The isochroman- and 1,3-dihydroisobenzofuran-annulation on carbohydrate templates via [2+2+2]-cyclotrimerization and synthesis of some tricyclic nucleosides

Article abstract of DOI:10.1016/j.tet.2010.06.011

The synthesis of enantiopure tricyclic systems comprising isochroman or dihydroisobenzofuran units integrated with sugar templates has been documented. The alkyne cylotrimerization reaction has been employed with easily accessible sugar diynes for the key

Full text of DOI:10.1016/j.tet.2010.06.011

Tetrahedron 66 (2010) 6085e6096
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The isochroman- and 1,3-dihydroisobenzofuran-annulation on carbohydrate
templates via [2þ2þ2]-cyclotrimerization and synthesis of some tricyclic
nucleosides
*
Sharad B. Suryawanshi, Mangesh P. Dushing, Rajesh G. Gonnade, C.V. Ramana
National Chemical Laboratory (CSIR, India), Dr. Homi Bhabha Road, Pune 411008, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of enantiopure tricyclic systems comprising isochroman or dihydroisobenzofuran units
integrated with sugar templates has been documented. The alkyne cylotrimerization reaction has been
employed with easily accessible sugar diynes for the key bicyclic ring construction and thus a provision
to alter the functional groups on the newly formed aromatic rings. By selecting two representative tri-
merization products, we have synthesized the tricyclic nucleosides by simple synthetic manipulations.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 28 December 2009
Received in revised form 1 June 2010
Accepted 2 June 2010
Available online 10 June 2010
Keywords:
Dihydroisobenzopyran
Dihydroisobenzofuran
[2þ2þ2] Cyclotrimerization
Modified nucleosides
Vorbrüggen reaction
1. Introduction
CeC and/or Ceheteroatom bonds in a single step), complete atom
economy, and the availability of a wide range of catalysts that tol-
Access to collections of distinctive small molecules is an
important aspect in the realm of chemical genetics and for identi-
fying new therapeutic candidates.1 Several philosophies addressing
an ensemble of target molecules either in a forward or a backward
sense have been put forward with the ultimate aim of providing
flexible and diverse routes that have the potential of addressing
both the number and function with ease.2e4 Designing effective
routes to construct complex cyclic structures through transition
metal catalyzed reactions has been recognized as an attractive
strategy for delivering molecular diversity. In this respect, cyclo-
addition reactions are considered to be strategically useful, where
more than one carbonecarbon or carboneheteroatom bonds are
formed.5
We have been exploring the synthesis of a variety of homochiral
complex small molecules and also of diverse natural products by
employing the transition metal catalyzed reactions on easily avail-
able carbohydrate derivatives.6 In particular, we have been focusing
on the [2þ2þ2]-cyclotrimerization reaction and its application on
sugar templates.7e12 The [2þ2þ2]-cycloaddition reactions are
characterized by high synthetic efficiency (the formation of several
erate a myriad of protecting/functional groups.13 The utility of this
reaction is exemplified in the synthesis of a variety of complex
natural products consisting of aromatic rings.14
The scope of the cyclotrimerization reaction on sugar tem-
plates has been less explored and limited mainly to the synthesis
of C-aryl glycosides.9e11 An early example in this context is an
expedient synthesis of spirocyclic C-arylglycoside whose frame-
work is closely related to that of papulacandins by McDonald and
co-workers.9 Recently, Yamamoto and co-workers,10 and Kotora
and co-workers11 have independently reported
a
[2þ2þ2]-
cyclotrimerization approach for the synthesis of C-aryl ribosides
and C-aryldeoxyribosides, respectively. In this context, recently
we have documented a [2þ2þ2]-cyclotrimerization on a sugar
derived building block for constructing enantiomeric tricyclic
molecular skeletons consisting of isochroman units.8 One such
building block has been examined for its suitability in the prep-
aration of a tricyclic nucleoside by simple synthetic manipula-
tions. Considering the simplicity of the [2þ2þ2]-alkyne
cyclotrimerization combined with our interest in exploiting
simple carbohydrate building blocks for constructing useful mo-
lecular diversity, we intend to further explore this reaction for
building modified sugar (spiro)-annulated tricyclic homochiral
scaffolds; we also intend to explore the further utilization of
these scaffolds for the synthesis of tricyclic nucleosides.
* Corresponding author. Tel.: þ91 20 25902577; fax: þ91 20 25902629; e-mail
address: vr.chepuri@ncl.res.in (C.V. Ramana).
0040-4020/$ e see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2010.06.011

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S.B. Suryawanshi et al. / Tetrahedron 66 (2010) 6085e6096
The two structural units that we have intended to append on
catalyst ([RhCl(PPh3)3])21 were smooth and gave the corresponding
tricyclic compound 9 in 61% yield. The optimized conditions for this
reaction involve the heating of the diyne with the diol in toluene/
ethanol mixture (4:1) at 80 ꢀC. The spectral and analytical data of 9
were in accordance with the assigned structure. In the NOESY
spectrum, the observed cross peaks between C(4)eH and the aro-
sugar skeletons are the isochroman (3,4-dihydro-1H-benzo[c]
pyran)15 and 1,3-dihydroisobenzofuran,16 as these are present in
a wide range of natural products and also in commercially
available drugs (Fig. 1). We have selected the diynes 1 and 2e4
(Fig. 2) for
a linear isochromannulation and for the spiro-
isobenzofurannulation, respectively.17 Our proposed strategy is
shown in Figure 2.
matic ring proton at d 7.24 has helped in assigning the ratios of the
regiomeric compounds resulting from unsymmetric alkynes.
O
O
OR
O
OH
OH
O
O
O
1,3-Dihydro-
RO
OH
Isochroman
O
isobenzofuran
HO
O
HO
HO
OH
Papulacandins
O
Me
H
N
Me
NH
O
OH
O
O
N
R
R
R
O
O
O
O
O
O
HO
O
F
O
n
R''
O
O
n = 0,1
HO
R'
2
R = n-C7H15
Paecilospirone
Investigational
benzannulated nucleosides
Investigational
herbicide
NC
S-(+)-Citalopram
Figure 1. Natural products and/or (investigational) drugs with isochroman and 1,3-dihydroisobenzofuran rings.
O
HN
O
O
R''
O
R'
R
N
O
O
O
[2+2+2]-
Vorbrüggen
O
R'
+
O
R'
OH
glycosylation
Cyclotrimerization
O
O
R
O
O
R
H
N
O
PO
O
O
O
PO
R'
R
O
O
O
N
"
O
"
R''
+
R'
R
HO
OH
O
O
O
R'
R
O
TBSO
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
1
2
3
4
Figure 2. The intended [2þ2þ2]-cyclotrimerization approach for benzopyranannulation and isobenzofuranulation on sugar templates, glycosidation with pyrimidine base, and the
selected sugar diyne substrates 1e4.
2. Results and discussion
To illustrate the flexibility of our strategy, several mono- and
disubstituted alkynes were employed as the substrates (Table 1,
entries 2e10). With acetylene (entry 2) and dimethyl acetylene
dicarboxylate (entry 4) as the substrates, the cyclotrimerization
reaction proceeded effectively at 80 ꢀC in a sealed tube to afford 10
and 12 in 65% and 45% yields, respectively. Interestingly, the
reaction of 1 with dimethyl acetylene dicarboxylate did not proceed
at different temperatures under atmospheric pressure. Next steri-
cally crowded alkynes such as dodec-6-yne (entry 5), bis-(trime-
thylsilyl)acetylene (entry 6) and diphenyl acetylene (entry 7) are
employed for the trimerization reaction with the diyne 1. The
reactions are sluggish and no identifiable products could be
Scheme 1 describes the synthesis of the key diynes 1e4. The
diyne 1 was prepared from the known diol 518 in 78% overall yield
through sodium metaperiodate mediated cleavage and subsequent
OhiraeBestmann alkynylation19 of the intermediate aldehyde. The
diynes 2e4 were prepared by simple propargylation of the known
alkynols 6,6e 7,6e and 8,20 respectively.
With the fully elaborated diyne framework 1e4 in place, we first
examined the cyclotrimerization of diyne 1 (Table 1, entry 1) with
2-butyne-1,4-diol by employing some commonly used trimeriza-
tion catalysts. We found that the reactions with Wilkinson’s

S.B. Suryawanshi et al. / Tetrahedron 66 (2010) 6085e6096
6087
O
O
O
Next, the cyclotrimerization of diyne 2 with various symmetric-
disubstituted and monosubstituted alkynes were investigated and
the results are given in Table 1 (entries 11e20). We examined the
cyclotrimerization of diyne 2 and butyne-1,4-diol under conditions
similar to those used in the reaction with diyne 1. The reaction was
clean and gave the corresponding spiro-dihydroisobenzofurannu-
lated derivative 16 in 68% yield (Table 1, entry 11). The structure of
compound 16 was assigned with the help of 1H, 13C NMR and other
analytical data. In the 1H NMR spectrum of 16, two aromaticeH
i) NaIO4, MeOH/H2O
HO
1
N2
HO
ii)
O
O
P
OMe
MeO
5
O
K2CO3, MeOH, rt, 6 h
78%
O
O
O
Br
O
appeared as singlets at
and C(20)eH of the furanose ring appeared as a doublets at
and
4.39 (J1,2¼3.5 Hz), respectively. The C(4)eH appeared down-
field (
4.27) as doublet with J¼8.5 Hz. The observed cross peaks
between benzylic CH2 and the aromatic ring proton at 7.27 in the
d
7.09 and
d
7.27. The characteristic C(10)eH
5.99
2
3
4
O
d
NaH, THF
0 °C - rt, 4 h
95%
OH
d
6
d
d
O
O
Br
NOESY spectrum was helpful in assigning the ratios of the regio-
meric compounds resulting from unsymmetric alkynes (Fig. 3)
O
TBSO
O
NaH, THF
0 °C - rt, 3 h
92%
OH
7
O
a
b
O
O
O
7.09
O
7.24
O
Br
H
O
H
O
O
O
HO
HO
O
NaH, THF
0 °C - rt, 4 h
94%
HO
HO
O
O
OH
O
8
H
H
6.99 H
H
H
H
7.27
Scheme1. Synthesis of diynes 1e4.
Figure 3. Observed through spatial contacts in the NOESY spectra of compounds (a) 9
and (b) 16.
isolated. The cyclotrimerization of diyne
1
with the mono-
substituted alkynes, such as phenyl acetylene (entry 8), N-prop-
argyl phthalimide (entry 9), and 1-hexadecyne (entry 10) gave
inseparable regiomeric mixtures 13e15, respectively in good
yields.22
The results of the cyclotrimerization of diynes 1 and 2 with
various symmetric-disubstituted and monosubstituted alkynes are
given in Table 1 (entries 11e20). In the case of sterically crowded
alkynes, such as bis-(trimethylsilyl)acetylene (entry 16) and
Table 1
Cyclotrimerization of diynes 1 and 2 with various symmetrically disubstituted and monosubstituted alkynes
O
O
O
O
O
O
O
O
2
R'
1
+
+
R
R'
R'
R
O
O
R
RhCl(PPh3)3 (5 mol%)
toluene/ethanol (4:1), 80 °C, 8 h
Entry
1
Product (s)
Yield
61%
Alkyne
Entry
11
Product (s)
Yield (%)
68
9 (R¼R0¼CH2OH)
16 (R¼R0¼CH2OH)
17 (R¼R0¼H)
HOH2C
CH2OH
2
3
4
5
6
7
8
10 (R¼R0¼H)
11 (R¼R0¼CH2OAc)
12 (R¼R0¼CO2Me)
No product
65%
57%
45%
d
12
13
14
15
16
17
18
76
65
52
43
d
H
AcOH2C
MeO2C
H
18 (R¼R0¼CH2OAc)
19 (R¼R0¼CO2Me)
CH2OAc
CO2Me
n-C5H11
20 (R¼R0¼C5H11
)
n-C5H11
No product
d
Diyne self trimerization
Diyne self trimerization
TMS
Ph
TMS
Ph
No product
d
d
13a (R¼Ph,R0¼H)
13b (R¼H,R0¼Ph)
(1:4)
72%
21a (R¼Ph,R0¼H)
21b (R¼H,R0¼Ph)
(1:3)
69
Ph
O
9
14a (R¼CH2NPhth,R0¼H)
14b (R¼H,R0¼CH2NPhth)
(1:3)
67%
49%
19
20
22a (R¼CH2NPhth,R0¼H)
22b (R¼H,R0¼CH2NPhth)
(2:3)
72%
52%
N
O
15a (R¼n-C14H29,R0¼H)
23a (R¼n-C14H29,R0¼H)
n-C14H29
10
15b (R¼H,R0¼n-C14H29
)
23b (R¼H,R0¼n-C14H29
)
(1:1)
(1:1)

6088
S.B. Suryawanshi et al. / Tetrahedron 66 (2010) 6085e6096
diphenyl acetylene (entry 17) we observed the dimerized products
of diyne 2 (see Supplementary data for the NMR). Whereas, the
cyclotrimerization of 2 with the other sterically crowded alkyne
dodec-6-yne (entry 15), gave the expected product 20 in moderate
yield. Similar to the diyne 1, the trimerization reaction of the diyne
2 with phenyl acetylene (entry 18), N-propargyl phthalimide (entry
19), and 1-hexadecyne (entry 20) gave inseparable regiomeric
mixtures 21e23, respectively in good yields.22 Next, we examined
the scope of trimerization with diynes 3 and 4. The results of the
trimerization of diynes 3 and 4 with selected alkynes are given in
Table 2.
Vorbrüggen26 conditions afforded the protected nucleosides 33e35,
respectively. The structures of the protected nucleosides 33e35
were assigned with the help of extensive NMR spectroscopy studies.
The C(10)eH and C(20)eH of the furanose ring appeared as doublets
at
d
6.16 and
d
5.22 (J¼1.6 Hz), respectively revealing the anomeric
configuration as
b
. The assigned -configuration of the glycosidic
b
linkage was further confirmed by single crystal X-ray analysis of 33
(Fig. 4a).27e29
Subjecting 33e35 to Zemplen0s deacetylation gave the tricyclic
nucleosides 36e38 in excellent yields. The structural integrity and
b-configuration of compound 36 were established with the help of
Table 2
Cyclotrimerization of diynes 3 and 4 with mono- and disubstituted alkynes
O
O
TBSO
R'
O
O
O
O
O
O
3
4
+
+
R
R'
O
R
O
R
R'
RhCl(PPh3)3 (5 mol%)
toluene/ethanol (4:1)
80 °C, 8 h
Entry
1
Product(s)
Yield
72%
Alkyne
Entry
5
Product (s)
Yield
73%
24 (R¼R0¼H)
28 (R¼R0¼H)
H
AcOH2C
MeO2C
H
25 (R¼R0¼CH2OAc)
26 (R¼R0¼CO2Me)
60%
67%
78%
6
7
8
29 (R¼R0¼CH2OAc)
30 (R¼R0¼CO2Me)
65%
67%
75%
CH2OAc
CO2Me
2
3
4
27a (R¼Ph,R0¼H)
27b (R¼H,R0¼Ph)
(1:3)
31a (R¼Ph,R0¼H)
31b (R¼H,R0¼Ph)
(3:1)
Ph
3. Synthesis of modified nucleosides
COSY and NOESY. For example, in the 1H NMR spectrum of 36, the
characteristic C(10)eH and C(20)eH of the furanose ring appeared at
Considering the importance of modified nucleosides in antiviral
and anticancer drug discovery programs,23 we intended to carry out
glycosylation of the cyclotrimerization products with easily avail-
able pyrimidine nucleobases, which should effectively address the
synthesis of either conformationally restricted24 or spiroannulated
nucleosides.25 We examined the feasibility of the synthesis of
modified tricyclic nucleosides by employing isochroman 10. The
isochroman derivative 10 was subjected to acid catalyzed acetonide
hydrolysis using acetic acid followed by acetylation of the hydro-
lyzed derivative by using acetic anhydride and Et3N in dichloro-
methane toafford a 1:1 anomeric mixtureof 32 (Scheme 2). Next, we
proceeded to synthesize tricyclic nucleosides using 32. The treat-
ment of 32 with uracil, thymine, and 5-fluorouracil under modified
d
5.89 (s) and 4.52 (s), respectively. In the NOESY experiments of 36
(Fig. 5a), C(4)eH showed spatial interaction with C(30)eH as well as
with C(10)eH. A similar
-configuration was assigned for 37 and 38
by comparing their chemical shifts and coupling constants with
b
those of 36. The b-configuration was confirmed by single crystal
X-ray analysis of 37 (Fig. 4b).27
We executed a similar sequence of reactions with C(3)espi-
robenzofurannulated ribose derivative 24 (Scheme 3). Global
deprotection of 24 by heating in 60% acetic acid at the reflux tem-
perature for 2 h gave the corresponding lactols, which was sub-
sequently subjected to acetylation using acetic anhydride and Et3N
in dichloromethane toafford39 in 83% yield in two steps(Scheme 3).
In the 1H NMR spectrum of 39, C(1)eH appeared as a doublet at
d
6.04 with an 8.5 Hz couplingconstant. TheC(3)eH alsoappeared as
a doublet at
5.31 with an J¼8.2 Hz and the two C(5)eH2 as a doublet
at
4.01 (J¼8.1 Hz). The large coupling constants observed indicated
the formation of a -pyranoside framework during the per-
d
OAc
OAc
O
O
O
i) 60% AcOH, reflux, 2 h
d
b
O
ii) Ac2O, Et3N, DMAP
CH2Cl2, rt, 1 h
O
O
acetylation of the intermediate lactols.30 Next we proceeded to carry
out the synthesis of tricyclic nucleosides using 39. The treatment of
39 with uracil, thymine, and 5-fluorouracil under conditions similar
to those employed for the glycosylation of 32 afforded the protected
nucleosides 40e42. The structures of the protected nucleosides
40e42 were assigned with the help of extensive NMR spectroscopy
32
10
87%
uracil or thymine
or 5-fluorouracil
BSA, TMSOTf
BSA =
TMS
TMSO
N
CH3CN, 50 °C, 2 h
H
N
H
O
O
N
O
O
NaOMe, MeOH
rt, 20 min
studies. The anomeric proton of 40 resonated as a doublet at d 5.72
O
O
N
N
with a coupling constant J¼8.2 Hz in the 1H NMR spectrum. The
R
R
assigned b-configuration of the glycosidic linkage and the pyranose
OH
OAc
O
O
form of the sugar ring were further confirmed by single crystal X-ray
analysis of 40 (Fig. 4c).
36 (R = H)
37
96%
33 (R = H)
82%
(R = CH3) 79%
35 (R = F) 78%
34
(R = CH3) 95%
Subjecting 40e42 to Zemplen’s deacetylation afforded the tri-
38 (R = F) 92%
cyclic spironucleosides 43e45. The structural integrity and
b-con-
Scheme 2. Synthesis of benzopyrannulated nucleosides.
figuration of compound 44 were established with the help of COSY

S.B. Suryawanshi et al. / Tetrahedron 66 (2010) 6085e6096
6089
Figure 4. ORTEP Structures of (a) compound 33 (b), Compound 37 and (c) compound 40.
drawbacks of terminal alkynes. By selecting a representative trime-
rization product from each family, we synthesized tricyclic nucleo-
sides by simple synthetic manipulations. Considering the importance
of modified nucleosides (antiviral agents, antisense therapeutic and
diagnostic agents) in medicinal chemistry programs, the results from
the present investigation could be further explored for a strategic
construction of related small moleculelibraries. Work inthis direction
is ongoing in our laboratory.
O
a
b
7.51
H
4.17
H
N
5.90
H
H
O
OH
N
O
H
H
O
O
NH
O
N
5.89
HO
3.91
H
O
H
O
H
H
4.72
O
4.23
H
5.24
3.83
H
H
5.69
4.09
4.22
Figure 5. Observed through spatial contacts in the NOESY spectra of compounds (a) 36
and (b) 44.
4. Experimental
4.1. General methods
OAc
O
Air and/or moisture sensitive reactions were carried out in
anhydrous solvents under an argon atmosphere in oven-dried
glassware. All anhydrous solvents were distilled prior to use: Tolu-
ene from Na and benzophenone; CH2Cl2 and DMF from CaH2; MeOH
and EtOH from Mg cake. Commercial reagents were used without
purification. Column chromatography was carried out by using
Spectrochem silica gel (100e200 mesh). Optical rotations were
determined on a Jasco DIP-370 digital polarimeter. Specific optical
TBSO
O
O
O
OAc
i) 60% AcOH, reflux, 2 h
AcO
O
ii) Ac2O, Et3N, DMAP
CH2Cl2, rt, 1 h
O
24
39
83%
uracil or thymine
or 5-fluorouracil
BSA, TMSOTf
rotations [a]
D are given in 10ꢁ1 deg cm2 gꢁ1. 1H and 13C NMR spec-
CH3CN, 50 °C, 2 h
H
N
H
N
troscopy measurements were carried out on Bruker AC 200 MHz or
Bruker DRX 400 MHz spectrometers, and TMS was used as internal
standard. The 1H and 13C NMR chemical shifts are reported in parts
per million downfield from tetramethylsilane and the coupling
constants (J) are reported in Hertz (Hz). The following abbreviations
are used to designate signal multiplicity: s¼singlet, d¼doublet,
t¼triplet, q¼quartet, m¼multiplet, br¼broad. The multiplicity of the
13C NMR signals was assigned with the help of DEPT spectra and the
terms s¼singlet, d¼doublet, t¼triplet, and q¼quartet represent C
(quaternary), CH, CH2, and CH3, respectively. Mass spectroscopy was
carried out on an API QStar Pulsar (Hybrid Quadrupole-TOF LC/MS/
MS) spectrometer. Elemental analysis data were obtained on
a Thermo Finnigan Flash EA 1112 Series CHNS Analyzer.
O
O
O
O
R
R
N
N
NaOMe, MeOH
rt, 20 min
O
O
OH
OAc
HO
AcO
O
O
43
40
(R = H)
44 (R = CH3) 90%
45
95%
(R = H)
84%
41 (R = CH3) 76%
42
(R = F)
93%
(R = F)
77%
Scheme 3. Synthesis of spiro-isobenzofurannulated nucleosides.
and NOESY experiments. For example, in the 1H NMR spectrum of
44, the characteristic C(10)eH and C(20)eH of the pyranose ring
4.1.1. 1,2-O-Isopropylidene-3-O-propargyl-a-D-xylo-hexofuranose
appeared at
d
5.90 (d) and 4.23 (t), respectively, with J1,2¼9.5 Hz.
(1). To a solution of diol 5 (1.5 g, 5.8 mmol) in methanol (25 mL)
and water (2 mL), NaIO4 (1.4 g, 7.0 mmol) was added and stirred for
30 min at room temperature. The mixture was filtered through
Celite and concentrated under reduced pressure. The residue was
extracted with ethyl acetate, washed with brine, dried over Na2SO4,
filtered, and concentrated under reduced pressure to afford an
intermediate aldehyde (1.2 g). To a suspension of the above alde-
hyde (1.2 g, 7.9 mmol) and K2CO3 (1.4 g, 10.3 mmol) in methanol
(30 mL), OhiraeBestmann reagent (1.85 g, 9.5 mmol) was added at
room temperature and stirred for 6 h. The reaction mixture was
concentrated under reduced pressure, and the crude material was
partitionated between water and ethyl acetate. The organic phase
was separated, dried (Na2SO4), and concentrated under reduced
The C(20)eOH resonated as a doublet at 4.17 ppm (J¼9.2 Hz), indi-
cating a strong intramolecular hydrogen bonding,31 and C(40)eH
appeared as a ddd (
d
4.09 ppm, J¼10.8, 8.8, 5.5 Hz). In the NOESY
experiments spectrum of 44 (Fig. 5b), C(10)eH showed spatial
interaction with C(40)eH and C(20)eOH, thus confirming the
assigned b-configuration. A similar b-configuration was assigned
for 43 and 45 by comparing their chemical shifts and coupling
constants with those of 44.
In summary, we have demonstrated the application of the
[2þ2þ2]-cyclotrimerization reaction to the synthesis of enantiopure
tricyclicsystemscomprisingtheisochromanordihydroisobenzofuran
units integrated with a sugar ring. The regioselectivity is one of the

6090
S.B. Suryawanshi et al. / Tetrahedron 66 (2010) 6085e6096
pressure. The purification of residue by silica gel column chroma-
tography (7% ethyl acetate in petroleum ether) gave 1 (920 mg, 78%
J¼9.3 Hz,1H), 4.48 (d, J¼6.2 Hz,1H), 4.53 (d, J¼2.4 Hz, 2H); 13C NMR
(CDCl3, 50 MHz): 25.2 (q), 25.9 (q), 26.2 (q), 26.2 (q), 56.3 (t), 61.2
(t), 71.3 (d), 73.0 (t), 74.5 (d), 74.9 (s), 77.6 (d), 77.6 (s), 79.0 (d), 80.3
(d), 105.5 (s), 109.9 (s), 112.2 (s) ppm; ESI-MS (m/z): 345.3 (100%,
[MþNa]þ), 361.3 (73%, [MþK]þ). Anal. Calcd for C17H22O6: C, 63.34;
H, 6.88. Found: C, 63.19; H, 6.97.
25
yield) as a colorless oil; Rf (25% ethyl acetate/pet. ether) 0.45; [
þ33.7 (c 1.3, CHCl3); IR (CHCl3)
1376, 1347, 1254, 1218, 1164,1078, 1028, 952, 861, 758, 667 cmꢁ1; 1H
NMR (CDCl3, 200 MHz):
a]
D
n
: 3291, 2990, 2938, 2120, 1455,
d
1.30 (s, 3H), 1.47 (s, 3H), 2.46 (t, J¼2.4 Hz,
1H), 2.55 (d, J¼2.3 Hz, 1H), 4.17 (d, J¼3.0 Hz, 1H), 4.40 (t, J¼2.2 Hz,
2H), 4.60 (d, J¼3.8 Hz, 1H), 4.80 (t, J¼2.6 Hz, 1H), 5.91 (d, J¼3.8 Hz,
4.3. Representative procedures for the [2D2D2]-
cyclotrimerization reactions of diynes 1e4
1H); 13C NMR (CDCl3, 50 MHz):
d 26.1 (q), 26.7 (q), 58.0 (t), 70.2 (d),
75.4 (d), 76.5 (d), 77.1 (s), 78.8 (s), 81.8 (d), 82.7 (d), 104.5 (d), 111.9
(s) ppm; ESI-MS (m/z): 223.2 (5%, [MþH]þ), 240.3 (15%, [MþNH4]þ),
245.2 (100%, [MþNa]þ), 261.2 (6%, [MþK]þ). Anal. Calcd for
C12H14O4: C, 64.85; H, 6.35. Found: C, 64.82; H, 6.38.
Procedure A: A solution of diyne 1 (0.5 mmol) and alkyne
(1.5 mmol) in 4:1 toluene/ethanol (12 mL) was degassed with dry
argon for 20 min. To this, Wilkinson’s catalyst [RhCl(PPh3)3]
(0.03 mmol) was added, and the mixture was heated at 80 ꢀC for
6 h and then allowed to cool to room temperature. The solvent
evaporated under reduced pressure. The residue was purified by
silica gel chromatography to procure the cyclotrimerization
product.
4.2. General procedure for the O-propargylation and
synthesis of diynes 2e4
To a suspension of alcohol 6 (8.0 g, 28 mmol), NaH (1.7 g,
42 mmol) in DMF (60 mL), propargyl bromide (3 mL, 34 mmol) was
added drop-wise at 0 ꢀC. The reaction mixture was allowed to
warm to room temperature, stirred for 2 h, quenched with slow
addition of cold water at 0 ꢀC and extracted with ethyl acetate. The
combined organic layer was washed with water, dried over Na2SO4,
concentrated, and purified by silica gel column chromatography
(10% ethyl acetate in light petroleum) to give 2 (8.5 g, 95%) as
a white powder.
Procedure B: A solution of diyne 1 (0.5 mmol) and alkyne
(1.5 mmol) in toluene/ethanol (12 and 3 mL, respectively) in
a sealed tube was degassed with dry argon for 20 min; thereafter,
Wilkinson’s catalyst [RhCl(PPh3)3] (0.03 mmol) was introduced and
the tube sealed by fusion. The sealed tube was transferred into
a steel bomb and heated at 80 ꢀC for 4 h. After cooling to room
temperature, the tube was broken and the mixture was transferred
into a round-bottom flask and concentrated under reduced pres-
sure. The residue was purified by silica gel chromatography (ethyl
acetate in petroleum ether) to give the cyclotrimerization product.
Procedure C: A solution of diyne 1 (0.5 mmol) in toluene (10 mL)
was degassed with dry acetylene for 20 min; then, Wilkinson’s
catalyst [RhCl(PPh3)3] (0.03 mmol) was introduced into the mix-
ture. The reaction mixture was sealed with septum and a copper
wire and cooled to ꢁ78 ꢀC, and acetylene gas was condensed by
continuous bubbling for 25 min. The reaction was transferred into
steel bomb, heated at 80 ꢀC for 4 h, and then allowed to cool to
room temperature. The solvent was evaporated under reduced
pressure. The residue was purified by silica gel chromatography
(ethyl acetate in petroleum ether) to afford the cyclotrimerized
product.
4.2.1. 1,2:5,6-Di-O-isopropylidene-3-C-ethynyl-3-O-propargyl-a-D-
allofuranose (2). Colorless oil; Rf (30% ethyl acetate/pet. ether) 0.55;
[
a
]
25 þ23.2 (c 2.3, CHCl3); IR (CHCl3)
n: 3306, 3018, 2991, 2937, 2112,
D
1456, 1384, 1309, 1217, 1166, 1135, 1076, 1030, 990, 844, 758 cmꢁ1
;
1H NMR (CDCl3, 200 MHz):
d 1.34 (s, 6H), 1.42 (s, 3H), 1.58 (s, 3H),
2.41 (t, J¼2.4 Hz, 1H), 2.75 (s, 1H), 4.04e4.11 (m, 3H), 4.31 (t,
J¼5.8 Hz, 1H), 4.41 (dd, J¼2.4, 9.1 Hz, 2H), 4.62 (d, J¼3.5 Hz, 1H),
5.76 (d, J¼3.5 Hz,1H); 13C NMR (CDCl3, 50 MHz):
d 25.4 (q), 26.6 (q),
26.9 (q), 26.9 (q), 54.7 (t), 66.2 (t), 74.4 (d), 74.5 (s), 78.2 (s), 79.7 (s),
80.4 (s), 81.0 (s), 81.2 (d), 83.4 (d), 104.0 (d), 109.2 (s), 113.8 (s) ppm;
ESI-MS (m/z): 323.3 (6%, [MþH]þ), 340.4 (6%, [MþNH4]þ), 335.4
(100%, [MþNa]þ). Anal. Calcd for C12H14O4: C, 63.34; H, 6.88. Found:
C, 63.19; H, 7.01.
4.3.1. 1,2-O-Isopropylidene-4-C,3-O-[o-{(3,4-bis(hydroxymethyl))}
4.2.2. 1,2-O-Isopropylidene-5-O-(tert-butyldimethylsilyl)-3-C-ethy-
phenylenemethylene]-a-D-xylotetrofuranose (9). Following pro-
nyl-3-O-propargyl-
a-D
-ribofuranose (3). The procedure used for the
cedure B, the cyclotrimerization of diyne 1 (120 mg, 0.54 mmol)
preparation of 2 was used with alkynol 7 (5 g, 16 mmol) to prepare
and butynediol (140 mg, 1.6 mmol) gave 9 (102 mg, 61%) as a vis-
25
diyne 3 (5.1 g, 92%) as a white solid. Mp: 105e110 ꢀC; Rf (20% ethyl
cous oil; Rf (30% ethyl acetate/pet. ether) 0.30; [
CHCl3); IR (CHCl3)
898 cmꢁ1 1H NMR (CDCl3, 200 MHz):
a
]
þ28.0 (c 1.2,
D
25
acetate/pet. ether) 0.50; [
a]
þ40.6 (c 1.1, CHCl3); IR (CHCl3)
n
:
n
: 3401, 3016, 2932, 1624, 1438, 1216, 1080, 1017,
1.35 (s, 3H), 1.58 (s, 3H),
D
3307, 2955, 2931, 2885, 2858, 2110, 1473, 1375, 1254, 1132, 1047,
;
d
876 cmꢁ1 1H NMR (CDCl3, 200 MHz):
;
d
0.06 (s, 6H), 0.88 (s, 9H),
3.90 (br s, 2H), 4.09 (d, J¼2.3 Hz, 1H), 4.48e4.55 (m, J¼12.7 Hz, 3H),
4.58 (d, J¼15.1 Hz, 1H), 4.59 (d, J¼12.7 Hz, 1H), 4.67 (d, J¼3.8 Hz,
1H), 4.70 (d, J¼15.1 Hz, 1H), 4.90 (d, J¼2.3 Hz, 1H), 5.93 (d, J¼3.8 Hz,
1.33 (s, 3H), 1.57 (s, 3H), 2.44 (t, J¼2.4 Hz, 1H), 2.66 (s, 1H),
3.81e3.97 (2dd, J¼3.9, 11.2 Hz, 2H), 4.15 (dd, J¼3.9, 6.7 Hz, 1H), 4.32
(dd, J¼2.4, 14.6 Hz, 1H), 4.45 (dd, J¼2.4, 14.6 Hz, 1H), 4.59 (d,
J¼3.6 Hz, 1H), 5.82 (d, J¼3.6 Hz, 1H); 13C NMR (CDCl3, 50 MHz):
1H), 6.99 (s, 1H), 7.24 (s, 1H); 13C NMR (CDCl3, 50 MHz):
d 26.1 (q),
26.7 (q), 62.7 (t, 2C), 67.0 (t), 73.1 (d), 79.8 (d), 84.4 (d), 104.9 (d),
111.7 (s), 124.6 (d), 128.4 (s), 130.9 (d), 134.4 (s), 138.2 (s), 140.2 (s)
ppm; ESI-MS (m/z): 309.4 (3%, [MþH]þ), 331.3 (100%, [MþNa]þ),
347.3 (4%, [MþK]þ). Anal. Calcd for C16H20O6: C, 62.33; H, 6.54.
Found: C, 62.12; H, 6.68.
d
ꢁ5.4 (q), ꢁ5.2 (q), 18.3 (s), 25.9 (q, 3C), 26.8 (q), 26.9 (q), 54.5 (t),
63.0 (t), 74.5 (d), 77.8 (d), 79.4 (s), 79.5 (s), 80.6 (s), 81.7 (d), 82.8 (d),
104.3 (d), 113.6 (s) ppm; ESI-MS (m/z): 367.5 (5%, [MþH]þ), 389.5
(100%, [MþNa]þ), 405.5 (67%, [MþK]þ). Anal. Calcd for C19H30O5Si:
C, 62.26; H, 8.25. Found: C, 62.12; H, 8.37.
4.3.2. 1,2-O-Isopropylidene-4-C,3-O-(o-phenylenemethylene)-a-D-
4.2.3. 1,2:4,5-Di-O-isopropylidene-3-C-ethynyl-3-O-propargyl-
a
-
D
-
xylotetrofuranose (10). Following the general procedure C, the
cyclotrimerization of diyne 1 (150 mg, 0.68 mmol) afforded 10
(109 mg, 65%) as a viscous oil; Rf (25% ethyl acetate/pet. ether) 0.55;
psicopyranose (4). The procedure used for preparing 3 was used
with alkynol 8 (2 g, 16 mmol), affording diyne 4 (2.1 g, 94%) as
a white solid. Mp: 104e106 ꢀC; Rf (30% ethyl acetate/pet. ether)
[a
]
25 þ21.6 (c 1.5, CHCl3); IR (CHCl3)
n
: 3018, 2927, 1612, 1458, 1376,
1.28
D
25
0.45; [
a
]
ꢁ139.5 (c 1.6, CHCl3); IR (CHCl3)
n
: 3271, 2989, 2939,
1216, 1164, 1091, 1020, 920 cmꢁ1; 1H NMR (CDCl3, 200 MHz):
d
D
2114, 1458, 1255, 1094, 1015, 981 cmꢁ1; 1H NMR (CDCl3, 200 MHz):
1.34 (s, 3H), 1.44 (s, 3H), 1.48 (s, 3H), 1.55 (s, 3H), 2.41 (t, J¼2.4 Hz,
1H), 2.73 (s, 1H), 3.97e4.08 (m, 2H), 4.19e4.28 (m, 2H), 4.43 (d,
(s, 3H), 1.50 (s, 3H), 4.07 (d, J¼2.4 Hz, 1H), 4.59 (d, J¼14.9 Hz, 1H),
4.60 (d, J¼3.8 Hz, 1H), 4.71 (d, J¼14.9 Hz, 1H), 4.88 (d, J¼2.4 Hz, 1H),
5.89 (d, J¼3.8 Hz, 1H), 6.94e6.99 (m, 1H), 7.17e7.23 (m, 2H),
d

S.B. Suryawanshi et al. / Tetrahedron 66 (2010) 6085e6096
6091
7.35e7.42 (m, 1H); 13C NMR (CDCl3, 50 MHz):
d
26.3 (q), 26.9 (q),
(2d, J¼3.6 Hz, 1H), 6.90e7.05 (m, 1H), 7.27e7.44 (m, 2H), 7.59e7.65
(m, 2H), 7.72e7.76 (m, 2H); 13C NMR (CDCl3, 50 MHz):
26.2 (q), 26.2
67.4 (t), 73.5 (d), 80.1 (d), 84.7 (d), 105.2 (d), 111.6 (s), 124.2 (d), 127.4
(d), 128.7 (d), 129.5 (s), 130.7 (d), 134.8 (s) ppm; ESI-MS (m/z): 266.3
(36%, [MþNH4]þ), 271.3 (100%, [MþNa]þ). Anal. Calcd for C14H16O4:
C, 67.73; H, 6.50%; Found: C, 67.88; H, 6.59%.
d
(q), 26.9 (q), 41.2 (t), 41.3 (t), 67.1 (t), 67.2 (t), 73.2 (d), 73.3 (d), 80.0 (d),
80.0 (d), 84.6 (d), 84.6 (d),105.1 (d),111.5 (s),111.6 (s), 123.4 (d), 124.6
(d), 127.8 (d), 128.5 (d), 128.5 (d), 128.9 (d), 129.2 (d), 129.8 (s), 130.7
(d),131.0 (d),132.1 (s),132.2 (s),133.9 (d),134.0 (d),134.4 (s),135.2 (s),
135.6 (s), 136.9 (s), 167.7 (s), 167.7 (s) ppm; ESI-MS (m/z): 425.4 (15%,
[MþNH4]þ), 430.5 (100%, [MþNa]þ). Anal. Calcd for C23H21NO6: C,
67.80; H, 5.20; N, 3.44. Found: C, 68.01; H, 5.43; N, 3.28.
4.3.3. 1,2-O-Isopropylidene-4-C,3-O-[o-{3,4-bis(acetyloxymethy)}
phenylenemethylene]-a-D-xylotetrofuranose (11). The general pro-
cedure A was followed. Diyne 1 (100 mg, 0.45 mmol) and diacetate of
2-butyne-1,4-diol (230 mg, 1.4 mmol) were used to obtain 11
(101 mg, 57%) as colorless oil; Rf (30% ethyl acetate/pet. ether) 0.35;
4.3.7. 1,2-O-Isopropylidene-4-C,3-O-[o-(3- or 4-tetradecyl)phenyl-
enemethylene]-a-D-xylotetrofuranose (15a/b). General procedure B
was followed. Diyne 1 (100 mg, 0.45 mmol) and 1-hexadecyne
(300 mg, 1.4 mmol) were used to afford a mixture of 15a and 15b
(98 mg, 49%)asa colorlessoil; Rf (30% ethyl acetate/pet. ether) 0.56; IR
25
[a]
þ6.8 (c 1.1, CHCl3); IR (CHCl3)
n
: 3020, 2932, 2854, 1740, 1614,
D
1454, 1244, 1064, 1118, 1104, 1081, 1022, 896 cmꢁ1; 1H NMR (CDCl3,
200 MHz): 1.35 (s, 3H),1.58 (s, 3H), 2.06 (s, 3H), 2.09 (s, 3H), 4.15 (d,
d
J¼2.3 Hz, 1H), 4.65 (d, J¼15.2 Hz, 1H), 4.69 (d, J¼3.8 Hz, 1H), 4.79 (d,
J¼15.2 Hz, 1H), 4.97 (d, J¼2.2 Hz, 1H), 5.14, 5.16 (2s, 4H), 5.97 (d,
J¼3.8 Hz, 1H), 7.11 (s, 1H), 7.55 (s, 1H); 13C NMR (CDCl3, 50 MHz):
(CHCl3)
NMR (CDCl3, 200 MHz):
n
:3017, 2926, 2854,1619,1465,1375,1245,1090,865 cmꢁ1;1H
d
0.86(t, J¼6.6 Hz, 3H),1.25 (brs,23H),1.36 (s,
d
20.8 (q), 20.9 (q), 26.2 (q), 26.8 (q), 63.2 (t), 63.3 (t), 67.0 (t), 72.9 (d),
3H), 1.53e1.58 (m, 4H), 2.52e2.61 (m, J¼3.7, 7.3 Hz, 2H), 4.13 (d,
J¼2.4 Hz, 1H), 4.64 (d, J¼15.1 Hz, 1H), 4.67 (d, J¼3.6 Hz, 1H), 4.76 (d,
J¼15.1 Hz, 1H), 4.93 (d, J¼2.3 Hz,1H), 5.97 (d, J¼3.7 Hz,1H), 6.85e6.97
(m, 1H), 7.09 (d, J¼7.8 Hz, 1H), 7.30e7.39 (m, 1H); 13C NMR (CDCl3,
79.9 (d), 84.5 (d), 105.1 (d), 111.6 (s), 125.7 (d), 129.9 (s), 131.7 (d),
133.8 (s), 134.9 (s), 135.1 (s), 170.3 (s), 170.4 (s) ppm; ESI-MS (m/z):
410.5 (37%, [MþNH4]þ), 415.4 (100%, [MþNa]þ), 431.4 (5%, [MþK]þ).
Anal. Calcd for C20H24O8: C, 61.22; H, 6.16%. Found: C, 61.15; H, 6.29.
50 MHz): d 4.2 (q), 22.7 (t), 26.3 (q), 26.9 (q), 29.3 (t), 29.4 (t), 29.4 (t),
29.6 (t), 29.6 (t), 29.7 (t), 31.4 (t), 32.0 (t), 35.6 (t), 35.9 (t), 67.3 (t), 67.5
(t), 73.5 (d), 73.7 (d), 80.1 (d), 80.1 (d), 84.7 (d),105.2 (d),111.5 (s),111.5
(s),124.1 (d),124.1 (d),126.6 (s),127.6 (d),128.9 (d),129.1 (s),130.4 (d),
130.5 (d), 131.9 (s), 134.5 (s), 142.1 (s), 143.6 (s) ppm; ESI-MS (m/z):
462.7 (27%, [MþNH4]þ), 467.7 (100%, [MþNa]þ). Anal. Calcd for
C28H44O4: C, 75.63; H, 9.97. Found: C, 75.80; H, 10.12.
4.3.4. 1,2-O-Isopropylidene-4-C,3-O-[o-{3,4-bis(methoxycarbonyl)}
phenylenemethylene]-
a
-D-xylotetrofuranose (12). Following the
general procedure B, the cycloaddition of diyne
1
(120 mg,
0.54 mmol) and dimethyl acetylene dicaboxylate (230 mg,
1.6 mmol) gave 12 (89 mg, 45%) as colorless oil; Rf (30% ethyl ace-
25
tate/pet. ether) 0.34; [
a
]
D
þ8.7 (c 1.4, CHCl3); IR (CHCl3)
n: 3022,
2994, 2955, 2847, 1726, 1620, 1578, 1437, 1215, 1163, 1093, 1045,
4.3.8. 1,2:5,6-Di-O-isopropylidene-3-C,3-O-[o-{(3,4-bis(hydrox-
ymethyl))}phenylenemethylene]-a-D-allofuranose (16). By following
895 cmꢁ1 1H NMR (CDCl3, 200 MHz):
;
d
1.35 (s, 3H), 1.56 (s, 3H),
3.83 (s, 3H), 3.88 (s, 3H), 4.16 (d, J¼2.4 Hz, 1H), 4.66 (d, J¼15.6 Hz,
1H), 4.68 (d, J¼3.8 Hz, 1H), 4.83 (d, J¼15.6 Hz, 1H), 4.95 (d, J¼2.4 Hz,
1H), 5.94 (d, J¼3.8 Hz, 1H), 7.38 (s, 1H), 7.91 (s, 1H); 13C NMR (CDCl3,
procedure A, cycloaddition of diyne 2 (100 mg, 0.31 mmol) and 2-
butyne-1,4-diol (80 mg, 0.93 mmol) gave 16 (86 mg, 68%) as col-
25
orless oil; Rf (20% ethyl acetate/pet. ether) 0.28; [
CHCl3); IR (CHCl3)
1123,1074,1022, 872, 842, 754, 724, 695, 667 cmꢁ1; 1H NMR (CDCl3,
200 MHz): 1.11 (s, 3H), 1.36 (s, 3H), 1.38 (s, 3H), 1.68 (s, 3H), 3.23
a
]
ꢁ4.8 (c 1.2,
D
50 MHz):
d
26.2 (q), 26.8 (q), 52.5 (q), 52.7 (q), 66.8 (t), 72.5 (d), 79.9
n: 3412, 2989, 2935, 2875, 1438, 1374, 1330, 1217,
(d), 84.5 (d), 105.2 (d), 111.8 (s), 124.8 (d), 130.4 (s), 131.6 (d), 132.5
(s), 132.6 (s), 138.3 (s), 166.8 (s), 167.6 (s) ppm; ESI-MS (m/z): 365.4
(29%, [MþH]þ), 387.4 (100%, [MþNa]þ), 403.4 (11%, [MþK]þ). Anal.
Calcd for C18H20O8: C, 59.34; H, 5.53. Found: C, 59.48; H, 5.70.
d
(br s, 2H), 3.55 (dt, J¼5.5, 8.5 Hz, 1H), 3.79 (dd, J¼5.9, 8.5 Hz, 1H),
3.93 (dd, J¼4.7, 8.6 Hz, 1H), 4.27 (d, J¼8.5 Hz, 1H), 4.39 (d, J¼3.5 Hz,
1H), 4.71 (d, J¼12.2 Hz, 1H), 4.73 (d, J¼12.2 Hz, 1H), 4.79 (d,
J¼12.0 Hz, 2H), 5.16 (d, J¼12.3 Hz, 1H), 5.23 (d, J¼12.3 Hz, 1H), 5.99
(d, J¼3.5 Hz,1H), 7.09 (s,1H), 7.27 (s,1H); 13C NMR (CDCl3, 50 MHz):
4.3.5. 1,2-O-Isopropylidene-4-C,3-O-[o-(3- or 4-phenyl)phenylene-
methylene]-a-D-xylotetrofuranose (13a/13b). The general procedure
A was followed. Diyne 1 (120 mg, 0.54 mmol) and phenyl acetylene
(0.2 mL, 1.6 mmol) were used to procure a mixture of 13a and 13b
(126 mg, 72%) as reddish oil; Rf (30% ethyl acetate/pet. ether) 0.53;
d 25.4 (q), 26.2 (q), 26.7 (q), 26.8 (q), 63.4 (t), 63.7 (t), 67.4 (t), 73.3
(t), 73.8 (d), 79.3 (d), 84.3 (d), 93.8 (s), 103.5 (d), 109.3 (s), 113.5 (s),
122.6 (d), 122.6 (d), 137.8 (s), 139.0 (s), 140.2 (s), 140.9 (s) ppm; ESI-
MS (m/z): 431.5 (100%, [MþNa]þ). Anal. Calcd for C21H28O8: C,
61.75; H, 6.91. Found: C, 61.87; H, 6.99.
IR (CHCl3)
NMR (CDCl3, 200 MHz):
n
: 3019, 2926,1679,1488, 1453,1384,1163, 1019 cmꢁ1; 1H
d
1.30 (s, 3H), 1.53 (s, 3H), 4.12 (d, J¼2.3 Hz,
1H), 4.62e4.82 (m, J¼3.8, 15.5 Hz, 3H), 4.94, 4.95 (2d, J¼2.3 Hz, 1H),
5.88, 5.92 (2d, J¼3.8 Hz, 1H), 7.18e7.53 (m, 8H); 13C NMR (CDCl3,
4.3.9. 1,2:5,6-Di-O-isopropylidene-3-C,3-O-(o-phenylenemethylene)-
a-D-allofuranose (17). General procedure C was followed. Diyne 2
50 MHz):
d
26.2 (q), 26.8 (q), 67.2 (t), 67.4 (t), 73.3 (d), 73.6 (d), 80.0
(d), 80.1 (d), 84.6 (d), 104.7 (d), 105.1 (d), 111.5 (s), 111.9 (s), 122.9 (d),
124.7 (d), 126.2 (d), 127.0 (d), 127.1 (d), 127.4 (d), 127.5 (d), 128.3 (d),
128.4 (s), 128.4 (d) 128.8 (d), 129.2 (d), 129.8 (s), 130.9 (d), 131.6 (d),
133.6 (s), 135.1 (s), 140.3 (s), 140.4 (s), 140.5 (s), 141.7 (s) ppm; ESI-
MS (m/z): 347.4 (100%, [MþNa]þ), 363.4 (34%, [MþK]þ). Anal. Calcd
for C20H20O4: C, 74.06; H, 6.21. Found: C, 73.93; H, 6.38.
(120 mg, 0.37 mmol) was used to obtain 17 (100 mg, 76%) as a viscous
oil; Rf (20% ethyl acetate/pet. ether) 0.30; [
(CHCl3)
873, 757 cmꢁ1; 1H NMR (CDCl3, 200 MHz):
a
]
25 þ12.9 (c 1.9, CHCl3); IR
D
n
:3019,2939,1461,1375,1216,1165,1074,1034,1017, 929,845,
d
1.03 (s, 3H), 1.29 (s, 3H),
1.31 (s, 3H), 1.61 (s, 3H), 3.47 (dt, J¼5.5, 8.3 Hz, 1H), 3.70 (dd, J¼5.8,
8.5 Hz,1H), 3.84 (dd, J¼5.1, 8.5 Hz,1H), 4.20 (d, J¼8.3 Hz,1H), 4.32 (d,
J¼3.5 Hz, 1H), 5.09 (d, J¼12.0 Hz, 1H), 5.18 (d, J¼12.0 Hz, 1H), 5.88 (d,
J¼3.5 Hz, 1H), 7.02 (dd, J¼1.2, 7.7 Hz, 1H), 7.16e7.33 (m, J¼1.2, 7.7 Hz,
4.3.6. 1,2-O-Isopropylidene-4-C,3-O-[o-(3- or 4-phthalimidomethyl)
phenylenemethylene]-
a
-D-xylotetrofuranose
(14a/14b). Following
3H); 13C NMR (CDCl3, 50 MHz):
d 25.4 (q), 26.3 (q), 26.7 (q), 26.9 (q),
the general procedure A, the cyclotrimerization of diyne 1 (130 mg,
0.59 mmol) and propargyl phthalamide (325 mg, 1.8 mmol) afforded
a mixture of 14a and 14b (160 mg, 67%) as a viscous oil; Rf (30% ethyl
67.4 (t), 73.4 (t), 73.8 (d), 79.4 (d), 84.3 (d), 93.7 (s),103.5 (d),109.0 (s),
113.3 (s), 121.3 (d), 121.4 (d), 127.3 (d), 128.7 (d), 137.4 (s), 140.4 (s)
ppm; ESI-MS (m/z): 371.0 (100%, [MþNa]þ). Anal. Calcd for C19H24O6:
C, 65.50; H, 6.94. Found: C, 65.37; H, 6.69.
acetate/pet. ether) 0.43; IR (CHCl3)
1460, 1376, 1247, 1164, 1088, 1019, 947 cmꢁ1
200 MHz):
1.26 (s, 3H), 1.48 (s, 3H), 4.02 (d, J¼2.2 Hz, 1H), 4.53 (d,
J¼15.6 Hz, 1H), 4.56 (d, J¼3.6 Hz, 1H), 4.64e4.89 (m, 4H), 5.84, 5.86
n
: 3017, 2924, 2854, 1770, 1714,
;
1H NMR (CDCl3,
d
4.3.10. 1,2:5,6-Di-O-isopropylidene-3-C,3-O-[o-{3,4-bis(acetylox-
ymethyl)}phenylenemethylene]-a-D-allofuranose (18). Starting from

6092
S.B. Suryawanshi et al. / Tetrahedron 66 (2010) 6085e6096
diyne 2 (150 mg, 0.46 mmol) and diacetate of 2-butyne-1,4-diol
(237 mg, 1.4 mmol) and following procedure A, 18 (129 mg, 65%)
was obtained as colorless oil; Rf (30% ethyl acetate/pet. ether) 0.42;
84.4 (d), 93.7 (s), 93.7 (s), 103.5 (d), 103.5 (d), 109.1 (s), 113.3 (s),
113.3 (s), 120.0 (d), 120.0 (d), 121.6 (d), 121.7 (d), 126.6 (d), 127.1 (d),
127.6 (d), 127.9 (d), 128.8 (d), 128.8 (d), 136.5 (s), 138.4 (s), 139.5 (s),
140.5 (s), 140.5 (s), 141.0 (s), 141.3 (s), 142.1 (s) ppm; ESI-MS (m/z):
447.8 (100%, [MþNa]þ). Anal. Calcd for C25H28O6: C, 70.74; H, 6.65.
Found: C, 70.79; H, 6.82.
[
a
]
25 ꢁ8.4 (c 1.3, CHCl3); IR (CHCl3)
n: 3019, 2939, 1739, 1610, 1461,
D
1384, 1375, 1332, 1216, 1165, 1074, 1034, 1017, 929, 845, 757 cmꢁ1
;
1H NMR (CDCl3, 200 MHz):
d 1.10 (s, 3H), 1.34 (s, 3H), 1.36 (s, 3H),
1.66 (s, 3H), 2.08, 2.09 (2s, 6H), 3.50 (ddd, J¼4.6, 5.7, 8.5 Hz, 1H),
3.79 (dd, J¼4.7, 8.5 Hz, 1H), 3.91 (dd, J¼4.7, 8.5 Hz, 1H), 4.23 (d,
J¼8.5 Hz, 1H), 4.34 (d, J¼3.6 Hz, 1H), 5.09e5.24 (3d, J¼12.1 Hz, 6H),
5.94 (d, J¼3.6 Hz, 1H), 7.08 (s, 1H), 7.29 (s, 1H); 13C NMR (CDCl3,
4.3.14. 1,2:5,6-Di-O-isopropylidene-3-C,3-O-[o-(3- or 4-phthalimi-
domethyl)phenylenemethylene]-a-D-allofuranose (22a/22b). By fol-
lowing procedure A, cycloaddition of diyne 2 (130 mg, 0.4 mmol)
and propargyl phthalamide (224 mg, 1.2 mmol) gave a mixture of
22a and 22b (147 mg, 72%) as a viscous oil; Rf (35% ethyl acetate/pet.
50 MHz): d 20.9 (q, 2C), 25.5 (q), 26.4 (q), 26.8 (q), 26.9 (q), 63.4 (t),
63.7 (t), 67.4 (t), 73.3 (t), 73.8 (d), 79.2 (d), 84.3 (d), 93.8 (s), 103.4
(d), 109.2 (s), 113.5 (s), 122.6 (d), 123.0 (d), 133.9 (s), 135.6 (s), 138.2
(s), 141.3 (s), 170.3 (s, 2C) ppm; ESI-MS (m/z): 493.3 (4%, [MþH]þ),
510.4 (20%, [MþNH4]þ), 515.3 (100%, [MþNa]þ). Anal. Calcd for
C25H32O10: C, 60.97; H, 6.55. Found: C, 60.82; H, 6.71.
ether) 0.32; IR (CHCl3)
n
: 3020, 2991, 2936, 1771, 1716, 1395, 1216,
1.07 (s, 3H), 1.31, 1.35
1074, 1024 cmꢁ1; 1H NMR (CDCl3, 200 MHz):
d
(2s, 6H), 1.64, 1.66 (2s, 3H), 3.45e3.55 (m, 1H), 3.72e3.80 (m, 1H),
3.84e3.93 (m, 1H), 4.22 (dd, J¼3.4, 8.4 Hz, 1H), 4.32 (dd, J¼3.5,
9.6 Hz, 1H), 4.85 (s, 2H), 5.09 (d, J¼12.1 Hz, 1H), 5.18 (d, J¼12.1 Hz,
1H), 5.88, 5.98 (2d, J¼3.6 Hz, 1H), 7.00e7.30 (m, 2H), 7.34e7.42 (m,
1H), 7.68e7.75 (m, 2H), 7.80e7.87 (m, 2H); 13C NMR (CDCl3,
4.3.11. 1,2:5,6-Di-O-isopropylidene-3-C,3-O-[o-{3,4-bis(methox-
ycarbonyl)}phenylenemethylene]-a-D-allofuranose (19). Procedure B
was followed. Diyne 2 (150 mg, 0.46 mmol) and dimethyl acetylene
50 MHz): d 25.4 (q), 26.3 (q), 26.4 (q), 26.7 (q), 26.9 (q), 26.9 (q), 41.2
dicarboxylate (0.4 mL, 2.7 mmol) were used to afford 19 (112 mg,
(t), 41.4 (t), 67.3 (t), 67.4 (t), 73.2 (t), 73.8 (d), 73.8 (d), 79.2 (d), 79.3
(d), 84.3 (d), 93.6 (s), 93.7 (s), 103.4 (d), 103.5 (d), 109.0 (s), 109.1 (s),
113.3 (s), 121.6 (d), 121.6 (d), 122.1 (d), 123.4 (d), 128.0 (d), 129.2 (d),
132.0 (s), 134.0 (d), 135.8 (s), 137.1 (s), 137.2 (s), 138.1 (s), 140.2 (s),
141.2 (s), 167.7 (s) ppm; ESI-MS (m/z): 508.4 (7%, [MþH]þ), 525.4
(27%, [MþNH4]þ), 530.3 (100%, [MþNa]þ). Anal. Calcd for
C28H29NO8: C, 66.26; H, 5.76; N, 2.76. Found: C, 66.30; H, 5.82; N,
2.70.
25
52%) as colorless oil; Rf (30% ethyl acetate/pet. ether) 0.40; [
ꢁ10.2 (c 0.9, CHCl3); IR (CHCl3)
1383,1219,1165,1125,1075,1053, 985, 922, 843, 755 cmꢁ1; 1H NMR
(CDCl3, 200 MHz): 1.08 (s, 3H), 1.34, 1.36 (2s, 6H), 1.65 (s, 3H), 3.46
a]
D
n: 3021, 2989, 2954,1735,1621,1579,
d
(ddd, J¼4.4, 5.5, 9.1 Hz, 1H), 3.82 (s, 2H), 3.89 (s, 6H), 4.19 (d,
J¼9.1 Hz, 1H), 4.37 (d, J¼3.6 Hz, 1H), 5.15 (d, J¼12.9 Hz, 1H), 5.24 (d,
J¼12.9 Hz, 1H), 5.97 (d, J¼3.6 Hz, 1H), 7.39 (s, 1H), 7.57 (s, 1H); 13C
NMR (CDCl3, 50 MHz): d 25.2 (q), 26.2 (q), 26.6 (q), 52.6 (q), 53.2 (q,
2C), 67.5 (t), 73.0 (t), 73.6 (d), 79.3 (d), 84.1 (d), 93.8 (s), 103.3 (d),
109.3 (s), 113.4 (s), 121.9 (d, 2C), 131.6 (s), 133.0 (s), 140.9 (s), 144.1
(s), 167.2 (s), 167.4 (s) ppm; ESI-MS (m/z): 487.0 (100%, [MþNa]þ).
Anal. Calcd for C23H28O10: C, 59.48; H, 6.08. Found: C, 59.59; H, 6.02.
4.3.15. 1,2:5,6-Di-O-isopropylidene-3-C,3-O-[o-(3- or 4-tetradecyl)
phenylenemethylene]-a-D-allofuranose (23a/23b). Procedure B was
followed. Diyne 2 (120 mg, 0.37 mmol) and 1-hexadecyne (248 mg,
1.1 mmol) were used to afford a mixture of 23a and 23b (105 mg,
52%) as a colorless oil; Rf (25% ethyl acetate/pet. ether) 0.45; IR
4.3.12. 1,2:5,6-Di-O-isopropylidene-3-C,3-O-[3,4-di(n-pentyl)phenyl-
(CHCl3)
n
: 3019, 2987, 2927, 2855, 1618, 1458, 1373, 1249, 1217, 1167,
enemethylene]-
a-D
-allofuranose (20). Following procedure B, using
1074, 1025, 873 cmꢁ1
;
1H NMR (CDCl3, 200 MHz):
d
0.87 (t,
diyne 3 (130 mg, 0.4 mmol) and 6-dodecyne (0.34 mL, 1.6 mmol),
a mixture of 20 (84 mg, 43%) was obtained as colorless oil; Rf (35%
J¼6.4 Hz, 3H), 1.10 (s, 3H), 1.24 (br s, 20H), 1.34e1.36 (m, 7H),
1.53e1.59 (m, 3H), 1.67 (s, 3H), 2.61 (t, J¼7.6 Hz, 2H), 3.54 (2d, J¼5.4,
7.9 Hz, 1H), 3.72 (2dd, J¼5.8, 8.4 Hz, 1H), 3.88 (2dd, J¼5.2, 8.4 Hz,
1H), 4.26, 4.27 (2d, J¼7.9 Hz, 1H), 4.36, 4.37 (2d, J¼3.6 Hz, 1H), 5.10
(d, J¼11.8 Hz, 1H), 5.19 (d, J¼11.8 Hz, 1H), 5.92, 5.95 (2d, J¼3.6 Hz,
1H), 6.83, 7.03 (2s, 1H), 6.95, 7.07 (2d, J¼7.7 Hz, 1H), 7.10, 7.11 (2d,
J¼7.8 Hz, 1H); 13C NMR (CDCl3, 50 MHz): 14.1 (q) 22.7 (t), 25.5 (q),
26.4 (q), 26.7 (q), 27.0 (q), 29.3 (t), 29.4 (t), 29.5 (t), 29.6 (t), 29.7 (t),
31.6 (t), 31.8 (t), 32.0 (t), 35.9 (t), 67.2 (t), 67.3 (t), 73.4 (t), 73.4 (t),
73.9 (d), 79.5 (d), 79.5 (d), 84.4 (d), 84.4 (d), 93.6 (s), 93.6 (s), 103.5
(d), 103.6 (d), 109.0 (s), 113.3 (s), 121.1 (d), 121.2 (d), 121.2 (d), 121.2
(d), 127.7 (d), 129.0 (d), 134.8 (s), 137.7 (s), 137.8 (s), 140.7 (s), 142.4
(s), 143.7 (s) ppm; ESI-MS (m/z): 567.1 (100%, [MþNa]þ). Anal. Calcd
for C33H52O6: C, 72.76; H, 9.62. Found: C, 72.59; H, 9.78.
ethyl acetate/pet. ether) 0.34; [
n
a]
25 þ18.7 (c 1.0, CHCl3); IR (CHCl3)
D
: 2986, 2930, 2859, 1620, 1331, 1249, 1218, 1075, 873 cmꢁ1
;
1H
NMR (CDCl3, 200 MHz):
d
0.89 (2 t, J¼6.7 Hz, 6H), 1.11 (s, 3H),
1.24e1.38 (m, 15H), 1.58 (s, 3H), 1.67 (s, 3H), 2.11 (t, J¼7.6 Hz, 4H),
3.48e3.59 (m, 1H), 3.76 (dd, J¼5.8, 8.4 Hz, 1H), 3.91 (ddd, J¼4.6, 6.2,
8.4 Hz, 1H), 4.22 (d, J¼8.4 Hz, 1H), 4.33 (d, J¼3.6 Hz, 1H), 5.12 (d,
J¼12.0 Hz,1H), 5.21 (d, J¼12.0 Hz,1H), 5.82 (d, J¼3.6 Hz,1H), 7.09 (s,
1H), 7.31 (s, 1H); 13C NMR (CDCl3, 50 MHz):
d 14.0 (q, 2C), 22.5 (t),
22.5 (t), 25.4 (q), 25.5 (q), 26.6 (q), 26.7 (q), 28.0 (t), 28.3 (t), 28.8 (t),
30.3 (t), 31.2 (t), 31.5 (t), 67.3 (t), 73.3 (t), 73.8 (d), 83.3 (d), 84.4 (d),
93.7 (s), 103.4 (d), 109.1 (s), 113.3 (s), 120.9,(d), 120.9 (d), 121.6 (s),
137.9 (s), 139.3 (s), 139.7 (s) ppm; ESI-MS (m/z): 511.2 (100%,
[MþNa]þ). Anal. Calcd for C29H44O6: C, 71.28; H, 9.08. Found: C,
71.40; H, 9.26.
4.3.16. 1,2-O-Isopropylidene-5-O-(tert-butyldimethylsilyl)-3-C,3-O-
(o-phenylenemethylene)-a-D-ribofuranose (24). By following pro-
4.3.13. 1,2:5,6-Di-O-isopropylidene-3-C,3-O-[o-(3- or 4-phenyl)phe-
cedure C, cycloaddition of the diyne 3 (200 mg, 0.55 mmol) with
nylenemethylene]-
a
-
D
-allofuranose (21a/21b). General procedure A
acetylene gave 24 (152 mg, 71%) as a colorless oil; Rf (20% ethyl
25
was followed. Diyne 2 (110 mg, 0.33 mmol) and phenyl acetylene
(0.2 mL, 1.9 mmol) were used to afford a mixture of 21a and 21b
(98 mg, 69%) as reddish oil; Rf (30% ethyl acetate/pet. ether) 0.42; IR
acetate/pet. ether) 0.28; [
a
]
þ36.4 (c 1.1, CHCl3); IR (CHCl3)
n:
D
3077, 3019, 2955, 2930, 2858, 1608, 1462, 1383, 1255, 1167, 1087,
1049, 939 cmꢁ1 1H NMR (CDCl3, 200 MHz):
;
d
ꢁ0.09, ꢁ0.08 (2s,
(CHCl3)
n
: 3020, 2991, 2936,1620,1375,1215,1165, 1974,1044,1028,
6H), 0.80 (s, 9H), 1.36 (s, 3H), 1.69 (s, 3H), 3.30 (dd, J¼5.2, 11.1 Hz,
1H), 3.54 (dd, J¼6.5, 11.1 Hz, 1H), 4.35 (d, J¼3.6 Hz, 1H), 4.46 (dd,
J¼5.2, 6.5 Hz, 1H), 5.17 (d, J¼12.5 Hz, 1H), 5.23 (d, J¼12.5 Hz, 1H),
5.99 (d, J¼3.6 Hz, 1H), 7.16 (dd, J¼1.6, 7.5 Hz, 1H), 7.24 (d, J¼7.5 Hz,
873, 843 cmꢁ1
;
1H NMR (CDCl3, 200 MHz):
d
1.13 (s, 3H), 1.38 (s,
3H), 1.40 (s, 3H), 1.69 (s, 3H), 3.56e3.68 (m, 1H), 3.80, 3.84 (2dd,
J¼5.7, 8.5 Hz, 1H), 3.95 (dd, J¼8.5, 4.9 Hz, 1H), 4.31 (br d, J¼8.3 Hz,
1H), 4.42, 4.44 (2d, J¼3.6, Hz, 1H), 5.21 (d, J¼12.1 Hz, 1H), 5.29 (d,
J¼12.1 Hz, 1H), 5.98, 6.00 (2d, J¼3.6 Hz, 1H), 7.15 (d, J¼7.9 Hz, 1H),
1H), 7.29e7.40 (m, 2H); 13C NMR (CDCl3, 50 MHz):
d
ꢁ5.9 (q), ꢁ5.8
(q), 17.9 (s), 25.5 (q, 3C), 26.1 (q), 26.6 (q), 61.9 (t), 73.0 (t), 79.8 (d),
83.6 (d), 93.1 (s), 103.4 (d), 112.9 (s), 121.0 (d), 121.4 (d), 127.3 (d),
128.4 (d), 136.9 (s), 139.4 (s) ppm; ESI-MS (m/z): 410.7 (47%,
7.29e7.60 (m, 7H); 13C NMR (CDCl3, 50 MHz):
d 25.5 (q), 26.3 (q),
26.7 (q), 26.9 (q), 67.3 (t), 67.4 (t), 73.3 (t), 73.4 (t), 73.9 (d), 79.4 (d),

S.B. Suryawanshi et al. / Tetrahedron 66 (2010) 6085e6096
6093
[MþNH4]þ), 415.3 (100%, [MþNa]þ), 431.3 (67%, [MþK]þ). Anal.
IR (CHCl3)
n
: 3077, 3016, 2987, 2935, 2867, 1609, 1460, 1380, 1247,
Calcd for C21H32O5Si: C, 64.25; H, 8.22. Found: C, 64.32; H, 8.14.
1090, 1064, 979, 885 cmꢁ1
;
1H NMR (CDCl3, 200 MHz):
d
1.32 (s,
6H), 1.52 (s, 3H), 1.59 (s, 3H), 3.46 (d, J¼9.0 Hz, 1H), 4.08 (d,
J¼9.0 Hz, 1H), 4.25e4.29 (m, 3H), 4.48 (d, J¼5.3 Hz, 1H), 5.11 (d,
J¼12.3 Hz, 1H), 5.23 (d, J¼12.3 Hz, 1H), 7.19 (dd, J¼7.2, 2.1 Hz, 1H),
4.3.17. 1,2-O-Isopropylidene-5-O-(tert-butyldimethylsilyl)-3-C,3-O-
[o-{3,4-bis(acetyloxymethyl)} phenylenemethylene]-a-D-ribofuranose
(25). Procedure A was followed. Diyne 3 (150 mg, 0.41 mmol) and
7.27e7.41 (m, 3H); 13C NMR (CDCl3, 50 MHz):
d 25.6 (q), 25.7 (q),
diacetate of 2-butyne-1,4-diol (209 mg, 1.2 mmol) were used to
obtain 25 (132 mg, 60%) as colorless oil; Rf (25% ethyl acetate/pet.
26.1 (q), 26.6 (q), 59.8 (t), 71.1 (d), 72.5 (t), 73.7 (t), 76.6 (d), 86.7 (s),
106.6 (s), 109.3 (s), 112.8 (s), 120.5 (d), 123.5 (d), 127.3 (d), 128.7 (d),
138.2 (s), 140.7 (s) ppm; ESI-MS (m/z): 349.2 (9%, [MþH]þ), 366.2
(100%, [MþNH4]þ), 371.2 (12%, [MþNa]þ), 387.2 (17%, [MþK]þ).
Anal. Calcd for C19H24O6: C, 65.50; H, 6.94. Found: C, 65.62; H, 7.03.
25
ether) 0.32; [
a
]
D
þ25.0 (c 2.6, CHCl3); IR (CHCl3)
n: 3020, 2930,
2857, 1745, 1626, 1472, 1375, 1221, 1078, 1023, 874, 838, 756,
667 cmꢁ1; 1H NMR (CDCl3, 200 MHz):
d
ꢁ0.11, ꢁ0.10 (2s, 6H), 0.76
(s, 9H), 1.34 (s, 3H), 1.66 (s, 3H), 2.07, 2.08 (2s, 6H), 3.27 (dd, J¼5.2,
11.0 Hz, 1H), 3.53 (dd, J¼6.6, 11.0 Hz, 1H), 4.31 (d, J¼3.6 Hz, 1H), 4.42
(dd, J¼5.2, 6.5 Hz, 1H), 5.09e5.22 (m, 6H), 5.97 (d, J¼3.6 Hz, 1H),
4.3.21. 1,2:4,5-Di-O-isopropylidene-3-C,3-O-[o-{3,4-bis(acetylox-
ymethyl)}phenylenemethylene]-a-D-psicopyranose (29). Following
procedure A, cycloaddition of diyne 4 (130 mg, 0.4 mmol) and
7.17 (s, 1H), 7.28 (s, 1H); 13C NMR (CDCl3, 50 MHz):
d
ꢁ5.7 (q), ꢁ5.6
(q), 18.2 (s), 20.8 (q), 25.7 (q, 3C), 25.8 (q), 26.3 (q), 26.7 (q), 61.9 (t),
63.3 (t), 63.5 (t), 73.0 (t), 79.7 (d), 83.6 (d), 93.3 (s), 103.5 (d), 113.3
(s), 122.5 (d), 123.2 (d), 134.1 (s), 135.5 (s), 137.8 (s), 140.4 (s), 170.4
(s), 170.4 (s) ppm; ESI-MS (m/z): 554.6 (36%, [MþNH4]þ), 559.5
(100%, [MþNa]þ), 575.5 (35%, [MþK]þ). Anal. Calcd for C27H40O9Si:
C, 60.42; H, 7.51. Found: C, 60.29; H, 7.67.
diacetate of 2-butyne-1,4-diol (206 mg, 1.2 mmol) gave 29 (130 mg,
25
65%) as a viscous oil; Rf (20% ethyl acetate/pet. ether) 0.35; [
ꢁ111.43 (c 1.4, CHCl3); IR (CHCl3)
1381, 1090, 980 cmꢁ1; 1H NMR (CDCl3, 200 MHz):
a]
D
n
: 3020, 2989, 2937, 1736, 1600,
1.29 (s, 3H),1.33
d
(s, 3H), 1.49 (s, 3H), 1.55 (s, 3H), 2.03 (s, 3H), 2.06 (s, 3H), 3.44 (d,
J¼9.0 Hz, 1H), 4.03 (d, J¼9.0 Hz, 1H), 4.24e4.26 (m, 3H), 4.45 (d,
J¼5.3 Hz, 1H), 5.07e5.21 (m, J¼12.5, 12.8 Hz, 6H), 7.23 (s, 1H), 7.42
4.3.18. 1,2-O-Isopropylidene-5-O-(tert-butyldimethylsilyl)-3-C,3-O-
(s, 1H); 13C NMR (CDCl3, 50 MHz):
d 20.7 (q), 20.8 (q), 25.5 (q), 25.6
[o-{3,4-bis(methoxycarbonyl)}
phenylenemethylene]-
a
-
D
-ribofur-
(q), 26.0 (q), 26.3 (q), 59.8 (t), 63.4 (t), 63.4 (t), 71.0 (d), 72.6 (t), 73.5
(t), 76.5 (d), 86.7 (s), 106.5 (s), 109.4 (s), 112.8 (s), 122.1 (d), 124.9 (d),
134.0 (s), 135.3 (s), 139.1 (s), 141.0 (s), 170.4 (s), 170.5 (s) ppm; ESI-
MS (m/z): 510.8 (43%, [MþNH4]þ), 515.7 (100%, [MþNa]þ), 531.7
(17%, [MþK]þ). Anal. Calcd for C25H32O10: C, 60.97; H, 6.55. Found:
C, 60.82; H, 6.68.
anose] (26). Following procedure B, cycloaddition of the diyne 3
(130 mg, 0.36 mmol) and dimethyl acetylene dicarboxylate
(0.13 mL, 1.1 mmol) gave 26 (121 mg, 67%) as colorless oil; Rf (25%
ethyl acetate/pet. ether) 0.38; [
a]
25 þ6.6 (c 0.7, CHCl3); IR (CHCl3)
n:
D
3021, 2955, 2858, 1730, 1621, 1271, 1216, 1022 cmꢁ1
;
1H NMR
(CDCl3, 200 MHz):
d
ꢁ0.10 (2s, 6H), 0.76 (s, 9H), 1.33 (s, 3H), 1.66 (s,
3H), 3.25 (dd, J¼5.7, 11.1 Hz, 1H), 3.57 (dd, J¼6.2, 11.0 Hz, 1H), 3.89
(2s, 6H), 4.33 (d, J¼3.7 Hz, 1H), 4.41 (t, J¼5.9 Hz, 1H), 5.20 (s, 2H),
6.00 (d, J¼3.7 Hz, 1H), 7.49 (s, 1H), 7.55 (s, 1H); 13C NMR (CDCl3,
4.3.22. 1,2:4,5-Di-O-isopropylidene-3-C,3-O-[o-{3,4-bis(methox-
ycarbonyl)}phenylenemethylene]-a-D-psicopyranose (30). Cycload-
dition of diyne 4 (130 mg, 0.4 mmol) and dimethyl acetylene
dicarboxylate (0.15 mL, 1.2 mmol) following procedure B gave 30
50 MHz):
d
ꢁ5.7 (q), ꢁ5.6 (q), 18.2 (s), 25.7 (q, 2C), 26.3 (q), 26.7 (q),
52.8 (q), 52.9 (q), 61.6 (t), 72.9 (t), 79.5 (d), 83.5 (d), 93.5 (s), 103.5
(d), 113.5 (s), 121.9 (d), 122.5 (d), 131.7 (s), 133.2 (s), 140.6 (s), 143.4
(s), 167.2 (s), 167.7 (s) ppm; ESI-MS (m/z): 509.5 (11%, [MþH]þ),
526.6 (30%, [MþNH4]þ), 531.5 (100%, [MþNa]þ), 547.5 (9%,
[MþK]þ). Anal. Calcd for C25H36O9Si: C, 59.03; H, 7.13. Found: C,
58.91; H, 7.20.
(129 mg, 69%) as white solid; Rf (30% ethyl acetate/pet. ether) 0.40;
25
mp: 78e81 ꢀC; [
a]
ꢁ136.5 (c 0.8, CHCl3); IR (CHCl3)
n: 3019,
D
2990, 2938, 2874, 1779, 1730, 1622, 1437, 1383, 1216, 1091, 980,
877, 667 cmꢁ1 1H NMR (CDCl3, 200 MHz):
;
d
1.30 (s, 3H), 1.35 (s,
3H), 1.50 (s, 3H), 1.57 (s, 3H), 3.41 (d, J¼9.1 Hz, 1H), 3.86 (s, 3H),
3.88 (s, 3H), 4.06 (d, J¼9.1 Hz, 1H), 4.25e4.28 (m, 3H), 4.45 (d,
J¼5.3 Hz, 1H), 5.14 (d, J¼13.1 Hz, 1H), 5.26 (d, J¼13.1 Hz, 1H), 7.49
4.3.19. 1,2:4,5-Di-O-isopropylidene-3-C,3-O-[o-(3- or 4-phenyl)phe-
(s, 1H), 7.82 (s, 1H); 13C NMR (CDCl3, 50 MHz):
d 25.4 (q), 25.6 (q),
nylenemethylene]-
a
-
D
-ribopyranose] (27a/27b). General procedure
25.8 (q), 26.2 (q), 52.6 (q), 52.7 (q), 59.8 (t), 70.8 (d), 72.5 (t), 73.5
(t), 76.5 (d), 86.7 (s), 106.1 (s), 109.5 (s), 113.0 (s), 121.1 (d), 124.8
(d), 130.9 (s), 133.5 (s), 141.6 (s), 144.0 (s), 167.1 (s), 168.0 (s) ppm;
ESI-MS (m/z): 465.5 (14%, [MþH]þ), 487.5(100%, [MþNa]þ), 503.5
(33%, [MþK]þ). Anal. Calcd for C23H28O10: C, 59.48; H, 6.08. Found:
C, 59.69; H, 6.14.
A was followed. Diyne 3 (130 mg, 0.36 mmol) and phenyl acetylene
(0.2 mL, 1.8 mmol) were used to obtain a mixture of 27a and 27b
(130 mg, 78%) as a reddish viscous oil; Rf (30% ethyl acetate/pet.
ether) 0.42; IR (CHCl3)
n
: 3019, 2955, 2857, 1600, 1472, 1255, 1085,
ꢁ0.15, ꢁ0.14 (2s, 6H),
1016, 837 cmꢁ1; 1H NMR (CDCl3, 200 MHz):
d
0.72 (s, 9H), 1.29, 1.30 (2s, 3H), 1.62 (s, 3H), 3.27e3.32 (2dd, J¼5.2,
11.0 Hz, 1H), 3.51, 3.57 (2dd, J¼6.6, 11.0 Hz, 1H), 4.32, 4.33 (2d,
J¼3.6 Hz, 1H), 4.40e4.43 (m, 1H), 5.13e5.19 (m, J¼13 Hz, 2H), 5.94,
5.95 (2d, J¼3.6 Hz, 1H), 7.14e7.31 (m, 2H), 7.36e7.50 (m, 6H); 13C
4.3.23. 1,2:4,5-Di-O-isopropylidene-3-C,3-O-[o-(3- or 4-phenyl)phe-
nylenemethylene]-a-D-psicopyranose (31a/31b). General procedure
A was followed. Diyne 4 (140 mg, 0.43 mmol) and phenyl acetylene
(0.2 mL, 1.7 mmol) were used to procure a mixture of 31a and 31b
(138 mg, 75%) as amorphous solid; Rf (25% ethyl acetate/pet. ether)
NMR (CDCl3, 50 MHz):
d
ꢁ5.7 (q), ꢁ5.5 (q), 18.2 (s), 25.8 (q), 26.3
(q), 26.8 (q), 62.1 (t), 62.1 (d), 73.1 (t), 73.2 (t), 79.9 (d), 83.8 (d), 93.3
(s), 93.4 (s), 103.6 (d), 103.6 (d), 113.2 (s), 113.2 (s), 119.9 (d), 120.3
(d), 121.5 (d), 121.9 (d), 126.8 (d), 127.1 (d), 127.5 (d), 127.9 (d), 128.8
(d), 136.2 (s), 138.0 (s), 138.8 (s), 140.5 (s), 140.5 (s), 141.1 (s), 142.1
(s) ppm; ESI-MS (m/z): 492.0 (100%, [MþNa]þ), 508.0 (25%,
[MþK]þ). Anal. Calcd for C27H36O5Si: C, 69.20; H, 7.74. Found: C,
69.12; H, 7.81.
0.50; mp: 71e73 ꢀC; IR (CHCl3)
n
: 3019, 2935, 1601, 1382, 1133, 1091,
1.27, 1.28, 1.31 (3s, 6H), 1.48
879 cmꢁ1; 1H NMR (CDCl3, 200 MHz):
d
(s, 3H), 1.56 (s, 3H), 3.49 (br d, J¼9.0 Hz, 1H), 4.05, 4.07 (2d,
J¼9.0 Hz, 1H), 4.22e4.28 (m, 3H), 4.46, 4.49 (2d, J¼5.3 Hz, 1H), 5.10,
5.11 (2d, J¼12.3 Hz, 1H), 5.19, 5.24 (2d, J¼12.3 Hz, 1H), 7.19e7.39 (m,
5H), 7.44e7.53 (m, 3H); 13C NMR (CDCl3, 50 MHz):
d 25.6 (q), 25.7
(q), 26.2 (q), 26.3 (q), 26.5 (q), 26.6 (q), 59.7 (t), 59.8 (t), 71.1 (d), 72.6
(t), 73.6 (t), 73.7 (t), 76.6 (d), 86.6 (s), 86.7 (s), 106.7 (s), 109.4 (s),
112.8 (s), 119.4 (d), 120.9 (d), 122.3 (d), 123.8 (d), 126.8 (d), 126.9 (d),
127.2 (d), 127.3 (d), 128.1 (d), 128.7 (d), 137.3 (s), 139.1 (s), 139.4 (s),
140.7 (s), 140.8 (s), 141.0 (s), 142.2 (s) ppm; ESI-MS (m/z): 425.7 (9%,
[MþH]þ), 442.7 (53%, [MþNH4]þ), 447.7 (100%, [MþNa]þ), 463.7
4.3.20. 1,2:4,5-Di-O-isopropylidene-3-C,3-O-(o-phenylene-
methylene)-a-D-psicopyranose (28). General procedure C was fol-
lowed. The cycloaddition of diyne 4 (150 mg, 0.47 mmol) with
acetylene gave 28 (118 mg, 73%) as crystalline solid; Rf (20% ethyl
acetate/pet. ether) 0.30; mp: 91e94 ꢀC; [
a
]
25 ꢁ183.5 (c 1.3, CHCl3);
D

6094
S.B. Suryawanshi et al. / Tetrahedron 66 (2010) 6085e6096
(16%, [MþK]þ). Anal. Calcd for C25H28O6: C, 70.74; H, 6.65. Found: C,
1.0, CHCl3); IR (CHCl3)
n: 3196, 3019, 2927, 2851, 1752, 1697, 1466,
70.52; H, 6.79.
1372, 1270, 1228, 1110, 1061, 875 cmꢁ1; 1H NMR (CDCl3, 200 MHz):
d
1.77 (d, J¼1.1 Hz, 3H), 2.16 (s, 3H), 4.20 (d, J¼2.7 Hz, 1H), 4.74 (d,
4.4. Synthesis of nucleosides 36e38
J¼15.2 Hz, 1H), 4.89 (d, J¼15.2 Hz, 1H), 4.92 (d, J¼2.1 Hz, 1H), 5.22
(d, J¼2.0 Hz, 1H), 6.21 (d, J¼2.1 Hz, 1H), 7.13 (dd, J¼2.5, 7.3 Hz, 1H),
7.22 (d, J¼1.1 Hz, 1H), 7.32e7.38 (m, 2H), 7.46 (dd, J¼2.5, 7.2 Hz, 1H),
4.4.1. 1,2-Di-O-acetyl-4-C-(o-phenylenemethylene)-b-D-xylo-te-
trofuranose (32). Compound 10 (700 mg, 2.82 mmol) in 60% acetic
acid (20 mL) was heated under reflux temperature for 2 h. The re-
action mixture was neutralized by slow addition of solid K2CO3 and
extracted in ethyl acetate. Combined ethyl acetate extracts were
dried (Na2SO4) and concentrated under reduced pressure. The
crude lactols (570 mg, 3.5 mmol) were dissolved in dry CH2Cl2
(15 mL). TEA (5 mL) and catalytic DMAP were added and the mix-
ture was cooled to 0 ꢀC. To this, acetic anhydride (0.77 mL,
8.22 mmol) was added and the contents were stirred at 0 ꢀC for 1 h
and then at room temperature for 1 h. The reaction mixture was
quenched with cold 2 N HCl and extracted in CH2Cl2. Combined
organic phase was washed with satd NaHCO3 and water, dried over
Na2SO4, and filtered and concentrated under reduced pressure.
Purification of the residue by silica gel column chromatography
(15% ethyl acetate in petroleum ether) gave a mixture of diacetates
32 (717 mg, 87% yield) as colorless oil; Rf (20% ethyl acetate/pet.
9.03 (s, 1H); 13C NMR (CDCl3, 50 MHz):
d 2.5 (q), 20.6 (q), 67.2 (t),
74.7 (d), 78.9 (d), 81.6 (d), 88.9 (d),111.0 (s),124.2 (d),127.7 (d),127.9
(s), 129.2 (d), 130.4 (d), 134.1 (s), 136.3 (d), 150.4 (s), 163.9 (s), 169.4
(s) ppm; ESI-MS (m/z): 359.3 (19%, [MþH]þ), 381.2 (100%,
[MþNa]þ). Anal. Calcd for C18H18N2O6: C, 60.33; H, 5.06; N, 7.82.
Found: C, 60.26; H, 4.98; N, 7.76.
4.4.4. 1-[2-O-Acetyl-3-O,4-C-(o-phenylenemethylene)-b-D-xylo-te-
trofuranosyl]-5-fluorouracil (35). Following the procedure used for
the preparation of 33, glycosylation of acetates 32 (100 mg,
0.34 mmol) with 5-fluorouracil (89 mg, 0.68 mmol) gave the nu-
cleoside 35 (96 mg, 78% yield) as a white solid; Rf (60% ethyl ace-
25
tate/pet. ether) 0.31; mp: 194e196 ꢀC; [
a
]
þ2.2 (c 1.1, CHCl3); IR
D
(CHCl3)
1466, 1373, 1345, 1268, 1224, 1091, 1072, 879 cmꢁ1; 1H NMR (CDCl3,
200 MHz):
n: 3239, 3109, 3078, 3024, 2925, 2894, 2853, 1752, 1715,
d
2.17 (s, 3H), 4.20 (d, J¼2.5 Hz, 1H), 4.73 (d, J¼15.2 Hz,
ether) 0.30; IR (CHCl3)
n
: 3032, 2903, 1751, 1638, 1432, 1374, 1242,
1H), 4.90 (d, J¼15.2 Hz, 1H), 4.97 (d, J¼2.5 Hz, 1H), 5.22 (d, J¼1.4 Hz,
1H), 6.15 (t, J¼1.6 Hz, 1H), 7.13 (dd, J¼2.3, 6.4 Hz, 1H), 7.33e7.39 (m,
2H), 7.42e7.46 (m, 1H), 7.50 (d, J¼6.32 Hz, 1H), 9.65 (br s, 1H); 13C
1219, 1087, 1012, 925, 909 cmꢁ1; 1H NMR (CDCl3, 200 MHz):
d
1.94,
2.12, 2.13, 2.16 (4s, 6H), 4.26 (d, J¼3.9 Hz, 0.3H), 4.42 (dd, J¼2.4,
4.3 Hz, 0.7H), 4.61 (2d, J¼14.5 Hz,1H), 4.79, 4.84 (2d, J¼14.5 Hz,1H),
5.03 (t, J¼4.3 Hz, 1H), 5.30 (s, 0.3H), 5.36 (dd, J¼2.4, 4.6 Hz, 0.7H),
6.16 (s, 0.3H), 6.52 (d, J¼4.7 Hz, 0.7H), 7.06e7.13 (m, 1H), 7.26e7.32
NMR (CDCl3, 50 MHz): d 20.5 (q), 67.1 (t), 75.4 (d), 78.4 (d), 81.5 (d),
89.4 (d), 124.8 (d, J¼35.1 Hz), 125.2 (d), 127.5 (s), 127.7 (d), 129.4 (d),
130.5 (d), 133.9 (s), 140.8 (d, J¼238.5 Hz), 149.0 (s), 156.4 (d,
J¼27.2 Hz), 169.4 (s) ppm; ESI-MS (m/z): 385.2 (100%, [MþNa]þ).
Anal. Calcd C17H15FN2O6: C, 56.36; H, 4.17; N, 7.73. Found: C, 56.25;
H, 4.29; N, 7.60.
(m, 2H), 7.42e7.50 (m, 1H); 13C NMR (CDCl3, 50 MHz):
d 20.4 (q),
20.7 (q), 20.9 (q), 21.0 (q), 66.5 (t), 66.9 (t), 72.7 (d), 75.7 (d), 77.7 (d),
78.8 (d), 79.2 (d), 81.6 (d), 94.4 (d), 99.6 (d), 124.2 (d), 124.4 (d),
127.6 (d), 128.4 (d), 128.6 (d), 129.5 (s), 129.9 (d, 2C), 130.0 (d), 130.3
(s), 134.3 (s), 134.8 (s), 168.9 (s), 169.1 (s), 169.2 (s), 169.4 (s) ppm;
ESI-MS (m/z): 315.0 (100%, [MþNa]þ), 331.1 (10%, [MþK]þ). Anal.
Calcd for C15H16O6: C, 61.64; H, 5.52. Found: C, 61.50; H, 5.67.
4.4.5. 1-[3-O,4-C-(o-Phenylenemethylene)-b-D-xylo-tetrofuranosyl]
uracil (36). A solution of 33 (80 mg, 0.36 mmol) and catalytic
NaOMe in methanol (2 mL) was stirred at room temperature for
20 min. The reaction mixture was concentrated under reduced
pressure and the crude was purified by silica gel column chroma-
tography to afford the tricyclic nucleoside 36 (67 mg, 96% yield) as
4.4.2. 1-[2-O-Acetyl-3-O,4-C-(o-phenylenemethylene)-b-D-xylo-te-
trofuranosyl]uracil (33). A solution of acetates 32 (100 mg,
0.34 mmol), uracil (77 mg, 0.68 mmol), and N,O-bis(trimethylsilyl)
acetamide (0.42 mL, 1.71 mmol) in anhydrous CH3CN (5 mL) was
heated to reflux for 15 min. The reaction mixture was cooled to 0 ꢀC
and TMSOTf (0.12 mL, 0.68 mmol) was added. The reaction mixture
was stirred at 50 ꢀC for 2 h, quenched with cold aq NaHCO3, and
extracted with EtOAc. The combined organic layer was washed
with water, dried over Na2SO4, and filtered and concentrated under
reduced pressure. Purification of the residue by silica gel column
chromatography (45% ethyl acetate in petroleum ether) afforded
a
white solid; Rf (70% ethyl acetate/pet. ether) 0.41; mp:
25
140e143 ꢀC; [
3108, 3068, 2923, 2844, 2252, 1775, 1695, 1464, 1393, 1322, 1265,
1114, 1097, 1059, 999 cmꢁ1 1H NMR (CDCl3, 200 MHz):
4.22 (d,
a
]
D
þ60.4 (c 1.9, CHCl3); IR (CHCl3)
n: 3383, 3218,
;
d
J¼1.9 Hz, 1H), 4.52 (s, 1H), 4.64 (d, J¼15.1 Hz, 1H), 4.72 (d, J¼15.1 Hz,
1H), 5.24 (d, J¼1.9 Hz, 1H), 5.48 (d, J¼8.0 Hz, 1H), 5.65 (br s, 1H),
5.89 (s, 1H), 7.10 (dd, J¼2.3, 8.1 Hz, 1H), 7.15 (d, J¼8.0 Hz, 1H),
7.34e7.36 (m, 2H), 7.51 (dd, J¼2.3, 8.1 Hz, 1H), 10.61 (br s, 1H); 13C
NMR (CDCl3, 50 MHz): d 66.9 (t), 77.1 (d), 80.1 (d), 80.7 (d), 94.2 (d),
the nucleoside 33 (97 mg, 82% yield) as a crystalline solid; Rf (60%
101.1 (d), 124.3 (d), 127.8 (d), 128.8 (s), 129.2 (d), 130.8 (d), 134.3 (s),
140.7 (d), 151.1 (s), 164.2 (s) ppm; ESI-MS (m/z): 325.0 (100%,
[MþNa]þ), 341.0 (7%, [MþK]þ). Anal. Calcd for C15H14N2O5: C,
59.60; H, 4.67; N, 9.27. Found: C, 59.52; H, 4.76; N, 9.18.
25
ethyl acetate/pet. ether) 0.35; mp: 214e216 ꢀC; [
a
]
ꢁ8.6 (c 1.0,
D
CHCl3); IR (CHCl3)
n: 3241, 3032, 2927, 2253, 1750, 1686, 1461, 1371,
1320, 1268, 1225, 1108, 1066, 909 cmꢁ1; 1H NMR (CDCl3, 200 MHz):
d
2.17 (s, 3H), 4.19 (d, J¼2.6 Hz, 1H), 4.72 (d, J¼15.2 Hz, 1H), 4.87 (d,
J¼15.2 Hz, 1H), 4.96 (d, J¼2.6 Hz, 1H), 5.22 (d, J¼1.6 Hz, 1H), 5.60
(dd, J¼2.1, 8.2 Hz, 1H), 6.16 (d, J¼1.6 Hz, 1H), 7.11 (dd, J¼2.1, 8.2 Hz,
1H), 7.32e7.48 (m, 4H), 9.21 (br s, 1H); 13C NMR (CDCl3, 50 MHz):
4.4.6. 1-[3-O,4-C-O-(Phenylenemethylene)-b-D-xylo-tetrofuranosyl]
thymine (37). Deacetylation of 34 (70 mg, 0.2 mmol) following
the procedure described above gave nucleoside 37 (57 mg, 95%
d
20.7 (q), 67.3 (t), 75.4 (d), 78.8 (d), 81.7 (d), 89.3 (d), 102.5 (d),
yield) as crystalline solid; Rf (70% ethyl acetate/pet. ether) 0.45;
25
124.4 (d), 127.8 (d), 127.9 (s), 129.4 (d), 130.6 (d), 134.1 (s), 140.5 (d),
150.2 (s),163.1 (s),169.2 (s) ppm; ESI-MS (m/z): 345.1 (6%, [MþH]þ),
367.0 (100%, [MþNa]þ). Anal. Calcd for C17H16N2O6: C, 59.30; H,
4.68; N, 8.14. Found: C, 59.09; H, 4.80; N, 8.26.
mp: 177e179 ꢀC; [
a
]
þ40.0 (c 1.0, MeOH); IR (Nujol)
n: 3392,
D
3220, 3065, 2924, 2854, 1668, 1462, 1377, 1270, 1099, 1062,
916 cmꢁ1 1H NMR (CDCl3, 200 MHz):
;
d
1.61 (d, J¼1.0 Hz, 3H),
4.25 (d, J¼2.6 Hz, 1H), 4.52 (s, 1H), 4.64 (d, J¼15.2 Hz, 1H), 4.74 (d,
J¼15.2 Hz, 1H), 5.23 (d, J¼2.6 Hz, 1H), 5.78 (br s, 1H), 5.93 (s, 1H),
6.97 (d, J¼1.1 Hz, 1H), 7.08e7.13 (m, 1H), 7.33e7.38 (m, 2H),
4.4.3. 1-[2-O-Acetyl-3-O,4-C-(o-phenylenemethylene)-b-D-xylo-te-
trofuranosyl]thymine (34). Following the above procedure, the
glycosylation of acetates 32 (100 mg, 0.34 mmol) with thymine
(86 mg, 0.68 mmol) gave 34 (97 mg, 79% yield) as white solid; Rf
7.47e7.54 (m, 1H), 10.62 (s, 1H); 13C NMR (CDCl3, 50 MHz):
d 2.4
(q), 66.8 (t), 76.8 (d), 80.2 (d), 80.8 (d), 93.8 (d), 109.2 (s), 124.2
(d), 127.8 (d), 128.9 (s), 129.1 (d), 130.7 (d), 134.3 (s), 137.0 (d),
151.0 (s), 164.7 (s) pp; ESI-MS (m/z): 339.1 (100%, [MþNa]þ),
(60% ethyl acetate/pet. ether) 0.35; mp: 192e194 ꢀC; [
a
]
25 ꢁ18.9 (c
D

S.B. Suryawanshi et al. / Tetrahedron 66 (2010) 6085e6096
6095
355.1 (13%, [MþK]þ). Anal. Calcd for C16H16N2O5: C, 60.75; H,
50 MHz): d 12.4 (q),19.9 (q), 20.2 (q), 64.5 (t), 69.9 (d), 71.3 (d), 74.2 (t),
5.10; N, 8.86. Found: C, 60.59; H, 4.97; N, 8.98.
79.5 (d), 89.7 (s),111.5 (s),120.5 (d),121.5 (d),127.7 (d),129.1 (d),134.5
(s),135.3 (d),140.7 (s),150.6 (s),163.7 (s),169.3 (s),169.6 (s) ppm; ESI-
MS (m/z): 431.2 (10%, [MþH]þ), 453.3 (100%, [MþNa]þ), 469.3 (8%,
[MþK]þ). Anal. Calcd for C21H22N2O8: C, 58.60; H, 5.15; N, 6.51. Found:
C, 58.76; H, 4.99; N, 6.63.
4.4.7. 1-[3-O,4-C-(o-Phenylenemethylene)-b-D-xylo-tetrofuranosyl]-
5-fluorouracil (38). Following the procedure used for the preparation
of 36, deacetylation of compound 35 (85 mg, 0.23 mmol) gave 38
(70 mg, 92% yield) as crystalline solid; Rf (70% ethyl acetate/pet. ether)
0.40; mp: 142e144 ꢀC; [
a]
D
25 þ58.5 (c 1.3, MeOH); IR (Nujol)
n: 3400,
4.5.4. 1-[2,4-Di-O-acetyl-3-C,3-O-(o-phenylenemethylene)-b-D-ribo-
3217, 3067, 2924, 2854, 1712, 1461, 1377, 1256, 1081, 964, 909,
pyranosyl]-5-fluorouracil (42). A procedure similar to the one used
for the glycosylation of diacetate 32 was employed. Triacetates 39
(120 mg, 0.33 mmol) and 5-fluorouracil (86 mg, 0.66 mmol) gave
compound 42 (110 mg, 77% yield) as a white solid; Rf (50% ethyl
761 cmꢁ1; 1H NMR (CDCl3, 200 MHz):
d
4.26 (d, J¼2.6 Hz,1H), 4.52 (s,
1H), 4.65 (d, J¼15.1 Hz, 1H), 4.76 (d, J¼15.1 Hz, 1H), 5.24 (d, J¼2.6 Hz,
1H), 5.48 (br s, 1H), 5.87 (d, J¼1.0 Hz, 1H), 7.11 (dd, J¼2.2, 6.8 Hz, 1H),
7.22 (d, J¼6.3 Hz, 1H), 7.31e7.41 (m, 2H), 7.50 (dd, J¼2.2, 6.3 Hz, 1H),
10.84 (d, J¼3.5 Hz, 1H); 13C NMR (CDCl3þmethanol-d4, 50 MHz):
acetate/pet. ether) 0.42; mp: 216e218 ꢀC; [
IR (CHCl3)
1219, 1072, 1043, 904 cmꢁ1
a
]
25 þ38.7 (c 1.5, CHCl3);
D
n
: 3217, 3084, 3023, 2930, 2874, 1732, 1673, 1463, 1373,
d
66.7 (t), 76.4 (d), 80.1 (d, 2C), 92.9 (d), 124.1 (d), 125.1 (d, J¼36.4 Hz),
;
1H NMR (CDCl3, 200 MHz):
d
1.58 (s,
127.5 (d), 128.1 (s), 129.0 (d), 130.3 (d), 133.9 (s), 139.5 (d, J¼234.1 Hz),
149.1 (s),157.7 (d, J¼29.4 Hz), ppm; ESI-MS (m/z): 321.1 (4%, [MþH]þ),
343.1 (100%, [MþNa]þ), 359.0 (13%, [MþK]þ). Anal. Calcd for
C15H13FN2O5:C, 56.25;H, 4.09;N, 7.75. Found:C,56.37;H, 4.18;N, 7.83.
3H), 1.71 (s, 3H), 4.03 (d, J¼8.2 Hz, 2H), 5.15 (d, J¼12.1 Hz, 1H), 5.21
(d, J¼12.1 Hz, 1H), 5.32 (d, J¼9.3 Hz, 1H), 5.38 (t, J¼8.2 Hz, 1H), 6.12
(d, J¼9.3 Hz, 1H), 7.12e7.21 (m, 3H), 7.24e7.28 (m, 1H), 7.53 (d,
J¼6.0 Hz, 1H), 9.81 (br s, 1H); 13C NMR (CDCl3, 50 MHz):
d 19.8 (q),
20.2 (q), 64.4 (t), 69.7 (d), 71.3 (d), 74.2 (t), 80.0 (d), 89.6 (s), 120.5
(d), 121.3 (d), 124.2 (d, J¼34.2 Hz), 127.7 (d), 129.1 (d), 134.3 (s),
140.4 (d, J¼239.1 Hz), 140.6 (s), 149.2 (s), 157 (d, J¼26.6 Hz), 169.5
(s), 169.8 (s) ppm; ESI-MS (m/z): 435.4 (20%, [MþH]þ), 452.47 (35%,
[MþNH4]þ), 457.44 (100%, [MþNa]þ). Anal. Calcd for C20H19FN2O8:
C, 55.30; H, 4.41; N, 6.45. Found: C, 55.21; H, 4.50; N, 6.51.
4.5. Synthesis of nucleosides 43e45
4.5.1. 1,2,4-Tri-O-acetyl-3-C,3-O-(o-phenylenemethylene)
b-D-ribo-
pyranose (39). The procedure for preparing 32 was repeated with
compound 24 (600 mg, 1.53 mmol) to prepare the triacetates 39
(462 mg, 83% yield) as colorless oil Rf (30% ethyl acetate/pet. ether)
0.42; IR (CHCl3)
n
: 3025, 2952, 2872, 1751, 1611, 1463, 1371, 1265,
4.5.5. 1-[3-C,3-O-(o-Phenylenemethylene)-b-D-ribopyranosyl]uracil
1070,1039, 941, 755 cmꢁ1; 1H NMR (CDCl3, 200 MHz):
d
1.70 (s, 3H),
(43). Deacetylation of 40 (90 mg, 0.22 mmol), as followed in the
preparation of 36, gave nucleoside 43 (68 mg, 95% yield) as a white
1.74 (s, 3H), 2.09 (s, 3H), 4.01 (d, J¼8.1 Hz, 2H), 5.19 (d, J¼12.0 Hz,
1H), 5.22 (d, J¼12.0 Hz, 1H), 5.31 (d, J¼8.5 Hz, 1H), 5.33 (t, J¼8.4 Hz,
1H), 6.04 (d, J¼8.5 Hz, 1H), 7.19 (d, J¼7.87 Hz, 1H), 7.23e7.33 (s, 3H);
solid; Rf (10% i-PrOH/CH2Cl2) 0.35; mp: 138e140 ꢀC; [
a
]
25 þ56.5 (c
D
0.4, MeOH); IR (Nujol)
n: 3393, 3018, 2961, 2854, 1679, 1459, 1377,
13C NMR (CDCl3, 50 MHz):
d
20.1 (q), 20.3 (q), 20.9 (q), 63.1 (t), 70.2
1243, 1062 cmꢁ1; 1H NMR (methanol-d<GK>4, 200 MHz):
d 3.85 (t,
(d), 71.9 (d), 74.2 (t), 90.0 (s), 91.8 (d), 120.3 (d), 122.0 (d), 127.7 (d),
128.9 (d), 134.7 (s), 140.6 (s), 169.0 (s), 169.3 (s), 169.4 (s) ppm; ESI-
MS (m/z): 387.2 (100%, [MþNa]þ), 403.2 (12%, [MþK]þ). Anal. Calcd
for C18H20O8: C, 59.34; H, 5.53. Found: C, 59.22; H, 5.60.
J¼10.8 Hz, 1H), 3.94 (dd, J¼5.4, 10.8 Hz, 1H), 4.03 (dd, J¼5.4, 10.8 Hz,
1H), 4.06 (d, J¼9.5 Hz, 1H), 5.22 (d, J¼11.8 Hz, 1H), 5.27 (d,
J¼11.8 Hz,1H), 5.73 (d, J¼8.1 Hz,1H), 5.86 (d, J¼9.5 Hz,1H), 7.25 (dd,
J¼6.1, 1.55 Hz, 1H), 7.30e7.35 (m, 2H), 7.38e7.40 (m, 1H), 7.79 (d,
J¼8.1 Hz, 1H); 13C NMR (methanol-d<GK>4, 50 MHz):
d 68.8 (t),
4.5.2. 1-[2,4-Di-O-acetyl-3-C,3-O-(o-phenylenemethylene)-
b
-
D-ribo-
71.4 (d), 72.7 (d), 75.8 (t), 83.7 (d), 93.9 (s), 103.2 (d), 121.8 (d), 122.3
(d), 128.6 (d), 129.4 (d), 139.5 (s), 142.9 (d), 143.0 (s), 152.9 (s), 166.1
(s) ppm; ESI-MS (m/z): 333.60 (19.12%, [Mþ1]þ), 355.60 (100%,
[MþNa]þ), 371.57 (11.03%, [MþK]þ). Anal. Calcd for C16H16N2O6: C,
57.83; H, 4.85; N, 8.43. Found: C, 57.95; H, 4.98; N, 8.56.
pyranosyl]uracil (40). A procedure similar to the one used for the
glycosylation of diacetate 32 was employed. Triacetates 39 (120 mg,
0.33 mmol) and uracil (74 mg, 0.66 mmol) were used to obtain nu-
cleoside 40 (115 mg, 84% yield) as crystalline solid; Rf (50% ethyl ac-
etate/pet. ether) 0.38; mp: 213e215 ꢀC; [
(CHCl3)
a
]
25 þ52.7 (c 1.1, CHCl3); IR
D
n
: 3214, 3021, 2962, 2928, 2873,1754, 1695, 1634, 1456,1373,
4.5.6. 1-[3-C,3-O-(o-Phenylenemethylene)-b-D-ribopyranosyl]thy-
1219, 1071, 1041, 810, 765 cmꢁ1; 1H NMR (CDCl3, 200 MHz):
d
1.57 (s,
mine (44). Deacetylation of 41 (80 mg, 0.19 mmol), as followed in
the preparation of 36, afforded nucleoside 44 (58 mg, 90% yield) as
a crystalline solid; Rf (10% i-PrOH/CH2Cl2) 0.40; mp: 116e118 ꢀC;
3H),1.70 (s, 3H), 4.01 (d, J¼8.1 Hz, 2H), 5.14 (d, J¼12.3 Hz,1H), 5.22 (d,
J¼12.3 Hz, 1H), 5.25e5.33 (m, 2H), 5.72 (d, J¼8.2 Hz, 1H), 6.15 (d,
J¼9.4 Hz,1H), 7.12e7.27 (m, 4H), 7.39 (d, J¼8.2 Hz,1H), 9.10 (br s,1H);
[a
]
25 þ30.0 (c 0.8, MeOH); IR (Nujol)
n: 3371, 3017, 2925, 2855,1653,
D
13C NMR(CDCl3, 50 MHz):
d
19.8 (q), 20.2(q), 64.4 (t), 69.8(d), 71.2(d),
1463, 1377, 1064, 762 cmꢁ1; 1H NMR (acetone-d<GK>6, 500 MHz):
74.2 (t), 79.5 (d), 89.6 (s),103.1 (d),120.5 (d),121.4 (d),127.7 (d),129.0
(d),134.3 (s),139.7 (d),140.6 (s),150.5 (s),163.0 (s),169.3 (s),169.6 (s)
ppm; ESI-MS (m/z): 417.5 (40%, [MþH]þ), 439.5 (100%, [MþNa]þ),
455.5 (19%, [MþK]þ). Anal. Calcd for C20H20N2O8: C, 57.69; H, 4.84; N,
6.73. Found: C, 57.56; H, 4.94; N, 6.86.
d
1.85 (d, J¼1.07 Hz, 3H), 3.83 (t, J¼10.8 Hz, 1H), 3.91 (br d, J¼8.8 Hz,
C(4)-OH, 1H), 3.93 (dd, J¼5.5, 10.8 Hz, 1H), 4.09 (ddd, J¼10.8, 8.8,
5.5 Hz), 4.17 (d, J¼8.5 Hz, C(2)eOH, 1H), 4.23 (dd, J¼8.8, 9.5 Hz, 1H),
5.24 (d, J¼11.7 Hz,1H), 5.29 (d, J¼11.7 Hz,1H), 5.90 (d, J¼9.5 Hz,1H),
7.27e7.28 (m, 1H), 7.30e7.35 (m, 2H), 7.40e7.42 (m, 1H), 7.63 (q,
J¼1.1 Hz, 1H), 10.12 (br s, 1H); 13C NMR (acetone-d<GK>6, 50 MHz):
4.5.3. 1-[2,4-Di-O-acetyl-3-C,3-O-(o-phenylenemethylene)-
b
-
D-ribo-
d 12.3 (q), 68.5 (t), 71.1 (d), 72.2 (d), 75.3 (t), 82.8 (d), 93.5 (s), 110.8
pyranosyl]thymine (41). Following the procedure used for the prep-
aration of 33, glycosylation of triacetates 39(110 mg, 0.30 mmol)with
thymine (76 mg, 0.60 mmol) gave compound 41 (99 mg, 76% yield) as
a crystalline solid; Rf (50% ethyl acetate/pet. ether) 0.40; mp:
(s), 121.4 (d), 122.0 (d), 127.9 (d), 128.7 (d), 137.1 (d), 139.7 (s), 142.5
(s), 152.0 (s), 164.2 (s) ppm; ESI-MS (m/z): 369.1 (100%, [MþNa]þ),
385.2 (6%, [MþK]þ). Anal. Calcd for C17H18N2O6: C, 58.96; H, 5.24; N,
8.09. Found: C, 59.10; H, 5.06; N, 7.97.
158e160 ꢀC; [
a]
D
25 þ20.0 (c 1.2, CHCl3); IR (CHCl3)
n
: 3389, 3020, 2874,
1745, 1686, 1461, 1373, 1216, 1150, 1071, 1042, 985 cmꢁ1
;
1H NMR
4.5.7. 1-[3-C,3-O-(o-Phenylenemethylene)-b-D-ribopyranosyl]-5-
(CDCl3, 200 MHz):
d
1.61 (s, 3H), 1.74 (s, 3H), 1.91 (s, 3H), 4.05 (dd,
fluorouracil (45). The deacetylation of compound 42 (90 mg,
0.21 mmol) was carried out according to the procedure used for the
preparation of 36, giving nucleoside 45 (67 mg, 93% yield) as
a crystalline solid; Rf (10% i-PrOH/CH2Cl2) 0.40; mp: 153e155 ꢀC;
J¼7.3, 9.1 Hz, 2H), 5.19 (d, J¼12.1 Hz, 1H), 5.25 (d, J¼12.1 Hz, 1H), 5.33
(dd, J¼7.3, 9.1 Hz, 1H), 5.35 (d, J¼9.5 Hz, 1H), 6.18 (d, J¼9.5 Hz, 1H),
7.19e7.23 (m, 2H), 7.26e7.32 (m, 3H), 9.37 (br s,1H); 13C NMR (CDCl3,

6096
25
S.B. Suryawanshi et al. / Tetrahedron 66 (2010) 6085e6096
5669e5672; (f) Hudlicky, T.; Moser, M.; Banfield, S. C.; Rinner, U.; Chapius, J.-C.;
[
a]
þ44.0 (c 0.7, MeOH); IR (Nujol)
n
: 3387, 3021, 2920, 2854,
1698, 1666, 1461, 1377, 1284, 1245, 1063, 914, 756 cmꢁ1 1H NMR
(methanol-d<GK>4, 200 MHz):
3.85 (t, J¼10.9 Hz, 1H), 3.95 (dd,
D
Pettit, G. R. Can. J. Chem. 2006, 84, 1313e1337; (g) Ramana, C. V.; Salian, S. R.;
Gonnade, R. G. Eur. J. Org. Chem. 2007, 5483e5486; (h) Alayrac, C.; Schollmeyer,
D.; Witulski, B. Chem. Commun. 2009, 1464e1466.
;
d
15. (a) Larghi, E. L.; Kaufman, T. S. Synthesis 2006, 187e220; (b) Arimitsu, S.;
Hammond, G. B. J. Org. Chem. 2006, 71, 8665e8668; (c) Rodrigo, R. Tetrahedron
1988, 44, 2093e2135; (d) Markaryan, E. A.; Samodurova, A. G. Russ. Chem. Rev.
1989, 58, 479e493; (e) Curtis, P. J.; Grove, J. F. Nature 1947, 160, 574e575;
(f) Grove, J. F.; Hitchcock, P. B. J. Chem. Soc., Perkin Trans. 1 1986, 1145e1146;
(g) Parisot, D.; Devys, D. M.; Ferezou, J. P.; Barbier, M. Phytochemistry 1983, 22,
1301e1303; (h) Pushan, W.; Xuanliang, G.; Yixiong, W.; Fukuyama, Y.; Miura, I.;
Sugawara, M. Phytochemistry 1984, 23, 2033e2038.
J¼5.3, 10.7 Hz, 1H), 3.99e4.04 (m, 2H), 5.22 (d, J¼11.9 Hz, 1H), 5.26
(d, J¼11.9 Hz, 1H), 5.84 (dd, J¼1.5, 9.5 Hz, 1H), 7.23e7.25 (m, 1H),
7.29e7.38 (m, 3H), 7.94 (d, J¼6.5 Hz, 1H); 13C NMR (methanol-
d<GK>4, 50 MHz): d 68.5 (t), 71.0 (d), 72.5 (d), 75.6 (t), 83.6 (d), 93.5
(s), 121.6 (d), 121.9 (d), 124.4 (d, J¼34.3 Hz), 128.4 (d), 129.2 (d),
139.0 (s), 141.7 (d, J¼235.1 Hz), 142.5 (s), 151.2 (s), 159.1 (d,
J¼26.9 Hz) ppm; ESI-MS (m/z): 351.5 (18%, [MþH]þ), 373.5 (100%,
[MþNa]þ). Anal. Calcd for C16H15FN2O6: C, 54.86; H, 4.32; N, 8.00.
Found: C, 54.71; H, 4.48; N, 8.13.
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Acknowledgements
We thank the Department of Science and Technology (SR/S5/
GC-20/2007) for funding and CSIR (New Delhi) for the research
fellowships granted to SBS and MPD.
17. For aromatic ring annulation on sugar templates see: (a) Martin, O. R. Carbo-
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18. Adharvana, M.; Chari, K. S. Synthesis 2005, 708e710.
Supplementary data
1H, 13C spectra of selected compounds and 2D NMR spectra
wherever applicable. Supplementary data associated with this ar-
ticle can be found in online version at doi:10.1016/j.tet.2010.06.011.
These data include MOL files and InChIKeys of the most important
compounds described in this article.
19. (a) Ohira, S. Synth. Commun. 1989, 19, 561e564; (b) Roth, G. J.; Liepold, B.;
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27. X-ray intensity data of compounds 33, 37, and 40 was collected on a Bruker
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a
¼0.
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71073 A) radiation at room temperature. All the data were corrected for Lor-
entzian, polarization, and absorption effects using Bruker’s SAINT and SADABS
programs. SHELX-97 ( Sheldrick, G. M. SHELX-97 Program for Crystal Structure
Solution and Refinement; University of Gottingen: Germany, 1997; )25,26 was
used for structure solution and full-matrix least-squares refinement on F2.
Hydrogen atoms were included in the refinement as per the riding model.
28. Sheldrick, G. M. SHELX-97 Program for Crystal Structure Solution and Refinement;
University of Gottingen: Germany, 1997.
29. The crystallographic data has been deposited with the Cambridge Crystallo-
graphic Data Centre as deposition No. CCDC768342 (33) CCDC768343 (37) and
CCDC768344 (40). Copies of the data can be obtained, free of charge, on ap-
plication to the CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: þ44 1223
336033; e-mail: deposit@ccdc.cam.ac.uk].
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