The influence of electronic factors on Pd-mediated cycloisomerization: a systematic investigation of competitive 6-exo-dig versus 7-endo-dig cyclizations of sugar alkynols

Article abstract of DOI:10.1016/j.tet.2009.09.071

Pd-mediated cycloisomerization of 3-C-propargyl-ribo- and allofuranose derivatives was investigated in detail to understand the influence of electronic factors on the regioselectivity (6-exo- vs 7-endo) of alkynol cycloisomerization leading either to a si

Full text of DOI:10.1016/j.tet.2009.09.071

Tetrahedron 65 (2009) 9819–9832
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The influence of electronic factors on Pd-mediated cycloisomerization:
a systematic investigation of competitive 6-exo-dig versus 7-endo-dig
cyclizations of sugar alkynols
*
C.V. Ramana , Boddeti Induvadana, Burgula Srinivas, Kommagalla Yadagiri,
Madhusudhan N. Deshmukh, Rajesh G. Gonnade
National Chemical Laboratory, Pune 411 008, Maharashtra, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Pd-mediated cycloisomerization of 3-C-propargyl-ribo- and allofuranose derivatives was investigated in
detail to understand the influence of electronic factors on the regioselectivity (6-exo- vs 7-endo) of
alkynol cycloisomerization leading either to a six- or seven-membered ring. In general, the 6-exo-dig
mode of cyclization is facile and is independent of electronic factors. With some of the alkynols, a re-
gioselective (7-endo?) hydration of the alkyne unit was observed and this has been attributed to the
participation of C(3)–OH. When the C(3)–OH was protected as its benzyl ether, cycloisomerization of
these alkynols occurred exclusively in a 6-exo-dig mode resulting in the corresponding [3.2.1]-bicyclic
ketals. Additional control experiments conducted were in support of the participation of C(3)–OH in
regioselective alkyne hydration.
Received 11 June 2009
Received in revised form
17 September 2009
Accepted 17 September 2009
Available online 19 September 2009
Keywords:
Palladium
Alkynol cycloisomerization
Bridged bicyclic ketal
Sonogashira coupling
Sugar alkynol
Ó 2009 Elsevier Ltd. All rights reserved.
1. Introduction
the ꢀI effect of furanose ring and the þM effect of the aryl
substituents influences the mode of cyclization. The presence of
The intramolecular addition of C- and heteroatom nucleophiles
across the alkynes falls under the broad category of cyclo-
isomerization reactions.1 The cycloisomerization is projected as
a tool for synthesis of oxygen-containing heterocycles encom-
passing functionalized furan, pyran, benzopyran, and spiroketal
skeletons.2 Various transition metals like palladium, gold, plati-
num, tungsten, molybdenum, ruthenium, rhodium, and iridium
have been explored as catalysts in cycloisomerization reactions.3
The key issue of the cycloisomerization reactions is the mode of
cyclization, i.e., exo-dig versus endo-dig.4 In this context, recently
we reported a systematic investigation dealing with the influence
of electronic and steric factors over competitive 5-exo-dig versus
6-endo-dig cyclizations mediated by the Pd(CH3CN)2Cl2 complex.5,6
Using a large set of substrates for the projected cycloisomerization
reaction, we noticed that Pd promoted cycloisomerization reactions
were substantially influenced by electronic factors, which is in
contrast with the base promoted cycloisomerizations.6 From the
results obtained, we concluded that competitive balance between
a þM substituent (–OMe) on the aromatic ring in general enforced
a 6-endo-dig while the presence of a ꢀM group (–NO2) favored
5-exo-dig modes of cyclization. In the cases where the exo-mode of
ring closure is disfavored due to ring strain we noticed exclusive
6-endo cyclization.6b
Compared to the competitive 5-exo-dig/6-endo-dig case, reports
concerning the 6-exo-dig/7-endo-dig cyclizations are less
frequent.7,8 The seminal publications by Utimoto et al. on the Pd-
mediated cycloisomerization of
u-alkynols show that 5-exo and
6-exo-dig cyclizations are more favored over their competitive endo-
dig cyclizations.2f A one pot Sonogashira coupling and cyclo-
isomerization of 3-, 4-, and 5-alkynols with aryl halides were studied
by Santelli and co-workers using the tedicyp ligand.7c In general,
6-exo-dig mode of cyclizations was documented and the cyclizations
are favored only with electron deficient aryl halides whereas with
electron rich aryl halides, only coupling products were isolated.
Results published by Luo et al. showed that oxypalladation and
cross-coupling of acetylenic alkoxides generally prefer to undergo 6-
exo-ring closure.5h Liu and de Brabander reported regiochemical
control in the cycloisomerization of electronically unbiased internal
alkynes by selecting appropriate catalysts and conditions.7d While
our work was in progress, Ley and co-workers reported the selective
* Corresponding author. Tel.: þ91 20 25902577; fax: þ91 20 25902629.
E-mail address: vr.chepuri@ncl.res.in (C.V. Ramana).
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.09.071

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C.V. Ramana et al. / Tetrahedron 65 (2009) 9819–9832
7-endo cyclization of alkyne diols by employing PtCl4 as the
catalyst.7e
hydrolysis of the 5,6-O-acetonide group of 26–30 with cat. H2SO4 in
methanol completed the synthesis of the projected cyclo-
isomerization substrates 13–17.
In continuation of our interest in the Pd-mediated cyclo-
isomerization of sugar alkynol and the synthesis of natural prod-
ucts having either bridged- or spiro-bicyclic ketal units, we were
interested to learn the control of electronic factors over the com-
petitive 6-exo-dig versus 7-endo-dig modes of cyclization.6 Herein
we describe our investigations in this direction, employing two sets
of 3-C-propargylfuranosyl derivatives (Fig. 1) 8–12, and 13–17. With
the first set of compounds 8–12, the cycloisomerization should lead
either to [3.4.0]- or [3.5.0]-dioxabicyclic enol ether derivatives,
whereas the formation of fused [3.2.1]- or [4.2.1]-bicyclicacetal
derivatives is possible from the second set of compounds 13–17
(Fig. 1).
The palladium-catalyzed cycloisomerization reactions of model
3-C-propargyl-ribofuranose derivatives 8–12 were carried out in
the presence of Pd(CH3CN)2Cl2 in MeCN at room temperature. The
results are summarized in Table 1. The parent compound 8 gave
exclusively the fused dihydropyran 31 resulting from the double
bond isomerization of the intermediate exo-methylene derivative.13
A doublet resonating at 1.79 (d, J¼0.8 Hz, 3H) ppm in the 1H NMR
spectrum of compound 31 indicated the presence of a methyl group
attached to an olefin. There is one additional signal in the downfield
region 4.40 (br q, J¼0.8 Hz, 1H) ppm along with the sugar ring
protons and it was characterized as the internal olefinic proton. The
Figure 1. Competitive 6-exo-dig versus 7-endo-dig cyclizations, some representative examples, and designed substrates 8–17.
2. Results and discussion
assigned structure of 31 was further supported by the 13C NMR
spectrum where signals corresponding to the primary methyl and
endocyclic tertiary olefinic-CH and endocyclic quaternary
–C appeared at 20.3 (q), 95.0 (d), and 156.2 (s) ppm, respectively.
Cycloisomerization of alkynol 9 (Table 1) afforded the 6-exo-
product 32 along with small amounts of the hemiketal 33. The
structure of compound 32 was determined with the help of NMR
spectroscopy, which shows the characteristic benzylic protons at
3.36 (d, J¼16.5 Hz, 1H), 3.40 (d, J¼16.5 Hz, 1H) ppm, and endocyclic
olefinic proton at 4.40 (br d, J¼1.1, Hz, 1H) ppm in 1H NMR (Table 1).
Peaks at 40.5 (t) for the benzylic CH2, at 96.2 (d) for olefinic-CH, and
at 158.5 (s) for the quaternary olefinic carbon in 13C NMR indicate
the 6-exo-dig cyclization with the concomittant isomerization of the
double bond. The structure of compound 32 was further confirmed
The synthesis of the requisite model 3-C-propargyl-ribofuranose
derivatives 8–12 started with propargylation of the known 3-ulose
derivative 189 under Barbier conditions to afford 20 along with the
allene 19 (Scheme 1).10 The Sonogashira coupling11 of 20 with
different aryl iodides was carried out to obtain compounds 21–24.
The TBS group present at O-5 of 20–24 was subsequently removed
by using TBAF/THF to give the first set of cycloisomerization sub-
strates 8–12. The synthesis of the projected cycloisomerization
substrates 13–17 was carried out in a similar way following the
Sonogashira coupling with the 3-C-propargyl-allofuranose
derivative 26 (prepared according to the literature procedure from
ulose 25) (Scheme 1)12 affording compounds 27–30. The selective
Scheme 1. Synthesis of (a) 3-C-propargyl-ribo- (8–12) and (b) allofuranose derivatives (13–17).

C.V. Ramana et al. / Tetrahedron 65 (2009) 9819–9832
9821
Table 1
Pd-mediated cycloisomerization of alkynols 8–12
Ar
d (ppm)
8
9
10
11
12
H-
Ph-
4-MeOPh–
4-O2NPh–
3-O2NPH–
31 (64%) 4.40
32 (60%) 4.40
34 (16%) 4.40
36 (60%) 4.51
38 (53%) 4.53
d
d
d
33 (19%)
d
35 (55%)
d
37 (14%)
39 (13%)
d
from its single crystal X-ray structural analysis.15–17 The character-
istic internal methylene protons of pyran at 1.57 (d, J¼14.1 Hz, 1H),
1.69 (d, J¼14.1 Hz, 1H) ppm, and benzylic CH2 protons at 2.82
(d, J¼13.6 Hz, 1H), 3.03 (d, J¼13.6 Hz, 1H) ppm in the 1H NMR
spectrum of compound 33 indicated the assigned ketal structure,
which was further supported by the 13C NMR spectrum where the
characteristic peaks at 37.0 (t) for internal CH2, 47.5 (t) for benzylic
CH2, 95.5 (s) for hemiketal carbon appeared. With alkynol 10,
cycloisomerization gave the dihydropyran 34 (6-exo) and the keto
compound 35. Cycloisomerization of alkynols 11 and 12 gave dihy-
dropyran derivatives 36 and 38 and the hemiketals 37 and 39,
respectively. The dihydropyrans 31, 32, 34, 36, and 38 and the ketals
33, 37, and 39 have similar NMR spectral pattern (Table 1). The single
crystal X-ray analyses of (Fig. 2) of ketals 37 and 39 unambiguously
proved their structures.15–17
The results of the Pd(CH3CN)2Cl2 catalyzed cycloisomerizations
of the 3-C-propargyl-allofuranose derivatives 13–17 are given in
Scheme 2. As indicated in Table 2, the cycloisomerization of mon-
osubstituted alkynol 13 gave exclusively [3.2.1]-bicyclic acetal 40.
The appearance of the methylene unit protons separately as dou-
blets at
d 1.62 and 1.95 with a large geminal coupling constant
(14.7 Hz) in the 1H NMR spectrum of 4014 clearly indicates that this
methylene unit has no coupled adjacent-H and thus established the
assigned [3.2.1]-bicyclic acetal structure. The presence of a quater-
nary carbon at 105.3 (s) ppm in the 13C NMR spectrum corre-
sponding to the ketal carbon further confirms the assigned structure
to 40. The cycloisomerization of p-nitrophenyl substituted alkynol
16 also gave exclusively the exo-cyclic product 43 where the
methylene protons resonated as doublets at
d 1.66 and 2.01 with
a large geminal coupling constant (14.4 Hz) in the 1H NMR spec-
trum and the characteristic ketal carbon at 105.7 (s) ppm in the 13C
NMR spectrum. The cycloisomerization of alkynols 14, 15, and 17,
gave exclusively keto derivatives 41, 42, and 44, respectively. The
structure of 41 was deduced from the 1H NMR spectrum where all
the four methylene protons resonated separately as dd or ddd be-
tween 1.81 and 3.40 ppm thus displaying the through bond con-
nectivity between all of them. The appearance of a quaternary
carbon singlet around 200 ppm in the 13C NMR spectrum
confirmed the presence of a carbonyl carbon. Characteristic NMR
peaks of 41, 42, and 44 are given in Table 3.
To summarize, the cycloisomerization of 3-C-propargyl-ribo-
furanose derivatives 8, 9, 11, and 12 resulted in exclusive 6-exo-dig
products. With compound 10, the keto compound 35 was isolated
as the major product. The enol ether 34 resulting from a 6-exo-dig
cyclization followed by isomerization was obtained as the minor
product. The cycloisomerization of alkyne diols 13–17, the alkynols
13 and 16 gave the [3.2.1]-bicyclic acetals 40 and 43, whereas the
other three alkynols 14, 15, and 16 gave the ketones 41, 42, and 44,
respectively. The constitution of these products indicated a regio-
selective hydration of the internal alkyne resulting exclusively a- to
the phenyl ring. The exclusive formation of 6-exo products from the
phenyl derivative 9 and the 3-NO2 phenyl derivatives 12 and 17 is
interesting since the cyclization of the corresponding substrates
without the propagylic –CH2 (Fig. 3)6c gave both 5-exo and 6-endo
products in varying ratios. This indicates a nominal influence of the
electronic factors on the regioselectivity of alkynol cylization where
the competition is between 6-exo- versus 7-endo cyclizations, the
latter being energetically more demanding. This was supported by
the formation of 6-exo-product from the PMP derivative 14.
The formation of the keto compounds 35, 41, 42, and 44, there
are three possibilities that exist (Fig. 4). They are: (a) the hydrolysis
of the intermediate 7-endo products, (b) the hydration of the alkyne
directly,18 and (c) hydration assisted by the C(3)–OH (initial cycli-
zation in a 5-endo manner and hydrolysis of intermediate dihy-
drofuran derivative, path ii). However, formation of the keto
compounds with the same regioselectivity from PMP and also from
Figure 2. ORTEP structures of compounds (a) 32, (b) 37, and (c) 39.

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C.V. Ramana et al. / Tetrahedron 65 (2009) 9819–9832
Scheme 2. Synthesis of 3-O-benzyl protected 3-C-propargyl-allofuranose derivatives 50–54.
Table 2
Pd-mediated cycloisomerization of alkynols 13–17
Ar
d (ppm)
13
14
15
16
17
H–
Ph–
4-MeOPh–
4-O2NPh–
3-O2NPH–
40 (70%) (1.62 and 1.95)
d
d
41 (66%)
42 (60%)
d
d
43 (70%) (1.66 and 2.01)
d
44 (60%)
Figure 4. The two possible modes for the formation of ketones 41, 42, and 44.
acetonide of resulting products 45–49 was selectively hydro-
lyzed to prepare the alkyne diols 50–54 (Scheme 2). The details
of the Pd-mediated cycloisomerization of compounds 50–54 are
given in Table 4. With all the substrates, we isolated [3.2.1]-bi-
cyclic acetals resulting from the 6-exo-dig mode of cyclization
(Fig. 5). The exclusive formation of the 6-exo-product from 52 is
remarkable and suggests the absence of electronic influence on
the 6-exo- versus 7-endo competition, with the former being
found to be energetically more facile. These results are in sup-
port of the participation of C(3)–OH in alkyne hydration. To
cross-check this, the acetonides 28 and 47 were exposed to the
cycloisomerization conditions (Scheme 3) anticipating hydration
at least with the compound 28. However, the bicyclic ketals 61
and 57 were obtained, respectively, from the alkynes 28 and 47.
The assigned structure for 61 was deduced from the NMR
spectral analysis, wherein the four methylene protons resonated
separately at 1.52, 2.05–2.21, 2.36–2.54, and 3.69 ppm in the 1H
NMR. The exclusive formation of the 6-exo-product 61 from the
3-O-benzyl derivative could be resulting from the initial
hydrolysis of the terminal acetonide group19 followed by the
Table 3
1H and 13C chemical shifts for 41, 42, and 44
R
Ph (41)
4-MeOPh (42)
3-NO2Ph (44)
da
db
1.88
2.30
1.87
2.30
1.90
2.31
dc
3.10
3.04
3.10
dd
3.39
3.33
198.6
3.40
199.9
dC]O
200.0
the 3-NO2 derivative rules out the possibility of both the direct
hydration of alkyne unit or hydrolysis of the initially formed 7-
endo-product. The only option left is the participation of C(3)–OH in
a 5-endo fashion and subsequent hydrolysis.
In order to probe in this direction, we have protected the 3ꢁ-
OH as its benzyl ether 45 and subjected it to the Sonogashira
coupling with the four aryl iodides. Subsequently, the terminal
Table 4
Pd-mediated cycloisomerization of substrates 50–54 and characteristic chemical
shifts
Ar
50
51
52
53
54
H–
Ph–
4-MeOPh–
4-O2NPh–
3-O2NPH–
55 (82%) (1.37 and 2.33)
56 (82%) (1.29 and 2.27)
57 (81%) (1.27 and 2.24)
58 (68%) (1.38 and 2.32)
59 (67%) (1.35 and 2.33)
d
d
d
d
Figure 3. Observed exo/endo selectivities in the competitive 5-exo- versus 6-endo and
6-exo- versus 7-endo cyclization.
60 (17%)

C.V. Ramana et al. / Tetrahedron 65 (2009) 9819–9832
9823
(8–12) is indicative of the nature of the nucleophile (reactivity of
1ꢁ-OH>2ꢁ-OH). In the former case (13–16), the incoming
nucleophile in a 6-exo-mode is a 2ꢁ-OH whereas the same in the
latter case (8–12) is
a
1ꢁ-OH. In both the instances the
competing nucleophile in a 5-endo mode is a 3ꢁ-OH.
3. Conclusions
In summary, electronic control over the 6-exo-dig versus 7-endo-
dig modes of cyclizations in Pd-mediated cycloisomerization
reaction has been studied in detail. The 3-C-propargyl allo- and
ribofuranose derivatives, with systematic variation of functional
groups at the other side of alkyne, were employed to understand the
competitive balance between the inductive effect of the furanose
ring and the mesomeric effect of the aryl substituent. Unlike with 3-
C-alkynyl allo- and ribofuranose derivatives, where the regiose-
lectivity of the cyclization was in line with the electronic control,
with the 3-C-propargyl-ribo derivatives, we observed complete 6-
exo-dig selectivity without any electronic interference. However,
intermediate exo-cyclic enol ethers isomerized to more stable
endocyclic enol ethers. With 1,2-O-isopropylidene-3-C-propargyl-
allofuranose derivatives, competitive hydration of the alkyne unit
with complete regioselectivity was observed. The cyclo-
isomerization of the corresponding 3-O-benzyl protected allofur-
anose derivatives revealed that the ketones are resulting from the
participation of C(3)–OH in a 5-endo fashion followed by the hy-
drolysis of the intermediate dihydrofuran derivative. This was sup-
ported by the Pd-mediated cyclization of the selected diacetonides
having the PMP group on alkyne and with either C(3)–OH free or
with the corresponding O-benzyl ether. Overall, these results in-
dicate that in the Pd-mediated alkynol cycloisomerizations, the 6-
exo-dig mode of cyclization is favored over the 7-endo-dig mode of
cyclization and is not influenced by electronic factors.
4. Experimental
4.1. General methods
Air and/or moisture sensitive reactions were carried out in an-
hydrous solvents under an atmosphere of argon in oven-dried
glassware. All anhydrous solvents were distilled prior to use: THF
from Na and benzophenone; DMF and CH3CN from CaH2; MeOH
from Mg cake. Commercial reagents were used without purification.
Column chromatography was carried out by using Spectrochem
silica gel (60–120 mesh). Optical rotations were determined on
Figure 5. ORTEP structures of compounds (a) 56 and (b) 58.
cycloisomerization of the intermediate alkynol 52, both being
the reactions catalyzed by the Pd(II) complex. The formation of
a [4.2.1]-bicyclic ketal 61 could be explained by initial C(3)–OH
assisted alkyne hydration of 28 resulting in a ketone, which
subsequently would undergo an intramolecular ketal exchange.
It is seen that these control experiments with the acetonides
provided further evidence of the active role of C(3)–OH in alkyne
hydration. The formation of keto compounds indicates a com-
peting 5-endo-dig cyclization over the 6-exo-dig even in the
cases where the former is not supported by the electronic
factors. The fact that the alkyne hydration was a competitive
side reaction in the allo-series (13–16), but not in the ribo-series
a Jasco DIP-370 digital polarimeter. Specific optical rotations [a]D are
given in 10ꢀ1 deg cm2 gꢀ1. 1H and 13C NMR spectroscopy measure-
ments were carried out on Bruker AC 200 MHz or Bruker DRX
500 MHz spectrometers, and TMS was used as internal standard. 1H
and 13C NMR chemical shifts are reported in parts per million
downfield from tetramethylsilane and 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 13C NMR
signals was assigned with the help of DEPT spectra and the abbre-
viations used: s¼singlet, d¼doublet, t¼triplet, 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 Analyser.
4.2. Barbier reaction of ketone 18 with propargy bromide
Zn (5.05 g, 77.69 mmol), propargyl bromide (4.15 mL,
46.62 mmol), in THF (50 mL) was stirred vigorously for 30 min, to
which a solution of ketone 18 (4.7 g, 15.53 mmol) in THF (50 mL)
Scheme 3. Pd-mediated cycloisomerization of acetonides 28 and 47.

9824
C.V. Ramana et al. / Tetrahedron 65 (2009) 9819–9832
was added and the stirring was continued for another 30 min. The
reaction mixture was cooled to 0 ꢁC and saturated NH4Cl (25 mL)
was added dropwise for 30 min and stirring was continued over-
night. Reaction mixture was filtered through Celite pad and the
solvent was evaporated under vacuum and extracted with ethyl
acetate, washed with brine, dried (Na2SO4), and concentrated.
Purification of the crude by column chromatography (10% ethyl
acetate in petroleum ether) afforded 19 (1.8 g, 34%) as semi-solid
and 20 (2.7 g, 51%) as colorless syrup, respectively.
(480 mg, 1.40 mmol); iodoanisole (360 mg, 1.54 mmol); TPP
(36 mg, 0.14 mmol); Pd(PPh3)2Cl2 (98 mg, 0.14 mmol); CuI (26 mg,
0.14 mmol); Et3N (5 mL) and DMF (2.5 mL). The crude residue was
purified by column chromatography (15% ethyl acetate in petro-
25
leum ether) afforded 22 (520 mg, 83%) as colorless syrup. [
(c 1, CHCl3). IR (CHCl3):
665 cmꢀ1 1H NMR (200 MHz, CDCl3):
a]
þ5.3
D
n
3500, 2931, 1607, 1510, 1248, 835, 778,
0.08 (s, 6H), 0.89 (s, 9H),
.
d
1.37 (s, 3H), 1.59 (s, 3H), 2.58 (d, J¼17.1 Hz, 1H), 2.76 (d, J¼17.1 Hz,
1H), 2.75–2.85 (br s, 1H), 3.79 (s, 3H), 3.85–3.89 (m, 2H), 3.94 (dd,
J¼3.6, 6.5 Hz, 1H), 4.53 (d, J¼3.9 Hz, 1H), 5.83 (d, J¼3.9 Hz, 1H), 6.79
(dt, J¼2.6 8.8 Hz, 2H), 7.33 (dt, J¼2.6, 8.8 Hz, 2H). 13C NMR (50 MHz,
4.2.1. 1,2-O-Isopropylidene-5-O-(tert-butyldimethylsilyl)-3-C-(prop-
25
adienyl)-
n
a-D
-ribofuranose (19). [
a]
þ14.2 (c 1.8, CHCl3). IR (CHCl3):
CDCl3):
d
ꢀ5.5 (q), ꢀ5.4 (q), 18.2 (s), 23.8 (t), 25.8 (q, 3C), 26.5 (q),
D
3547, 2931, 1957, 1376, 1216, 1086, 838, 757, 668 cmꢀ1
.
1H NMR
26.6 (q), 54.9 (q), 61.0 (t), 78.4 (s), 82.2 (d), 82.2 (d), 82.7 (s), 82.8 (s),
103.8 (d), 112.2 (s), 113.6 (d, 2C), 115.2 (s), 132.9 (d, 2C), 159.2 (s)
ppm. ESI-MS: m/z 471.1 (100%, [MþNa]þ). Anal. Calcd for
C24H36O6Si: C, 64.25; H, 8.09. Found: C, 64.13; H, 7.95.
(200 MHz, CDCl3): 0.07 (s, 6H), 0.88 (s, 9H), 1.34 (s, 3H), 1.59
d
(s, 3H), 2.76 (br s, 1H), 3.77 (s, 1H), 3.80 (s, 1H), 3.97 (dd, J¼1.0,
5.4 Hz,1H), 4.35 (d, J¼3.7 Hz,1H), 4.92 (s, 1H), 4.95 (d, J¼1.1 Hz, 1H),
5.24 (dd, J¼0.6 6.5 Hz, 1H), 5.69 (d, J¼3.7 Hz, 1H). 13C NMR (50 MHz,
CDCl3):
d
ꢀ5.4 (q), ꢀ5.3 (q), 18.3 (s), 25.9 (q, 3C), 26.6 (q), 26.7 (q),
4.3.3. 1,2-O-Isopropylidene-5-O-(tert-butyldimethylsilyl)-3-C-[30-(4-
nitrophenyl)-prop-20-ynyl]-
a-D-ribofuranose (23). Reagents: alkyne
20 (480 mg, 1.40 mmol); 4-iodonitrobenzene (522 mg, 2.1 mmol);
TPP (36 mg, 0.14 mmol); Pd(PPh3)2Cl2 (98 mg, 0.14 mmol); CuI
(26 mg, 0.14 mmol); Et3N (6 mL) and DMF (3 mL). The residue
obtained was purified by column chromatography (15% ethyl ac-
62.1 (t), 78.0 (s), 78.7 (t), 82.1 (d), 83.3 (d), 90.3 (d), 104.0 (d), 112.7
(s), 207.0 (s) ppm. ESI-MS: m/z 365.6 (100%, [MþNa]þ). Anal. Calcd
for C17H30O5Si: C, 59.61; H, 8.83. Found: C, 59.54; H, 8.73.
4.2.2. 1,2-O-Isopropylidene-5-O-(tert-butyldimethylsilyl)-3-C-[prop-
25
20-ynyl]-
a-D
-ribofuranose (20). [
a
]
D
þ7.6 (c 1.3, CHCl3). IR (CHCl3):
n
etate in petroleum ether) to give 23 (550 mg, 85%) as yellow
3503, 3311, 2253, 1375, 1255, 1101, 910, 838, 788, 735, 648 cmꢀ1. 1H
syrup. [
a
]
þ10.9 (c 1, CHCl3). IR (CHCl3):
n
3542, 2930, 1594, 1520,
25
D
NMR (200 MHz, CDCl3): 0.06 (s, 6H), 0.88 (s, 9H), 1.37 (s, 3H), 1.58
d
1343, 1106, 838, 751, 688 cmꢀ1. 1H NMR (200 MHz, CDCl3):
d 0.08
(s, 3H), 2.03 (t, J¼2.6 Hz, 1H), 2.35 (ddd, J¼0.7, 2.7, 17.1 Hz, 1H), 2.57
(dd, J¼2.7 17.1 Hz, 1H), 2.79 (br d, J¼0.8 Hz, 1H), 3.77–3.90 (m, 3H),
4.48 (d, J¼3.9 Hz, 1H), 5.79 (d, J¼3.9 Hz, 1H). 13C NMR (50 MHz,
(s, 6H), 0.90 (s, 9H), 1.39 (s, 3H), 1.60 (s, 3H), 2.64 (d, J¼17.3 Hz,
1H), 2.85 (d, J¼17.3 Hz, 1H), 2.85 (br d, J¼0.6 Hz, 1H), 3.85–3.89 (m,
2H), 3.92 (dd, J¼3.0, 6.4 Hz, 1H), 4.49 (d, J¼3.9 Hz, 1H), 5.84 (d,
J¼3.9 Hz, 1H), 7.55 (dt, J¼2.2, 8.9 Hz, 2H), 8.16 (dt, J¼2.2, 8.9 Hz,
CDCl3):
d
ꢀ5.5 (q), ꢀ5.4 (q), 18.2 (s), 22.9 (t), 25.8 (q, 3C), 26.5 (q),
26.6 (q), 60.8 (t), 71.1 (d), 78.1 (s), 79.1 (s), 81.8 (d), 82.0 (d), 103.7
(d), 112.4 (s) ppm. ESI-MS: m/z 365.6 (100%, [MþNa]þ). Anal. Calcd
for C17H30O5Si: C, 59.61; H, 8.83. Found: C, 59.55; H, 8.75.
2H). 13C NMR (50 MHz, CDCl3):
d
ꢀ5.4 (q), ꢀ5.3 (q), 18.3 (s), 24.1
(t), 25.9 (q, 3C), 26.5 (q), 26.7 (q), 60.8 (t), 78.5 (s), 81.4 (s), 82.0 (d,
2C), 90.9 (s), 103.8 (d), 112.6 (s), 123.4 (d, 2C), 130.1 (s), 132.4 (d,
2C), 146.9 (s) ppm. ESI-MS: m/z 486.2 (100%, [MþNa]þ). Anal.
Calcd for C23H33NO7Si: C, 59.59; H, 7.17; N, 3.02. Found: C, 59.47;
H, 7.14; N, 3.09.
4.3. General procedure for Sonogashira coupling
To a solution of alkyne (1 mmol), iodobenzene (1 mmol) in Et3N
(3 mL) and DMF (1.5 mL), TPP was added followed by Pd(PPh3)2Cl2
(0.1 mmol), and the reaction mixture was flushed with argon for
30 min. CuI (0.11 mmol) was added and flushed with argon for
10 min and stirred at rt for 12 h. The reaction mixture was parti-
tioned between ethyl acetate, water and the organic layer was
separated, washed with brine, dried (Na2SO4), and concentrated.
The crude residue was purified by column chromatography.
4.3.4. 1,2-O-Isopropylidene-5-O-(tert-butyldimethylsilyl)-3-C-[30-(3-
nitrophenyl)-prop-20-ynyl]-
a-D-ribofuranose (24). Reagents: alkyne
20 (500 mg, 1.46 mmol); 3-iodonitrobenzene (545 mg, 2.19 mmol);
TPP (38 mg, 0.146 mmol); Pd(PPh3)2Cl2 (102 mg, 0.14 mmol); CuI
(28 mg, 0.146 mmol); Et3N (8 mL) and DMF (4 mL). The residue
obtained was purified by column chromatography (15% ethyl ace-
tate in petroleum ether) gave 24 (490 mg, 72%) as yellow syrup.
25
[a
]
þ9.1 (c 1, CHCl3). IR (CHCl3):
n
3543, 2930, 1532, 1351, 1100,
D
4.3.1. 1,2-O-Isopropylidene-5-O-(tert-butyldimethylsilyl)-3-C-[30-
838, 758, 673 cmꢀ1. 1H NMR (200 MHz, CDCl3):
d 0.09 (s, 6H), 0.90
phenyl-prop-20-ynyl]-
a-D
-ribofuranose (21). Reagents: alkyne 20
(s, 9H), 1.39 (s, 3H), 1.60 (s, 3H), 2.62 (d, J¼17.3 Hz, 1H), 2.84
(d, J¼17.3 Hz, 1H), 2.85 (d, J¼0.8 Hz, 1H), 3.86–3.95 (m, 3H), 4.51
(d, J¼4.0 Hz, 1H), 5.84 (d, J¼4.0 Hz, 1H), 7.47 (t, J¼8.0 Hz, 1H), 7.71
(dt, J¼1.3, 7.7 Hz, 1H), 8.14 (ddd, J¼1.1, 2.3, 8.2 Hz, 1H), 8.26 (t,
(500 mg, 1.46 mmol); iodobenzene (0.16 mL, 1.46 mmol); TPP
(38 mg, 0.146 mmol); Pd(PPh3)2Cl2 (102 mg, 0.146 mmol); CuI
(28 mg, 0.146 mmol); Et3N (5 mL) and DMF (2.5 mL). The crude
residue was purified by column chromatography (10% ethyl acetate
J¼1.9 Hz, 1H). 13C NMR (50 MHz, CDCl3):
d
ꢀ5.4 (q), ꢀ5.3 (q), 18.3
in petroleum ether) to obtain 21 (515 mg, 84%) as a white solid. Mp
(s), 23.9 (t), 25.9 (q, 3C), 26.5 (q), 26.7 (q), 60.9 (t), 78.4 (s), 80.7 (s),
82.0 (d), 82.1 (d), 88.0 (s), 103.8 (d), 112.6 (s), 122.6 (d), 125.0 (s),
126.4 (d), 129.1 (d), 137.3 (d), 148.0 (s) ppm. ESI-MS: m/z 486.3
(100%, [MþNa]þ). Anal. Calcd for C23H33NO7Si: C, 59.59; H, 7.17; N,
3.02. Found: C, 59.65; H, 7.24; N, 3.12.
25
56–57 ꢁC. [
a
]
þ22.3 (c 1, CHCl3). IR (CHCl3):
n
3543, 2954, 1599,
1H NMR (200 MHz,
0.04 (s, 6H), 0.85 (s, 9H), 1.33 (s, 3H), 1.55 (s, 3H), 2.57
D
1491, 1375, 1254, 1057, 837, 778, 691 cmꢀ1
CDCl3):
.
d
(d, J¼17.2 Hz, 1H), 2.75 (d, J¼17.2 Hz, 1H), 2.82 (br s, 1H), 3.83–3.86
(m, 2H), 3.92 (dd, J¼6.2, 4.0 Hz, 1H), 4.51 (d, J¼3.9 Hz, 1H), 5.81 (d,
J¼3.9 Hz, 1H), 7.20–7.27 (m, 3H), 7.33–7.40 (m, 2H). 13C NMR
4.4. General procedure for the desilylation of compounds
20–24 using TBAF
(50 MHz, CDCl3):
d
ꢀ5.4 (q), ꢀ5.2 (q), 18.3 (s), 24.0 (t), 25.9 (q, 3C),
26.7 (q), 26.7 (q), 61.1 (t), 78.6 (s), 82.2 (d, 2C), 83.2 (s), 84.5 (s),
104.0 (d), 112.5 (s), 123.2 (s), 127.9 (d), 128.2 (d, 2C), 131.7 (d, 2C)
ppm. ESI-MS: m/z 441.3 (100%, [MþNa]þ). Anal. Calcd for
C23H34O5Si: C, 65.99; H, 8.19. Found: C, 65.80; H, 8.32.
Silyl ether (1 mmol) was dissolved in THF (10 mL) and cooled to
0 ꢁC. To this, TBAF (1.2 mL, 1.2 mmol, 1 M solution) was added and
allowed to stir for 0.5 h while warming the reaction mixture to rt.
Solvent was evaporated under reduced pressure, and the residue
was purified by column chromatography (50–60% ethyl acetate in
petroleum ether) to afford the corresponding alkynol.
4.3.2. 1,2-O-Isopropylidene-5-O-(tert-butyldimethylsilyl)-3-C-[30-(4-me-
thoxyphenyl)-prop-20-ynyl]-
a-D-ribofuranose (22). Reagents: alkyne 20

C.V. Ramana et al. / Tetrahedron 65 (2009) 9819–9832
9825
4.4.1. 1,2-O-Isopropylidene-3-C-[prop-20-ynyl]-
a
-
D
-ribofuranose
[MþNa]þ). Anal. Calcd for C17H19NO7: C, 58.45; H, 5.48; N, 4.01.
25
(8). 92% Yield, colorless oil. [
a
]
þ20.7 (c 1, CHCl3). IR (CHCl3):
n
Found: C, 58.28; H, 5.20; N, 4.12.
D
3500, 3301, 2260, 1355, 1245, 1110, 907, 837, 785, 740, 650 cmꢀ1
.
1H NMR (200 MHz, CDCl3):
d
1.37 (s, 3H), 1.57 (s, 3H), 2.08 (t,
4.5. Sonogashira coupling of alkynol 26 with aryl iodides
J¼2.7 Hz, 1H), 2.38 (dd, J¼2.6, 17.1 Hz, 1H), 2.56 (dd, J¼2.6,
17.1 Hz, 1H), 2.93 (s, 1H), 3.69–4.04 (m, 4H), 4.48 (d, J¼3.9 Hz,
4.5.1. 1,2:5,6-Di-O-isopropylidene-3-C-[30-phenyl-prop-20-ynyl]-
a-D-
1H), 5.81 (d, J¼3.9 Hz, 1H). 13C NMR (50 MHz, CDCl3):
d
22.6 (t),
allofuranose (27). Reagents: alkyne 26 (500 mg, 1.68 mmol); iodo-
benzene (514 mg, 2.52 mmol); TPP (44 mg, 0.168 mmol);
Pd(PPh3)2Cl2 (118 mg, 0.168 mmol); CuI (32 mg, 0.168 mmol); Et3N
(6 mL) and DMF (3 mL). The crude residue was purified by column
26.3 (q), 26.4 (q), 59.7 (t), 71.4 (d), 78.1 (s), 78.9 (s), 81.5 (d), 81.7
(d), 103.5 (d), 112.6 (s) ppm. ESI-MS: m/z 251.3 (100%, [MþNa]þ).
Anal. Calcd for C11H16O5: C, 57.88; H, 7.07. Found: C, 57.80; H,
7.10.
chromatography (10% ethyl acetate in petroleum ether) to obtain 27
25
(480 mg, 76%) as a yellow solid. Mp 117–124 ꢁC. [
a
]
þ5.80 (c 0.8,
D
4.4.2. 1,2-O-Isopropylidene-3-C-[30-phenyl-prop-20-ynyl]-
a
-
-ribo-
CHCl3). IR (CHCl3):
n
3020, 2936,1384, 1216,1084, 758, 669 cmꢀ1. 1H
1.35 (s, 3H), 1.36 (s, 3H), 1.45 (s, 3H), 1.59
25
furanose (9). 91% Yield, white solid. Mp 121–122 ꢁC. [
(c 1, CHCl3). IR (CHCl3):
1110, 875, 755, 667 cmꢀ1 1H NMR (200 MHz, CDCl3):
d 1.38 (s,
a
]
Dþ23.7
NMR (200 MHz, CDCl3): d
D
n
3449, 3018, 1734, 1490, 1376, 1216,
(s, 3H), 2.75 (d, J¼17.1 Hz, 1H), 2.88 (s, 1H), 2.94 (d, J¼17.1 Hz, 1H),
3.84 (d, J¼8.3 Hz, 1H), 3.93 (dd, J¼5.0, 8.3 Hz, 1H), 4.09–4.27 (m,
2H), 4.57 (d, J¼3.8 Hz, 1H), 5.80 (d, J¼3.8 Hz, 1H), 7.24–7.30 (m, 3H),
.
3H), 1.60 (s, 3H), 2.19 (br s, 1H), 2.61 (d, J¼17.1 Hz, 1H), 2.76 (d,
J¼17.1 Hz, 1H), 2.97 (br s, 1H), 3.80–3.90 (m, 2H), 3.98 (dd,
J¼3.7, 6.4 Hz, 1H), 4.52 (d, J¼3.9 Hz, 1H), 5.86 (d, J¼3.9 Hz, 1H),
7.25–7.31 (m, 3H), 7.36–7.43 (m, 2H). 13C NMR (125 MHz,
7.34–7.41 (m, 2H). 13C NMR (50 MHz, CDCl3):
d 24.6 (t), 25.3 (q), 26.5
(q), 26.7 (q, 2C), 67.9 (t), 73.4 (d), 79.0 (s), 82.0 (d), 82.7 (d), 83.3 (s),
84.0 (s), 104.0 (d), 109.7 (s), 112.6 (s), 123.1 (s), 128.0 (d), 128.2 (d,
2C), 131.5 (d, 2C) ppm. ESI-MS: m/z 397.3 (100%, [MþNa]þ). Anal.
Calcd for C21H26O6: C, 67.36; H, 7.00. Found: C, 67.19; H, 7.16.
CDCl3):
d 23.9 (t), 26.6 (q), 26.7 (q), 60.2 (t), 78.5 (s), 82.0 (d),
82.3 (d), 83.4 (s), 84.1 (s), 103.8 (d), 112.7 (s), 123.1 (s), 128.1 (d),
128.2 (d, 2C), 131.7 (d, 2C) ppm. ESI-MS: m/z 327.1 (100%,
[MþNa]þ). Anal. Calcd for C17H20O5: C, 67.09; H, 6.62. Found: C,
66.95; H, 6.67.
4.5.2. 1,2:5,6-Di-O-isopropylidene-3-C-[30-(4-methoxyphenyl)-prop-
20-ynyl]-
a-D-allofuranose (28). Reagents: alkyne 26 (380 mg,
1.27 mmol); 1-iodo-4-methoxybenzene (291 mg, 1.42 mmol); TPP
(33 mg, 0.127 mmol); Pd(PPh3)2Cl2 (89 mg, 0.127 mmol); CuI
4.4.3. 1,2-O-Isopropylidene-3-C-[30-(4-methoxyphenyl)-prop-20-
ynyl]-
a
-
D
-ribofuranose (10). 93% Yield, white solid. Mp 120–121 ꢁC.
(24 mg, 0127 mmol); Et3N (6 mL), and in DMF (3 mL) the coupling
25
25
[
a]
þ23.5 (c 1.1, CHCl3). IR (CHCl3):
n
3461, 2937, 1606, 1509, 1247,
product 28 (360 mg, 70%) was obtained as colorless oil. [
1.1, CHCl3). IR (CHCl3):
1181, 835, 758 cmꢀ1. 1H NMR (200 MHz, CDCl3):
a
]
þ8.8 (c
D
D
1031, 833, 755, 667 cmꢀ1. 1H NMR (200 MHz, CDCl3):
d
1.38 (s, 3H),
n
3528, 3019, 1607, 1510, 1480, 1375, 1216,
1.35 (s, 3H), 1.36
1.59 (s, 3H), 1.90–1.99 (m, 1H), 2.60 (d, J¼17.1 Hz, 1H), 2.76 (d,
J¼17.1 Hz, 1H), 2.89 (br s, 1H), 3.79 (s, 3H), 3.86–3.93 (m, 2H), 4.00
(dd, J¼3.8, 6.6 Hz, 1H), 4.53 (d, J¼3.9 Hz, 1H), 5.86 (d, J¼3.9 Hz, 1H),
6.81 (dt, J¼2.8, 8.8 Hz, 2H), 7.34 (dt, J¼2.8, 8.8 Hz, 2H). 13C NMR
d
(s, 3H), 1.44 (s, 3H), 1.59 (s, 3H), 2.74 (d, J¼17.0 Hz, 1H), 2.86 (d,
J¼16.9 Hz, 1H), 2.86 (s, 1H) 3.78 (s, 3H), 3.84 (d, J¼8.3 Hz, 1H), 3.93
(dd, J¼5.1, 8.34 Hz, 1H), 4.08–4.27 (m, 2H), 4.56 (d, J¼3.8 Hz, 1H),
5.79 (d, J¼3.8 Hz, 1H), 6.79 (dt, J¼2.4, 8.8 Hz, 2H), 7.31 (dt, J¼2.8,
(125 MHz, CDCl3): d 23.8 (t), 26.5 (q), 26.5 (q), 55.2 (q), 60.1 (t), 78.5
(s), 81.8 (d), 82.2 (d), 82.4 (s), 83.1 (s), 103.7 (d), 112.6 (s), 113.8 (d,
2C), 115.0 (s), 133.0 (d, 2C), 159.3 (s) ppm. ESI-MS: m/z 357.0 (100%,
[MþNa]þ). Anal. Calcd for C18H22O6: C, 64.66; H, 6.63. Found: C,
64.45; H, 6.47.
8.8 Hz, 2H) ppm. 13C NMR (50 MHz, CDCl3):
d 24.7 (t), 25.4 (q), 26.6
(q), 26.8 (q, 2C), 55.2 (q), 68.1 (t), 73.5 (d), 79.2 (s), 82.1 (d), 82.3 (s),
82.8 (d), 90.8 (s), 104.2 (d), 109.8 (s), 112.7 (s), 113.9 (d, 2C), 115.3 (s),
133.0 (d, 2C), 159.4 (s) ppm. ESI-MS: m/z 427.3 (100%, [MþNa]þ).
Anal. Calcd for C22H28O7: C, 65.33; H, 6.98. Found: C, 65.29; H, 6.81.
4.4.4. 1,2-O-Isopropylidene-3-C-[30-(4-nitrophenyl)-prop-20-ynyl]-
a-
25
D
-ribofuranose (11). 90% Yield, yellowish syrup. [
a
]
þ32.9 (c 1,
4.5.3. 1,2:5,6-Di-O-isopropylidene-3-C-[30-(4-nitrophenyl)-prop-20-
ynyl]-a-D-allofuranose (29). Reagents: alkyne 26 (426 mg,
D
CHCl3). IR (CHCl3):
n
3548, 3020, 1594, 1520, 1344, 1215, 855, 757,
1.39 (s, 3H), 1.60 (s, 3H), 1.86
668 cmꢀ1. 1H NMR (200 MHz, CDCl3):
d
1.43 mmol); iodo-4-nitrobenzene (533 mg, 2.14 mmol); TPP (37 mg,
0.143 mmol); Pd(PPh3)2Cl2 (100 mg, 0.143 mmol); CuI (27 mg,
0.143 mmol); Et3N (6 mL) and DMF (3 mL). The crude residue was
purified by column chromatography (10% ethyl acetate in petroleum
(br s, 1H), 2.66 (d, J¼17.3 Hz, 1H), 2.85 (d, J¼17.3 Hz, 1H), 2.93 (br s,
1H), 3.86–3.94 (m, 2H), 3.98 (dd, J¼3.6, 6.8 Hz, 1H), 4.51 (d,
J¼3.9 Hz, 1H), 5.87 (d, J¼3.9 Hz, 1H), 7.55 (dt, J¼2.2, 8.9 Hz, 2H), 8.16
(dt, J¼2.2, 8.9 Hz, 2H). 13C NMR (125 MHz, CDCl3):
d
23.9 (t), 26.4
ether) to obtain 29 (380 mg, 63%) as a colorless gum. [
CHCl3). IR (CHCl3): 3330, 2925, 1607, 1510, 1737, 1594, 1343, 1081,
855, 758 cmꢀ1. 1H NMR (200 MHz, CDCl3):
1.32 (s, 3H), 1.35 (s, 3H),
a]
25 0.0 (c 1.0,
D
(q), 26.6 (q), 60.0 (t), 78.4 (s), 81.6 (s), 81.7 (d), 81.9 (d), 90.3 (s),
103.6 (d), 112.8 (s), 123.4 (d, 2C), 129.9 (s), 132.4 (d, 2C), 146.9 (s)
ppm. ESI-MS: m/z 372.1 (100%, [MþNa]þ). Anal. Calcd for
C17H19NO7: C, 58.45; H, 5.48; N, 4.01. Found: C, 58.25; H, 5.59; N,
4.18.
n
d
1.42 (s, 3H), 1.57 (s, 3H), 2.72 (d, J¼17.2 Hz, 1H), 2.93 (s, 1H), 2.98 (d,
J¼17.2 Hz, 1H), 3.79 (dt, J¼2.7, 8.4 Hz, 1H), 3.90 (dt, J¼3.3, 7.6 Hz, 1H),
4.06–4.18 (m, 2H), 4.52 (d, J¼3.8 Hz, 1H), 5.76 (d, J¼3.8 Hz, 1H), 7.50
(dt, J¼2.4, 8.8 Hz, 2H), 8.11 (dt, J¼2.3, 8.6 Hz, 2H). 13C NMR (50 MHz,
4.4.5. 1,2-O-Isopropylidene-3-C-[30-(3-nitrophenyl)-prop-20-ynyl]-
a
-
CDCl3): d 24.6 (t), 25.3 (q), 26.6 (q), 26.7 (q), 26.7 (q), 68.0 (t), 73.4 (d),
25
D
-ribofuranose (12). 91% Yield, yellow syrup. [
a
]
þ25.2 (c 1,
79.0 (s), 81.8 (d), 81.8 (s), 82.5 (d), 90.4 (s),103.9 (d),109.9 (s),112.8 (s),
123.5 (d, 2C),130.0 (s),132.4 (d, 2C), 146.9 (s) ppm. ESI-MS: m/z 442.1
(100%, [MþNa]þ). Anal. Calcd for C21H25NO8: C, 60.14; H, 5.96; N, 3.34.
Found: C, 60.01; H, 5.86; N, 3.22.
D
CHCl3). IR (CHCl3):
n
3491, 2991, 1531, 1352, 1216, 1005, 874, 758,
668 cmꢀ1 1H NMR (200 MHz, CDCl3):
. d 1.39 (s, 3H), 1.59 (s, 3H),
2.06 (br s, 1H), 2.62 (d, J¼17.3 Hz, 1H), 2.81 (d, J¼17.3 Hz, 1H),
2.96 (br s, 1H), 3.84–3.92 (m, 2H), 3.96 (dd, J¼3.5, 6.7 Hz,
1H), 4.50 (d, J¼3.9 Hz, 1H), 5.85 (d, J¼3.9 Hz, 1H), 7.46 (t,
J¼8.0 Hz, 1H), 7.70 (dt, J¼1.3, 7.7 Hz, 1H), 8.13 (ddd, J¼1.1, 2.3,
8.2 Hz, 1H), 8.24 (t, J¼1.8 Hz, 1H). 13C NMR (125 MHz, CDCl3):
4.5.4. 1,2:5,6-Di-O-isopropylidene-3-C-[30-(3-nitrophenyl)-prop-20-
ynyl]-a-D-allofuranose (30). Reagents: alkyne 26 (320 g, 1.07 mmol);
1-iodo-3-nitrobenzene (399 mg, 1.60 mmol); TPP (28 mg,
0.107 mmol); Pd(PPh3)2Cl2 (50 mg, 0.107 mmol); CuI (20 mg,
0.107 mmol); Et3N (5 mL) and DMF (2.5 mL). The crude residue was
purified by column chromatography (10% ethyl acetate in petroleum
d
23.6 (t), 26.4 (q), 26.5 (q), 59.9 (t), 78.3 (s), 80.9 (s), 81.7 (d),
81.9 (d), 87.4 (s), 103.6 (d), 112.8 (s), 122.8 (d), 124.8 (s), 126.4 (d),
129.2 (d), 137.4 (d), 147.9 (s) ppm. ESI-MS: m/z 372.1 (100%,

9826
C.V. Ramana et al. / Tetrahedron 65 (2009) 9819–9832
25
ether) to obtain 30 (300 mg, 67%) as a thick liquid. [
CHCl3). IR (CHCl3):
669 cmꢀ1. 1H NMR (200 MHz, CDCl3):
a
]
þ3.1 (c 1.8,
CHCl3). IR (CHCl3):
n
3436, 3020, 1595, 1345, 1216, 1084, 750,
1.36 (s, 3H),1.58 (s, 3H), 2.77
D
n
3552, 3020, 1532, 1375, 1216, 1075, 758,
1.33 (s, 3H), 1.36 (s, 3H), 1.43
669 cmꢀ1. 1H NMR (200 MHz, CDCl3):
d
d
(d, J¼17.3 Hz, 1H), 3.05 (d, J¼17.3 Hz, 1H), 3.47 (br s, 3H), 3.68–3.88
(m, 4H), 4.54 (d, J¼3.8 Hz, 1H), 5.80 (d, J¼3.9 Hz, 1H), 7.53 (dt, J¼2.1,
8.8 Hz, 2H), 8.13 (dt, J¼2.2, 8.8 Hz, 2H). 13C NMR (50 MHz, CDCl3):
(s, 3H), 1.58 (s, 3H), 2.71 (d, J¼17.2 Hz, 1H), 2.94 (s, 1H), 2.97 (d,
J¼16.9 Hz, 1H), 3.81 (dt, J¼2.8, 8.4 Hz,1H), 3.91 (dt, J¼2.9, 7.5 Hz,1H),
4.07–4.20 (m, 2H), 4.54 (d, J¼3.9 Hz, 1H), 5.77 (d, J¼3.8 Hz, 1H), 7.44
(t, J¼7.9 Hz, 1H), 7.67 (dt, J¼1.5, 7.5 Hz, 1H), 8.10 (ddd, J¼1.2, 2.4,
d
24.1 (t), 26.4 (q, 2C), 64.3 (t), 70.1 (d), 79.0 (d), 79.2 (s), 81.8 (s),
82.1 (d), 90.3 (s), 103.6 (d), 112.9 (s), 123.5 (d, 2C), 129.9 (s), 132.4 (d,
2C), 146.9 (s) ppm. ESI-MS: m/z 402.0 (100%, [MþNa]þ). Anal. Calcd
for C18H21NO8: C, 56.99; H, 5.58; N, 3.69. Found: C, 56.83; H, 5.47; N,
3.64.
8.3 Hz,1H), 8.20 (t, J¼1.8 Hz,1H). 13C NMR (50 MHz, CDCl3):
d 24.1 (t),
25.0 (q), 26.3 (q), 26.4 (q), 26.4 (q), 67.7 (t), 73.1 (d), 78.7 (s), 80.7 (s),
81.5 (d), 82.3 (d), 87.4 (s), 103.6 (d),109.5 (s),112.5 (s),122.4 (d),124.7
(s), 126.1 (d), 129.0 (d), 137.1 (d), 147.7 (s) ppm. ESI-MS: m/z 442.1
(100%, [MþNa]þ). Anal. Calcd for C21H25NO8: C, 60.14; H, 5.96; N, 3.34.
Found: C, 59.99; H, 6.03; N, 3.22.
4.6.5. 1,2-O-Isopropylidene-3-C-[30-(3-nitrophenyl)-prop-20-ynyl]-
a-D-
25
allofuranose (17). Colorless gum. [
a]
þ41.1 (c 2.0, CHCl3). IR (CHCl3):
n
D
3436, 3081, 1520, 1376, 1217, 1097, 758, 669 cmꢀ1. 1H NMR (200 MHz,
CDCl3):
4.6. General procedure for the acetonide hydrolysis
of compounds 26–30
d
1.36 (s, 3H), 1.58 (s, 3H), 2.74 (d, J¼17.3 Hz, 1H), 3.05 (d,
J¼17.3 Hz, 1H), 3.37 (br s, 3H), 3.67–3.88 (m, 4H), 4.56 (d, J¼3.9 Hz, 1H),
5.79 (d, J¼3.8 Hz, 1H), 7.44 (t, J¼7.8 Hz, 1H), 7.69 (dt, J¼1.3, 7.8 Hz, 1H),
8.10 (ddd, J¼1.0, 2.3, 8.2 Hz, 1H), 8.21 (t, J¼1.9 Hz, 1H). 13C NMR
A solution of alkyne (1 mmol) in MeOH (30 mL) was treated
with dil H2SO4 (15 mL, 0.8% in water) dropwise and stirred at rt for
5 h. The reaction mixture was quenched with NaHCO3 (2.5 g),
concentrated under reduced pressure. The residue was portioned
between ethyl acetate/water and the aqueous layer was extracted
with ethyl acetate. The combined organic layers were dried (NaSO4)
and concentrated. The crude residue was purified by column
chromatography (60–80% ethyl acetate in petroleum ether) to ob-
tain the alkyne diols 13–17.
(50 MHz, CDCl3): d 24.1 (t), 26.5 (q), 26.5 (q), 64.3 (t), 70.1 (d), 79.2 (d),
79.3 (s), 82.4 (d), 83.3 (s), 84.2 (s), 103.7 (d), 112.8 (s), 123.0 (s), 128.1 (s),
128.2 (d, 2C), 131.6 (d, 2C) ppm. ESI-MS: m/z 402.3 (100%, [MþNa]þ).
Anal. Calcd for C18H21NO8: C, 56.99; H, 5.58; N, 3.69. Found: C, 56.81; H,
5.08; N, 3.52.
4.7. Pd-mediated cyclization of alkynols 8–17
4.7.1. 1,2-O-Isopropylidene-3-C-(20-hydroxy-prop-1-enyl)-20,5-anhy-
dro-a-D-ribofuranose (31). A solution of 8 (90 mg, 0.39 mmol) and
Pd(CH3CN)2Cl2 (10 mg, 0.04 mmol) in acetonitrile (10 mL) was
stirred at rt under argon atmosphere for 6 h. The reaction mixture
was concentrated and purified by silica gel chromatography (15%
4.6.1. 1,2-O-isopropylidene-3-C-[prop-20-ynyl]-
a
-
D
-allofuranose
25
(13). 79% Yield, colorless syrup. [
(CHCl3):
NMR (200 MHz, CDCl3):
a
]
þ25.8 (c 1.0, CHCl3). IR
D
n
3449, 2986, 1987, 1375, 1245, 1047, 874, 758, 669 cmꢀ1. 1H
d
1.35 (s, 3H), 1.58 (s, 3H), 2.09 (t, J¼2.6 Hz,
1H), 2.50 (dd, J¼2.6, 17.2 Hz, 1H), 2.78 (dd, J¼2.6, 17.2 Hz, 1H), 3.21
(br s, 1H), 3.54–3.81 (m, 4H), 3.81 (br s, 2H), 4.50 (d, J¼3.8 Hz, 1H),
ethyl acetate in petroleum ether) to obtain 31 (58 mg, 64%) as
25
syrup. [
a
]
D
ꢀ31.3 (c 2.5, CHCl3). IR (CHCl3):
n
3432, 3019,1672,1376,
5.73 (d, J¼3.8 Hz, 1H). 13C NMR (50 MHz, CDCl3):
d
23.1 (t), 26.5 (q
1216, 1116, 876, 756, 667 cmꢀ1. 1H NMR (400 MHz, CDCl3):
d 1.35 (s,
2C), 64.3 (t), 70.0 (d), 70.7 (d), 71.6 (s), 79.0 (d), 82.4 (d), 93.1 (s),
103.9 (d), 109.8 (s) ppm. ESI-MS: m/z 259.1 (100%, [Mþ1]þ). Anal.
Calcd for C12H18O6: C, 55.81; H, 7.02. Found: C, 55.73; H, 7.25.
3H), 1.56 (s, 3H), 1.79 (d, J¼0.8 Hz, 3H), 2.89 (br s 1H), 3.90 (dd,
J¼1.2, 12.6 Hz, 2H), 4.19 (d, J¼3.7 Hz, 1H), 4.31 (dd, J¼1.6, 12.6 Hz,
1H), 4.40 (br q, J¼0.8 Hz, 1H), 5.72 (d, J¼3.7 Hz, 1H). 13C NMR
(100 MHz, CDCl3): d 20.3 (q), 26.8 (q), 27.0 (q), 63.1 (t), 71.3 (s), 76.9
4.6.2. 1,2-O-Isopropylidene-3-C-[30-(phenyl)-prop-20-ynyl]-
a
-
D
-allo-
(d), 83.5 (d), 95.0 (d), 104.2 (d), 112.7 (s), 156.2 (s) ppm. ESI-MS: m/z
251.1 (100%, [MþNa]þ). Anal. Calcd for C11H16O5: C, 57.88; H, 7.07.
Found: C, 57.83; H, 7.05.
25
furanose (14). 75% Yield, white solid. Mp 115–119 ꢁC. [
a]
þ22.7 (c
D
1, CHCl3). IR (CHCl3):
n
3439, 3020, 1385, 1216, 1084, 757, 669 cmꢀ1
1.34 (s, 3H), 1.57 (s, 3H), 2.75 (d,
.
1H NMR (200 MHz, CDCl3):
d
J¼17.2 Hz, 1H), 2.97 (d, J¼17.2 Hz, 1H), 3.29 (br s, 3H), 3.66–3.89 (m,
4.7.2. Pd-mediated cyclization of 9. A solution of 9 (100 mg,
4H), 4.55 (d, J¼3.7 Hz, 1H), 5.79 (d, J¼3.7 Hz, 1H), 7.25–7.28 (m, 3H),
0.33 mmol) and Pd(CH3CN)2Cl2 (8 mg, 0.03 mmol) in acetonitrile
(10 mL) was stirred at rt under argon atmosphere for 6 h. The re-
action mixture was concentrated and the residue obtained was
purified by silica gel chromatography (20%, 30% ethyl acetate in
petroleum ether) to obtain 32 (60 mg, 60%) and 33 (20 mg, 19%) as
colorless solids.
7.37–7.42 (m, 2H). 13C NMR (50 MHz, CDCl3):
d 24.1 (t), 26.5 (q), 26.5
(q), 64.3 (t), 70.1 (d), 79.2 (d), 79.3 (s), 82.4 (d), 83.4 (s), 84.2 (s),
103.7 (d), 112.8 (s), 123.0 (s), 128.1 (d), 128.2 (d, 2C), 131.6 (d, 2C)
ppm. ESI-MS: m/z 357.2 (100%, [MþNa]þ). Anal. Calcd for C18H22O6:
C, 64.66; H, 6.63. Found: C, 64.56; H, 6.79.
4.6.3. 1,2-O-Isopropylidene-3-C-[30-(4-methoxyphenyl)-prop-20-
4.7.2.1. 1,2-O-Isopropylidene-3-C-(20-hydroxy-20-benzyl-E-vinyl)-
25
ynyl]-
132 ꢁC. [
1384, 1246, 1034, 728, 669 cmꢀ1. 1H NMR (200 MHz, CDCl3):
a-
D
-allofuranose (15). 69% Yield, colorless solid. Mp 130–
20,5-anhydro]-
1, CHCl3). IR (CHCl3):
668 cmꢀ1. 1H NMR (400 MHz, CDCl3):
a-D
-ribofuranose (32). Mp 118–119 ꢁC. [
a
]
ꢀ67.8 (c
D
25
a
]
D
þ21.9 (c 1.3, CHCl3). IR (CHCl3):
n
3477, 3019, 1464,
1.37
n
3533, 3019, 1669, 1376, 1216, 1115, 875, 756,
1.35 (s, 3H),1.57 (s, 3H), 2.89
d
d
(s, 3H), 1.59 (s, 3H), 2.67 (br s, 1H), 2.76 (d, J¼17.0 Hz, 1H), 2.94 (d,
J¼17.0 Hz, 1H), 3.08 (br s, 1H), 3.70 (dd, J¼4.8, 11.5 Hz, 1H), 3.79 (s,
3H), 3.81–3.87 (m, 2H), 3.72 (br s, 1H), 3.94–4.02 (m, 1H), 4.52 (d,
J¼3.9 Hz,1H), 5.79 (d, J¼3.9 Hz,1H), 6.80 (dt, J¼8.9, 2.1 Hz, 2H), 7.33
(br s, 1H), 3.36 (d, J¼16.5 Hz, 1H), 3.40 (d, J¼16.5 Hz, 1H), 3.84 (d,
J¼12.3 Hz, 1H), 3.92 (br d, J¼1.1 Hz, 1H), 4.16 (d, J¼3.7 Hz, 1H), 4.33
(dd, J¼1.4, 12.4 Hz, 1H), 4.40 (br d, J¼1.1, Hz, 1H), 5.71 (d, J¼3.7 Hz,
1H), 7.18–7.29 (m, 5H). 13C NMR (100 MHz, CDCl3):
d 26.8 (q), 27.0
(d, J¼8.9, 2.6 Hz, 2H). 13C NMR (50 MHz, CDCl3):
d
24.1 (t), 26.5 (q),
(q), 40.5 (t), 63.4 (t), 71.3 (s), 77.1 (d), 83.4 (d), 96.2 (d), 104.2 (d),
112.7 (s), 126.5 (d), 128.4 (d, 2C), 129.0 (d, 2C), 137.0 (s), 158.5 (s)
ppm. ESI-MS: m/z 327.0 (100%, [MþNa]þ). Anal. Calcd for C17H20O5:
C, 67.09; H, 6.62. Found: C, 67.10; H, 6.78.
26.6 (q), 55.2 (q), 64.4 (t), 70.0 (d), 79.3 (d), 79.4 (s), 82.5 (s), 82.5
(d), 83.3 (s), 103.7 (d), 112.8 (s) 113.9 (d, 2C), 115.0 (s), 133.0 (d, 2C),
159.5 (s) ppm. ESI-MS: m/z 387.2 (100%, [MþNa]þ). Anal. Calcd for
C19H24O7: C, 62.63; H, 6.64. Found: C, 62.59; H, 6.71.
4.7.2.2. Crystallographic data for 32. C17H20O5: M¼304.33,
crystal dimensions 0.65ꢂ0.25ꢂ0.11 mm3, orthorhombic, space
4.6.4. 1,2-O-Isopropylidene-3-C-[30-(4-nitrophenyl)-prop-20-ynyl]-
a-D-
25
allofuranose (16). 81% Yield, colorless gum. [
a
]
þ16.5 (c 0.8,
group
P
212121, a¼6.0693(14), b¼12.689(3), c¼20.174(5) Å,
D

C.V. Ramana et al. / Tetrahedron 65 (2009) 9819–9832
9827
V¼1553.7 (6) Å3, Z¼4, rcalcd¼1.301 g cmꢀ3
,
m
(Mo K
a
)¼0.095 mmꢀ1
,
CHCl3). IR (CHCl3):
n
3505, 2988, 2923, 1671, 1519, 1347, 1064, 875,
F(000)¼648, 2qmax¼50.00ꢁ, T¼297(2) K, 7855 reflections collected,
733, 648 cmꢀ1. 1H NMR (200 MHz, CDCl3):
d 1.35 (s, 3H),1.56 (s, 3H),
2722 unique, 2507 observed (I>2
s
(I)) reflections, 202 refined pa-
2.99 (br s, 1H), 3.43 (d, J¼16.3 Hz, 1H), 3.51 (d, J¼16.3 Hz, 1H), 3.84
(dd, J¼0.8, 12.4 Hz, 1H), 3.93 (dd, J¼1.8, 3.2 Hz, 1H), 4.21 (d,
J¼3.7 Hz, 1H), 4.34 (ddd, J¼0.6, 2.0, 12.4 Hz, 1H), 4.52 (d, J¼1.8 Hz,
1H), 5.73 (d, J¼3.7 Hz, 1H), 7.36 (dt, J¼2.5, 8.7 Hz, 2H), 8.13 (dt,
rameters,
R
value 0.0323, wR2¼0.0697 (all data R¼0.0362,
wR2¼0.0725), S¼1.101, minimum and maximum transmission
0.9410 and 0.9893; maximum and minimum residual electron
densities þ0.117 and ꢀ0.137 e Åꢀ3
.
J¼2.5, 8.7 Hz, 2H). 13C NMR (50 MHz, CDCl3):
d 26.6 (q), 26.8 (q),
40.3 (t), 63.5 (t), 71.2 (s), 76.7 (d), 83.1 (d), 97.2 (d), 104.0 (d), 112.9
(s), 123.6 (d, 2C),129.6 (d, 2C),144.8 (s), 146.8 (s), 156.7 (s) ppm. ESI-
MS: m/z 372.1 (100%, [MþNa]þ). Anal. Calcd for C17H19NO7: C,
58.45; H, 5.48; N, 4.01. Found: C, 58.40; H, 5.43; N, 4.02.
4.7.2.3. 1,2-O-Isopropylidene-3-C-(20-oxo-30-phenyl-propyl)-
a-D-
ribofuranose-(20-C,5-O)-hemiketal (33). Mp 144–145 ꢁC. [
25
a
]
ꢀ8.4
D
(c 1, CHCl3). IR (CHCl3):
n
3522, 3019, 1684, 1376, 1216, 1010, 875,
1.33 (s, 3H),1.55 (s, 3H),
756, 668 cmꢀ1. 1H NMR (400 MHz, CDCl3):
d
1.57 (d, J¼14.1 Hz, 1H), 1.69 (d, J¼14.1 Hz, 1H), 2.82 (d, J¼13.6 Hz,
1H), 3.03 (d, J¼13.6 Hz, 1H), 3.20 (br s, 1H), 3.69 (s, 1H), 3.81 (s, 1H),
3.96 (d, J¼13.8 Hz, 1H), 4.06 (d, J¼3.7 Hz, 1H), 4.12 (dd, J¼1.8,
13.8 Hz, 1H), 5.74 (d, J¼3.7 Hz, 1H), 7.21–7.28 (m, 5H). 13C NMR
4.7.4.2. 1,2-O-Isopropylidene-3-C-[20-oxo-30(4-nitrophenyl)-pro-
pyl]-a-D
-ribofuranose-(20-C,5-O)-hemiketal (37). Mp 149–150 ꢁC.
25
[a
]
ꢀ11.6 (c 1.2, CHCl3). IR (CHCl3):
n
3397, 2923, 1597, 1511, 1345,
D
1043, 862, 733, 648 cmꢀ1. 1H NMR (400 MHz, CDCl3):
d
1.34 (s, 3H),
(100 MHz, CDCl3):
d
26.5 (q, 2C), 37.0 (t), 47.5 (t), 57.6 (t), 74.1 (d),
1.55 (s, 3H), 1.61 (d, J¼14.1 Hz, 1H), 1.71 (d, J¼14.1 Hz, 1H), 2.96 (d,
J¼13.6 Hz, 1H), 3.10 (d, J¼13.6 Hz, 1H), 3.08 (br s, 1H), 3.67 (br s, 1H),
3.99 (d, J¼14.0 Hz,1H), 4.07 (d, J¼3.8 Hz,1H), 4.12 (dd, J¼2.2,14.0 Hz,
1H), 4.44 (s, 1H), 5.78 (d, J¼3.8 Hz, 1H), 7.47 (dt, J¼2.4, 8.7 Hz, 2H),
74.5 (s), 82.7 (d), 95.5 (s), 103.7 (d), 112.8 (s), 126.9 (d), 128.2 (d, 2C),
130.9 (d, 2C), 135.1 (s) ppm. ESI-MS: m/z 345.1 (100%, [MþNa]þ).
Anal. Calcd for C17H22O6: C, 63.34; H, 6.88. Found: C, 63.28; H, 6.82.
8.14 (dt, J¼2.4, 8.7 Hz, 2H). 13C NMR (100 MHz, CDCl3):
d 26.3 (q),
4.7.3. Pd-mediated cyclization of 10. A solution of 10 (120 mg,
0.36 mmol) and Pd(CH3CN)2Cl2 (9 mg, 0.04 mmol) in acetonitrile
(10 mL)wasstirredatrtunderargonatmospherefor6 h. Thereaction
mixturewasconcentratedandresidueobtained waspurified bysilica
gel chromatography (20%, 60% ethyl acetate in petroleum ether) to
obtain 34 (20 mg, 16%) and 35 (70 mg, 55%) as colorless syrups.
26.4 (q), 37.0 (t), 47.1 (t), 57.5 (t), 73.7 (d), 74.7 (s), 82.1 (d), 95.1 (s),
103.6 (d),113.0 (s),123.1 (d, 2C),131.7 (d, 2C),143.4 (s),147.0 (s) ppm.
ESI-MS: m/z 390.1 (100%, [MþNa]þ). Anal. Calcd for C17H21NO8: C,
55.58; H, 5.76; N, 3.81. Found: C, 55.55; H, 5.74; N, 3.75.
4.7.4.3. Crystallographic data for 37. C17H21NO8: M¼367.35,
crystal dimensions 0.77ꢂ0.31ꢂ0.18 mm3, monoclinic, space group P21,
4.7.3.1. 1,2-O-Isopropylidene-3-C-[20-hydroxy-20-(4-methoxy-
a¼5.4991(14), b¼17.126(4), c¼9.123(2) Å,
b
¼95.765(4), V¼854.9(4) Å3,
25
benzyl)-E-vinyl]-20,5-anhydro-
a
-D-ribofuranose (34). [
a
]
ꢀ49.8 (c
Z¼2, rcalcd¼1.427 g cmꢀ3
,
m
(Mo
Ka
)¼0.114 mmꢀ1
F(000)¼388,
,
D
1.2, CHCl3). IR (CHCl3):
n
3479, 2926,1741,1669, 1512,1248, 875, 757,
1.35 (s, 3H),1.57 (s, 3H), 2.89
2
qmax¼50.00ꢁ, T¼297(2) K, 6696 reflections collected, 3262 unique,
666 cmꢀ1. 1H NMR (200 MHz, CDCl3):
d
3100 observed (I>2s(I)) reflections, 297 refined parameters, R value
(br s, 1H), 3.29 (d, J¼16.0 Hz, 1H), 3.37 (d, J¼17.3 Hz, 1H), 3.78 (s,
3H), 3.84 (dd, J¼0.9,12.4 Hz,1H), 3.94 (dd, J¼1.6, 3.0 Hz,1H), 4.19 (d,
J¼3.7 Hz, 1H), 4.34 (ddd, J¼0.6, 2.0, 12.4 Hz, 1H), 4.40 (d, J¼0.9 Hz,
1H), 5.73 (d, J¼3.7 Hz, 1H), 6.82 (dt, J¼2.98.7 Hz, 2H), 7.11 (dt, J¼2.9,
0.0355, wR2¼0.0881 (all data R¼0.0374, wR2¼0.0902), S¼1.045,
minimum and maximum transmission 0.9172 and 0.9797; maximum
and minimum residual electron densities þ0.295 and ꢀ0.138 e Åꢀ3
.
8.7 Hz, 2H). 13C NMR (50 MHz, CDCl3):
d
26.7 (q), 27.0 (q), 39.6 (t),
4.7.5. Pd-mediated cyclization of 12. A solution of 12 (150 mg,
0.43 mmol) and Pd(CH3CN)2Cl2 (11 mg, 0.04 mmol) in acetonitrile
(15 mL) was stirred at rt under argon atmosphere for 6 h. The re-
action mixture was concentrated and the residue obtained was
purified by silica gel chromatography (25%, 30% ethyl acetate in
petroleum ether) to obtain 38 (80 mg, 53%) as yellow syrup and 39
(20 mg, 13%) as yellow solid.
55.2 (q), 63.4 (t), 71.3 (s), 77.1 (d), 83.4 (d), 95.9 (d), 104.2 (d), 112.8
(s), 113.8 (d, 2C), 129.0 (s), 130.0 (d, 2C), 158.3 (s), 159.0 (s) ppm. ESI-
MS: m/z 357.1 (100%, [MþNa]þ). Anal. Calcd for C18H22O6: C, 64.66;
H, 6.63. Found: C, 64.58; H, 6.55.
4.7.3.2. 1,2-O-Isopropylidene-3-C-[30-oxo-30-(4-methoxyphenyl)-
25
propyl]-
n
a-D
-ribofuranose (35). [
a
]
þ13.3 (c 2.3, CHCl3). IR (CHCl3):
D
3491, 2936, 1673, 1601, 1512, 1171, 877, 755, 666 cmꢀ1
.
1H NMR
4.7.5.1. 1,2-O-Isopropylidene-3-C-[20-hydroxy-20-(3-nitrobenzyl)-
25
(200 MHz, CDCl3):
d
1.34 (s, 3H), 1.57 (s, 3H), 1.89 (dd, J¼6.3, 8.5 Hz,
E-vinyl]-20,5-anhydro-
CHCl3). IR (CHCl3):
667 cmꢀ1. 1H NMR (200 MHz, CDCl3):
a
-D
-ribofuranose (38). [
a]
ꢀ49.7 (c 2,
D
1H),1.94 (dd, J¼8.2, 6.5 Hz,1H), 2.85 (br s, 1H), 2.99 (ddd, J¼17.7, 8.1,
6.2 Hz, 1H), 3.25 (ddd, J¼6.3, 8.3, 17.7 Hz, 1H), 3.78–3.84 (m, 2H),
3.86 (s, 3H), 3.94 (dd, J¼4.1 6.6 Hz, 1H), 4.22 (d, J¼3.9 Hz, 1H), 5.81
(d, J¼3.9 Hz, 1H), 6.91 (dt, J¼2.9, 8.9 Hz, 2H), 7.94 (dt, J¼2.9, 8.9 Hz,
n
3506, 2989, 1671, 1530, 1351, 1215, 874, 756,
1.36 (s, 3H),1.57 (s, 3H), 2.98
d
(s, 1H), 3.44 (d, J¼16.4 Hz, 1H), 3.52 (d, J¼16.4 Hz, 1H), 3.86 (dd,
J¼0.9,12.4 Hz,1H), 3.94 (dd, J¼1.8, 3.2 Hz,1H), 4.23 (d, J¼3.7 Hz,1H),
4.35 (ddd, J¼0.6, 2.0, 12.4 Hz, 1H), 4.53 (d, J¼1.9 Hz, 1H), 5.78 (d,
J¼3.7 Hz, 1H), 7.46 (dt, J¼2.5, 8.6 Hz, 1H), 7.54 (dt, J¼1.4, 7.7 Hz, 1H),
2H). 13C NMR (50 MHz, CDCl3):
d 24.5 (t), 26.4 (q, 2C), 31.9 (t), 55.4
(q), 60.5 (t), 78.6 (s), 81.0 (d), 82.7 (d), 103.6 (d), 112.5 (s), 113.7 (d,
2C), 129.7 (s), 130.3 (d, 2C), 163.5 (s), 198.3 (s) ppm. ESI-MS: m/z
375.1 (100%, [MþNa]þ). Anal. Calcd for C18H24O7: C, 61.35; H, 6.86.
Found: C, 61.30; H, 6.82.
8.06–8.11 (m, 2H).13C NMR (50 MHz, CDCl3):
d 26.6 (q), 26.8 (q), 40.0
(t), 63.4 (t), 71.2 (s), 76.7 (d), 83.1 (d), 97.2 (d), 104.0 (d), 112.8 (s),
121.7 (d), 123.6 (d), 129.2 (d), 135.0 (d), 139.2 (s), 148.2 (s), 156.7 (s)
ppm. ESI-MS: m/z 372.1 (100%, [MþNa]þ). Anal. Calcd for C17H19NO7:
C, 58.45; H, 5.48; N, 4.01. Found: C, 58.41; H, 5.42. N, 3.99.
4.7.4. Pd-mediated cyclization of 11. A solution of 11 (100 mg,
0.29 mmol) and Pd(CH3CN)2Cl2 (7 mg, 0.03 mmol) in acetonitrile
(10 mL) was stirred at rt under argon atmosphere for 6 h. The re-
action mixture was concentrated and the crude residue obtained
was purified by silica gel chromatography (25%, 30% ethyl acetate in
petroleum ether) to obtain 36 (60 mg, 60%) as yellow syrup and 37
(15 mg, 14%) as yellow solid.
4.7.5.2. 1,2-O-Isopropylidene-3-C-[20-oxo-30-(3-nitrophenyl)-pro-
pyl]-a-D
-ribofuranose-(20-C,5-O)-hemiketal (39). Mp 152–153 ꢁC.
25
[a
]
ꢀ14.0 (c 1.5, CHCl3). IR (CHCl3):
n
3478, 2929, 1529, 1351, 1216,
D
1052, 876, 757, 667 cmꢀ1. 1H NMR (400 MHz, CDCl3):
d
1.33 (s, 3H),
1.55 (s, 3H), 1.61 (d, J¼14.0 Hz, 1H), 1.73 (d, J¼14.0 Hz, 1H), 2.94 (d,
J¼13.6 Hz, 1H), 3.10 (d, J¼13.6 Hz, 1H), 3.11 (br s, 1H), 3.68 (br s, 1H),
3.98 (d, J¼14.0 Hz,1H), 4.08 (s,1H), 4.13 (dd, J¼2.1,12.4 Hz,1H), 4.45
(s, 1H), 5.79 (d, J¼3.8 Hz, 1H), 7.44 (t, J¼7.9 Hz, 1H), 7.66 (dt, J¼1.2,
4.7.4.1. 1,2-O-Isopropylidene-3-C-[20-hydroxy-20-(4-nitrobenzyl)-
25
E-vinyl]-20,5-anhydro-
a-D
-ribofuranose (36). [
a
]
ꢀ61.0 (c 2,
D

9828
C.V. Ramana et al. / Tetrahedron 65 (2009) 9819–9832
7.7 Hz,1H), 8.10 (ddd, J¼1.1, 2.3, 8.1 Hz,1H), 8.16 (t, J¼1.8 Hz,1H). 13
C
n
3437, 2927, 1671, 1376, 1218, 1084, 771, 669 cmꢀ1
.
1H NMR
1.31 (s, 3H), 1.55 (s, 3H), 1.87 (ddd, J¼5.9, 8.3,
NMR (100 MHz, CDCl3):
d
26.2 (q), 26.3 (q), 36.9 (t), 46.9 (t), 57.5 (t),
(200 MHz, CDCl3):
d
73.7 (d), 74.6 (s), 82.1 (d), 95.0 (s), 103.6 (d),112.9 (s),121.8 (d),125.6
(d), 128.8 (d), 137.1 (d), 137.6 (s), 148.0 (s) ppm. ESI-MS: m/z 390.1
(100%, [MþNa]þ). Anal. Calcd for C17H21NO8: C, 55.58; H, 5.76; N,
3.81. Found: C, 55.53; H, 5.70; N, 3.75.
14.5 Hz, 1H), 2.30 (ddd, J¼6.2, 8.2, 14.7 Hz, 1H), 3.04 (ddd, J¼5.9, 8.2,
14.1 Hz, 1H), 3.05 (br s, 1H), 3.29 (br s, 1H), 3.33 (ddd, J¼6.2, 8.3,
14.8 Hz, 1H), 3.65 (dd, J¼3.7, 10.8 Hz, 1H), 3.75–3.85 (m, 3H), 3.83 (s,
3H), 3.83 (br s, 1H), 4.25 (d, J¼3.8 Hz, 1H), 5.73 (d, J¼3.8 Hz, 1H),
6.90 (dt, J¼2.7, 8.9 Hz, 2H), 7.95 (dt, J¼2.7, 8.9 Hz, 2H). 13C NMR
4.7.5.3. Crystallographic data for 39. C17H21NO8: M¼367.35,
crystaldimensions0.97ꢂ0.05ꢂ0.03 mm3, orthorhombic, spacegroup
P 212121, a¼5.5126(16), b¼16.461(5), c¼19.369(6) Å, V¼1757.5(9) Å3,
(50 MHz, CDCl3): d 24.6 (t), 26.3 (q), 26.5 (q), 31.9 (t), 55.4 (q), 64.6
(t), 69.8 (d), 79.2 (s), 79.5 (d), 80.9 (d), 103.5 (d), 112.6 (s), 113.7 (d,
2C), 129.6 (s), 130.3 (d, 2C), 163.5 (s), 198.6 (s) ppm. ESI-MS: m/z
405.1 (100%, [MþNa]þ). Anal. Calcd for C19H26O8: C, 59.68; H, 6.85.
Found: C, 59.72; H, 6.70.
Z¼4, rcalcd¼1.388 g cmꢀ3
,
m
(Mo
K
a
)¼0.111 mmꢀ1
F(000)¼776,
,
2
qmax¼50.00ꢁ, T¼297(2) K, 8849 reflections collected, 3087 unique,
2292 observed (I>2s(I)) reflections, 237 refined parameters, R value
0.0494, wR2¼0.0852 (all data R¼0.0770, wR2¼0.0945), S¼1.029,
4.7.9. Pd-mediated cyclization of 16. To a solution of 16 (100 mg,
0.26 mmol) in acetonitrile (20 mL) was added Pd(CH3CN)2Cl2
(22 mg, 0.08 mmol) and the reaction mixture was stirred at rt un-
der argon atmosphere for 6 h. The reaction mixture was concen-
trated and the crude was purified by silica gel chromatography (35%
ethyl acetate in petroleum ether) to procure 43 (70 mg, 70%) as pale
yellow oil.
minimumand maximumtransmission0.8999and0.9965;maximum
and minimum residual electron densities þ0.173 and ꢀ0.178 e Åꢀ3
.
4.7.6. Pd-mediated cyclization of 13. To a solution of 13 (100 mg,
0.39 mmol) in acetonitrile (20 mL) was added Pd(CH3CN)2Cl2
(22 mg, 0.08 mmol) and the reaction mixture was stirred at rt un-
der argon atmosphere for 1 h. The reaction mixture was concen-
trated and purified by silica gel chromatography (40% ethyl acetate
in petroleum ether) to obtain 40 (70 mg, 70%) as a white solid.
4.7.9.1. 1,2-O-Isopropylidene-3-C-[20-oxo-30-(4-nitrophenyl)-pro-
25
pyl]-
CHCl3). IR (CHCl3):
634 cmꢀ1. 1H NMR (200 MHz, CDCl3):
d
a
-
D
-allofuranose-(20-C,5-O,6-O)-ketal (43). [
a
]
D
þ16.9 (c 2.2,
n
3462, 2985, 1638, 1374, 1241, 1047, 847,
1.35 (s, 3H), 1.56 (s, 3H), 1.66
4.7.6.1. 1,2-O-Isopropylidene-3-C-(20-oxopropyl)]-
a
-
D
-allofur-
25
anose-(20-C,5-O,6-O)-ketal (40). Mp 139–140 ꢁC. [
a
]
D
ꢀ3.8 (c 2.2,
(d, J¼14.4 Hz, 1H), 2.01 (d, J¼14.4 Hz, 1H), 3.04 (d, J¼0.9 Hz, 1H),
3.10 (d, J¼16.3 Hz, 1H), 3.17 (d, J¼16.3 Hz, 1H), 3.55 (dd, J¼5.7,
7.2 Hz, 1H), 3.71 (br s, 1H), 4.09 (d, J¼3.7 Hz, 1H), 4.14 (d, J¼7.2 Hz,
1H), 4.62 (d, J¼5.2 Hz, 1H), 5.85 (d, J¼3.7 Hz, 1H), 7.44 (dt, J¼2.2,
8.7 Hz, 2H), 8.12 (d, J¼2.3, 8.7 Hz, 2H). 13C NMR (50 MHz, CDCl3):
CHCl3). IR (CHCl3):
NMR (200 MHz, CDCl3):
n
3538, 3020, 1386, 1216, 1052, 730, 669 cmꢀ1. 1H
1.32 (s, 3H), 1.45 (s, 3H), 1.54 (s, 3H), 1.62
d
(d, J¼14.7 Hz, 1H), 1.95 (d, J¼14.7 Hz, 1H), 3.04 (s, 1H), 3.70 (s, 1H),
3.82 (dd, J¼5.9, 7.1 Hz, 1H), 4.05 (d, J¼3.7 Hz, 1H), 4.13 (d, J¼7.2 Hz,
1H), 4.65 (d, J¼5.4 Hz, 1H), 5.82 (d, J¼3.5 Hz, 1H). 13C NMR (50 MHz,
d
26.6 (q), 26.7 (q), 41.1 (t), 42.8 (t), 65.6 (t), 73.7 (d), 74.9 (s), 78.0
CDCl3):
d
24.0 (q), 26.6 (q), 26.8 (q), 41.8 (t), 65.2 (t), 73.7 (d), 74.8
(d), 83.7 (d), 104.0 (d), 105.7 (s), 112.9 (s), 123.0 (d, 2C), 131.5 (d, 2C),
142.7 (s), 147.0 (s) ppm. ESI-MS: m/z 402.1 (100%, [MþNa]þ). Anal.
Calcd for C18H21NO8: C, 56.99; H, 5.58; N, 3.69. Found: C, 56.84; H,
5.49; N, 3.44.
(s), 77.6 (d), 83.7 (d), 103.9 (d), 105.3 (s), 112.7 (s) ppm. ESI-MS: m/z
281.1 (100%, [MþNa]þ). Anal. Calcd for C12H18O6: C, 55.81; H, 7.02.
Found: C, 55.67; H, 7.26.
4.7.7. Pd-mediated cyclization of 14. To a solution of 14 (130 mg,
0.39 mmol) in acetonitrile (10 mL) was added Pd(CH3CN)2Cl2
(11 mg, 0.04 mmol) and the reaction mixture was stirred at rt under
argon atmosphere for 2 h. The reaction mixture was concentrated
and purified by silica gel chromatography (40% ethyl acetate in
petroleum ether) to obtain 41 (90 mg, 66%) as a colorless syrup.
4.7.10. Pd-mediated cyclization of 17. To a solution of 17 (80 mg,
0.21 mmol) in acetonitrile (10 mL) was added Pd(CH3CN)2Cl2
(11 mg, 0.04 mmol) and the reaction mixture was stirred at rt under
argon atmosphere for 6 h. Usual workup and purification of the
crude by silica gel chromatography (40% ethyl acetate in petroleum
ether) gave 44 (50 mg, 60%) as yellow oil.
4.7.7.1. 1,2-O-Isopropylidene-3-C-[30-oxo-30-(phenyl)-propyl]-
a-D-
4.7.10.1. 1,2-O-Isopropylidene-3-C-[30-oxo-30-(3-nitrophenyl)-
25
25
allofuranose (41). [
a
]
þ35.4 (c 2.0, CHCl3). IR (CHCl3):
n
3439, 3020,
propyl]-a-
D-allofuranose (44). [
a
]
D
þ11.4 (c 1.8, CHCl3). IR (CHCl3):
n
D
1683, 1385, 1216, 1083, 758, 669 cmꢀ1
.
1H NMR (200 MHz, CDCl3):
3439, 3020, 1683, 1385, 1216, 1083, 758, 669 cmꢀ1
.
1H NMR
d
1.31 (s, 3H),1.56 (s, 3H),1.88 (ddd, J¼5.7, 8.3,14.5 Hz, 1H), 2.29 (br s,
(200 MHz, CDCl3):
d
1.32 (s, 3H), 1.56 (s, 3H), 1.90 (ddd, J¼5.8, 8.3,
1H), 2.30 (ddd, J¼6.1, 8.5,14.5 Hz,1H), 3.09 (br s,1H), 3.10 (ddd, J¼5.7,
8.2, 14.1 Hz, 1H), 3.39 (ddd, J¼6.1, 8.5, 14.5 Hz, 1H), 3.40 (br s, 1H),
3.65 (dd, J¼3.7, 10.9 Hz, 1H), 3.80–3.86 (m, 3H), 4.25 (d, J¼3.8 Hz,1H),
5.74 (d, J¼3.7 Hz, 1H), 7.39–7.67 (m, 3H), 7.93–7.98 (m, 2H). 13C NMR
14.5 Hz, 1H), 2.31 (ddd, J¼6.2, 8.3, 14.8 Hz, 1H), 2.33 (br s, 1H), 3.10
(ddd, J¼5.9, 8.3, 14.3 Hz, 1H), 3.11 (br s, 1H), 3.39 (br s, 1H), 3.40
(ddd, J¼6.4, 8.5, 14.6 Hz, 1H), 3.66 (dd, J¼4.5, 11.4 Hz, 1H), 3.79–3.91
(m, 3H), 4.26 (d, J¼3.8 Hz, 1H), 5.75 (d, J¼3.8 Hz, 1H), 7.32 (ddd,
J¼1.5, 6.1, 7.7 Hz, 1H), 7.45 (dt, J¼2.2, 7.4, Hz, 1H), 7.77 (ddt, J¼6.1,
8.5, 14.5 Hz, 1H), 7.96 (dt, J¼1.2, 6.9 Hz, 1H). 13C NMR (50 MHz,
(50 MHz, CDCl3):
d 24.4 (t), 26.3 (q), 26.5 (q), 32.4 (t), 64.5 (t), 69.8
(d), 79.2 (s), 79.4 (d), 80.9 (d), 103.4 (d), 112.7 (s), 128.0 (d, 2C), 128.6
(d, 2C), 133.2 (d), 136.6 (s), 200.0 (s) ppm. ESI-MS: m/z 375.3 (100%,
[MþNa]þ). Anal. Calcd for C18H24O7: C, 61.35; H, 6.86. Found: C, 61.19;
H, 7.04.
CDCl3):
d 24.4 (t), 26.4 (q), 26.5 (q), 32.4 (t), 64.5 (t), 69.8 (d), 79.2
(s), 79.5 (d), 80.9 (d), 103.5 (d), 112.7 (s), 124.9 (d), 128.0 (d), 128.6
(d), 133.2 (s), 138.6 (d), 153.3 (s), 200.0 (s) ppm. ESI-MS: m/z 420.1
(100%, [MþNa]þ). Anal. Calcd for C18H23NO9: C, 54.40; H, 5.83; N,
3.52. Found: C, 54.58; H, 5.58; N, 3.29.
4.7.8. Pd-mediated cyclization of 15. To a solution of 15 (40 mg,
0.11 mmol) in acetonitrile (10 mL) was added Pd(CH3CN)2Cl2
(11 mg, 0.04 mmol) and the reaction mixture was stirred at rt under
argon atmosphere for 4 h. Usual work followed by purification of
crude by silica gel chromatography (40% ethyl acetate in petroleum
ether) afforded 42 (25 mg, 60%) as a gum.
4.8. Synthesis of 1,2:5,6-di-O-isopropylidine-3-O-benzyl-3-C-
(prop-20-ynyl)-
a-D-allofuranose (45)
To a solution of alcohol 26 (1.5 g, 5.03 mmol) in dry DMF
(15 mL), NaH (181 mg, 7.54 mmol) was added portionwise at 0 ꢁC
and stirred for 30 min, followed by benzyl bromide (0.720 mL,
6.03 mmol). After stirring for additional 12 h at rt, the reaction
4.7.8.1. 1,2-O-Isopropylidene-3-C-[30-oxo-30-(4-methoxyphenyl)-
25
propyl]-
a
-D-allofuranose (42). [
a]
þ12.0 (c 0.8, CHCl3). IR (CHCl3):
D

C.V. Ramana et al. / Tetrahedron 65 (2009) 9819–9832
9829
mixture was quenched at 0 ꢁC by adding satd Na2SO4, poured into
water, and extracted with ethyl acetate. The combined organic
phases were washed with water, brine, dried (Na2SO4), and con-
centrated. Purification of the crude by column chromatography
(15% ethyl acetate in petroleum ether) yielded the benzyl de-
517.68 (100%, [MþNa]þ). Anal. Calcd for C29H34O7: C, 70.43; H, 6.93.
Found: C, 70.61; H, 6.78.
4.9.3. 1,2:5,6-Di-O-isopropylidine-3-O-benzyl-3-C-[30-(4-nitro-
phenyl)-prop-20-ynyl]-
a-D-allofuranose (48). Reagents: alkyne 45
rivative 45 (1.37 g, 70%) as colorless oil. Rf (20% EtOAc/pet. ether)
(350 mg, 0.901 mmol); 4-iodonitrobenzene (336 mg, 1.351 mmol);
TPP (24 mg, 0.0901 mmol); Pd(PPh3)2Cl2 (63 mg, 0.0901 mmol); CuI
(17 mg, 0.0901 mmol); Et3N (6 mL) and DMF (3 mL). The crude
residue was purified by column chromatography (10% ethyl acetate
25
0.4. [
a
]
D
þ45.2 (c 1.0, CHCl3). IR (CHCl3):
n
3284, 3089, 3065, 2987,
1H NMR (200 MHz,
1.34 (s, 3H), 1.37 (s, 3H), 1.39 (s, 3H), 1.60 (s, 3H), 2.13 (t,
2933, 2220, 1606, 1455, 1382, 844 cmꢀ1
CDCl3):
.
d
J¼2.8 Hz, 1H), 2.63 (dd, J¼2.7 Hz, 17.3 Hz, 1H), 2.82 (dd, J¼2.7 Hz,
17.3 Hz, 1H), 4.01 (dd, J¼5.3 Hz, 8.5 Hz, 1H), 4.10 (dd, J¼6.0 Hz,
8.5 Hz, 1H), 4.18 (d, J¼7.3 Hz, 1H), 4.25 (dt, J¼5.8 Hz, 7.3 Hz, 1H),
4.76 (d, J¼3.8 Hz, 1H), 4.78 (d, J¼11.5 Hz, 1H), 4.87 (d, J¼11.3 Hz,
1H), 5.81 (d, J¼3.8 Hz, 1H), 7.26 (t, J¼3.5 Hz, 1H), 7.32 (t, J¼7.0 Hz,
in petroleum ether) to give 48 (339 mg, 74%) as yellow syrup. Rf (20%
25
EtOAc/pet. ether) 0.4. [
a
]
þ27.9 (c 1.9, CHCl3). IR (CHCl3):
n
3065,
1H
1.34 (s, 3H), 1.39 (s, 3H), 1.41 (s, 3H), 1.62
D
2930, 2223, 1667, 1594, 1519, 1345, 1217, 1060, 855, 755 cmꢀ1
NMR (200 MHz, CDCl3):
.
d
(s, 3H), 2.89 (d, J¼17.4 Hz, 1H), 3.09 (d, J¼17.4 Hz, 1H), 4.00–4.31 (m,
4H), 4.76 (d, J¼3.8 Hz,1H), 4.84 (d, J¼11.2 Hz,1H), 4.93 (d, J¼11.2 Hz,
1H), 5.84 (d, J¼3.8 Hz,1H), 7.28–7.33 (m, 2H), 7.36–7.45 (m, 3H), 7.50
(br dt, J¼2.1, 8.9 Hz, 2H), 8.16 (br dt, J¼2.1, 8.9 Hz, 2H) ppm. 13C NMR
2H), 7.40 (d, J¼7.0 Hz, 2H). 13C NMR (50 MHz, CDCl3):
d 21 (t), 25.3
(q), 26.6 (q), 26.8 (q), 27.0 (q), 67.4 (t), 67.5 (t), 72.1 (s), 73.4 (d),
79.1 (d), 81.6 (d), 82.3 (d), 83.7 (s), 104.4 (d), 109.5 (s), 112.8 (s),
127.2 (d, 3C), 128.0 (d, 2C), 138 (s) ppm. ESI-MS: m/z 411.52 (100%,
[MþNa]þ), 427.51 (89%, [MþK]þ). Anal. Calcd for C22H28O6: C,
68.02; H, 7.27. Found: C, 68.12; H, 7.06.
(50 MHz, CDCl3): d 22.7 (t), 25.3 (q), 26.5 (q), 26.7 (q), 26.9 (q), 67.5
(t, 2C), 73.4 (d), 81.5 (d), 82.1 (s), 82.7 (d), 84.1 (s), 90.6 (s), 104.1 (d),
109.5 (s), 112.9 (s), 123.5 (d, 2C), 127.1 (d, 2C), 127.2 (d), 128.0 (d, 2C),
129.9 (s),132.2 (d, 2C),138.7 (s),146.9 (s) ppm. ESI-MS (m/z): 509.77
(13%, [Mþ1]þ), 532.76 (100%, [MþNa]þ). Anal. Calcd for C28H31NO8:
C, 66.00; H, 6.13; N, 2.75. Found: C, 65.83; H, 6.33; N, 2.86.
4.9. Sonogashira coupling of compound 45 with aryliodides
4.9.1. 1,2:5,6-Di-O-isopropylidine-3-O-benzyl-3-C-([30-phenyl-prop-
20-ynyl])-
a-D
-allofuranose (46). Reagents: alkyne 45 (250 mg,
4.9.4. 1,2:5,6-Di-O-isopropylidine-3-O-benzyl-3-C-[30-(3-nitro-
phenyl)-prop-20-ynyl]-
a-D-allofuranose (49). Reagents: alkyne 45
(350 mg, 0.901 mmol); 3-iodonitrobenzene (336 mg, 1.351 mmol);
TPP (24 mg, 0.0901 mmol); Pd(PPh3)2Cl2 (63 mg, 0.0901 mmol); CuI
(17 mg, 0.0901 mmol); Et3N (6 mL) and DMF (3 mL). The crude resi-
due was purified by column chromatography (10% ethyl acetate in
0.643 mmol); iodobenzene (0.11 mL, 0.961 mmol); TPP (17 mg,
0.0643 mmol); Pd(PPh3)2Cl2 (45 mg, 0.0643 mmol); CuI (12 mg,
0.0643 mmol); Et3N (5 mL) and DMF (2.5 mL). The crude residue
was purified by column chromatography (10% ethyl acetate in
petroleum ether) to obtain 46 (221 mg, 73%) as a yellow syrup. Rf
25
(30% EtOAc/pet. ether) 0.6. [
a
]
þ63.2 (c 2.0, CHCl3). IR (CHCl3):
n
petroleum ether) gave 49 (320 mg, 72%) as yellow syrup. Rf (20%
D
25
3063, 2987, 2935, 2223, 1953, 1731, 1677, 1598, 1491, 1454, 1372,
EtOAc/pet. ether) 0.4. [
a
]
þ50.9 (c 1.5, CHCl3). IR (CHCl3):
n 3066,
D
844, 756 cmꢀ1 1H NMR (400 MHz, CDCl3):
.
d
1.32 (s, 3H), 1.36 (s,
2989, 2933, 2402, 2229, 1730, 1573, 1532, 1351, 1217, 1075, 875, 845,
3H), 1.39 (s, 3H), 1.59 (s, 3H), 2.83 (d, J¼17.1 Hz, 1H), 3.00 (d,
J¼17.1 Hz, 1H), 4.01–4.05 (m, 1H), 4.11 (dt, J¼2.2, 6.3 Hz, 1H), 4.21
(d, J¼7.0 Hz, 1H), 4.31–4.36 (m, 1H), 4.77 (d, J¼3.5 Hz, 1H), 4.82 (d,
J¼11.3 Hz, 1H), 4.92 (d, J¼11.3 Hz, 1H), 5.85 (d, J¼3.5 Hz, 1H), 7.28–
7.32 (m, 6H), 7.36–7.38 (m, 2H), 7.41 (d, J¼7.0 Hz, 2H) ppm. 13C
756 cmꢀ1. 1H NMR (200 MHz, CDCl3):
d
1.35 (s, 3H), 1.39 (s, 3H), 1.42
(s, 3H), 1.62 (s, 3H), 2.87 (d, J¼17.4 Hz, 1H), 3.07 (d, J¼17.4 Hz, 1H),
4.01–4.38 (m, 4H), 4.76 (d, J¼3.8 Hz, 1H), 4.84 (d, J¼11.2 Hz, 1H), 4.94
(d, J¼11.2 Hz, 1H), 5.84 (d, J¼3.8 Hz, 1H), 7.28–7.37 (m, 3H), 7.41–7.46
(m, 2H), 7.49 (d, J¼8.1 Hz, 1H), 7.62 (dt, J¼1.3, 7.8 Hz, 1H), 8.14 (ddd,
J¼1.1, 2.3, 8.1 Hz, 1H), 8.21 (t, J¼1.8 Hz, 1H) ppm. 13C NMR (125 MHz,
NMR (100 MHz, CDCl3):
d 22.5 (t), 25.3 (q), 26.6 (q), 26.8 (q), 27.0
(q), 67.4 (t), 67.5 (t), 73.5 (d), 81.8 (d), 82.5 (d), 83.7 (s), 84.1 (s),
84.5 (s), 104.4 (d), 109.4 (s), 112.8 (s), 123.0 (s), 127.0 (d), 127.2 (d,
2C), 128.0 (d, 2C), 128.1 (d), 128.3 (d, 2C), 131.4 (d, 2C) 138.9 (s)
ppm. ESI-MS (m/z): 487.57 (47%, [MþNa]þ), 503.55 (100%,
[MþK]þ). Anal. Calcd for C28H32O6: C, 72.39; H, 6.94. Found: C,
72.47; H, 6.71.
CDCl3): d 22.5 (t), 25.3 (q), 26.5 (q), 26.7 (q), 26.9 (q), 67.5 (t), 67.6 (t),
73.4 (d), 81.4 (s), 81.5 (d), 82.7 (d), 84.0 (s), 87.7 (s),104.1 (d),109.5 (s),
112.9 (s),122.8 (d),124.8 (s),126.2 (d),127.0 (d, 2C),127.2 (d),128.0 (d,
2C),129.3 (d), 137.2 (d),138.7 (s),148.0 (s) ppm. ESI-MS (m/z): 509.77
(13%, [Mþ1]þ), 532.76 (100%, [MþNa]þ). Anal. Calcd for C28H31NO8: C,
66.00; H, 6.13; N, 2.75. Found: C, 65.83; H, 6.16; N, 2.66.
4.9.2. 1,2:5,6-Di-O-isopropylidine-3-O-benzyl-3-C-([30-(4-methox-
yphenyl)-prop-20-ynyl])-
a-D-allofuranose (47). Reagents: alkyne 45
4.10. The acetonide hydrolysis of compounds 46–50
(200 mg, 0.515 mmol); iodoanisole (181 mg, 0.772 mmol); TPP
(13 mg, 0.0515 mmol); Pd(PPh3)2Cl2 (36 mg, 0.0515 mmol); CuI
(10 mg, 0.0515 mmol); Et3N (5 mL) and DMF (2.5 mL). The crude
residue was purified by column chromatography (15% ethyl acetate
A solution of alkyne (1 mmol) in MeOH (30 mL) was treated
with dil. H2SO4 (15 mL, 0.8% in water) dropwise and stirred at rt for
5 h. The reaction mixture was quenched with NaHCO3 (2.5 g),
concentrated under reduced pressure. The residue was portioned
between ethyl acetate/water and the aqueous layer was extracted
with ethyl acetate. The combined organic layers were dried (NaSO4)
and concentrated. The crude residue was purified by column
chromatography (30–60% ethyl acetate in petroleum ether) to ob-
tain the alkyne diols 50–54.
in petroleum ether) afforded 47 (178 mg, 70%) as colorless syrup. Rf
25
(30% EtOAc/pet. ether) 0.6. [
a
]
þ50.0 (c 2.5, CHCl3). IR (CHCl3):
n
D
3065, 2988, 2540, 2222, 1725, 1666, 1606, 1455, 1373, 1170, 1075,
834, 756 cmꢀ1. 1H NMR (400 MHz, CDCl3):
d
1.34 (s, 3H),1.37 (s, 3H),
1.41 (s, 3H), 1.61 (s, 3H), 2.82 (d, J¼17.2 Hz, 1H), 2.99 (d, J¼17.2 Hz,
1H), 3.80 (s, 3H), 4.04 (dd, J¼5.5, 8.3 Hz, 1H), 4.23 (dd, J¼6.0, 8.3 Hz,
1H), 4.26 (d, J¼7.3 Hz, 1H), 4.33–4.37 (m, 1H), 4.78 (d, J¼3.8 Hz, 1H),
4.83 (d, J¼11.3 Hz,1H), 4.93 (d, J¼11.3 Hz,1H), 5.84 (d, J¼3.8 Hz,1H),
6.82 (br d, J¼8.8 Hz, 2H), 7.26 (d, J¼7.3 Hz, 1H), 7.30–7.33 (m, 4H),
4.10.1. 1,2-O-Isopropylidine-3-O-benzyl-3C-propynyl-
a-D-allofur-
anose (50). 94% Yield as colorless gum. Rf (20% EtOAc/pet. ether)
25
0.1. [
2119, 1953, 1724, 1666, 1455, 1384, 872, 755 cmꢀ1
(500 MHz, CDCl3):
a
]
þ31.2 (c 2.4, CHCl3). IR (CHCl3):
n
3488, 3304, 3065, 2988,
D
7.43 (br d, J¼7.3 Hz, 2H) ppm. 13C NMR (100 MHz, CDCl3):
d
22.5 (t),
.
1H NMR
25.4 (q), 26.6 (q), 26.8 (q), 27.0 (q), 55.2 (q), 67.3 (t), 67.5 (t), 73.5 (d),
81.9 (d), 82.6 (d), 82.9 (s), 83.5 (s), 84.1 (s), 104.4 (d), 109.4 (s), 112.8
(s), 113.9 (d, 2C), 115.2 (s), 127.1 (d), 127.2 (d, 2C), 128.0 (d, 2C), 132.8
(d, 2C),138.9 (s),159.4 (s) ppm. ESI-MS (m/z): 495.63 (18%, [Mþ1]þ),
d
1.37 (s, 3H), 1.61 (s, 3H), 2.22 (t, J¼2.8 Hz, 1H),
2.71 (dd, J¼2.7, 17.3 Hz, 1H), 2.77 (dd, J¼2.7, 17.3 Hz, 1H), 2.84 (br s,
1H), 3.66 (dd, J¼5.2, 11.5 Hz, 1H), 3.78 (dd, J¼3.0, 11.5 Hz, 1H), 3.95–
3.97 (m, 1H), 4.07 (t, J¼8.8 Hz, 1H), 4.65 (d, J¼3.8 Hz, 1H), 4.74 (d,

9830
C.V. Ramana et al. / Tetrahedron 65 (2009) 9819–9832
J¼10.4 Hz, 1H), 4.85 (d, J¼10.4 Hz, 1H), 5.76 (d, J¼3.8 Hz, 1H), 7.27–
7.30 (d, J¼7.4 Hz, 1H), 7.34 (t, J¼7.7 Hz, 2H), 7.40 (d, J¼7.1 Hz, 2H).
J¼10.4 Hz, 1H), 4.89 (d, J¼10.4 Hz, 1H), 5.83 (d, J¼3.6 Hz, 1H), 7.30
(d, J¼7.1 Hz, 1H), 7.34 (t, J¼7.7 Hz, 2H), 7.42 (d, J¼7.4 Hz, 2H), 7.48 (t,
J¼8.0 Hz, 1H), 7.67 (d, J¼7.4 Hz, 1H), 8.16 (dd, J¼8.2 Hz, 2.0 Hz, 1H),
13C NMR (125 MHz, CDCl3):
d 21.3 (t), 26.6 (q, 2C), 64.3 (t), 68.1 (t),
69.5 (d), 72.6 (s), 78.7 (d), 78.9 (d), 81.4 (d), 84.3 (s), 104.0 (d), 113.2
(s), 127.7 (d), 127.8 (d, 2C), 128.3 (d, 2C), 137.6 (s) ppm. ESI-MS: m/z
349.41 (2%, [Mþ1]þ), 371.42 (100%, [MþNa]þ). Anal. Calcd for
C19H24O6: C, 65.50; H, 6.94. Found: C, 65.68; H, 6.78.
8.21 (s, 1H) ppm. 13C NMR (125 MHz, CDCl3):
d 22.2 (t), 26.7 (q, 2C),
64.4 (t), 68.2 (t), 69.7 (d), 78.8 (d), 81.5 (s), 81.7 (d), 84.7 (s), 87.1 (s),
104.1 (d), 113.4 (s), 123.1 (d), 124.5 (s) 126.3 (d), 127.7 (d, 2C), 127.9
(d), 128.4 (d, 2C), 129.4 (d), 137.4 (d), 137.5 (s), 148.0 (s) ppm. ESI-MS
(m/z): 492.53 (100%, [MþNa]þ). Anal. Calcd for C25H27NO8: C, 63.96;
H, 5.80; N, 2.98. Found: C, 64.83; H, 5.67; N, 2.72.
4.10.2. 1,2-O-Isopropylidine-3-O-benzyl-3C-[30-(phenyl)-prop-2
ynyl]- -allofuranose (51). 88% Yield, colorless syrup. Rf (30%
EtOAc/pet. ether) 0.2. [
2925, 1725, 1598, 1217, 1087, 1026, 873.58, 756 cmꢀ1
(400 MHz, CDCl3): 1.38 (s, 3H), 1.62 (s, 3H), 2.32 (br s, 1H), 2.89 (d,
a-
a-D
25
a]
þ71.8 (c 0.4, CHCl3). IR (CHCl3):
n
3480,
4.11. Pd-mediated cyclization of alkynols 50–54
D
.
1H NMR
d
4.11.1. 1,2-O-Isopropylidine-3-O-benzyl-3C-[30-(2-oxypropyl])-
a-D-
J¼2.3 Hz, 1H), 2.93 (d, J¼17.3 Hz, 1H), 2.98 (d, J¼17.3 Hz, 1H), 3.70
(dd, J¼4.3, 11.3 Hz, 1H), 3.81 (dd, J¼2.2, 11.3 Hz, 1H), 4.04–4.08 (m,
1H), 4.12 (d, J¼8.8 Hz, 1H), 4.68 (d, J¼3.8 Hz, 1H), 4.79 (d, J¼10.3 Hz,
1H), 4.92 (d, J¼10.3 Hz, 1H), 5.81 (d, J¼3.8 Hz, 1H), 7.28–7.33 (m,
allofuranose-(20-C,5-O,6-O)-ketal (55). To a solution of 50 (115 mg,
0.33 mmol) in acetonitrile (6 mL) was added Pd(CH3CN)2Cl2
(42 mg, 0.165 mmol) and the reaction mixture was stirred at rt
under argon atmosphere for 6 h. The reaction mixture was con-
centrated and purified by silica gel chromatography (15% ethyl
6H), 7.38–7.43 (m, 3H) ppm. 13C NMR (100 MHz, CDCl3):
d 22.2 (t),
26.7 (q), 26.7 (q), 64.4 (t), 68.2 (t), 69.6 (d), 78.9 (d), 81.6 (d), 84.1 (s),
84.2 (s), 84.7 (s), 104.1 (d), 113.2 (s), 122.6 (s), 127.8 (d), 127.9 (d, 2C),
128.3 (d, 2C),128.3 (d),128.4 (d, 2C),131.5 (d, 2C),137.9 (s) ppm. ESI-
MS (m/z): 425.54 (3%, [Mþ1]þ), 447.55 (100%, [MþNa]þ). Anal.
Calcd for C25H28O6: C, 70.74; H, 6.65. Found: C, 70.54; H, 6.48.
acetate in petroleum ether) to obtain 55 (97 mg, 84%) as a white
25
solid. Rf (20% EtOAc/pet. ether) 0.2. Mp 143–145 ꢁC. [
a
]
D
þ6.5 (c 0.8,
CHCl3). IR (CHCl3):
n
3063, 2986, 1731, 1606, 1384, 1155, 1057, 866,
1.37 (d, J¼14.9 Hz, 1H), 1.38
742 cmꢀ1. 1H NMR (500 MHz, CDCl3):
d
(s, 3H), 1.53 (s, 3H), 1.59 (s, 3H), 2.33 (d, J¼14.9 Hz, 1H), 3.83 (dd,
J¼6.1, 6.8 Hz, 1H), 4.01 (s, 1H), 4.21 (d, J¼6.9 Hz, 1H), 4.31 (d,
J¼3.6 Hz, 1H), 4.55 (d, J¼10.5 Hz, 1H), 4.63 (d, J¼10.5 Hz, 1H), 4.68
(d, J¼3.6 Hz, 1H), 5.01 (d, J¼3.6 Hz,1H), 7.28 (t, J¼7.4 Hz,1H), 7.34 (t,
J¼7.1 Hz, 2H), 7.45 (d, J¼7.1 Hz, 2H) ppm. 13C NMR (125 MHz,
4.10.3. 1,2-O-Isopropylidine-3-O-benzyl-3C-[30-(4-methoxyphenyl)-
prop-20-ynyl]-
a-D-allofuranose (52). 87% Yield, colorless syrup. Rf
25
(30% EtOAc/pet. ether) 0.2. [
3542, 3013, 2934, 2541, 2403, 2050, 1727, 1606, 1510, 873, 833,
755 cmꢀ1 1H NMR (400 MHz, CDCl3):
1.38 (s, 3H), 1.62 (s, 3H),
a
]
þ61. 2 (c 1.7, CHCl3). IR (CHCl3):
n
D
CDCl3): d 24.2 (q), 26.9 (q), 27.1 (q), 35.8 (t), 65.1 (t), 66.5 (t), 74.0 (d),
.
d
77.8 (d), 80.4 (s), 83.0 (d), 104.8 (s), 104.9 (d), 113.2 (s), 127.4 (d),
127.7 (d, 2C), 128.2 (d, 2C), 138.4 (s) ppm. ESI-MS: (m/z) 371.34
(100%, [MþNa]þ), 387.33 (42%, [MþK]þ). Anal. Calcd for C19H24O6:
C, 65.50; H, 6.94. Found: C, 65.23; H, 6.64.
2.38 (br s, 1H), 2.90 (d, J¼17.8 Hz, 1H), 2.92 (s, 1H), 2.95 (d,
J¼17.8 Hz, 1H), 3.70 (d, J¼9.5 Hz, 1H), 3.80 (s, 3H), 4.08 (br s, 1H),
4.09 (s, 1H), 4.66 (d, J¼3.8 Hz, 1H), 4.78 (d, J¼10.3 Hz, 1H), 4.92 (d,
J¼10.3 Hz, 1H), 5.80 (d, J¼3.8 Hz, 1H), 6.82 (d, J¼8.8 Hz, 2H), 7.28–
7.35 (m, 5H), 7.42 (d, J¼6.8 Hz, 2H) ppm. 13C NMR (100 MHz,
4.11.2. 1,2-O-Isopropylidene-3-O-benzyl-3C-[20-oxo-30-phenyl-pro-
pyl]-a-D
-allofuranose-(20-C,5-O,6-O)-ketal (56). To a solution of 51
CDCl3):
d
22.2 (t), 26.7 (q), 26.7 (q), 55.2 (q), 64.4 (t), 68.1 (t), 69.6
(d), 79.0 (d), 81.7 (d), 82.5 (s), 84.0 (s), 84.7 (s), 104.1 (d), 113.2 (s),
114.0 (d, 2C), 114.7 (s), 127.7 (d), 127.8 (d, 2C), 128.3 (d, 2C), 132.9
(d, 2C), 137.7 (s), 159.6 (s) ppm. ESI-MS (m/z): 455.62 (12%,
[Mþ1]þ), 477.62 (100%, [MþNa]þ). Anal. Calcd for C26H30O7: C,
68.71; H, 6.65. Found: C, 68.91; H, 6.35.
(97 mg, 0.2284 mmol) in acetonitrile (10 mL) was added
Pd(CH3CN)2Cl2 (29 mg, 0.112 mmol) and the reaction mixture was
stirred at rt under argon atmosphere for 2 h. The reaction mixture
was concentrated and purified by silica gel chromatography (15%
ethyl acetate in petroleum ether) to obtain 56 (80 mg, 82%) as
a yellow color solid. Rf (30% EtOAc/pet. ether) 0.5. Mp 141–143 ꢁC.
25
4.10.4. 1,2-O-Isopropylidine-3-O-benzyl-3C-[30-(4-nitrophenyl)-
[a
]
þ47.0 (c 0.4, CHCl3). IR (CHCl3):
n
3063, 2952, 1734, 1605,
D
prop-20-ynyl]-
a-
D
-allofuranose (53). 89% Yield, yellow syrup. Rf
1455, 1059, 1021, 873, 754, 699 cmꢀ1 1H NMR (200 MHz, CDCl3):
.
25
(30% EtOAc/pet. ether) 0.2. [
3471, 3013, 2926, 2453,1929,1733,1606,1518,1350,1225,1119, 875,
856, 758 cmꢀ1. 1H NMR (500 MHz, CDCl3):
1.40 (s, 3H),1.64 (s, 3H),
a
]
þ31.3 (c 1.1, CHCl3). IR (CHCl3):
n
d
1.29 (d, J¼14.9 Hz, 1H), 1.35 (s, 3H), 1.57 (s, 3H), 2.27 (d,
D
J¼14.9 Hz, 1H), 3.08 (d, J¼14.3 Hz, 1H), 3.11 (d, J¼14.3 Hz, 1H), 3.72
(dd, J¼5.9 Hz, 6.7 Hz, 1H), 4.00 (s, 1H), 4.20 (d, J¼6.9 Hz, 1H), 4.25
(d, J¼3.6 Hz, 1H), 4.47 (d, J¼10.5 Hz, 1H), 4.52 (d, J¼10.5 Hz, 1H), 4.
67 (dd, J¼1.1, 5.1 Hz, 1H), 5.85 (d, J¼3.5 Hz, 1H), 7.24–7.28 (m, 3H),
7.29–7.35 (m, 5H), 7.38–7.40 (m, 2H) ppm. 13C NMR (50 MHz,
d
2.83 (br s, 1H), 2.99 (d, J¼17.6 Hz, 1H), 3.01 (d, J¼17.6 Hz, 1H), 3.71
(dd, J¼4.7, 11.5 Hz 1H), 3.82 (dd, J¼3.3, 11.5 Hz 1H), 4.05–4.08 (m,
1H), 4.13 (d, J¼8.8 Hz, 1H), 4.66 (d, J¼3.8 Hz, 1H), 4.82 (d, J¼10.4 Hz,
1H), 4.87 (d, J¼10.4, 1H), 5.82 (d, J¼3.8 Hz, 1H), 7.30–7.35 (m, 3H),
7.40 (d, J¼8.0 Hz, 2H), 7.51 (d, J¼8.8 Hz, 2H), 8.16 (d, J¼8.8 Hz,
2H) ppm. 13C NMR (125 MHz, CDCl3): 22.3 (t), 26.7 (q, 2C), 64.4 (t),
68.2 (t), 69.7 (d), 78.8 (d), 81.7 (s), 82.5 (s), 84.8 (s), 89.9 (d), 104.1
(d),113.5 (s),123.6 (d, 2C),127.7 (d, 2C),127.9 (d),128.4 (d, 2C),129.5
(s), 132.4 (d, 2C), 137.5 (s), 147.1 (s) ppm. ESI-MS (m/z): 492.53
(100%, [MþNa]þ). Anal. Calcd for C25H27NO8: C, 63.96; H, 5.80; N,
2.98. Found: C, 63.73; H, 5.90; N, 2.74.
CDCl3):
d 26.8 (q), 27.1 (q), 34.3 (t), 43.8 (t), 65.3 (t), 66.6 (t), 73.9
(d), 78.0 (d), 80.5 (s), 83.0 (d), 104.9 (d), 105.9 (s), 113.1 (s), 126.6
(d), 127.4 (d), 127.8 (d, 2C), 128.0 (d, 2C), 128.1 (d, 2C), 130.4 (d, 2C),
135.4 (s), 138.3 (s) ppm. ESI-MS (m/z): 447.40 (100%, [MþNa]þ).
463.38 (87%, [MþKþ]). Anal. Calcd for C25H28O6: C, 70.74; H, 6.65.
Found: C, 70.44; H, 6.85.
4.11.2.1. Crystallographic data for 56. C25H28O6: M¼424.47, crys-
tal dimensions 0.59ꢂ0.19ꢂ0.04 mm3, orthorhombic, space group P
212121, a¼6.174(2), b¼9.766(4), c¼37.152(14) Å, V¼2240.2(15) Å3,
4.10.5. 1,2-O-Isopropylidine-3-O-benzyl-3C-[30-(3-nitrophenyl)-
prop-20-ynyl]-
EtOAc/pet. ether) 0.2. [
3085, 2928, 2229, 1671, 1606, 1530, 1455, 1374, 1167, 1083, 875,
756 cmꢀ1. 1H NMR (500 MHz, CDCl3):
1.4 (s, 3H), 1.64 (s, 3H), 1.88
a-
D
-allofuranose (54). 84% Yield, yellow syrup. Rf (30%
Z¼4, rcalcd¼1.259 g cmꢀ3
,
m
(Mo K
a
)¼0.089 mmꢀ1, F(000)¼904,
25
a
]
D
þ49.5 (c 1.1, CHCl3). IR (CHCl3):
n
3479,
2
qmax¼50.00ꢁ, T¼297(2) K, 11,062 reflections collected, 3937
unique, 3769 observed (I>2s(I)) reflections, 282 refined parame-
d
ters, R value 0.1143, wR2¼0.2463 (all data R¼0.1271, wR2¼0.2533),
S¼1.247, minimum and maximum transmission 0.9964 and 0.9495;
maximum and minimum residual electron densities þ0.583 and
(br s, 1H), 2.42 (br s, 1H), 2.97 (d, J¼17.6 Hz, 1H), 3.03 (d, J¼17.6 Hz,
1H), 3.71 (dd, J¼4.6, 11.5 Hz, 1H), 3.82 (dd, J¼3.1, 11.5 Hz, 1H), 4.05–
4.07 (m, 1H), 4.14 (d, J¼8.8 Hz, 1H), 4.68 (d, J¼3.6 Hz, 1H), 4.83 (d,
ꢀ0.272 e Åꢀ3
.

C.V. Ramana et al. / Tetrahedron 65 (2009) 9819–9832
9831
25
4.11.3. 1,2-O-Isopropylidine-3-O-benzyl-3C-[20-oxo-30-(4-methoxy-
phenyl) propyl]-
-allofuranose-(20-C,5-O,6-O)-ketal (57). To a so-
lution of 52 (100 mg, 0.220 mmol) in acetonitrile (6 mL) was added
Pd(CH3CN)2Cl2 (28 mg, 0.108 mmol) and the reaction mixture was
stirred at rt under argon atmosphere for 6 h. The reaction mixture
was concentrated and the crude was purified by silica gel chro-
matography (15% ethyl acetate in petroleum ether) to procure 57
EtOAc/pet. ether) 0.3. Mp 95–97 ꢁC. [
(CHCl3):
755 cmꢀ1. 1H NMR (400 MHz, CDCl3):
a
]
þ15.9 (c 0.9, CHCl3). IR
D
a
-D
n 3066, 2926, 1727, 1607, 1529, 1350, 1167, 1060, 873,
d
1.35 (d, J¼14.3 Hz, 1H), 1.37
(s, 3H), 1.39 (d, J¼14.6 Hz, 1H), 1.58 (s, 3H), 3.18 (s, 2H), 3.58 (t,
J¼6.0 Hz,1H), 4.02 (br s,1H), 4.19 (d, J¼7.0 Hz,1H), 4.32 (d, J¼3.5 Hz,
1H), 4.54 (d, J¼10.8 Hz, 1H), 4.57 (d, J¼10.8 Hz, 1H), 4.83 (dd, J¼1.7,
5.5 Hz, 1H), 5.90 (d, J¼3.5 Hz, 1H), 7.29 (d, J¼7.3 Hz, 1H), 7.34 (t,
J¼7.5 Hz, 2H), 7.41 (d, J¼7.3 Hz, 2H), 7.45 (t, J¼8.1 Hz, 1H), 7.68 (d,
J¼7.8 Hz, 1H), 8.10 (dd, J¼1.3, 8.3 Hz, 1H), 8.21 (t, J¼1.8 Hz 1H) ppm.
(90 mg, 90%) as white solid. Rf (20% EtOAc/pet. ether) 0.3. Mp 127–
25
129 ꢁC. [
a]
þ27.6 (c 0.7, CHCl3). IR (CHCl3):
n
3064, 2932, 1889,
1H NMR
1.27 (d, J¼14.8 Hz, 1H), 1.34 (s, 3H), 1.57 (s, 3H),
D
1723, 1612, 1373, 1301, 1114, 1059, 873, 833, 755 cmꢀ1
(500 MHz, CDCl3):
.
13C NMR (100 MHz, CDCl3):
d 26.8 (q), 27.1 (q), 34.9 (t), 42.7 (t), 65.5
d
(t), 66.7 (t), 73.9 (d), 77.8 (d), 80.5 (s), 82.9 (d), 104.9 (d), 105.2 (s),
113.3 (s), 121.8 (d), 125.4 (d), 127.5 (d), 127.6 (d, 2C), 128.2 (d, 2C),
128.7 (d), 136.9 (d), 137.1 (s), 138.2 (s), 147.9 (s) ppm. ESI-MS (m/z):
492.56 (50%, [MþNa]þ), 508.54 (100%, [MþK]þ). Anal. Calcd for
C25H27NO8: C, 63.96; H, 5.80; N, 2.98. Found: C, 63.74; H, 5.60; N,
2.78.
2.24 (d, J¼14.8 Hz, 1H), 3.02 (s, 2H), 3.71 (t, J¼6.33 Hz, 1H), 3.78 (s,
3H), 3.99 (s, 1H), 4.18 (d, J¼6.9 Hz, 1H), 4.24 (d, J¼3.6 Hz, 1H), 4.47
(d, J¼10.7 Hz, 1H), 4.51 (d, J¼10.7 Hz, 1H), 4.65 (d, J¼4.6 Hz, 1H),
5.84 (d, J¼3.6 Hz, 1H), 6.83 (d, J¼8.5 Hz, 2H), 7.25 (d, J¼8.8 Hz, 2H),
7.30–7.33 (m, 2H), 7.39 (d, J¼7.2 Hz, 2H), 7.47–7.51 (m, 1H) ppm. 13C
NMR (125 MHz, CDCl3): d 26.8 (q), 27.1 (q), 34.2 (t), 42.9 (t), 55.1 (q),
65.3 (t), 66.6 (t), 73.9 (d), 78.0 (d), 80.5 (s), 83.0 (d), 104.9 (d), 105.9
(s), 113.1 (s) 113.5 (d, 2C), 127.4 (d), 127.5 (s), 127.7 (d, 2C), 128.1 (d,
2C), 131.3 (d, 2C), 138.4 (s), 158.4 (s) ppm. ESI-MS (m/z): 477.41
(100%, [MþNa]þ), 493.39 (55%, [MþK]þ). Anal. Calcd for C26H30O7:
C, 68.71; H, 6.65. Found: C, 68.59; H, 6.81.
4.11.5.2. 1,2-O-Isopropylidene-3-O-benzyl-3C-[20-hydroxy-20-(3-
nitro-benzyl)-E-vinyl]-20,5-anhydro-
a-
D
-allofuranose (60). Rf (20%
3456,
1H NMR
1.37 (s, 3H), 1.58 (s, 3H), 1.88 (br s, 1H), 3.18 (s,
25
EtOAc/pet. ether) 0.2. [
a
]
þ32.2 (c 1.3, CHCl3). IR (CHCl3):
n
D
3016, 2929, 1719, 1531, 1375, 1215, 1090, 887, 756 cmꢀ1
(400 MHz, CDCl3):
.
d
2H), 3.58 (dd, J¼6.8, 6.0 Hz, 1H), 4.02 (br s, 1H), 4.12 (q, J¼7.3 Hz,
1H), 4.19 (d, J¼7.3 Hz, 1H), 4.32 (d, J¼3.5 Hz, 1H), 4.53 (d, J¼10.8 Hz,
1H), 4.57 (d, J¼10.8 Hz, 1H), 4.63 (dd, J¼1.8, 5.3 Hz, 1H), 5.91 (d,
J¼3.5 Hz, 1H), 7.32 (d, J¼7.0 Hz, 1H), 7.34 (t, J¼7.0 Hz, 2H), 7.41 (d,
J¼7.0 Hz, 2H), 7.45 (t, J¼8.0 Hz, 1H), 7.69 (d, J¼7.8 Hz, 1H), 8.11 (dd,
J¼1.5, 8.0 Hz, 1H), 8.22 (s, 1H) ppm. 13C NMR (125 MHz, CDCl3):
4.11.4. 1,2-O-Isopropylidine-3-O-benzyl-3C-[20-oxo-30-(4-nitro-
phenyl)propyl]-a-D
-allofuranose-(20-C,5-O,6-O)-ketal (58). A solu-
tion of 53 (150 mg, 0.319 mmol) and Pd(CH3CN)2Cl2 (41 mg,
0.158 mmol) in acetonitrile (6 mL) was stirred at rt under argon
atmosphere for 6 h. The reaction mixture was concentrated and the
residue obtained was purified by silica gel chromatography (15%,
d
26.9 (q), 27.1 (q), 42.8 (t), 65.5 (t), 66.7 (t), 73.97 (d), 77.2 (d), 77.9
18% ethyl acetate in petroleum ether) to obtain 58 (103 mg, 68%) as
(d), 80.6 (s), 82.9 (d), 104.9 (d), 105.2 (s), 113.3 (s), 121.8 (d), 125.5
(d),127.5 (d),127.7 (d, 2C),128.2 (d, 2C),128.7 (d),136.9 (d),137.1 (s),
138.2 (s), 148.0 (s) ppm. ESI-MS (m/z): 491.41 (34%, [MþNa]þ),
508.41 (100%, [MþK]þ). Anal. Calcd for C25H27NO8: C, 63.96; H,
5.80; N, 2.98. Found: C, 63.64; H, 5.66; N, 2.77.
25
yellow solid. Rf (20% EtOAc/pet. ether) 0.3. Mp 173–175 ꢁC. [
a]
D
þ14.4 (c 0.5, CHCl3). IR (CHCl3):
n
3070, 2925,1929, 1732, 1606,1518,
1H NMR (500 MHz, CDCl3):
1349, 1225, 1119, 1018, 876, 747 cmꢀ1
.
d
1.37 (s, 3H), 1.38 (d, J¼14.6 Hz, 1H), 1.58 (s, 3H), 2.32 (d, J¼14.6 Hz,
1H), 3.17 (s, 2H), 3.58 (t, J¼6.3 Hz, 1H), 4.01 (s, 1H), 4.19 (d, J¼7.1 Hz,
1H), 4.31 (d, J¼3.3 Hz, 1H), 4.54 (d, J¼10.7 Hz, 1H), 4.56 (d,
J¼10.7 Hz, 1H), 4.63 (d, J¼4.4 Hz, 1H), 5.90 (d, J¼3.3 Hz, 1H), 7.29 (d,
J¼7.1 Hz, 1H), 7.34 (t, J¼7.1 Hz, 2H), 7.41 (d, J¼7.1 Hz, 2H), 7.50 (d,
J¼8.8 Hz, 2H), 8.13 (d, J¼8.8 Hz, 2H) ppm. 13C NMR (125 MHz,
4.12. Pd-mediated cyclization of 28
To a solution of 28 (50 mg, 0.12 mmol) in acetonitrile (10 mL)
was added Pd(CH3CN)2Cl2 (11 mg, 0.04 mmol) and the reaction
mixture was stirred at rt under argon atmosphere for 6 h. The re-
action mixture was concentrated and purified by silica gel chro-
matography (35% ethyl acetate in petroleum ether) to obtain 61
(28 mg, 56%) as a white solid.
CDCl3): d 26.9 (q), 27.1 (q), 35.0 (t), 43.0 (t), 65.5 (t), 66.7 (t), 73.9 (d),
77.8 (d), 80.6 (s), 82.9 (d), 104.9 (d), 105.3 (s), 113.3 (s), 123.1 (d, 2C),
127.5 (d), 127.6 (d, 2C), 128.2 (d, 2C), 131.5 (d, 2C), 138.2 (s), 142.9 (s),
146.9 (s) ppm. ESI-MS (m/z): 493.70 (80%, [MþNa]þ), 508.56 (100%,
[MþK]þ). Anal. Calcd for C25H27NO8: C, 63.96; H, 5.80; N, 2.98.
Found: C, 64.24; H, 5.60; N, 2.81.
4.12.1. 1,2-O-Isopropylidene-3-C-[30-oxo-30-(4-methoxyphenyl) pro-
pyl]-a-D
-allofuranose-(30-C,5-O,6-O)-ketal (61). Mp 175–178 ꢁC.
4.11.4.1. Crystallographic data for 58. C25H27NO8: M¼469.48,
crystal dimensions 0.46ꢂ0.14ꢂ0.09 mm3, orthorhombic, space group
P 212121. a¼5.9696(9), b¼16.175(2), c¼23.804(4) Å, V¼2298.5(6) Å3,
25
[a
]
ꢀ29.4 (c 1.0, CHCl3). IR (CHCl3):
n
3439, 3020, 1620, 1339, 1216,
D
929, 758, 669 cmꢀ1. 1H NMR (200 MHz, CDCl3):
d
1.36 (s, 3H), 1.52
(dd, J¼5.0, 12.6 Hz, 1H), 1.61 (s, 3H), 2.05–2.21 (m, 2H), 2.36–2.54
(m, 1H), 3.69 (d, J¼8.3 Hz, 1H), 3.72 (d, J¼8.2 Hz, 1H), 3.79 (s, 3H),
3.98 (br s, 1H), 4.03 (d, J¼8.7 Hz, 1H), 4.20 (d, J¼3.5 Hz, 1H), 4.80 (br
d, J¼5.3 Hz, 1H), 5.80 (d, J¼3.7 Hz, 1H), 6.84 (dt, J¼2.3, 8.9 Hz, 2H),
Z¼4, rcalcd¼1.357 g cmꢀ3
,
m
(Mo
K
a
)¼0.102 mmꢀ1
F(000)¼992,
,
2
qmax¼50.00ꢁ, T¼297(2) K, 18,048 reflections collected, 4519 unique,
4519 observed (I>2s(I)) reflections, 309 refined parameters, R value
0.0488, wR2¼0.1076 (all data R¼0.0539, wR2¼0.1099), S¼1.216,
7.41 (dt, J¼2.7, 8.9 Hz, 2H). 13C NMR (50 MHz, CDCl3):
d 26.2 (q), 26.7
minimum and maximum transmission 0.9912 and 0.9547; maximum
(q), 28.4 (t), 36.6 (t), 55.2 (q), 65.5 (t), 76.7 (d), 79.5 (s), 81.7 (d), 85.9
(d), 102.7 (d), 110.7 (s), 112.8 (s), 113.5 (d, 2C), 125.8 (d, 2C), 135.0 (s),
159.4 (s) ppm. ESI-MS: m/z 365.1 (100%, [MþH]þ). Anal. Calcd for
C19H24O7: C, 62.63; H, 6.64. Found: C, 62.58; H, 6.62.
and minimum residual electron densities þ0.209 and ꢀ0.138 e Åꢀ3
.
4.11.5. Pd-mediated cyclization of 54. A solution of 54 (90 mg,
0.192 mmol) and Pd(CH3CN)2Cl2 (25 mg, 0.096 mmol) in acetoni-
trile (6 mL) was stirred at rt under argon atmosphere for 6 h. The
reaction mixture was concentrated and the residue obtained was
purified by silica gel chromatography (15%, 18% ethyl acetate in
petroleum ether) to obtain 59 (64 mg, 71%) as yellow solid and 60
(15 mg, 17%) as yellow oil.
Acknowledgements
We thank the Ministry of Science and Technology for funding
through the Department of Science and Technology under the
Green Chemistry Program (NO. SR/S5/GC-20/2007). Financial sup-
port from the CSIR (New Delhi) in the form of research fellowships
to B.I., B.S., and K.Y. is gratefully acknowledged.
4.11.5.1. 1,2-O-Isopropylidine-3-O-benzyl-3C-[20-oxo-30-(3-nitro-
phenyl)-propyl]-a-D
-allofuranose-(20-C,5-O,6-O)-ketal (59). Rf (20%

9832
C.V. Ramana et al. / Tetrahedron 65 (2009) 9819–9832
Chem. 2009, 74, 2842–2845; (f) Ramana, C. V.; Mallik, R.; Sahoo, G. Tetrahedron
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15. X-ray intensity data of compounds 32, 37, 39, 56, and 58 was collected on
a Bruker SMART APEX CCD diffractometer with graphite-monochromatized
(Mo K
a
¼0.71073 Å) radiation at room temperature. All the data were corrected
for Lorentzian, 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)16
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.
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University of Gottingen: Germany, 1997.
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lographic Data Centre as deposition Nos. CCDC674813 (32), CCDC674814
(37), CCDC674815 (39), CCDC745161 (56), and CCDC745162 (58). Copies of
the data can be obtained, free of charge, on application 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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