1 arom. H); 7.98 ± 8.04 +m, 2 arom. H); 9.13 +br. s,
NH). 13C-NMR +75 MHz, CDCl3): 164.6 +s, CˆO); 152.8 +d, C+2)); 151.2 +s, C+6)); 149.7 +s, C+4)); 142.1
+d, C+8)); 133.6 +s); 132.8 +d); 128.9 +2d); 127.9 +2d); 123.7 +s, C+5)); 114.8 +s, Me2C); 91.2 +d, C+1')); 85.0
+d, C+4')); 84.4 +d, C+2')); 83.4 +d, C+3')); 79.4 +s, C+6')); 71.1 +s, C+7')); 27.2, 25.4 +2q, Me2C); 23.4 +t, C+5')).
‡
FAB-MS: 420 +[M ‡ 1] ).
9-[5,6,7-Trideoxy-2,3-O-isopropylidene-b-d-ribo-hept-6-ynofuranosyl]adenine +12). At 258, a soln. of 10
+143.0 mg, 0.291 mmol) in MeOH +3.6 ml) was treated with 25% aq. NH4OH +3.6 ml), stirred at 608 for 1 h, and
evaporated. FC +4.0 g of silica gel; CHCl3/acetone 1 :2) gave 12 +89.0 mg, 97%). White solid. Rf +CHCl3/acetone
1:2) 0.46. M.p. 668. [a]2D5 ˆ À53.5 +c ˆ 1.02, CHCl3). UV +CHCl3): 259.0 +10000). IR +CHCl3): 3413w, 3307m,
2995m, 2100w, 1632s, 1588m, 1499w, 1473m, 1423w, 1384m, 1376m, 1330m, 1295m, 1248m, 1156m, 1095s, 1047m,
998w, 931w, 905w, 871m. 1H-NMR +300MHz, CDCl3): see Table 4; additionally, 1.39, 1.61 +2s, Me2C); 5.97 +br. s,
NH2). 13C-NMR +75 MHz, CDCl3): 156.0 +s, C+6)); 153.5 +d, C+2)); 149.6 +s, C+4)); 140.0 +d, C+8)); 120.5
+s, C+5)); 114.8 +s, Me2C); 91.2 +d, C+1')); 85.3 +d, C+4')); 84.5 +d, C+2')); 83.8 +d, C+3')); 79.7 +s, C+6')); 70.9
‡
+s, C+7')); 27.2, 25.4 +2q, Me2C); 23.4 +t, C+5')). FAB-MS: 316 +[M ‡ 1] ).
N6-Benzoyl-2',3'-O-isopropylidene-5'-O-9triethylsilyl)adenosin-8-yl-98 ! 7')-N6-benzoyl-9-[6,7-dideoxy-2,3-
O-isopropylidene-5-O-9triethylsilyl)-b-d-allo-hept-6-ynofuranosyl]adenine +14a). At 258, a soln. of 13 [2]
+247.6 mg, 0.38 mmol) and 5 +209.1 mg, 0.38 mmol) in dry Et3N +14 ml) was treated with CuI +7.6 mg,
39.9 mmol), P+fur)3 +5.4 mg, 23.3 mmol) and [Pd2+dba)3] +12.0 mg, 13.1 mmol), stirred for 1 h, warmed to 808,
stirred for 40 min, and evaporated. A soln. of the residue in CHCl3 +20 ml) was washed with 2% aq. Na2+EDTA)
soln. +2 Â 10 ml), dried +Na2SO4), and evaporated. FC +20 g of silica gel; hexane/acetone 7:4) gave 14a
+362.6 mg, 89%). Light yellow solid. Rf +hexane/acetone 7:4) 0.48. M.p. 1168. [a]2D5 ˆ À1.5 +c ˆ 1.02, CHCl3).
UV +CHCl3): 292.0 +39000), 250.0 +29000). IR +CHCl3): 3407w, 3006m, 2959m, 2913w, 2878w, 2230w, 1710m,
1610s, 1585s, 1511w, 1458s, 1422w, 1385m, 1330m, 1248m, 1157w, 1090s, 1004w, 972w, 869w, 818w. 1H-NMR
+300 MHz, CDCl3): see Table 5; additionally, 0.49 +q, J ˆ 8.0, +MeCH2)3Si); 0.725 +q, J ˆ 8.3), 0.730 +q, J ˆ 7.8 )
++MeCH2)3Si); 0.86, 0.99 +2t, J ˆ 8.0, 2 +MeCH2)3Si); 1.39, 1.43, 1.61, 1.65 +4s, 2 Me2C); 7.42 ± 7.53 +m, 4 ar-
om. H); 7.53 ± 7.62 +m, 2 arom. H); 7.98 +d, J ˆ 7.4, 4 arom. H); 9.12, 9.22 +2 br. s, 2 NH). 13C-NMR +75 MHz,
CDCl3): 164.9 +s, 2 CˆO); 153.7, 153.0 +2d, C+2/I), C+2/II)); 151.3, 150.6 +2s, C+6/I), C+6/II)); 150.1, 150.0 +2s,
C+4/I), C+4/II)); 142.6 +d, C+8/I)); 136.7 +s, C+8/II)); 133.9 +2s); 133.0 +2d); 129.0 +4d); 128.1 +4d); 123.7 +s, C+5/
I)); 123.0 +s, C+5/II)); 114.9, 114.3 +2s, 2 Me2C); 96.0 +s, C+6'/I)); 91.2, 90.9 +2d, C+1'/I), C+1'/II)); 89.2, 88.4 +2d,
C+4'/I), C+4'/II)); 84.3, 83.3 +2d, C+2'/I), C+2'/II)); 82.3, 81.6 +2d, C+3'/I), C+3'/II)); 74.6 +s, C+7'/I)); 63.6
+d, C+5'/I)); 63.0 +t, C+5'/II)); 27.20, 27.18, 25.46, 25.40 +4q, 2 Me2C); 6.7, 6.6 +2q, 2 +MeCH2)3Si); 4.7, 4.2

2988
Helvetica Chimica Acta ± Vol. 83 +2000)
Table 5. Selected 1H-NMR Chemical Shifts [ppm] and Coupling Constants [Hz] of the Silyl Ethers 14a ± d, 15b ±
d, and 16 in CDCl3 and of the Diols 17 and 19 in 9D6)DMSO Solution
14a
8.81b)
14b
8.29
14ca) 14d
15b
8.29
15ca) 15da) 16a)
17
8.12b)
19
8.13b)
HÀC+2/I)
HÀC+8/I)
HÀC+1'/I)
HÀC+2'/I)
HÀC+3'/I)
HÀC+4'/I)
HÀC+5'a/I)
HÀC+5'b/I)
HÀC+2/II)
HÀC+1'/II)
HÀC+2'/II)
HÀC+3'/II)
HÀC+4'/II)
HÀC+5'a/II)
HÀC+5'b/II)
J+1',2'/I)
8.83
8.28
6.43
5.50
5.26
4.53
4.96
±
8.28
8.81
8.27
6.29
5.56
5.17
4.56
2.99
3.13
8.40
6.25
5.62
5.14
4.29
3.64
3.74
2.2
8.28
8.17
6.23
5.64
5.11
4.60
2.92
3.07
8.34
6.27
5.66
5.16
4.31
3.68
3.74
1.9
8.46b)
8.29b)
6.21
5.52
4.91
4.78
4.86
±
8.25
6.255
5.42
5.25
4.50
4.96
±
8.04
6.21
5.41
5.23
4.46
4.95
±
8.79
6.27
5.68
5.15
4.29
3.66
3.77
1.8
8.15
6.42
5.63
5.25
4.51
4.79
±
8.10
6.32
5.48
5.17
4.53
2.96
3.14
8.78
6.15
5.68
5.15
4.31
3.65
3.76
1.8
8.38
6.13
5.32
5.12
4.36
4.90d)
±
8.29
6.20
5.36
5.14
4.24
4.80c)
±
8.79b)
6.245
5.69
5.15
4.29
3.65
3.77
2.0
8.36
6.19
5.63
5.12
4.25
3.65
3.75
2.1
8.34
6.21
5.64
5.14
4.27
3.67
3.78
8.32b)
6.27
5.73
5.20
4.32
3.67
3.79
1.8
8.19b)
6.23
5.49
4.98
4.09
3.46d)
3.55d)
3.3
8.15b)
6.02
5.40
4.92
4.10
3.42c)
3.52c)
2.5
< 1
J+2',3'/I)
J+3',4'/I)
J+4',5'a/I)
J+4',5'b/I)
J+5'a,5'b/I)
J+1',2'/II)
J+2',3'/II)
J+3',4'/II)
6.5
2.8
5.8
±
±
2.5
6.5
3.5
6.5
2.8
6.5
±
±
2.0
6.5
3.5
6.3
2.9
6.2
±
±
1.8
6.3
3.4
6.5
2.2
7.8
±
6.5
3.5
6.3
6.3
17.7
2.3
6.5
3.5
6.5
6.3
3.6
5.7
5.7
17.4
1.8
6.3
3.4
6.6
6.3
3.0
7.3
5.6
17.4
1.7
6.3
3.3
6.8
6.0
< 1
3.5
±
±
1.5
6.5
3.3
6.8
6.8
10.5
6.0
2.5
5.5
±
±
3.0
6.5
3.3
6.2
2.0
6.5
±
±
3.3
6.0
2.8
±
1.5
6.5
3.2
6.7
6.7
10.5
J+4',5'a/II)
J+4',5'b/II)
J+5'a,5'b/II)
6.5
6.5
10.5
6.5
6.5
10.5
6.6
6.6
10.6
5.5
5.5
13.5
5.5
5.5
12.5
6.5
10.5
6.6
10.6
6.8
10.3
a) Assignment based on a DQFCOSY.GRASP spectrum. b) Assignment may be interchanged. c) Line
broadening due to coupling with OH group. d) J+5'a/I,OH) ˆ 6.8, J+5'a/II,OH) ˆ J+5'b/II,OH) ꢃ 6.0 Hz.
‡
+2t, 2 +MeCH2)3Si). FAB-MS: 1073 +[M ‡ 1] ). Anal. calc. for C54H68N10Si2 +1073.36): C 60.43, H 6.39, N 13.05;
found: C 60.43, H 6.45, N 12.96.
N6-Benzoyl-2',3'-O-isopropylidene-5'-O-9triethylsilyl)adenosin-8-yl-98 ! 7')-9-[6,7-dideoxy-2,3-O-isopro-
pylidene-5-O-9triethylsilyl)-b-d-allo-hept-6-ynofuranosyl]adenine +14b). At 258, a soln. of 13 +51.1 mg,
79.0 mmol) and 6 +35.2 mg, 79.0 mmol) in dry Et3N +2.6 ml) was treated with CuI +1.5 mg, 7.9 mmol), P+fur)3
+1.1 mg, 4.7 mmol) and [Pd2+dba)3] +2.8 mg, 3.1 mmol), stirred for 2 h, and evaporated. A soln. of the residue in
CHCl3 +12 ml) was washed with 2% aq. Na2+EDTA) soln. +2 Â 5.0 ml), dried +Na2SO4), and evaporated. FC
+4.0 g of silica gel; CHCl3/acetone 7:4) gave 14b +63.2 mg, 83%). White solid. Rf +CHCl3/acetone 7:4) 0.46. M.p.
1138. [a]2D5 ˆ ‡7.3 +c ˆ 1.01, CHCl3). UV +CHCl3): 317.0 +23000), 305.0 +32000), 253.0 +29000). IR +CHCl3):
3412w, 2997m, 2958m, 2914w, 2878m, 2230w, 1710m, 1631s, 1608s, 1586s, 1510w, 1469s, 1423m, 1384m, 1376m,
1330m, 1266m, 1248m, 1157m, 1091s, 1004m, 972m, 870m, 818w. 1H-NMR +300 MHz, CDCl3): see Table 5;
additionally, 0.49 +q, J ˆ 8.0, +MeCH2)3Si); 0.717 +q, J ˆ 8.3), 0.720 +q, J ˆ 7.6) ++MeCH2)3Si); 0.87, 0.99 +2t, J ˆ
8.0, 2 +MeCH2)3Si); 1.39, 1.42, 1.60, 1.63 +4s, 2 Me2C); 5.95 +br. s, NH2); 7.47 +t, J ˆ 7.8, 2 arom. H); 7.57 +br. t, J ˆ
7.8, 1 arom. H); 7.97 +d, J ˆ 7.8, 2 arom. H); 9.37 +br. s, NH). 13C-NMR +75 MHz, CDCl3): 164.8 +s, CˆO); 155.6
+s, C+6/I); 153.5, 153.1 +2d, C+2/I), C+2/II)); 150.3 +s, C+6/II)); 149.7, 149.2 +2s, C+4/I), C+4/II)); 140.1 +d, C+8/
I)); 136.5 +s, C+8/II)); 133.8 +s); 132.7 +d); 128.8 +2d); 127.9 +2d); 122.5, 120.1 +2s, C+5/I), C+5/II)); 114.5, 114.1
+2s, 2 Me2C); 96.3 +s C+6'/I)); 91.0, 90.7 +2d, C+1'/I), C+1'/II)); 89.2, 88.2 +2d, C+4'/I), C+4'/II)); 84.1, 83.2
+2d, C+2'/I), C+2'/II)); 82.2, 81.7 +2d, C+3'/I), C+3'/II)); 74.2 +s, C+7'/I)); 63.5 +d, C+5'/I)); 62.9 +t, C+5'/II)); 27.15,
‡
27.10, 25.5, 25.4 +4q, 2 Me2C); 6.7, 6.6 +2q, 2 +MeCH2)3Si); 4.7, 4.2 +2t, 2 +MeCH2)3Si). FAB-MS: 970 +[M ‡ 1] ).
Anal. calc. for C47H64N10O9Si2 +969.26): C 58.24, H 6.66, N 14.07; found: C 57.81, H 6.62, N 13.98.

Helvetica Chimica Acta ± Vol. 83 +2000)
2989
2',3'-O-Isopropylidene-5'-O-9triethylsilyl)adenosin-8-yl-98 ! 7')-N6-benzoyl-9-[6,7-dideoxy-2,3-O-isopropyl-
idene-5-O-9triethylsilyl)-b-d-allo-hept-6-ynofuranosyl]adenine +14c). According to the preparation of 14a,
treatment of 3 +74.5 mg, 0.136 mmol) with 5 +74.8 mg, 0.136 mmol) gave 14c +119.7 mg, 91%). White solid. Rf
+CHCl3/acetone 3 :2) 0.53. M.p. 1218. [a]2D5 ˆ ‡8.5 +c ˆ 1.00, CHCl3). UV +CHCl3): 284.0 +32000), 248.0 +13000).
IR +CHCl3): 3410w, 3208w, 3008m, 2959m, 2913w, 2878m, 2230w, 1709m, 1631s, 1613s, 1586s, 1506w, 1480m,
1456s, 1414w, 1384m, 1376m, 1328m, 1295m, 1248s, 1157m, 1087s, 1005m, 971w, 928w, 868m. 1H-NMR
+500 MHz, CDCl3, assignment based on a DFQCOSY.GRASP spectrum): see Table 5; additionally, 0.49 +q, J ˆ
7.9, +MeCH2)3Si); 0.741 +q, J ˆ 8.2), 0.748 +q, J ˆ 7.8) ++MeCH2)3Si); 0.86, 1.01 +2t, J ˆ 7.9, 2 +MeCH2)3Si); 1.38,
1.44, 1.59, 1.66 +4s, 2 Me2C); 6.63 ± 6.80 +br. s, NH2); 7.50 +t, J ˆ 7.4, 2 arom. H); 7.59 +t, J ˆ 7.5, 1 arom. H); 8.00
+d, J ˆ 7.3, 2 arom. H); 9.09 +br. s, NH). 13C-NMR +75 MHz, CDCl3): 164.8 +s, CˆO); 156.1 +s, C+6/II)); 154.2,
153.0 +2d, C+2/I), C+2/II)); 151.1 +s, C+6/I)); 150.1, 148.9 +2s, C+4/I), C+4/II)); 143.5 +d, C+8/I)); 133.9 +2s, C+8/
II), 1 arom. C); 133.0 +d); 129.1 +2d); 128.0 +2d); 123.7 +s, C+5/I)); 119.8 +s, C+5/II)); 114.8, 114.1 +2s, 2 Me2C);
94.8 +s, C+6'/I)); 91.4, 90.7 +2d, C+1'/I), C+1'/II)); 90.1, 88.6 +2d, C+4'/I), C+4'/II)); 84.3, 83.6 +2d, C+2'/I), C+2'/
II)); 82.6, 82.4 +2d, C+3'/I), C+3'/II)); 74.6 +s, C+7'/I)); 63.7 +d, C+5'/I)); 63.2 +t, C+5'/II)); 27.15, 27.10, 25.5, 25.4
‡
+4q, 2 Me2C); 6.7, 6.6 +2q, 2 +MeCH2)3Si); 4.8, 4.3 +2t, 2 +MeCH2)3)Si). FAB-MS: 969 +[M ‡ 1] ).
2',3'-O-Isopropylidene-5'-O-9triethylsilyl)adenosin-8-yl-98 ! 7')-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-
9triethylsilyl)-b-d-allo-hept-6-ynofuranosyl]adenine +14d). According to the preparation of 14b, treatment of 3
+119.5 mg, 0.218 mmol) with 6 +97.2 mg, 0.218 mmol) gave 14d +158.7 mg, 84%). White solid. Rf +CHCl3/EtOH
10 :1) 0.52. M.p. 1198. [a]2D5 ˆ ‡59.2 +c ˆ 1.06, CHCl3). UV +CHCl3): 295.0 +20000), 266.0 +21000). IR +CHCl3):
3412w, 3206w, 2993m, 2958m, 2914w, 2878m, 2230w, 1633s, 1588m, 1472w, 1415w, 1375w, 1328m, 1295w, 1248w,
1157w, 1090s, 1005w, 972w, 870w, 818w, 649w, 574w, 516w, 507w. 1H-NMR +300 MHz, CDCl3): see Table 5;
additionally, 0.50 +q, J ˆ 8.1, +MeCH2)3Si); 0.717 +q, J ˆ 8.3), 0.720 +q, J ˆ 7.6) ++MeCH2)3Si); 0.88, 0.99 +2t, J ˆ
8.1, 2 +MeCH2)3Si); 1.38, 1.44, 1.59, 1.65 +4s, 2 Me2C); 6.34 +br. s, NH2); 6.80 ± 7.22 +br. s, NH2). 13C-NMR
+75 MHz, CDCl3): 156.0, 155.9 +2s, C+6/I), C+6/II)); 153.8, 153.0 +2d, C+2/I), C+2/II)); 148.9, 148.7 +2s, C+4/I),
C+4/II)); 140.5 +s, C+8/II)); 133.7 +d, C+8/I)); 120.1, 119.5 +2s, C+5/I), C+5/II)); 114.2, 113.8 +2s, 2 Me2C); 95.1
+s, C+6'/I)); 91.5, 90.5 +2d, C+1'/I), C+1'/II)); 90.0, 88.4 +2d, C+4'/I), C+4'/II)); 84.0, 83.5 +2d, C+2'/I), C+2'/II));
82.6, 82.5 +2d, C+3'/I), C+3'/II)); 74.3 +s, C+7'/I)); 63.5 +d, C+5'/I)); 63.1 +t, C+5'/II)); 27.1, 27.0, 25.4, 25.3
‡
+4q, 2 Me2C); 6.7, 6.6 +2q, 2 +MeCH2)3Si); 4.8, 4.2 +2t, 2 +MeCH2)3Si). FAB-MS: 865 +[M ‡ 1] ). Anal. calc. for
C40H60N10O8Si2 +865.15): C 55.53, H 6.99, N 16.19; found: C 55.29, H 6.93, N 15.99.
N6-Benzoyl-2',3'-O-isopropylidene-5'-O-9triethylsilyl)adenosin-8-yl-98 ! 7')-9-95,6,7-trideoxy-2,3-O-isopro-
pylidene-b-d-ribo-hept-6-ynofuranosyl)adenine +15b). According to the preparation of 14b, treatment of 13
+182.3 mg, 0.280 mmol) with 12 +88.2 mg, 0.28 mmol; 5.5 h at r.t.) gave 15b +141.5 mg, 60%). Light yellow solid.
Rf +CHCl3/acetone 2 :3) 0.52. M.p. 1288. [a]D25 ˆ À44.2 +c ˆ 1.00, CHCl3). UV +CHCl3): 304.0 +29000), 252.0
+28000). IR +CHCl3): 3412w, 2997m, 2958m, 2877w, 2245w, 1710m, 1632s, 1609s, 1586s, 1151w, 1470s, 1424m,
1384m, 1376m, 1330s, 1248s, 1157m, 1089s, 1004m, 871m. 1H-NMR +300 MHz, CDCl3): see Table 5; additionally,
0.49 +q, J ˆ 8.0, +MeCH2)3Si); 0.86 +t, J ˆ 8.0, +MeCH2)3Si); 1.39 +br. s, 2 Me); 1.59, 1.63 +2s, 2 Me2C); 6.08 +br. s,
NH2); 7.46 +t, J ˆ 7.8, 2 arom. H); 7.56 +t, J ˆ 7.8, 1 arom. H); 7.99 +d, J ˆ 7.8, 2 arom. H); 9.49 +br. s, NH).
13C-NMR +75 MHz, CDCl3): 165.0 +s, CˆO); 155.6 +s, C+6/I)); 153.3, 153.1 +2d, C+2/I), C+2/II)); 150.3 +s, C+6/
II)); 149.5, 149.1 +2s, C+4/I), C+4/II)); 140.2 +d, C+8/I)); 137.1 +s, C+8/II)); 133.8 +s); 132.7 +d); 128.7 +2d); 128.0
+2d); 122.5, 120.2 +2s, C+5/I), C+5/II)); 114.8, 114.1 +2s, 2 Me2C); 95.4 +s, C+6'/I)); 90.6, 90.5 +2d, C+1'/I), C+1'/
II)); 88.4, 84.4 +2d, C+4'/I), C+4'/II)); 84.3, 83.6 +2d, C+2'/I), C+2'/II)); 83.3, 82.2 +2d, C+3'/I), C+3'/II)); 71.3
+s, C+7'/I)); 62.9 +t, C+5'/II)); 27.2, 27.1, 25.41, 25.37 +4q, 2 Me2C); 24.4 +t, C+5'/I)); 6.6 +q, +MeCH2)3Si); 4.2
‡
+t, +MeCH2)3Si). FAB-MS: 839 +[M ‡ 1] ).
2',3'-O-Isopropylidene-5'-O-9triethylsilyl)adenosine-8-yl-98 ! 7')-N6-benzoyl-9-92,3-O-isopropylidene-
5,6,7-trideoxy-b-d-ribo-hept-6-ynofuranosyl)adenine +15c). At 258, a soln. of 3 +80.1 mg, 0.146 mmol) and 11
+61.4 mg, 0.146 mmol) in dry PhMe +2.1 ml) and dry Et3N +2.1 ml) was treated with CuI +3.0 mg, 15.8 mmol),
P+fur)3 +2.0 mg, 8.6 mmol) and [Pd2+dba)3] +5.2 mg, 5.7 mmol), stirred for 1 h, warmed to 808, stirred for 1 h, and
evaporated. A soln. of the residue in CHCl3 +16 ml) was washed with 2% aq. Na2+EDTA) soln. +2 Â 4.5 ml),
dried +Na2SO4), and evaporated. FC +7.0 g of silica gel; CHCl3/acetone 1 :1) gave 15c +90.9 mg, 71%). Light
yellow solid. Rf +CHCl3/EtOH 11:1) 0.43. M.p. 1388. [a]2D5 ˆ À39.4 +c ˆ 1.03, CHCl3). UV +CHCl3): 283.0
+29000). IR +CHCl3): 3411w, 2997m, 2957w, 2877w, 2245w, 1709m, 1631s, 1612s, 1586m, 1480m, 1456s, 1415w,
1384m, 1376m, 1328m, 1294m, 1248m, 1157w, 1086s, 1004w, 931w, 871w. 1H-NMR +500 MHz, CDCl3, assignment
based on a DQFCOSY.GRASP spectrum): see Table 5; additionally, 0.49 +q, J ˆ 7.9, +MeCH2)3Si); 0.86 +t, J ˆ
7.9, +MeCH2)3Si); 1.38, 1.42, 1.59, 1.65 +4s, 2 Me2C); 6.60 ± 6.80 +br. s, NH2); 7.51 +t, J ˆ 7.6, 2 arom. H); 7.60
+t, J ˆ 7.4, 1 arom. H); 7.99 +d, J ˆ 7.4, 2 arom. H); 9.07 +br. s, NH). 13C-NMR +75 MHz, CDCl3): 165.1
+s, CˆO); 155.9 +s, C+6/II)); 154.1, 153.0 +2d, C+2/I), C+2/II)); 151.4 +s, C+6/I)); 150.1, 148.9 +2s, C+4/I), C+4/II));

2990
Helvetica Chimica Acta ± Vol. 83 +2000)
143.2 +d, C+8/I)); 134.6 +s, C+8/II)); 133.9 +s); 133.0 +d); 129.0 +2d); 128.1 +2d); 123.9 +s, C+5/I)); 119.6 +s, C+5/
II)); 115.3, 114.0 +2s, 2 Me2C); 93.4 +s, C+6'/I)); 90.8, 90.6 +2d, C+1'/I), C+1'/II)); 88.7, 85.0 +2d, C+4'/I), C+4'/II));
84.9, 83.7 +2d, C+2'/I), C+2'/II)); 83.6, 82.6 +2d, C+3'/I), C+3'/II)); 71.8 +s, C+7'/I)); 63.1 +t, C+5'/II)); 27.2
+q, 2 Me), 25.5, 25.4 +2q) +2 Me2C); 24.4 +t, C+5'/I)); 6.6 +q, +MeCH2)3Si); 4.2 +t, +MeCH2)3Si). FAB-MS: 839
‡
+[M ‡ 1] ).
2',3'-O-Isopropylidene-5'-O-9triethylsilyl)adenosin-8-yl-98 ! 7')-9-95,6,7-trideoxy-2,3-O-isopropylidene-b-
d-ribo-hept-6-ynofuranosyl)adenine +15d). According to the preparation of 14b, treatment of 3 +49.0 mg,
89.5 mmol) with 12 +28.2 mg, 89.4 mmol; 5 h at r.t.) gave 15d +51.0 mg, 78%). Light yellow solid. Rf +CHCl3/
EtOH 6 :1) 0.52. M.p. 1338. [a]2D5 ˆ ‡39.5 +c ˆ 1.03, CHCl3). UV +CHCl3): 293.0 +22000), 266.0 +24000). IR
+CHCl3): 3412m, 3328w, 3201w, 2993m, 2958m, 2877w, 2245w, 1632s, 1588m, 1473m, 1416w, 1376m, 1329m,
1
1295m, 1248m, 1157m, 1086s, 1005w, 872m. H-NMR +300 MHz, CDCl3, assignment based on a DQFCOSY.-
GRASP spectrum): see Table 5; additionally, 0.50 +q, J ˆ 8.0, +MeCH2)3Si); 0.87 +t, J ˆ 7.9, +MeCH2)3Si); 1.39,
1.42, 1.60, 1.64 +4s, 2 Me2C); 6.35 ± 6.50, 6.55 ± 6.80 +2 br. s, 2 NH2). 13C-NMR +75 MHz, CDCl3): 156.0, 155.7
+2s, C+6/I), C+6/II)); 153.7, 153.1 +2d, C+2/I), C+2/II)); 149.1, 148.7 +2s, C+4/I), C+4/II)); 140.0 +d, C+8/I)); 134.4
+s, C+8/II)); 120.2, 119.4 +2s, C+5/I), C+5/II)); 114.6, 113.8 +2s, 2 Me2C); 93.5 +s, C+6'/I)); 91.2, 90.4 +2d, C+1'/I),
C+1'/II)); 88.5, 85.0 +2d, C+4'/I), C+4'/II)); 84.3, 83.8 +2d, C+2'/I), C+2'/II)); 83.5, 82.5 +2d, C+3'/I), C+3'/II)); 71.6
+s, C+7'/I)); 63.0 +t, C+5'/II)); 27.2, 27.0 +2q), 25.4 +q, 2 Me) +2 Me2C); 24.6 +t, C+5'/I)); 6.6 +q, +MeCH2)3Si); 4.2
‡
+t, +MeCH2)3Si). FAB-MS: 735 +[M ‡ 1] ).
2',3'-O-Isopropylidene-5'-O-9triethylsilyl)adenosin-8-yl-98 ! 7')-9-[6,7-dideoxy-2,3-O-isopropylidene-5-O-
9triethylsilyl)-a-l-talo-hept-6-ynofuranosyl]adenine +16). According to the preparation of 14b, treatment of 3
+170.9 mg, 0.312 mmol) with 8 +139.1 mg, 0.321 mmol) gave 16 +206.4 mg, 76%). White solid. Rf +CHCl3/EtOH
10 :1) 0.44. M.p. 1228. [a]2D5 ˆ ‡143.6 +c ˆ 1.00, CHCl3). UV +CHCl3): 296.0 +21000), 266.0 +22000). IR +CHCl3):
3467w, 3411m, 3338w, 3177w, 2993m, 2958s, 2913m, 2878m, 1633s, 1596s, 1472m, 1416m, 1384m, 1376m, 1328s,
1296m, 1248m, 1157m, 1130s, 1086s, 1005m, 912w, 868m, 824m. 1H-NMR +300 MHz, CDCl3, assignment based
on a DQFCOSY.GRASP spectrum): see Table 5; additionally, 0.45, 0.49 +2q, J ˆ 7.8, 2 +MeCH2)3Si); 0.77, 0.87
+2t, J ˆ 7.9, 2 +MeCH2)3Si); 1.41, 1.45, 1.61, 1.65 +4s, 2 Me2C); 7.90 ± 8.16 +br. s, 2 NH2). 13C-NMR +75 MHz,
CDCl3): 156.2, 156.1 +2s, C+6/I), C+6/II)); 154.0, 152.8 +2d, C+2/I), C+2/II)); 148.9, 148.8 +2s, C+4/I), C+4/II));
139.2 +d, C+8/I)); 133.5 +s, C+8/II)); 119.9, 119.8 +2s, C+5/I), C+5/II)); 113.9, 113.8 +2s, 2 Me2C); 94.4 +s, C+6'/I));
93.6, 90.7 +2d, C+1'/I), C+1'/I)); 89.8, 88.7 +2d, C+4'/I), C+4'/II)); 85.5, 83.6 +2d, C+2'/I), C+2'/II)); 82.6, 82.3
+2d, C+3'/I), C+3'/II)); 75.5 +s, C+7'/I)); 64.4 +d, C+5'/I)); 63.1 +t, C+5'/II)); 27.2, 27.0, 25.4, 25.3 +4q, 2 Me2C); 6.6,
‡
6.5 +2q, 2 +MeCH2)3Si); 4.2, 4.1 +2t, 2 +MeCH2)3Si). FAB-MS: 865 +[M ‡ 1] ).
2',3'-O-Isopropylideneadenosine-8-yl-98 ! 7')-9-96,7-dideoxy-2,3-O-isopropylidene-a-l-talo-hept-6-ynofur-
anosyl)adenine +17). At 258, a soln. of 16 +179.6 mg, 0.230 mmol) in 50% aq. THF +3.6 ml) was treated with
AcOH +3.6 ml), stirred for 6.5 h, evaporated, and co-evaporated several times with PhMe. The residue was
suspended in MeOH +2.0 ml), treated with SiO2 +765 mg), evaporated, and the residue charged on a silica gel
column. FC +12 g of silica gel; CHCl3/MeOH 7:1) gave 17 +128.8 mg, 97%). Light yellow solid. Rf +CHCl3/
MeOH 7:1) 0.44. M.p. 1668 +dec.). [a]2D5 ˆ À62.3 +c ˆ 0.82, DMSO). UV +DMSO): 302.0 +19000), 268.0
+20000). IR +KBr): 3338s, 3188s, 2987m, 2936m, 2210w, 1646s, 1600s, 1577s, 1479m, 1425m, 1376s, 1330s, 1300m,
1269m, 1215s, 1156m, 1081s, 921w, 850m, 798m. 1H-NMR +300 MHz, +D6)DMSO): see Table 5; additionally,
1.26, 1.34, 1.49, 1.57 +4s, 2 Me2C); 3.40 ± 3.60 +m, partially hidden by HDO signal, addn. of D2O ! 3.46/3.55,
2dd, J ˆ 13.5, 5.5, 2 HÀC+5'/II)); 4.90 +t, J ꢃ 6.2, addn. of D2O ! d, J ˆ 5.5, HÀC+5'/I)); 5.23 +t, J ꢃ 6.0,
exchanged with D2O, HOÀC+5'/II)); 6.73 +d, J ˆ 6.8, exchanged with D2O, HOÀC+5'/I)); 7.36 +br. s, exchanged
with D2O, NH2); 7.61 +br. s, exchanged with D2O, NH2). 13C-NMR +75 MHz, +D6)DMSO): 156.0, 155.9 +2s, C+6/
I), C+6/II)); 153.7, 152.5 +2d, C+2/I), C+2/II)); 148.5, 148.1 +2s, C+4/I), C+4/II)); 139.7 +d, C+8/I)); 132.1 +s, C+8/
II)); 119.0, 118.8 +2s, C+5/I), C+5/II)); 113.4, 113.2 +2s, 2 Me2C); 94.7 +s, C+6'/I)); 89.8, 89.5 +2d, C+1'/I), C+1'/
II)); 87.6, 86.6 +2d, C+4'/I), C+4'/II)); 83.1, 82.0 +2d, C+2'/I), C+2'/II)); 81.2, 81.1 +2d, C+3'/I), C+3'/II)); 73.5
‡
+s, C+7'/I)); 62.2 +d, C+5'/I)); 61.5 +t, C+5'/II)); 27.0, 26.9, 25.1, 25.0 +4q, 2 Me2C). FAB-MS: 637 +[M ‡ 1] ).
Anal. calc. for C28H32N10O8 ´ 0.5 H2O +645.63): C 52.09, H 5.15, N 21.69; found: C 52.25, H 5.20, N 21.74.
Adenosin-8-yl-98 ! 7')-9-96,7-dideoxy-a-l-talo-hept-6-ynofuranosyl)adenine +18). At 258, a soln. of 17
+89.0 mg, 0.14 mmol) in 80% aq. HCO2H +4.5 ml) was stirred for 20 h, evaporated, and co-evaporated several
times with PhMe. The residue was suspended in MeOH +3.0 ml), treated with reversed-phase SiO2 +130 mg),
evaporated, and the residue charged on a silica gel column. FC +4.0 g of reversed phase SiO2; MeOH/H2O 4 :5)
gave 18 +71.8 mg, 92%). White solid. Rf +BuOH/EtOH/H2O 4 :1 :1) 0.46. M.p. 2128 +dec.; 50% aq. MeOH).
[a]2D5 ˆ À5.0 +c ˆ 0.73, DMSO). UV +DMSO): 301.0 +19000), 269.0 +21000). IR +KBr): 3380s, 2932m, 2245w,
1652s, 1601s, 1578m, 1476m, 1422m, 1372m, 1331s, 1306s, 1273m, 1260m, 1212m, 1162w, 1125s, 1061s, 1034s,
984m, 903w, 846w, 796m. 1H-NMR +300 MHz, +D6)DMSO/D2O): see Table 3. 13C-NMR +75 MHz, +D6)DMSO):

Helvetica Chimica Acta ± Vol. 83 +2000)
2991
156.1, 156.0 +2s, C+6/I), C+6/II)); 153.2, 152.3 +2d, C+2/I), C+2/II)); 148.8, 148.2 +2s, C+4/I), C+4/II)); 139.9
+d, C+8/I)); 133.0 +s, C+8/II)); 119.2, 119.1 +2s, C+5/I), C+5/II)); 95.4 +s, C+6'/I)); 89.2, 87.8 +2d, C+1'/I), C+1'/II));
87.5, 86.5 +2d, C+4'/I), C+4'/II)); 73.0, 72.9 +2d, C+2'/I), C+2'/II)); 71.5, 70.8 +2d, C+3'/I), C+3'/II)); 70.7 +s, C+7'/
‡
I)); 62.0 +d, C+5'/I)); 61.9 +t, C+5'/II)). FAB-MS: 557 +[M ‡ 1] ). Anal. calc. for C22H24N10O8 ´ 0.8 H2O +570.91):
C 46.28, H 4.52, N 24.53; found: C 46.54, H 4.64, N 24.33.
2',3'-O-Isopropylideneadenosin-8-yl-98 ! 7')-9-96,7-dideoxy-2,3-O-isopropylidene-b-d-allo-hept-6-ynofura-
nosyl)adenine +19). At 258, a soln. of 14d +175.6 mg, 0.230 mmol) in 50% aq. THF +3.5 ml) was treated with
AcOH +3.5 ml), stirred for 8 h, evaporated, and co-evaporated several times with PhMe. A suspension of the
residue in MeOH +2.0 ml) was treated with SiO2 +400 mg), evaporated, and the residue charged on a silica gel
column. FC +6.0 g of silica gel; CHCl3/MeOH 8 :1) gave 19 +105.5 mg, 82%). White solid. Rf +CHCl3/MeOH
8 :1) 0.38. M.p. 1678 +dec.). [a]2D5 ˆ ‡1.6 +c ˆ 1.07, DMSO). UV +DMSO): 303.0 +19000), 271.0 +19000). IR
+KBr): 3333s, 3192s, 2987m, 2937m, 2210w, 1651s, 1599s, 1576s, 1479m, 1456m, 1420w, 1376s, 1329s, 1301m,
1268m, 1215s, 1156m, 1082s, 970w, 852m. 1H-NMR +300 MHz, +D6)DMSO): see Table 5; additionally, 1.26, 1.32,
1.47, 1.53 +4s, 2 Me2C); 5.15 +br. s, exchanged with D2O, HOÀC+5'/II)); 6.65 +br. s, exchanged with D2O,
HOÀC+5'/I)); 7.35 +br. s, exchanged with D2O, NH2); 7.59 +br. s, exchanged with D2O, NH2). 13C-NMR
+75 MHz, +D6)DMSO): 156.4, 156.3 +2s, C+6/I), C+6/II)); 154.0, 152.9 +2d, C+2/I), C+2/II)); 148.8, 148.4 +2s, C+4/
I), C+4/II)); 140.1 +d, C+8/I)); 132.3 +s, C+8/II)); 119.2, 119.0 +2s, C+5/I), C+5/II)); 113.5 +s, 2 Me2C); 95.2
+s, C+6'/I)); 89.9, 89.8 +2d, C+1'/I), C+1'/II)); 88.0, 86.6 +2d, C+4'/I), C+4'/II)); 83.4, 82.1 +2d, C+2'/I), C+2'/II));
81.5 +d, C+3'/I), C+3'/II)); 73.6 +s, C+7'/I)); 61.8 +d, C+5'/I)); 61.6 +t, C+5'/II)); 27.0, 26.9, 25.18, 25.14 +4q,
‡
2 Me2C). FAB-MS: 637 +[M ‡ 1] ). Anal. calc. for C28H32N10O8 +636.62): C 52.83, H 5.07, N 22.00; found:
C 52.88, H 5.26, N 22.07.
Adenosin-8-yl-98 ! 7')-9-96,7-dideoxy-b-d-allo-hept-6-ynofuranosyl)adenine +20). At 258, a soln. of 19
+117.1 mg, 0.184 mmol) in 80% aq. HCO2H +3.5 ml) was stirred for 14 h, evaporated, and co-evaporated several
times with PhMe. A suspension of the residue in MeOH +4.0 ml) was treated with reversed-phase SiO2
+200 mg), evaporated, and the residue charged on a silica gel column. FC +5.0 g of reversed phase SiO2; MeOH/
H2O 1:1) gave 20 +89.0 mg, 87%). White solid. Rf +BuOH/EtOH/H2O 4 :1 :1) 0.50. M.p. 1688 +dec.; 50% aq.
MeOH). [a]2D5 ˆ À84.4 +c ˆ 1.05, DMSO). UV +DMSO): 301.0 +17000), 271.0 +17000). UV +H2O): 296 +20000),
264 +25000), 231 +27000), 209 +30000). IR +KBr): 3331s, 2921m, 1657s, 1604s, 1577m, 1483m, 1424m, 1332s,
1309m, 1253m, 1220m, 1084s, 1060s, 879w, 844w, 796m. 1H-NMR +300 MHz, +D6)DMSO/D2O): see Table 3.
13C-NMR +75 MHz, +D6)DMSO): 156.1, 156.0 +2s, C+6/I), C+6/II)); 153.3, 152.3 +2d, C+2/I), C+2/II)); 149.0,
148.2 +2s, C+4/I), C+4/II)); 139.9 +d, C+8/I)); 132.9 +s, C+8/II)); 119.1 +s, C+5/I), C+5/II)); 94.5 +s, C+6'/I)); 89.3,
87.5 +2d, C+1'/I), C+1'/II)); 87.4, 86.6 +2d, C+4'/I), C+4'/II)); 73.6, 72.9 +2d, C+2'/I), C+2'/II)); 71.6, 70.9 +2d, C+3'/
‡
I), C+3'/II)); 70.4 +s, C+7'/I)); 62.3 +d, C+5'/I)); 62.1 +t, C+5'/II)). FAB-MS: 557 +[M ‡ 1] ). Anal. calc. for
C22H24N10O8 ´ H2O +574.51): C 45.99, H 4.56, N 24.38; found: C 46.23, H 4.47, N 24.04.
REFERENCES
Â
[1] S. Eppacher, N. Solladie, B. Bernet, A. Vasella, Helv. Chim. Acta 2000, 83, 1311.
[2] H. Gunji, A. Vasella, Helv. Chim. Acta 2000, 83, 1331.
[3] K. Sonogashira, Y. Tohda, N. Hagihara, Tetrahedron Lett. 1975, 50, 4467.
[4] J. Tomasz, Nucleic Acid Chem. 1978, 2, 765.
[5] H. Hayakawa, K. Haraguchi, H. Tanaka, T. Miyasaka, Chem. Pharm. Bull. 1987, 35, 72.
[6] H. Hayakawa, H. Tanaka, K. Sasaki, K. Haraguchi, T. Saitoh, F. Takai, T. Miyasaka, J. Heterocycl. Chem.
1989, 26, 189.
[7] H. Gunji, A. Vasella, unpublished results.
[8] A. Matsuda, H. Kosaki, Y. Saitoh, Y. Yoshimura, N. Minakawa, H. Nakata, J. Med. Chem. 1998, 41, 2676.
[9] T. D. W. Claridge, ꢀ High-Resolution NMR Techniques in Organic Chemistryꢁ, in ꢀTetrahedron Organic
Chemistry Seriesꢁ, Eds. J. E. Baldwin, F. R. S. Williams, and M. Williams, Pergamon, Amsterdam, 1999,
Vol. 19, p. 142.
[10] R. Bürli, A. Vasella, Helv. Chim. Acta 1999, 82, 485.
[11] W. Höbold, R. Radeglia, D. Klose, J. Prakt. Chem. 1976, 318, 519.
[12] M. I. Al-Hassan, I. M. Al-Najjar, I. M. Al-Oraify, Magn. Reson. Chem. 1989, 27, 1112.
[13] G. C. Levy, D. M. White, J. D. Cargioli, J. Magn. Reson. 1972, 8, 280.
[14] S. Manfredini, P. G. Baraldi, R. Bazzanini, M. Marangoni, D. Simoni, J. Balzarini, E. De Clercq, J. Med.
Chem. 1995, 38, 199.

2992
Helvetica Chimica Acta ± Vol. 83 +2000)
[15] R. M. Moriarty, W. R. Epa, A. K. Awasthi, Tetrahedron Lett. 1990, 31, 5877.
[16] M. Alami, F. Ferri, G. Linstrumelle, Tetrahedron Lett. 1993, 34, 6403.
[17] C. Cai, A. Vasella, Helv. Chim. Acta 1995, 78, 2053.
[18] R. Bürli, A. Vasella, Helv. Chim. Acta 1997, 80, 1027.
[19] R. Bürli, A. Vasella, Helv. Chim. Acta 1997, 80, 2215.
[20] T. V. Bohner, R. Beaudegnies, A. Vasella, Helv. Chim. Acta 1999, 82, 143.
[21] T. V. Bohner, O. Becker, A. Vasella, Helv. Chim. Acta 1999, 82, 198.
[22] E. Pretsch, T. Clerc, J. Seibl, W. Simon, ꢀTabellen zur Strukturaufklärung organischer Verbindungen mit
spektroskopischen Methodenꢁ, Springer-Verlag, Berlin, 1990, p. C120.
[23] P. A. A. Klusener, J. C. Hanekamp, L. Brandsma, P. von Rague-Schleyer, J. Org. Chem. 1990, 55, 1311.
[24] Y. Komoda, Y. Isogai, K. Satoh, Chem. Pharm. Bull. 1983, 31, 2771.
[25] M. Liu, R. D. Farrant, J. M. Gillam, J. K. Nicholson, J. D. Lindon, J. Magn. Reson., Ser. B 1995, 109, 275.
[26] K. B. Punit, A. Vasella, unpublished results.
[27] T. Ueda, Y. Nomoto, A. Matsuda, Chem. Pharm. Bull. 1985, 33, 3263.
[28] M. Ikehara, S. Uesugi, K. Tomita, Nucleic Acid Chem. 1978, 2, 837.
[29] H. Rosemeyer, G. Toth, B. Golankiewicz, Z. Kazimierczuk, W. Bourgeois, U. Kretschmer, H. P. Muth, F.
Seela, J. Org. Chem. 1990, 55, 5784.
[30] L. Poppe, W. E. Hull, J. Retey, Helv. Chim. Acta 1993, 76, 2367.
[31] L. H. Koole, H. de Boer, J. W. de Haan, C. A. G. Haasnoot, P. van Dael, H. M. Buck, J. Chem. Soc., Chem.
Commun. 1986, 362.
[32] S. J. Angyal, J. C. Christofides, J. Chem. Soc., Perkin Trans. 2 1996, 1485.
[33] B. Bernet, A. Vasella, Helv. Chim. Acta 2000, 83, 995.
[34] T. P. Prakash, R. Kumar, K. N. Ganesh, Tetrahedron 1993, 49, 4035.
Received July 12, 2000