Co- and homocyclotrimerization reactions of protected 1-alkynyl-2-deoxyribofuranose. Synthesis of C-nucleosides, C-di- and C-trisaccharide analogues

Article abstract of DOI:10.1016/j.tet.2008.03.046

Cyclotrimerization of β- or α-ethynyl-3,5-di-O-toluoyl-2-deoxy-d-ribofuranose with α,ω-diynes proceeded smoothly under Rh-catalysis to afford the corresponding β- or α-benzene C-nucleoside derivatives. Analogous co-cyclotrimerization of α- or β-propynyl- and -phenylethynyl-3,5-di-O-toluoyl-2-deoxy-d-ribofuranose with α,ω-diynes gave the corresponding arene derivatives only under microwave irradiation in the presence of a Rh-catalyst in moderate yields. Attempted homocyclotrimerization of β- or α-ethynyl-3,5-di-O-toluoyl-2-deoxy-d-ribofuranose under Rh-catalysis led only to enynes while the use of Ru-catalyst gave the desired 1,2,4- and 1,3,5-tri-(2-deoxyribofuranose-1-yl)benzene.

Full text of DOI:10.1016/j.tet.2008.03.046

Tetrahedron 64 (2008) 5200–5207
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Co- and homocyclotrimerization reactions of protected 1-alkynyl-
2-deoxyribofuranose. Synthesis of C-nucleosides, C-di- and
C-trisaccharide analogues
a
a
b
b,
a,b,
*
ꢀ
*
´
´
´
Petr Novak , Sylva Cıhalova , Miroslav Otmar , Michal Hocek , Martin Kotora
a Department of Organic and Nuclear Chemistry and Centre for New Antivirals and Antineoplastics, Faculty of Science, Charles University, Hlavova 8, 128 43 Praha 2, Czech Republic
b
´
Institute of Organic Chemistry and Biochemistry, v.v.i., Academy of Sciences of the Czech Republic, Flemingovo nam. 2, 166 10 Praha 6, Czech Republic
a r t i c l e i n f o
a b s t r a c t
Article history:
Cyclotrimerization of b- or a-ethynyl-3,5-di-O-toluoyl-2-deoxy-D-ribofuranose with a,u-diynes pro-
Received 14 December 2007
Received in revised form 1 March 2008
Accepted 13 March 2008
ceeded smoothly under Rh-catalysis to afford the corresponding b- or a-benzene C-nucleoside
derivatives. Analogous co-cyclotrimerization of a- or b-propynyl- and -phenylethynyl-3,5-di-O-toluoyl-
2-deoxy-
irradiation in the presence of a Rh-catalyst in moderate yields. Attempted homocyclotrimerization of
b- or a-ethynyl-3,5-di-O-toluoyl-2-deoxy- -ribofuranose under Rh-catalysis led only to enynes while the
use of Ru-catalyst gave the desired 1,2,4- and 1,3,5-tri-(2-deoxyribofuranose-1-yl)benzene.
Ó 2008 Elsevier Ltd. All rights reserved.
D-ribofuranose with a,u-diynes gave the corresponding arene derivatives only under microwave
Available online 15 March 2008
D
1. Introduction
C-Nucleosides (characterized by the replacement of the C–N
nucleosidic bond by a more stable C–C bond) are of particular
interest due to their applications in chemical biology (extension of
the genetic alphabet8 or model compounds for studying enzyme
mechanisms9). They are usually prepared by C-glycosidic C–C bond
forming reactions of organometallics with sugar derivatives very
often giving low yields and/or selectivities.10 Therefore, we are
working on the development of modular strategies enabling the
preparation of series of derivatives from one common easily
available intermediate (e.g., cross-coupling reactions of haloaryl-C-
nucleosides11). Based on our experiences in the use of transition
metal catalyzed cyclotrimerization reactions for the synthesis
of modified purine nucleosides,12 we have recently reported a
preliminary communication13 on an alternative approach to
C-nucleosides based on cyclotrimerization of 1-ethynyl-2-deoxy-
ribofuranose with a,u-diynes. Herein, we present a full report
on these results and describe further outcomes pertaining to
cyclotrimerizations and homocyclotrimerizations of other (2-
The cyclotrimerization of alkynes to benzene derivatives is
a highly efficient and atom economical method for the synthesis of
complex organic molecules. Its popularity stems from the fact that
it can be usually carried out under neutral reaction conditions and
the reaction has a high tolerance for various polar functional
groups. Although cyclotrimerization has been used in the syntheses
of many natural compounds or potentially biologically active
substances,1 its role in carbohydrate chemistry has been mainly
restricted to the synthesis of benzene rings from alkynes attached
to the sugar moiety through ether or amide linker.2,3 Another
example is the seminal work of McDonald who has shown that
cyclotrimerization of alkynes can be used for the synthesis of
C-arylglycosides.4 This class of compounds is of considerable in-
terest for pharmaceutical reasons, because of their stability toward
enzymatic and chemical hydrolysis. Although still in its infancy, the
synthesis of C-arylglycosides by cyclotrimerization is beginning to
attract attention. Thus, Yamamoto et al. have reported Ru-catalyzed
synthesis of various C-arylribosides5 and C-arylspiroribosides6
starting from protected 1-ethynylriboses. Moreover, recently
a protected 1-ethynyl-2-deoxyribose was used for the Sonogashira
cross-couplings and oxidative dimerizations.7
deoxy-D-ribofuranosyl)alkynes.
2. Results and discussion
2.1. Co-cyclotrimerization of 1b
According to the preliminary results, the cyclotrimerization of
an anomeric mixture with various diynes 2 gave the highest yields
of the corresponding benzene derivatives in the presence of a
catalytic amount of Rh(PPh3)3Cl (Wilkinson’s catalyst).13 The same
results were obtained also for the cyclotrimerization of pure
* Corresponding authors. Tel.: þ420 221 951 334; fax: þ420 221 951 326 (M.K.);
tel.: þ420 220 183 324; fax: þ420 220 183 559 (M.H.).
E-mail addresses: hocek@uochb.cas.cz (M. Hocek), kotora@natur.cuni.cz
(M. Kotora).
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.03.046

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P. Novak et al. / Tetrahedron 64 (2008) 5200–5207
5201
Table 1
2.3. Homocyclotrimerization of 1a and 1b
Rh-catalyzed cyclotrimerization of 1b with diynes 2 to 3b
O
TolO
Although the cyclotrimerizations of 1aproceeded generally in good
yields, we observed in many cases the formation of a side product in
various quantities. The sideproduct wasthe resultof theaddition of the
terminal triple bond of 1a onto the terminal triple bond of another
molecule of 1a yielding enyne 4a. It is important to note that the
formation of enyne 4b was not observed in the case of the cyclo-
trimerization of 1b. In order to get further information on the for-
mation of enynes 4, both alkynes 1b and 1a were subjected to
cyclotrimerization conditions (cat. RhCl(PPh3)3) in the absence of diyne
2 (Scheme 1). Surprisingly, the formation of homocyclotrimerization
products was not observed in any case. Instead,1a underwent reaction
to afford enyne 4a in 31% isolated yield. On the other hand, in the case
of alkyne 1b the formation of 4b was observed in only <5% yield and
most of the starting material remained unreacted. It was shown pre-
viously that terminal alkynes possessing propargylic hydroxy group or
sterically hindered groups (i.e., Me3Si, etc.) undergo head-to-head
dimerization to afford enynes.14 Inviewof this, it is not unexpected that
1a, which is sterically hindered alkyne bearing propargylic ether
moiety, is more prone to the head-to-head dimerization.
1
X
TolO
RhCl(PPh3)3
O
TolO
+
TolO
2
3
X
3 : a, X = C(COOEt)2; b, X = C(COMe)2; c, X = (COOEt)COMe;
d, X = C(COOEt)CN; e, X = NTs; f, X = O
Entry
Diyne 2
Product 3bx
Yield (%)
1
2
3
4
5
6
2a
2b
2c
2d
2e
2f
3ba
3bb
3bc
3bd
3be
3bf
95
81
62
52
12
32
1b-ethynyl-2-deoxy-
Table 1. The reactions with diynes 2a–2d (entries 1–4) gave rise to
the corresponding 1b-aryl-2-deoxy- -ribofuranoses 3ba–3bd in
D-ribofuranose 1b. The results are displayed in
D
O
TolO
good yields (52–95%). Nonetheless, in cases where the heterocyclic
ring was formed, such as in 3be and 3bf (entries 5 and 6), the yields
were rather low. Other transition metal complexes such as
TolO
O
TolO
Ni(cod)2/2PPh3, Cp
*
RuCl(cod), or Co(PPh3)3Br could also catalyze
1
4
cyclotrimerization but their generality with respect to structural
TolO
OTol
variation of diynes did not match with that of Rh(PPh3)3Cl.13
O
RhCl(PPh3)3
toluene, rt
OTol
OTol
2.2. Co-cyclotrimerization of 1a
O
TolO
O
Because the cyclotrimerizations of protected 1b-ethynyl-2-de-
oxy-D-ribofuranose with various diynes proceeded with the best
results under Rh-catalysis, the reactions of 1a were carried out in
the same manner. The results are presented in Table 2. The cyclo-
trimerization with diynes bearing carbonyl group functionality(ies)
2a–d proceeded uneventfully as expected. The corresponding 1a-
O
TolO
OTol
1
4
TolO
TolO
Scheme 1. Rh-catalyzed dimerization of 1b and 1a.
In the next step, we attempted to cyclotrimerize both anomers
(1a and 1b) by other transition metal catalysts (Scheme 2). For this
aryl-2-deoxy-D-ribofuranoses 3aa–3ad were obtained from good
to excellent isolated yields (53–95%) (entries 1–4). Once again the
cyclotrimerization with diynes 2e and 2f possessing a heteroatom
in the linker connecting both triple bonds gave the corresponding
products 3ae and 3af in low yields of 18% and 39%, respectively
(entries 5 and 6). The reaction with simple 1,6-heptadiyne 2g gave
3ag in surprisingly high yield of 83% (entry 7).
purpose, two Ru-catalysts were chosen: Cp
first generation carbene complex ((Cy3P)2Cl2Ru]CHPh).15 The
homocyclotrimerization of 1a in the presence of Cp Ru(cod)Cl
afforded a mixture (4:3 ratio) of 1,2,4- and 1,3,5-tris(2-deoxy-
ribos-1-yl)benzene 5a and 6a in only 13% isolated yield. Under the
same conditions, 1b afforded also an inseparable mixture of 1,2,4-
*
Ru(cod)Cl and Grubbs’
*
D
-
and 1,3,5-tris(2-deoxy-D-ribos-1-yl)benzene 5b and 6b (2:1 ratio),
Table 2
but in higher 40% isolated yield. Switching the catalyst for
(Cy3P)2Cl2Ru]CHPh did not substantially influence the composi-
tion of the regioisomeric mixtures: thus the cyclotrimerization
afforded a mixture of 5a and 6a in 45% (5:6 ratio) and the reaction
of 1b yielded 1:1 mixture of 5b and 6b in 30% isolated yield.
Rh-catalyzed cyclotrimerization of 1a with diynes 2 to 3a
O
TolO
O
TolO
1
TolO
RhCl(PPh3)3
TolO
3
+
R
2
X
R
R
X
catalyst
1
or 1
+
6
5
toluene, rt
3 : a, X = C(COOEt)2; b, X = C(COMe)2; c, X = (COOEt)COMe;
d, X = C(COOEt)CN; e, X = NTs; f, X = O; g = CH2
R
R
R
O
TolO
O
TolO
=
=
Entry
Diyne 2
Product 3ax
Yield (%)
TolO
TolO
1
2
3
4
5
6
7
2a
2b
2c
2d
2e
2f
3aa
3ab
3ac
3ad
3ae
3af
95
63
83
53
18
39
83
Cp*RuCl(cod)
(Cy3P)2Cl2Ru=CHPh
1
1
1
1
5 , 6 (4:3), 13%
5 , 6 (2:1), 40%
5 , 6 (5:6), 45%
5 , 6 (1:1), 30%
2g
3ag
Scheme 2. Ru-catalyzed homocyclotrimerization of 1a and 1b.

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P. Novak et al. / Tetrahedron 64 (2008) 5200–5207
5202
2.4. Synthesis and co-cyclotrimerization of 7 and 8
Initially, the co-cyclotrimerizations were performed with
a anomers 7a and 8a (entries 1–6) The reactions of the methyl
derivative 7a with 2a, 2b, and 2g (entries 1–3) yielded the corre-
sponding products 9aa, 9ab, and 9ag in 44, 15, and 12% isolated
yields, respectively. Similar results were also obtained with 8a
(entries 4–6), where products 10aa, 10ab, and 10ag were obtained
in 37, 12, and 16% yields, respectively. Then, the co-cyclo-
trimerizations with b anomers 7b and 8b were carried out (entries
7–12). The reactions of the methyl derivative 7b (entries 7–9) with
2a, 2b, and 2g yielded the corresponding products 9ba, 9bb, and
9bg in 41, 36, and 47% isolated yields, respectively. Similar results
were also obtained with 8b (entries 10–12), where products
10ba, 10bb, and 10bg were isolated in 40, 20, and 38% yields,
The successful co-cyclotrimerization of 1a and 1b with various
diynes raised a question as to whether also internal alkynes
attached to the deoxyriboside moiety could undergo the reaction.
Thus our effort was directed toward preparation of the corre-
sponding toluoylated 1-propynyl-2-deoxy-D-ribofuranose 7 and
1-phenylethynyl-2-deoxy- -ribofuranose 8. The reaction of 1-
D
chlorodeoxyribose with 1-propynyl magnesium bromide or phe-
nylethynyl magnesium bromide afforded in both cases the products
as 2:1 mixtures of a and b anomers of 7 and 8 (Scheme 3). The
propynyl derivative 7 was obtained in 75% yield, whereas the
phenylethynyl one 8 in 47% yield. The obtained anomeric mixtures
were resolved into individual anomers by HPLC.
respectively. In addition, other catalysts such as Cp
Ni(CO)2(PPh3)2
*
RuCl(cod)19 and
were also tested in cyclotrimerization of
20
7
(anomeric mixture) with 2a under microwave conditions. Regret-
tably, the first did not catalyze the reaction and the second afforded
9a (anomeric mixture) in only 18% yield.
R
O
TolO
O
TolO
Cl
BrMg
THF, rt
R
TolO
TolO
It should be emphasized that the data presented in Table 3 do
not represent real yields of the desired compounds. Although the
reactions in all cases proceeded well, always complex mixtures of
compounds were obtained. It took a great deal of work to isolate
and purify each target compound 9 or 10 to such degree that it
would enable unequivocal spectroscopic confirmation of their
structure. Thus, the reported yields represent the amount of
a compound isolated in analytical purity. Nonetheless, these results
clearly indicate that the protected 1-alkynyl-2-deoxyribofuranoses
possess the rather sterically hindered triple bond resulting in lower
reactivity. This was also confirmed by attempts to carry out
homocyclotrimerization under the above mentioned conditions.
Unfortunately, complex reaction mixtures were formed and the
desired products were not identified. On the other hand, the
obtained results demonstrate the usefulness of microwave irradi-
ation as a tool for forcing substrates, which otherwise do not react
under usual conditions, to undergo coupling.
7, R = Me, 2/1 α/β, 75%
8, R = Ph, 2/1 α/β, 47%
Scheme 3. Synthesis of 7 and 8.
The first attempts to carry out the co-cyclotrimerization of al-
kynes 7a, 7b, 8a, and 8b with various diynes under the previously
used conditions (10 mol % RhCl(PPh3)3, toluene) were not met with
success. The alkynes did not react and only oligomerization of
diynes was observed. This could probably be attributed to a greater
steric hindrance of the internal triple bond. Similar problems were
also observed in the cyclotrimerization of diynes with nitriles, and
were overcome by us16 and others17,18 by carrying out the reaction
under microwave irradiation. Thus, the next sets of reactions of
individual anomers were executed in acetonitrile under microwave
irradiation (Scheme 4). Gratifyingly, in all cases the reaction took
place and the desired products were obtained, although in mod-
erate yields (Table 3).
3. Conclusion
R
R
O
TolO
In conclusion, we have successfully developed the general pro-
tocol for the [2þ2þ2]-cyclotrimerization of 1a with various diynes
under mild reaction conditions. These results provide a further
insight into the scope and versatility of cyclotrimerization of a and
b anomers of protected 1-ethynyl-2-deoxyribofuranoses. Moreover,
it also showed that both anomers did not undergo homocyclo-
trimerization under Rh-catalysis and had different reactivity:
1a underwent head-to-head dimerization, whereas 1b did not
react. Homocyclotrimerization was successfully brought about by
Ru-catalysis: carbene complex ((Cy3P)2Cl2Ru]CHPh) was more
O
TolO
TolO
X
7 , 8
TolO
TolO
9 x, 10 x
RhCl(PPh3)3
+
X
CH3CN
O
mω
O
TolO
2a, 2b, 2g
R
TolO
TolO
7 , 8
9
x, 10
x
R
X
efficient for the reaction of 1a, whereas Cp Ru(cod)Cl gave better
*
7, 9, R = Me; 8, 10, R = Ph; x = a, b, g
yields with 1b. To the best of our knowledge, this is the first
example of homocyclotrimerization of C-ethynylsaccharides. Also
Scheme 4. Microwave-promoted cyclotrimerization of 7 and 8.
successful co-cyclotrimerization of 1-(2-deoxy-D-ribofuranose-1-yl)-
alkynes 7 and 8 with diynes to the corresponding benzene
derivatives was carried out. The reaction proceeded only under
microwave irradiation, probably due to a bigger steric hindrance of
the triple bond.
Table 3
Co-cyclotrimerization of 7a and 8a with diynes 2a, 2b, and 2g
Entry
Alkyne
Diyne 2
Product 9ax
Yield (%)
1
2
3
4
5
6
7
8
7a
2a
2b
2g
2a
2b
2g
2a
2b
2g
2a
2b
2g
9aa
9ab
9ag
10aa
10ab
10ag
9ba
9bb
9bg
44
15
12
37
12
16
41
36
47
40
20
38
4. Experimental
4.1. General
8a
7b
8b
All solvents were used as-obtained unless otherwise noted.
Toluene was distilled from benzophenone/Na, 1,2-dichloroethane,
and CH2Cl2 from CaH2 under Ar. Starting diynes 2 were prepared by
standard procedures by the reaction of propargyl bromide with the
corresponding C-acids under basic conditions.12b RhCl(PPh3)3,21
9
10
11
12
10ba
10bb
10bg

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P. Novak et al. / Tetrahedron 64 (2008) 5200–5207
5203
and a- and b-[2-deoxy-3,5-bis[O-(p-toluoyl)]-
ethyne13 were prepared according to previously published pro-
cedures. Cp RuCl(cod) and first generation Grubbs’ catalyst were
purchased from Strem Ltd. All reactions were carried out under an
argon atmosphere using Schlenk-tube technique or in a microwave
reactor Biotage Initiator.
D
-ribofuranosyl]-
22.6, 26.3, 27.1, 37.9, 39.5, 39.6, 39.7, 39.9, 41.2, 62.2, 62.2, 65.0, 65.3,
67.8, 73.4, 77.5, 80.5, 80.8, 83.3, 83.3,122.6,125.0,125.2,125.5,125.5,
126.8,129.1,129.2,129.2,129.6,130.7,130.8,135.8,139.8,139.9,141.1,
141.2,143.0,143.1,144.3,144.5,166.6,166.9,171.0,173.0, 202.1, 202.1;
IR nmax (CHCl3) 3029, 3011, 2986, 2925, 1715, 1612, 1446, 1272, 1245,
1178, 1106, 1020 cmꢁ1; HRMS (EI) calcd for C35H36O8: 584.2410,
found: 584.2393. Rf (2:1 hexane/EtOAc)¼0.24.
*
4.2. General procedure for RhCl(PPh3)3 catalyzed
cyclotrimerization of 1 with diynes
4.2.4. 1a-[2-Cyano-2-(ethoxycarbonyl)-1,3-dihydro-2H-inden-
5-yl]-1,2-dideoxy-3,5-di-O-(4-toluoyl)]-D-ribofuranose (3ad)
Into a solution of 1a-ethynyl-1,2-dideoxy-3,5-di-O-(4-toluoyl)-
-ribofuranose 1a (0.2 mmol, 76 mg) in dry toluene (3 mL) were
Compound 2d (80 mmol, 15.2 mg), 1a (67 mmol, 25.5 mg),
RhCl(PPh3)3 (6.7 mmol, 6.2 mg). Column chromatography (3:1 hex-
ane/EtOAc) afforded 20 mg (53%) as a colorless oil; [a]2D0 ꢁ2.7 (c
0.0055, CHCl3); 1H NMR (400 MHz, C6D6) d 0.82 (3H, t, J 7.0 Hz), 1.96
(3H, s), 1.96–2.01 (1H, m), 2.01 (3H, s), 2.41–2.48 (1H, m), 3.15–3.41
(4H, m), 3.78 (2H, q, J 7.0 Hz), 4.45 (1H, dd, J 11.2, 4.8 Hz), 4.51 (1H, dd,
J 11.2, 4.8 Hz), 4.62 (1H, td, J 5.2, 2.4 Hz), 5.01–5.04 (1H, m), 5.45–5.48
(1H, m), 6.76–7.06 (7H, m), 7.86 (2H, m), 8.21 (2H, m); 13C NMR
(100 MHz, C6D6) d 14.4, 22.0, 22.1, 41.1, 43.6, 43.9, 48.4, 63.5, 65.3,
77.5, 80.6, 83.4, 121.4, 122.6, 125.0, 126.0, 128.3, 130.1 (2ꢂ), 130.1
(2ꢂ), 130.7 (2ꢂ), 130.9 (2ꢂ), 138.0, 139.3, 144.0, 144.3, 144.7, 166.6,
166.9,169.2; IR nmax (CHCl3) 3029, 3011,1718,1612,1442,1373,1272,
1244, 1178, 1106, 1020, 840 cmꢁ1; HRMS (EI) calcd for C33H34N1O7:
567.2257, found: 567.2265. Rf (3:1 hexane/EtOAc)¼0.20.
D
added RhCl(PPh3)3 (0.02 mmol, 18.5 mg) and diyne 2 (0.24 mmol).
The reaction mixture was stirred at 20 ꢀC for 48 h or until the
consumption of the starting material (TLC). Then, the volatiles were
removed under reduced pressure and column chromatography of
the residue on silica gel afforded the title compound.
4.2.1. 1a-[2,2-Bis(ethoxycarbonyl)-1,3-dihydro-2H-inden-5-yl]-1,
2-dideoxy-3,5-di-O-(4-toluoyl)]-D-ribofuranose (3aa)
Compound 2a (80 mmol, 19 mg), 1a (67 mmol, 26 mg),
RhCl(PPh3)3 (6.7 mmol, 6 mg). Column chromatography (3:1 hex-
ane/EtOAc) afforded 40 mg (95%) of the title compound as a color-
less oil; [a]2D0 ꢁ1.05 (c 0.0285, CHCl3); 1H NMR (400 MHz, C6D6)
d 0.87 (3H, t, J 7.1 Hz), 0.88 (3H, t, J 7.1 Hz), 1.96 (3H, s), 2.00 (3H, s),
1.96–2.00 (1H, m), 2.39–2.46 (1H, m), 3.7–3.81 (4H, m), 3.91 (2H, q,
J 7.1 Hz), 3.94 (2H, q, J 7.1 Hz), 4.45 (1H, dd, J 11.6, 5.2 Hz), 4.50 (1H,
dd, J 11.6, 5.2 Hz), 4.58 (1H, td, J 5.2, 2.6 Hz), 5.04 (1H, m), 5.48 (1H,
m), 6.88–7.16 (7H, m), 7.88 (2H, m), 8.2 (2H, m); 13C NMR (100 MHz,
C6D6) d 14.6, 14.9, 22.0, 22.1, 41.2, 41.4, 41.6, 61.6, 62.2, 65.3, 77.5,
80.8, 83.2, 122.6, 125.0, 125.6, 128.5, 128.6, 128.8, 128.9, 130.1, 130.8
(2ꢂ), 130.9 (2ꢂ), 140.0, 141.2, 143.1, 144.2, 144.4, 166.6, 166.9, 172.2,
172.3; IR nmax (CHCl3) 3309, 3029, 2984, 1728, 1612, 1446, 1368,
1271, 1179, 1106, 1067, 1020, 861, 840 cmꢁ1; HRMS (EI) calcd for
4.2.5. 1a-(1,3-Dihydro-2-tosyl-2H-indol-5-yl)-1,2-dideoxy-3,
5-di-O-(4-toluoyl)-D-ribofuranose (3ae)
Compound 2e (0.24 mmol, 60 mg), 1a (0.2 mmol, 76 mg),
RhCl(PPh3)3 (0.02 mmol, 18.5 mg). Column chromatography (3:1
hexane/EtOAc) afforded 22 mg (18%) of the title compound as
a colorless oil; [a]2D0 þ7.1 (c 0.01025, CHCl3); 1H NMR (400 MHz,
C6D6) d 1.85 (3H, s), 1.89–1.93 (1H, m), 1.95 (3H, s), 2.00 (3H, s),
2.39–2.46 (1H, m), 4.38–4.51 (6H, m), 4.58 (1H, td, J 5.2, 2.4 Hz),
4.92–4.95 (1H, m), 5.44 (1H, m), 6.59–6.63 (1H, m), 6.73–6.77 (2H,
m), 6.85–6.90 (3H, m), 6.97–7.00 (2H, m), 7.36 (1H, s), 7.75–7.80
(2H, m), 7.82–7.86 (2H, m), 8.17–8.21 (2H, m); 13C NMR (100 MHz,
C6D6) d 21.7, 22.0, 22.1, 41.2, 54.3, 54.5, 65.2, 77.5, 80.4, 83.3, 120.8,
123.2, 126.0, 128.3, 128.5 (one signal is overlapped by solvent sig-
nal),130.0 (2ꢂ), 130.1 (2ꢂ), 130.4 (2ꢂ), 130.7 (2ꢂ), 130.8 (2ꢂ), 136.0,
C
36H38O9: 614.2516, found: 614.2507. Rf (3:1 hexane/EtOAc)¼0.24.
4.2.2. 1a-(2,2-Diacetyl-1,3-dihydro-2H-inden-5-yl)-1,2-dideoxy-
3,5-di-O-(4-toluoyl)]- -ribofuranose (3ab)
D
Compound 2b (70 mmol, 12 mg), 1a (58 mmol, 22 mg),
RhCl(PPh3)3 (5.8 mmol, 5.4 mg). Column chromatography (3:1
hexane/EtOAc) afforded 20 mg (63%) of the title compound as
a colorless oil; [a]2D0 ꢁ2.8 (c 0.0265, CHCl3); 1H NMR (400 MHz,
C6D6) d 1.38 (3H, s), 1.70 (3H, s), 1.96 (3H, s), 2.01 (3H, s), 2.02–2.08
(1H, m), 2.44–2.51 (1H, m), 3.15–3.30 (4H, m), 4.47 (1H, dd, J 11.6,
5.2 Hz), 4.52 (1H, dd, J 11.6, 5.2 Hz), 4.64 (1H, td, J 5.5, 2.7 Hz), 5.08
(1H, m), 5.48 (1H, m), 6.88–6.94 (5H, m), 7.09–7.12 (2H, m), 7.87
(2H, m), 8.21 (2H, m); 13C NMR (100 MHz, C6D6) d 20.0, 22.1, 26.6,
26.7, 38.1, 38.3, 41.2, 65.3, 75.6, 77.6, 80.7, 83.3, 122.7, 123.1, 125.5
(two signals are overlapped by solvent signal), 130.1 (2ꢂ), 130.1
(2ꢂ), 130.7 (2ꢂ), 130.9 (2ꢂ), 139.8, 141.0, 143.1, 144.3, 144.5, 166.6,
166.9, 204.3; IR nmax (CHCl3) 3029, 3011, 2926, 1717, 1703, 1612,
1440, 1359, 1272, 1178, 1106, 1020, 839 cmꢁ1; HRMS (EI) calcd for
136.2, 138.3, 143.7, 143.9, 144.4, 144.9, 166.5, 166.9; IR n
(CHCl3)
max
3275, 2923, 1723, 1708, 1610, 1451, 1347, 1264, 1160, 1093, 1017, 818,
755, 699 cmꢁ1; HRMS (EI) calcd for C36H35NO7S: 626.2213, found:
626.2238. Rf (3:1 hexane/EtOAc)¼0.20.
4.2.6. 1a-(1,3-Dihydroisobenzofuran-5-yl)-1,2-dideoxy-3,
5-di-O-(4-toluoyl)-D-ribofuranose (3af)
Compound 2f (0.178 mmol, 17 mg, 18.3 ml), 1a (0.148 mmol,
56 mg), RhCl(PPh3)3 (14.8 mmol, 13.7 mg). Column chromatography
(3:1 hexane/EtOAc) afforded 28 mg (39%) of the title compound as
a colorless oil; [a]D20 þ4.4 (c 0.0045, CHCl3); 1H NMR (400 MHz, C6D6)
d 1.95 (3H, s),1.96 (3H, s), 2.00–2.05 (1H, m), 2.45–2.52 (1H, m), 4.46
(1H, dd, J 11.6, 5.2 Hz), 4.52 (1H, dd, J 11.6, 5.2 Hz), 4.62 (1H, td, J 5.2,
2.4 Hz), 4.93 (4H, br s), 5.07 (1H, m), 5.50 (1H, m), 6.80–7.10 (7H, m),
7.84–7.86 (2H, m), 8.119–8.22 (2H, m); 13C NMR (100 MHz, C6D6)
d 22.0 (2ꢂ), 41.4, 65.3, 74.1, 74.2, 77.5, 80.7, 83.3, 119.2, 121.6, 125.7,
128.4 (one signal overlapped by solvent signal), 130.0 (2ꢂ), 130.1
(2ꢂ), 130.7 (2ꢂ), 130.9 (2ꢂ), 139.3, 140.7, 143.4, 144.3, 144.5, 166.6,
166.9; IR nmax (CHCl3) 3354, 2946, 2854,1717,1609,1448,1264,1176,
1103, 1043, 1017, 903, 840, 751, 691 cmꢁ1; HRMS (EI) calcd for
C
34H34O7: 472.2614, found: 472.2627. Rf (3:1 hexane/EtOAc)¼0.14.
4.2.3. 1a-[2-Acetyl-2-(ethoxycarbonyl)-1,3-dihydro-2H-inden-
5-yl]-1,2-dideoxy-3,5-di-O-(4-toluoyl)]- -ribofuranose (3ac)
D
Compound 2c (0.24 mmol, 43 mg), 1a (0.2 mmol, 75.6 mg),
RhCl(PPh3)3 (0.02 mmol, 18.5 mg). Column chromatography (3:1
hexane/EtOAc) afforded 97 mg (83%) of 1:1 mixture of dia-
stereoisomers as a colorless oil; [a]2D0 ꢁ1.3 (c 0.0525, CHCl3); 1H NMR
(400 MHz, C6D6) d 0.82 (3H, t, J 7.2 Hz), 0.86 (3H, t, J 6.8 Hz),1.83 (1H,
m),1.87 (3H, s),1.89 (3H, s),1.90 (3H, s),1.94 (3H, s),1.99 (3H, s), 2.01
(1H, m), 2.03 (3H, s), 2.45–2.49 (1H, m), 2.76–2.77 (1H, m), 3.31–3.62
(8H, m), 3.79–3.93 (4H, m), 4.44–4.51 (4H, m), 4.60–4.63 (2H, m),
5.07–5.10 (2H, m), 5.47–5.49 (2H, m), 6.89–7.20 (14, m), 7.87 (4H, m),
8.19 (4H, m); 13C NMR (100 MHz, C6D6) d 14.5 (2ꢂ), 22.1, 22.1 (2ꢂ),
C29H28O6: 472.1886, found: 472.1867. Rf (3:1 hexane/EtOAc)¼0.21.
4.2.7. 1a-(1,3-Dihydro-2H-inden-5-yl)-1,2-dideoxy-3,
5-di-O-(4-toluoyl)- -ribofuranose (3ag)
D
Compound 2g (0.24 mmol, 23 mg, 28 ml),1a (0.2 mmol, 75.6 mg),
RhCl(PPh3)3 (0.02 mmol, 18.5 mg). Column chromatography (3:1
hexane/EtOAc) afforded 78 mg (83%) of the title compound as

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P. Novak et al. / Tetrahedron 64 (2008) 5200–5207
5204
a colorless oil; [a]2D0 þ5.1 (c 0.01975, CHCl3); 1H NMR (400 MHz,
C6D6) d 1.84 (2H, q, J 7.2 Hz), 1.96 (3H, s), 1.97 (3H, s), 2.08–2.14 (1H,
m), 2.51–2.55 (1H, m), 2.71 (2H, t, J 7.2 Hz), 2.72 (2H, t, J 7.2 Hz), 4.78
(1H, dd, J 11.6, 5.2 Hz), 4.52 (1H, dd, J 11.6, 5.2 Hz), 4.65 (1H, J 5.2,
2.4 Hz), 5.11–5.14 (1H, m), 5.50–5.54 (1H, m), 6.86–6.90 (4H, m),
7.09–7.12 (1H, m), 7.17–7.18 (1H, m), 7.31 (1H, s), 7.90–7.93 (2H, m),
8.17–8.20 (2H, m); 13C NMR (100 MHz, C6D6) d 22.0 (2ꢂ), 26.6, 33.5,
33.7, 41.5, 65.4, 77.7, 81.0, 83.1, 122.8,124.8, 125.0, 128.8,129.2,129.9
(2ꢂ), 130.0 (2ꢂ), 130.8 (2ꢂ), 130.9 (2ꢂ), 142.0, 143.8, 144.2, 144.3,
145.0,166.6,166.9; IR nmax (CHCl3) 3381, 2919, 2861,1713,1610,1437,
1263, 1174, 1090, 1014, 831, 747, 689 cmꢁ1; HRMS (EI) calcd for
hexane/EtOAc) afforded 10 mg (13%, 4:3 5a/6a) of a mixture of the
title compounds. Conditions B. Compound 1a (0.2 mmol, 75.6 mg),
(PCy3)2Cl2Ru]CHPh (0.03 mmol, 25 mg), CH2Cl2 (3 mL). Column
chromatography (3:1 hexane/EtOAc) afforded 34 mg (45%, 5:6 5a/
6a) of a mixture of title compounds. Compounds 5a and 6a were
separated by HPLC (3:1 hexane/EtOAc). Unsymmetric product 5a. A
colorless oil; [a]D20 0 (c 0.0035, CHCl3). 1H NMR (400 MHz, C6D6)
d 1.96 (3H, s), 1.99 (3H, s), 2.00 (6H, s), 2.01 (3H, s), 2.03 (3H, s),
2.05–2.16 (3H, m), 2.44–2.50 (1H, m), 2.60–2.70 (2H, m), 4.40–4.61
(9H, m), 5.13–5.16 (1H, m), 5.30–5.33 (1H, m), 5.36–5.39 (1H, m),
5.45–5.51 (3H, m), 6.87–7.00 (12H, m), 7.33–7.36 (1H, m), 7.69–7.71
(1H, m), 7.79–7.82 (1H, m), 7.96–8.25 (12H, m); 13C NMR (100 MHz,
C6D6) d 22.1 (6ꢂ), 40.5, 40.95, 41.3, 65.0, 65.2, 65.3, 77.4 (2ꢂ), 77.5,
80.8 (2ꢂ), 81.5, 83.2 (2ꢂ), 83.4, 123.6, 125.6, 126.8, 128.2, 128.5,
130.0, 130.1, 130.2, 130.8, 130.9, 138.9, 141.2, 143.8, 144.2, 144.5,
144.6,166.7, 166.9; IR nmax (neat) 2956, 2920, 2855,1718,1613,1273,
1180, 1108, 752 cmꢁ1; HRMS (FAB) calcd for C69H66O15: 1135.4480,
found: 1135.4429. Symmetric product 6a. A colorless oil; [a]2D0 þ12.4
(c 0.00465, CHCl3); 1H NMR (400 MHz, C6D6) d 1.95 (9H, s), 2.00
(9H, s), 2.00–2.05 (3H, m), 2.45–2.49 (3H, m), 4.41–4.45 (6H, m),
4.62–4.63 (3H, m), 5.07–5.10 (3H, m), 5.47–5.49 (3H, m), 6.86–6.88
(6H, m), 6.94–6.96 (6H, m), 7.47 (3H, s), 7.92–7.94 (6H, m), 8.14–8.16
(6H, m); 13C NMR (100 MHz, C6D6) d 21.9, 41.3, 65.1, 77.4, 80.8, 83.2,
C
30H30O5: 470.2093, found: 470.2075. Rf (2:1 hexane/EtOAc)¼0.46.
4.2.8. 3(E)-1,4-Di[1a-(1,2-dideoxy-3,5-di-O-(4-toluoyl)-
D-ribofuranosyl)]but-3-en-1-yn (4a)
Into a solution of a-ethynyl-1,2-dideoxy-3,5-di-O-(4-toluoyl)-D-
ribofuranose 1a (0.2 mmol, 76 mg) in dry toluene (3 mL) was added
RhCl(PPh3)3 (0.02 mmol, 18.5 mg). The reaction mixture was stirred
at 20 ꢀC for 48 h or until consumption of the starting material (TLC).
Then, the solvent was evaporated under reduced pressure and the
residue was subjected to column chromatography (3:1 hexane/
EtOAc)that afforded 23 mg (31%) of the title compound as a colorless
oil; [a]2D0 þ34.2 (c 0.0095, CHCl3); 1H NMR (400 MHz, C6D6) d 1.60–
1.65 (2H, m), 1.955 (3H, s), 1.959 (3H, s), 1.963 (3H, s), 2.02 (3H, s),
2.04–2.13 (2H, m), 4.33–4.39 (2H, m), 4.39 (2H, dd, J 11.6, 4.4 Hz),
4.47 (2H, dd, J 11.6, 4.4 Hz), 4.58–4.60 (1H, m), 4.82–4.85 (1H, m),
5.33–5.38 (2H, m), 5.79 (1H, d, J 15.9 Hz), 6.13 (1H, dd, J 15.9, 5.6 Hz),
6.86–7.00 (8H, m), 8.00–8.02 (2H, m), 8.11–8.16 (6H, m); 13C NMR
(100 MHz, C6D6) d 22.0 (2ꢂ), 22.1 (2ꢂ), 30.9, 38.6, 40.3, 59.2, 65.2,
69.7, 77.0, 77.2, 79.3, 83.2, 83.3, 84.4, 91.2, 110.6, 128.2, 128.3, 128.6,
128.8,130.0,130.1,130.1,130.8,130.8,130.9,144.2,144.3,144.6,144.7,
122.6, 128.4, 130.0, 130.7, 144.2, 144.4, 144.5, 166.6, 166.8; IR n
max
(CHCl3) 2923, 2852, 1726, 1713, 1610, 1450, 1410, 1268, 1179, 1103,
1014, 841, 752, 689 cmꢁ1; HRMS (FAB) calcd for C69H66O15
:
1135.4480, found: 1135.4468. Rf (3:1 hexane/EtOAc)¼0.18.
4.3.2. Homocyclotrimerization of 1b to 1,2,4-tri[1b-(1,2-dideoxy-
3,5-di-O-(4-toluoyl)-D-ribofuranosyl)]benzene (5b) and 1,3,5-
tri[1b-(1,2-dideoxy-3,5-di-O-(4-toluoyl)-D-ribofuranosyl)]-
145.1, 166.5, 166.7, 166.8, 166.8; IR n
(CHCl3) 3408, 2914, 1726,
benzene (6b)
max
1708, 1606, 1446, 1401, 1370, 1263, 1174, 1094, 1014, 952, 836, 747,
689 cmꢁ1; MS (EI) no molecular peak, 576 (2), 524 (5), 368 (7), 236
(7), 198 (12), 149 (42). Rf (3:1 hexane/EtOAc)¼0.26.
Conditions A. Compound 1b (0.2 mmol, 75.6 mg), Cp
*
RuCl(cod)
(0.02 mmol, 7.6 mg), DCE (3 mL). Column chromatography (3:1
hexane/EtOAc) afforded 30 mg (40%, 2:1 5b/6b) of a mixture of the
title compounds. Conditions B. Compound 1b (0.2 mmol, 75.6 mg),
(PCy3)2Cl2Ru]CHPh (0.03 mmol, 25 mg), DCM (3 mL). Column
chromatography (3:1 hexane/EtOAc) afforded 23 mg (30%, 1:1 5b/
6b) of a mixture of the title compounds. The unseparable mixture of
symmetric 5b and unsymmetric product 6b. A colorless oil; [a]2D0 ꢁ8.2
(c 0.01225, CHCl3); 1H NMR (400 MHz, C6D6) d 1.96 (3H, s), 1.97 (9H,
s), 1.98 (9H, s), 1.99 (3H, s), 2.01 (9H, s), 2.02 (3H, s), 1.93–2.05 (6H,
m), 2.19–2.24 (3H, m), 2.44–2.51 (3H, m), 4.33–4.40 (6H, m), 4.50–
4.68 (12H, m), 5.16–5.20 (3H, m), 5.42–5.47 (3H, m), 5.47–5.55 (6H,
m), 6.86–6.98 (24H, m), 7.37 (1H, dd, J 8, 1.6 Hz), 7.52 (3H, s), 7.65
(1H, d, J 8 Hz), 7.84 (1H, d, J 1.6 Hz), 8.08–8.15 (24H, m); 13C NMR
(100 MHz, C6D6) d 22.0, 22.1 (2ꢂ), 30.9, 41.2, 41.5, 42.7, 65.6, 65.7,
78.2, 78.3 (2ꢂ), 78.4 (2ꢂ), 78.5, 81.6, 81.7, 84.0, 84.2, 84.3 (2ꢂ),
123.7, 124.1, 126.7, 126.9, 128.6, 129.2, 130.1, 130.8 (3ꢂ), 138.9, 139.3,
142.3, 143.0, 144.3 (2ꢂ), 144.4 (2ꢂ), 144.6, 166.6, 166.8, 166.8, 166.9
(2ꢂ); IR nmax (CHCl3) 3414, 2920, 1720, 1711, 1689, 1610, 1451, 1407,
1369, 1264, 1176, 1090, 1017, 837, 748, 691 cmꢁ1; HRMS (FAB) calcd
for C69H66O15: 1135.4480, found: 1135.4458. Rf (3:1 hexane/
EtOAc)¼0.18.
4.2.9. 3(E)-1,4-Di[1b-(1,2-dideoxy-3,5-di-O-(4-toluoyl)-
D-ribofuranosyl)]but-3-en-1-yn (4b)
Into a solution of b-ethynyl-1,2-dideoxy-3,5-di-O-(4-toluoyl)-D-
ribofuranose 1a (0.2 mmol, 76 mg) in dry toluene (3 mL) was added
RhCl(PPh3)3 (0.02 mmol, 18.5 mg). The reaction mixture was stirred
at 20 ꢀC for 48 h or until consumption of the starting material (TLC).
Then, the solvent was evaporated under reduced pressure and the
residue was subjected to column chromatography (3:1 hexane/
EtOAc) that afforded 7 mg (9%) of the title compound as a colorless
oil; 1H NMR (400 MHz, C6D6) d 1.55–1.67 (1H, m), 1.79–1.85 (1H, m),
1.97 (3H, s), 1.98 (3H, s), 1.99 (3H, s), 2.08–2.13 (1H, m), 2.23–2.29
(1H, m), 4.21–4.26 (2H, m), 4.37–4.48 (4H, m), 4.82–4.86 (1H, m),
5.33–5.40 (2H, m), 5.81 (1H, dt, J 16, 1.6 Hz), 6.05 (1H, dd, J 16,
5.8 Hz), 6.88–6.96 (8H, m), 8.00–8.07 (4H, m), 8.13–8.20 (4H, m). Rf
(3:1 hexane/EtOAc)¼0.26.
4.3. Generalprocedureforhomocyclotrimerizationof1aand1b
Into a solution of 1a- or 1b-ethynyl-1,2-dideoxy-3,5-di-O-(4-
toluoyl)-
D
-ribofuranose 1a or 1b (0.2 mmol, 76 mg) in dry solvent
4.4. 1a-Propynyl-1,2-dideoxy-3,5-di-O-(4-toluoyl)-
ribofuranose (7a) and 1b-propynyl-1,2-dideoxy-3,
D-
(3 mL) was added the appropriate Ru-catalyst. The reaction mixture
was stirred at 20 ꢀC for 48 h or until consumption of the starting
material (TLC). Then, the solvent was evaporated under reduced
pressure and the residue was subjected to column chromatography.
5-di-O-(4-toluoyl)-D-ribofuranose (7b)
Into a solution of 1-chloro-1,2-dideoxy-3,5-di-O-(4-toluoyl)-
D
-
ribofuranose (8 mmol, 3 g) in dry THF (45 mL) under argon was
slowly added 0.5 M solution of propynyl magnesium bromide
(8.5 mmol, 17 mL), the formed reaction mixture was stirred at room
temperature for 6 h, and then reduced to 1/3 of its volume in vacuo.
Diethyl ether (50 mL) was added and the solution was washed with
10% NH4Cl (aq) (20 mL), saturated solution of NaHCO3 (20 mL), and
4.3.1. Homocyclotrimerization of 1a to 1,2,4-tri[1a-(1,2-dideoxy-
3,5-di-O-(4-toluoyl)-
(1,2-dideoxy-3,5-di-O-(4-toluoyl)-
Condition A. Compound 1a (0.2 mmol, 75.6 mg), Cp
(0.02 mmol, 7.6 mg), DCE (3 mL). Column chromatography (3:1
D
-ribofuranosyl)]benzene (5a) and 1,3,5-tri[1a-
-ribofuranosyl)]benzene (6a)
RuCl(cod)
D
*

´
P. Novak et al. / Tetrahedron 64 (2008) 5200–5207
5205
dried (MgSO4). Removal of volatiles in vacuo and column chroma-
tography of the residue on silica gel (3:1 hexane/EtOAc) afforded
2.27 g (75%) of the anomeric mixture of 7a and 7b as a pale yellow
oil. Further separation of the obtained mixture by a preparative
HPLC afforded 0.73 g (24%) of 7a and 0.35 g (12%) of 7b as viscous
liquids. Compound 7a.1H NMR (400 MHz, C6D6) d 1.49 (3H, d, J 2 Hz),
1.99 (3H, s), 2.00 (3H, s), 2.10–2.19 (1H, m), 2.21–2.28 (1H, m), 4.38
(1H, dd, J 11.6, 5.6 Hz), 4.43 (1H, dd, J 11.6, 5.6 Hz), 4.56–4.60 (1H, m),
4.72–4.76 (1H, m), 5.35–5.38 (1H, m), 6.89–6.93 (4H, m), 8.08–8.12
(2H, m), 8.12–8.16 (2H, m); 13C NMR (100 MHz, C6D6) d 4.0, 22.0, 22.1,
40.6, 65.3, 69.3, 77.1, 80.4, 82.1, 82.8, 128.9 (2ꢂ), 130.0 (2ꢂ), 130.8
(2ꢂ),130.9 (2ꢂ),144.2 (2ꢂ),144.4 (2ꢂ),166.4,166.7; IR nmax (ATRGe)
1718, 1611, 1270, 1180, 1108, 1021, 752, 692 cmꢁ1; MS (FABþ) no
molecular peak, 589 (6), 515 (7), 387 (6), 275 (14), 201 (100). Com-
pound 7b. 1H NMR (400 MHz, C6D6) d 1.41 (1H, d, J 2 Hz),1.95 (3H, s),
1.99 (3H, s), 2.09–2.15 (1H, m), 2.22–2.29 (1H, m), 4.22–4.26 (1H, m),
4.45 (1H, dd, J 11.6, 4.9 Hz), 4.52 (1H, dd, J 11.6, 4.9 Hz), 4.78–4.83
(1H, m), 5.40–5.43 (1H, m), 6.86 (2H, m), 6.88–6.92 (2H, m), 7.98–
8.02 (2H, m), 8.16–8.20 (2H, m); 13C NMR (100 MHz, C6D6) d 3.9, 22.0,
22.1, 40.9, 65.6, 69.6, 77.6, 79.1, 82.6, 83.4, 130.0 (4ꢂ), 130.8 (2ꢂ),
130.9 (2ꢂ),144.0 (2ꢂ), 144.5 (2ꢂ), 166.8 (2ꢂ); IR nmax (ATR Ge) 1721,
1614, 1273, 1180, 755 cmꢁ1; MS (FABþ) no molecular peak, 589 (7),
515 (6), 387 (6), 275 (10), 201 (100). Rf (3:1 hexane/EtOAc)¼0.69.
(0.24–30 mmol). The reaction mixture was stirred in a microwave
reactor for 1 h (internal temperature reached 180 ꢀC). Then, vola-
tiles were removed under reduced pressure and column chroma-
tography of the residue on silica gel (3:1 hexane/EtOAc) afforded
the title compound.
4.6.1. 1a-(2,2-Bis(ethoxycarbonyl)-6-methylindan-5-yl)-1,2-dide-
oxy-3,5-di-O-(4-toluoyl)-D-ribofuranose (9aa)
Compound 7a (0.2 mmol, 78 mg), 2a (0.24 mmol, 57 mg); 56 mg
(44%) of the title compound as a yellowish oil; [a]2D0 0 (c 0.0022,
CHCl3); 1H NMR (400 MHz, C6D6) d 0.87 (3H, t, J 7.2 Hz), 0.89 (3H, t, J
7.2 Hz), 1.84 (1H, ddd, J 13.6, 6.4, 3.6 Hz), 1.94 (3H, s), 1.96 (3H, s),
2.02 (3H, s), 2.48 (1H, apparent quint, J 7.2 Hz), 3.70–3.87 (4H, m),
3.90–3.98 (4H, m), 4.42 (1H, dd, J 11.6, 4.8 Hz), 4.51 (1H, dd, J 11.6,
5.6 Hz), 4.65 (1H, td, J 5.2, 2.4 Hz), 5.25 (1H, apparent t, J 6.8 Hz),
5.51–5.54 (1H, m), 6.74 (1H, s), 6.88–6.90 (2H, m), 6.99–7.03 (2H,
m), 7.67 (1H, s), 7.98–8.01 (2H, m), 8.18–8.21 (2H, m); 13C NMR
(100 MHz, C6D6) d 14.6 (2ꢂ), 19.7, 22.0, 22.1, 39.8, 41.6, 41.7, 61.7,
62.1, 62.2, 65.4, 77.6, 78.6, 83.3, 122.0, 127.0, 128.2, 128.9, 129.2,
130.1 (2ꢂ), 130.1 (2ꢂ), 130.8 (2ꢂ), 130.7 (2ꢂ), 138.8, 139.8, 141.3,
144.2, 144.5, 166.6, 166.9, 172.3, 172.5; IR nmax (acetone) 3468, 2977,
2926, 2872,1726, 1713,1444, 1365, 1239, 1178, 1153, 1052,1014, 903,
859, 827, 707 cmꢁ1; MS (FABþ) MþH 393 (1), 231 (1), 154 (6), 119
(100). Rf (3:1 hexane/EtOAc)¼0.40.
4.5. 1a-Phenylethynyl-1,2-dideoxy-3,5-di-O-(4-toluoyl)-
D
-ribofuranose (8a) and 1b-phenylethynyl-1,2-dideoxy-3,
4.6.2. 1b-(2,2-Bis(ethoxycarbonyl)-6-methylindan-5-yl)-1,2-dide-
5-di-O-(4-toluoyl)- -ribofuranose (8b)
D
oxy-3,5-di-O-(4-toluoyl)-D-ribofuranose (9ba)
Compound 7b (0.2 mmol, 78 mg), 2a (0.24 mmol, 57 mg); 52 mg
(41%) of the title compound as a yellowish oil; [a]2D0 0 (c 0.00285,
CHCl3); 1H NMR (400 MHz, C6D6) d 0.87 (3H, t, J 7.2 Hz), 0.89 (3H, t, J
7.2 Hz),1.89 (1H, ddd, J 13.2,10.8, 6.4 Hz),1.99(3H, s), 2.01 (3H, s), 2.02
(3H, s), 2.30 (1H, ddd, J 13.6, 5.2,1.2 Hz), 3.61–3.80 (4H, m), 3.87–3.96
(4H, m), 4.37–4.40 (1H, m), 4.63 (1H, dd, J 11.6, 4 Hz), 4.66 (1H, dd, J
11.6, 4 Hz), 5.35 (1H, dd, J 10.8, 5.2 Hz), 5.53 (1H, apparent d, J 6.8 Hz),
6.73 (1H, s), 6.91–6.95 (4H, m), 7.67 (1H, s), 8.10–8.14 (2H, m), 8.16–
8.20 (2H, m); 13C NMR (100 MHz, C6D6) d 14.6 (2ꢂ), 19.7, 22.1 (2ꢂ),
41.1, 41.5, 61.6, 62.1, 65.6, 78.4, 78.8, 83.7,122.0,126.9 (two signals are
overlapped by solvent signal), 128.9, 130.1 (4ꢂ), 130.8 (2ꢂ), 130.9
(2ꢂ), 134.0, 139.3 (2ꢂ), 140.2, 144.6, 166.6, 166.9, 172.2 (2ꢂ); IR nmax
(acetone) 3468, 2977, 2932, 2901, 2869, 1726, 1713, 1441, 1365, 1239,
1182,1153, 1052, 1014, 859, 710 cmꢁ1; MS (FABþ) no molecular peak,
369 (1), 181 (7), 119 (100). Rf (3:1 hexane/EtOAc)¼0.40.
Into a solution of 1-chloro-1,2-dideoxy-3,5-di-O-(4-toluoyl)-D-
ribofuranose (8 mmol, 3 g) in dry THF (45 mL) under argon was
slowly added 1 M solution of phenylethynyl magnesium bromide
(8.5 mmol, 8.5 mL), the formed reaction mixture was then stirred at
room temperature for 6 h, and then reduced to 1/3 of its volume in
vacuo. Diethyl ether(50 mL) was addedand the solutionwas washed
with 10% NH4Cl (aq) (20 mL), saturated solution of NaHCO3 (20 mL),
and dried (MgSO4). Removal of volatiles in vacuo and column chro-
matography of the residue on silica gel (3:1 hexane/EtOAc) afforded
1.64 g (47%) of the anomeric mixtureof 8a and 8b as a paleyellow oil.
Further separation of the obtained mixture by a preparative HPLC
afforded 0.76 g (22%) of 8a and 0.34 g (10%) of 8b as viscous liquids.
Compound 8a. 1H NMR (300 MHz, C6D6) d 1.95 (3H, s), 1.97 (3H, s),
1.96–1.98 (1H, m), 2.18–2.22 (m,1H), 4.38 (1H, dd, J 11.6, 5.4 Hz), 4.45
(1H, dd, J 11.6, 5.4 Hz), 4.60–4.63 (1H, m), 4.90–4.94 (1H, m), 5.41–
5.45 (1H, m), 6.82–6.89 (4H, m), 6.93–6.97 (3H, m), 7.37–7.44 (2H,
m), 8.10–8.17 (4H, m);13CNMR(75 MHz, C6D6)d 22.0(2ꢂ), 40.4, 65.2,
69.7, 77.0, 83.4, 86.3, 90.4,124.1,129.1 (two signals are overlapped by
solvent signal), 129.2 (2ꢂ), 130.0 (4ꢂ), 130.8 (2ꢂ), 131.0 (2ꢂ), 132.7
(2ꢂ),144.2,144.4,166.7,166.8; IR nmax (ATRGe) 1718,1611,1270,1177,
1105,1018, 752 cmꢁ1; HRMS(FABþ) calcd for C35H36O7þH: 455.1859,
found: 455.1851. Rf (3:1 hexane/EtOAc)¼0.67. Compound 8b.1H NMR
(300 MHz, C6D6) d 1.94 (3H, s), 2.01 (3H, s), 2.12–2.19 (1H, m), 2.30–
2.40 (1H, m), 4.28 (1H, td, J 5.1, 2.4 Hz), 4.45–4.55 (2H, m), 4.94–5.00
(1H, m), 5.41–5.45 (1H, m), 6.82–6.85 (2H, m), 6.92–6.95 (5H, m),
7.35–7.38 (2H, m), 8.00–8.03 (2H, m), 8.17–8.20 (2H, m); 13C NMR
(75 MHz, C6D6) d 22.0, 22.1, 40.8, 65.5, 69.7, 77.6, 83.7, 86.7, 89.0,
123.8, 128.5 (two signals are overlapped by solvent signal), 129.2
(2ꢂ),130.0 (2ꢂ),130.1 (2ꢂ),130.8 (2ꢂ),130.9 (2ꢂ),132.7 (2ꢂ),144.1,
144.6, 166.4, 166.8; IR nmax (KBr) 1709, 1282, 1270, 1177, 1108, 1081,
752 cmꢁ1; HRMS (FABþ) calcd for C35H36O7þHþ: 455.1859, found:
455.1860. Rf (3:1 hexane/EtOAc)¼0.67.
4.6.3. 1a-(2,2-Diacetyl-6-methylindan-5-yl)-1,2-dideoxy-3,
5-di-O-(4-toluoyl)-D-ribofuranose (9ab)
Compound 7a (0.2 mmol, 78 mg), 2b (0.3 mmol, 53 mg); 17 mg
(15%) of the title compound as a yellowish oil; [a]2D0 ꢁ3.9 (c 0.0075,
CHCl3); 1H NMR (400 MHz, C6D6) d 1.70 (3H, s), 1.73 (3H, s), 1.88
(1H, ddd, J 13.7, 6.1, 3.7 Hz), 1.96 (3H, s), 1.97 (3H, s), 2.03 (3H, s),
2.53 (1H, ddd, J 13.9, 7.8, 7.1 Hz), 3.16–3.39 (4H, m), 4.44 (1H, dd, J
11.7, 5.2 Hz), 4.54 (1H, dd, J 11.9, 5.8 Hz), 4.73 (1H, td, J 5.4, 2.4 Hz),
5.28 (1H, apparent t, J 7.4 Hz), 5.51 (1H, ddd, J 6.4, 3.7, 2.4 Hz), 6.70
(1H, s), 6.88–6.90 (2H, m), 6.97–6.99 (2H, m), 7.60 (1H, s), 7.96–7.98
(2H, m), 8.20–8.22 (2H, m); 13C NMR (100 MHz, C6D6) d 19.9, 22.1
(2ꢂ), 26.6, 26.8, 38.2, 38.4, 39.9, 65.3, 75.6, 77.7, 78.6, 83.4, 122.2,
127.1, 127.9, 128.3, 130.1 (2ꢂ), 130.8 (2ꢂ), 130.9 (2ꢂ), 131.3 (2ꢂ),
133.6, 138.6, 139.6, 141.3, 144.3, 144.6, 166.6, 167.0, 204.5, 204.6; IR
n
max (acetone) 3408, 2949, 2918, 2847, 1708, 1690, 1610, 1441, 1352,
1263, 1174, 1098, 1022, 840, 747, 689 cmꢁ1; HRMS (FABþ) calcd for
C
0.35.
35H36O7þNaþ: 591.2359, found: 591.2350. Rf (3:1 hexane/EtOAc)¼
4.6. General procedure for cyclotrimerization of 7 with
diynes 2
4.6.4. 1b-(2,2-Diacetyl-6-methylindan-5-yl)-1,2-dideoxy-3,
5-di-O-(4-toluoyl)-D-ribofuranose (9bb)
Into a solution of 7a or 7b (0.2 mmol, 78 mg) in dry CH3CN
(4.5 ml) were added RhCl(PPh3)3 (0.02 mmol, 18.5 mg) and diyne 2
Compound 7b (0.2 mmol, 78 mg), 2b (0.3 mmol, 53 mg); 41 mg
(36%) of the title compound as a yellowish oil; [a]2D0 ꢁ8.2 (c 0.0037,

´
P. Novak et al. / Tetrahedron 64 (2008) 5200–5207
5206
CHCl3); 1H NMR (400 MHz, C6D6) d 1.66 (3H, s), 1.71 (3H, s), 1.93
(3H, s), 1.94–1.99 (1H, m), 2.00 (3H, s), 2.03 (3H, s), 2.36 (1H, ddd, J
14, 5.6, 1.2 Hz), 3.03–3.29 (4H, m), 4.38–4.41 (1H, m), 4.59 (1H, dd, J
11.6, 4 Hz), 4.79 (4H, dd, J 11.6 Hz), 5.38 (1H, dd, J 10.8, 5.2 Hz), 5.57
(1H, apparent d, J 6.8 Hz), 6.68 (1H, s), 6.80–6.84 (4H, m), 7.62 (1H,
s), 8.11–8.16 (4H, m); 13C NMR (100 MHz, C6D6) d 19.7, 22.1 (2ꢂ),
26.6, 26.7, 38.3, 38.9, 41.3, 65.6, 75.6, 78.5, 78.8, 83.8, 122.1, 127.0,
127.9, 128.3, 130.2 (2ꢂ), 130.1 (2ꢂ), 130.8 (2ꢂ), 131.3 (2ꢂ), 133.8,
CHCl3); 1H NMR (400 MHz, C6D6) d 0.885 (3H, t, J 7.2 Hz), 0.889 (3H,
t, J 7.5 Hz), 1.91–2.05 (1H, m), 1.98 (3H, s), 2.02 (3H, s), 2.30–2.39
(1H, m), 3.70–3.84 (4H, m), 3.89–3.98 (4H, m), 4.25 (1H, dd, J 11.6,
5.1 Hz), 4.37 (1H, dd, J 12, 5.7 Hz), 4.64 (1H, td, J 5.2, 2.4 Hz), 5.31–
5.36 (1H, m), 5.37–5.42 (1H, m), 6.86–6.92 (2H, m), 7.00–7.03 (6H,
m), 7.10–7.14 (2H, m), 7.88 (1H, s), 8.04–8.09 (4H, m); 13C NMR
(100 MHz, C6D6) d 14.6 (2ꢂ), 22.0, 22.1, 41.5, 41.7, 61.7, 62.3 (2ꢂ),
65.6, 77.8, 78.3, 78.6, 83.4,123.1,124.9,126.8,127.3,127.6 (2ꢂ),130.0
(2ꢂ), 130.1 (2ꢂ), 130.4 (2ꢂ), 130.8 (4ꢂ), 136.6, 140.2, 140.4, 140.7,
140.9, 142.5, 144.0, 144.5, 166.6, 166.8, 172.2, 172.4; IR nmax (acetone)
2985, 2917, 1721, 1709, 1610, 1443, 1365, 1266, 1239, 1176, 1105,
1069, 1018, 907, 841, 755, 701 cmꢁ1; HRMS (EI) calcd for C42H42O9:
690.2618, found: 690.2597. Rf (3:1 hexane/EtOAc)¼0.44.
139.0, 139.5, 140.0, 144.4, 144.7, 166.7, 166.9, 204.5, 204.6; IR n
max
(acetone) 3069, 3034, 2958, 2920, 2850, 1710, 1609, 1448, 1406,
1359, 1258, 1175, 1093, 1014, 865, 795, 751, 688 cmꢁ1; HRMS (FABþ)
calcd for C35H36O7þNaþ: 591.2359, found: 591.2370. Rf (3:1 hexane/
EtOAc)¼0.35.
4.6.5. 1a-(6-Methylindanyl)-1,2-dideoxy-3,5-di-O-(4-toluoyl)-
4.7.2. 1b-(2,2-Bis(ethoxycarbonyl)-6-phenylindan-5-yl)-1,
D-ribofuranose (9ag)
2-dideoxy-3,5-di-O-(4-toluoyl)-D-ribofuranose (10ba)
Compound 7a (0.2 mmol, 78 mg), 2g (0.3 mmol, 28 mg); 12 mg
Compound 8b (0.2 mmol, 90 mg), 2a (0.3 mmol, 71 mg); 55 mg
(40%) of the title compound as a yellowish oil; [a]2D0 ꢁ21.1 (c 0.0256,
CHCl3); 1H NMR (400 MHz, C6D6) d 0.87 (3H, t, J 7 Hz), 0.89 (3H, t, J
7 Hz),1.99 (3H, s), 2.02 (3H, s), 2.00–2.15 (2H, m), 3.60–3.83 (4H, m),
3.89–9.95 (4H, m), 4.19 (1H, td, J 5.2, 2.4 Hz), 4.56 (1H, dd, J 11.7,
4.2 Hz), 4.67 (1H, dd, J 11.7, 4.2 Hz), 5.38–5.43 (1H, m), 5.45–5.52
(1H, m), 6.87–6.98 (7H, m), 7.12–7.18 (3H, m), 7.79 (1H, s), 7.90–7.94
(2H, m), 8.18–8.22 (2H, m); 13C NMR (100 MHz, C6D6) d 14.6 (2ꢂ),
22.1 (2ꢂ), 30.9, 41.4, 41.5, 42.9, 61.6, 62.2, 65.5, 78.2, 78.8, 83.6,
123.0, 126.5, 127.8, 128.4, 128.6, 129.6 (2ꢂ), 130.0 (2ꢂ), 130.2 (2ꢂ),
130.4 (2ꢂ), 130.8 (2ꢂ), 130.9 (2ꢂ), 132.7, 138.7, 140.5, 141.1, 142.4,
144.3, 166.4, 166.9, 172.1, 172.3; IR nmax (acetone) 3027, 2979, 2956,
2923, 2851, 1727, 1610, 1454, 1365, 1269, 1242, 1179, 1108, 1066,
1018, 868, 800, 752, 701 cmꢁ1; HRMS (EI) calcd for C42H42O9:
690.261754, found: 690.262748. Rf (3:1 hexane/EtOAc)¼0.44.
(12%) of the title compound as a yellowish oil; [a]2D0 þ4.8 (c 0.0083,
CHCl3); 1H NMR (400 MHz, C6D6) d 1.85–2.00 (3H, m), 1.958 (3H, s),
1.963 (3H, s), 2.04 (3H, s), 2.53–2.60 (1H, m), 2.73–2.80 (4H, m),
4.45 (1H, dd, J 11.6, 5.2 Hz), 4.55 (1H, dd, J 11.6, 6 Hz), 4.69 (1H, td, J
5.6, 2.8 Hz), 5.31–5.34 (1H, apparent t, J 5.8 Hz), 5.55 (1H, m), 6.87–
6.90 (5H, m), 7.73 (1H, s), 7.97–8.01 (2H, m), 8.18–8.22 (2H, m); 13
C
NMR (100 MHz, C6D6) d 20.0, 22.0 (2ꢂ), 26.7, 33.6, 33.7, 40.2, 65.4,
77.7, 78.7, 83.2, 122.1, 127.1, 128.8 (two signals are overlapped by
solvent signal), 128.9, 129.9 (2ꢂ), 130.1 (2ꢂ), 130.9 (4ꢂ), 132.7,
140.0, 142.5, 143.6, 144.2, 144.4, 166.6, 166.9; IR nmax (acetone) 3404,
3065, 3034, 2923, 2850, 1720, 1710, 1609, 1448, 1406, 1372,
1264, 1178, 1102, 1020, 878, 840, 751, 691 cmꢁ1; HRMS (FABþ) calcd
for C31H32O5þNaþ: 507.2147, found: 507.2157. Rf (3:1 hexane/
EtOAc)¼0.64.
4.6.6. 1b-(6-Methylindanyl)-1,2-dideoxy-3,5-di-O-(4-toluoyl)-
4.7.3. 1a-(2,2-Diacetyl-6-phenylindan-5-yl)-1,2-dideoxy-3,
D-ribofuranose (9bg)
5-di-O-(4-toluoyl)-D-ribofuranose (10ab)
Compound 7b (0.2 mmol, 78 mg), 2g (0.3 mmol, 28 mg); 45 mg
Compound 8a (0.2 mmol, 90 mg), 2b (0.3 mmol, 53 mg); 15 mg
(12%) of the title compound as a yellowish oil; [a]2D0 ꢁ35.9 (c 0.0123,
CHCl3); 1H NMR (400 MHz, C6D6) d 1.69 (3H, s),1.72 (3H, s),1.97 (3H,
s), 2.03 (3H, s), 2.03–2.09 (1H, m), 2.30–2.44 (1H, m), 3.20–3.46 (4H,
m), 4.28 (1H, dd, J 11.6, 4.8 Hz), 4.39 (1H, dd, J 11.6, 5.6 Hz), 4.71 (1H,
td, J 5.2, 2.4 Hz), 5.30–5.33 (1H, m), 5.42 (1H, apparent t, J 7.2 Hz),
6.85–6.89 (2H, m), 6.90 (1H, s), 6.98–7.01 (2H, m), 7.10–7.20 (5H, m),
7.82 (1H, s), 8.01–8.04 (2H, m), 8.06–8.09 (2H, m); 13C NMR
(100 MHz, C6D6) d 22.0, 22.1, 26.6, 26.7, 38.2, 38.3, 41.6, 65.6, 75.7,
77.9, 78.6, 83.5, 123.2, 126.9, 128.0, 128.6 (one signal is overlapped
by solvent signal), 128.8 (2ꢂ), 129.2 (2ꢂ), 130.1 (2ꢂ), 130.2 (2ꢂ),
130.3 (2ꢂ), 130.8 (2ꢂ), 140.0, 140.4, 140.5, 140.9, 142.4, 144.1, 144.6,
166.6, 166.8, 204.2, 204.3; IR nmax (acetone) 2926, 2853, 1723, 1710,
(47%) of the title compound as a yellowish oil; [a]2D0 ꢁ21.8 (c 0.0055,
CHCl3); 1H NMR (400 MHz, C6D6) d 1.78–1.85 (2H, m), 1.95 (3H, s),
1.95–2.05 (1H, m), 1.995 (3H, s), 2.11 (3H, s), 2.38 (1H, ddd, J 13.6,
5.2, 1.2 Hz), 2.66–2.73 (4H, m), 4.41 (1H, td, J 5.2, 2.4 Hz), 4.66 (1H,
dd, J 11.7, 4.4 Hz), 4.67 (1H, dd, J 11.7, 4.4 Hz), 5.42 (1H, dd, J 10.8,
5.1 Hz), 5.57 (1H, apparent d, J 4.9 Hz), 6.84–6.88 (2H, m), 6.87 (1H,
s), 6.91–6.95 (2H, m), 7.71 (1H, s), 8.11–8.15 (2H, m), 8.17–8.19 (2H,
m); 13C NMR (100 MHz, C6D6) d 19.8, 22.0, 22.1, 26.6, 33.5 (2ꢂ), 41.3,
65.7, 78.5, 79.0, 83.6, 122.1, 127.0 (one signal is overlapped by sol-
vent signal), 129.2, 130.0 (2ꢂ), 130.1 (2ꢂ), 130.8 (2ꢂ), 130.9 (2ꢂ),
132.9, 138.22, 143.0, 143.9, 144.2, 144.5, 166.7, 166.9; IR n
(ace-
max
tone) 3002, 2948, 2920, 2850, 1720, 1609, 1454, 1375, 1267, 1175,
1102, 1020, 868, 751, 688 cmꢁ1
;
HRMS (FABþ) calcd for
1704, 1612, 1441, 1359, 1270, 1207, 1178, 1106, 1017, 754, 703 cmꢁ1
;
C
31H32O5þNaþ: 507.2147, found: 507.2162. Rf (3:1 hexane/EtOAc)¼
HRMS (FABþ) calcd for C40H37O8þNaþ: 653.2515, found: 653.2504.
Rf (3:1 hexane/EtOAc)¼0.35.
0.64.
4.7. General procedure for cyclotrimerization of 8 with
diynes 2
4.7.4. 1b-(2,2-Diacetyl-6-phenylindan-5-yl)-1,2-dideoxy-3,
5-di-O-(4-toluoyl)-D-ribofuranose (10bb)
Compound 8b (0.2 mmol, 90 mg), 2b (0.3 mmol, 53 mg); 25 mg
(20%) of the title compound as a yellowish oil; [a]2D0 ꢁ12.1 (c 0.0075,
CHCl3); 1H NMR (400 MHz, C6D6) d 1.65 (3H, s), 1.71 (3H, s), 2.00
(3H, s), 2.02 (3H, s), 2.00–2.15 (2H, m), 3.02–3.32 (4H, m), 4.20 (1H,
td, J 3.6, 2.4 Hz), 4.52 (1H, dd, J 11.6, 4 Hz), 4.77 (1H, dd, J 11.6, 4 Hz),
5.41–5.54 (1H, m), 5.50–5.52 (1H, m), 6.90 (1H, s), 6.89–6.92 (2H,
m), 6.93–6.96 (2H, m), 7.14–7.24 (5H, m), 7.73 (1H, s), 7.93–7.95 (2H,
m), 8.19–8.21 (2H, m); 13C NMR (100 MHz, C6D6) d 22.1 (2ꢂ), 26.6,
26.7, 38.1, 38.2, 43.0, 65.5, 75.6, 78.2, 78.8, 83.7, 123.1, 126.5, 127.9,
128.6 (two signals are overlapped by solvent signal), 128.8 (2ꢂ),
130.0 (2ꢂ), 130.2 (2ꢂ), 130.4 (2ꢂ), 130.7 (2ꢂ), 130.9 (2ꢂ), 138.8,
Into a solution of 8a or 8b (0.2 mmol, 90 mg) in dry CH3CN
(4.5 mL) were added RhCl(PPh3)3 (0.02 mmol, 18.5 mg) and diyne 2
(0.30 mmol). The reaction mixture was stirred in a microwave re-
actor for 1 h (internal temperature reached 180 ꢀC). Then, volatiles
were removed under reduced pressure and column chromatogra-
phy of the residue on silica gel (3:1 hexane/EtOAc) afforded a title
compound.
4.7.1. 1a-(2,2-Bis(ethoxycarbonyl)-6-phenylindan-5-yl)-1,
2-dideoxy-3,5-di-O-(4-toluoyl)-D-ribofuranose (10aa)
Compound 8a (0.2 mmol, 90 mg), 2a (0.3 mmol, 71 mg); 51 mg
140.3, 140.9, 141.0, 142.3, 144.4, 166.4, 166.9, 204.2, 204.3; IR n
max
(37%) of the title compound as a yellowish oil; [a]2D0 ꢁ13.7 (c 0.0027,
(acetone) 2953, 2917, 2851, 1715, 1700, 1610, 1478, 1440, 1356,

´
P. Novak et al. / Tetrahedron 64 (2008) 5200–5207
5207
1269, 1206, 1108, 1018, 841, 752, 707 cmꢁ1; HRMS (FABþ) calcd
References and notes
for C40H37O8þNaþ: 653.2515, found: 653.2506. Rf (3:1 hexane/
EtOAc)¼0.35.
1. For recent review, see: Kotha, S.; Brahmachary, E.; Lahiri, K. Eur. J. Org. Chem.
2005, 4741–4767 and references therein.
2. Kaufman, R. J.; Sidhu, R. S. J. Org. Chem. 1982, 47, 4941–4947.
3. (a) Das, S. K.; Roy, R. Tetrahedron Lett. 1999, 40, 4015–4018; (b) Dominique, R.;
Liu, B.; Das, S.; Roy, D. Synthesis 2000, 862–868.
4. McDonald, F. E.; Zhu, H. Y. H.; Holmquist, C. R. J. Am. Chem. Soc. 1995, 117,
6605–6606.
5. (a) Yamamoto, Y.; Saigoku, T.; Ohgai, T.; Nishiyama, H.; Itoh, K. Chem. Commun.
2004, 2702–2703; (b) Yamamoto, Y.; Saigoku, T.; Nishiyama, H.; Ohgai, T.; Itoh,
K. Org. Biomol. Chem. 2005, 3, 1768–1775; (c) Yamamoto, Y.; Yamashita, K.;
Hotta, T.; Hashimoto, T.; Kuikuchi, M.; Nishiyama, H. Chem.dAsian J. 2007, 2,
1388–1399.
4.7.5. 1a-(6-Phenylindanyl)-1,2-dideoxy-3,5-di-O-
(4-toluoyl)-D-ribofuranose (10ag)
Compound 8a (0.2 mmol, 90 mg), 2g (0.3 mmol, 28 mg); 17 mg
(16%) of the title compound as a yellowish oil; [a]2D0 ꢁ16 (c 0.0075,
CHCl3); 1H NMR (400 MHz, C6D6) d 1.80–1.88 (2H, m), 1.98 (6H, s),
2.09–2.14 (1H, m), 2.40–2.44 (1H, m), 2.58–2.82 (4H, m), 4.28 (1H,
dd, J 11.6, 4.8 Hz), 4.40 (1H, dd, J 11.6, 4.8 Hz), 4.66–4.69 (1H, m),
5.34–5.37 (1H, m), 5.44–5.47 (1H, m), 6.86–7.03 (7H, m), 7.10–7.14
(1H, m), 7.26–7.28 (2H, m), 7.92 (1H, s), 8.03–8.07 (4H, m); 13C NMR
(100 MHz, C6D6) d 22.1 (2ꢂ), 26.6, 33.4, 33.5, 41.7, 65.7, 78.0, 78.7,
83.3, 123.1, 125.1, 125.5, 126.8, 127.5, 127.7, 130.0 (2ꢂ), 130.5 (2ꢂ),
130.8 (2ꢂ), 130.8 (2ꢂ), 139.1, 140.2, 141.2, 142.2, 143.0, 143.9, 144.0,
144.4, 144.4, 145.0, 166.6, 166.8; IR nmax (acetone) 3404, 3065, 3034,
2923, 2850, 1720, 1710, 1609, 1448, 1406, 1372, 1264, 1178, 1102,
1020, 878, 840, 751, 691 cmꢁ1; HRMS (EI) calcd for C36H34O5:
546.2195, found: 546.2205. Rf (3:1 hexane/EtOAc)¼0.64.
6. Yamamoto, Y.; Hashimoto, T.; Hattori, K.; Kikuchi, M.; Nishiyama, H. Org. Lett.
2006, 8, 3565–3568.
7. Adamo, M. F. A.; Pergoli, R. Org. Lett. 2007, 9, 4443–4446.
8. Recent examples: (a) Kim, Y.; Leconte, A. M.; Hari, Y.; Romesberg, F. E. Angew.
Chem., Int. Ed. 2006, 45, 7809–7812; (b) Leconte, A. M.; Matsuda, S.; Hwang, G.
T.; Romesberg, F. E. Angew. Chem., Int. Ed. 2006, 45, 4326–4329; (c) Matsuda, S.;
Leconte, A. M.; Romesberg, F. E. J. Am. Chem. Soc. 2007, 129, 5551–5557.
9. Recent examples: (a) Beuck, C.; Singh, I.; Bhattacharya, A.; Hecker, W.; Parmar,
V.; Seitz, O.; Weinhold, E. Angew. Chem., Int. Ed. 2003, 42, 3958–3960; (b) Ya-
kovleva, L.; Lal, J.; Kool, E. T.; Shuman, S. J. Biol. Chem. 2006, 281, 35914–35921;
(c) Somoza, A.; Chelliserrykattil, J.; Kool, E. T. Angew. Chem., Int. Ed. 2006, 45,
4994–4997.
10. Reviews: (a) Wu, Q. P.; Simons, C. Synthesis 2004, 1533–1553; (b) Wellington,
W. E.; Benner, S. A. Nucleosides Nucleotides Nucleic Acids 2006, 25, 1309–1333.
4.7.6. 1b-(6-Phenylindanyl)-1,2-dideoxy-3,5-di-O-
(4-toluoyl)-D-ribofuranose (10bg)
ˇ
´
11. (a) Hocek, M.; Pohl, R.; Klepeta´rova, B. Eur. J. Org. Chem. 2005, 4525–4528; (b)
ˇ
´
Urban, M.; Pohl, R.; Klepeta´rova, B.; Hocek, M. J. Org. Chem. 2006, 71, 7322–
Compound 8b (0.2 mmol, 90 mg), 2g (0.3 mmol, 28 mg); 41 mg
(38%) of the title compound as a yellowish oil; [a]2D0 ꢁ17.5 (c 0.0080,
CHCl3); 1H NMR (400 MHz, C6D6) d 1.77–1.87 (2H, m), 1.97 (3H, s),
1.99 (3H, s), 2.07–2.21 (2H, m), 2.66–2.71 (4H, m), 4.19–4.23 (1H,
m), 4.64 (1H, dd, J 11.6, 4.4 Hz), 4.70 (1H, dd, J 11.6, 4.4 Hz), 5.45–
5.49 (1H, m), 5.51–5.53 (1H, m), 6.88–6.91 (7H, m), 7.04 (1H, s),
7.29–7.31 (2H, m), 7.81 (1H, s), 7.92–7.96 (2H, m), 8.19–8.23 (2H, m);
13C NMR (100 MHz, C6D6) d 22.0, 22.1, 26.4, 33.5, 33.6, 43.0, 65.6,
78.2, 78.9, 83.5, 123.0, 126.5, 128.0 (two signals are overlapped by
solvent signal), 129.2, 130.0 (2ꢂ), 130.0 (2ꢂ), 130.5 (2ꢂ), 130.8 (2ꢂ),
130.9 (2ꢂ),137.5,140.3,142.9,144.1,144.2,144.3,144.8,166.4,166.8;
IR nmax (acetone) 3026, 2952, 2922, 2848, 1719, 1611, 1455, 1373,
1265, 1174, 1100, 1018, 750, 698 cmꢁ1; HRMS (EI) calcd for
´ ˇ
´
7328; (c) Joubert, N.; Pohl, R.; Klepetarova, B.; Hocek, M. J. Org. Chem. 2007, 72,
6797–6805.
ˇ
´
12. (a) Turek, P.; Kotora, M.; Hocek, M.; Cisarova, I. Tetrahedron Lett. 2003, 44, 785–
ˇ
´
´
ˇ
´
788; (b) Turek, P.; Kotora, M.; Tislerova, I.; Hocek, M.; Votruba, I.; Cısarova, I.
J. Org. Chem. 2004, 69, 9224–9233; (c) Turek, P.; Nova´k, P.; Pohl, R.; Hocek, M.;
Kotora, M. J. Org. Chem. 2006, 69, 8978–8981.
13. Nova´k, P.; Pohl, R.; Hocek, M.; Kotora, M. Org. Lett. 2006, 8, 2051–2054.
14. For review, see: Ritleng, V.; Sirlin, C.; Pfeffer, M. Chem. Rev. 2002, 102,
1731–1769.
15. For examples on Grubbs first generation carbene complex catalyzed cyclo-
trimerizations, see: (a) Peters, J.-U.; Blechert, S. Chem. Commun. 1997, 1983–
1984; (b) Witulski, B.; Stengel, T.; Ferna´ndez-Herna´ndez, J. M. Chem. Commun.
2000, 1965–1966.
ˇ´
´
´
ˇ
´
16. (a) Hrdina, R.; Kadlcıkova, A.; Valterova, I.; Hodacova, J.; Kotora, M. Tetrahedron:
´
ˇ
´
Asymmetry 2006, 17, 3185–3191; (b) Hrdina, R.; Valterova, I.; Hodacova, J.;
Kotora, M. Adv. Synth. Catal. 2007, 349, 822–826.
17. (a) Zhou, Y.; Porco, J. A.; Snyder, J. K. Org. Lett. 2007, 9, 393–396; (b) Young, D. D.;
Deiters, A. Angew. Chem., Int. Ed. 2007, 47, 5178–5190.
18. Shanmugasundaram, M.; Aguirre, A. L.; Leyva, M.; Quan, B.; Martinez, L. F.
Tetrahedron Lett. 2007, 48, 7698–7701.
C
36H34O5: 546.2195, found: 546.2205. Rf (3:1 hexane/EtOAc)¼0.64.
19. Yamamoto, Y.; Okuda, S.; Itoh, K. Chem. Commun. 2001, 1102–1103.
20. (a) Meriwether, L. S.; Colthup, E. C.; Kennerly, G. W.; Reusch, R. N. J. Org. Chem.
1961, 26, 5155–5163; (b) Colthup, E. C.; Meriwether, L. S. J. Org. Chem. 1961, 26,
5169–5175; (c) Chalk, A. J.; Jerussi, R. A. Tetrahedron Lett. 1972, 61–62; (d)
Mu¨ller, E.; Scheller; Winter, W.; Wagner, F.; Meier, H. Chem.-Ztg. 1975, 99, 155–
157; (e) Scheller; Winter, W.; Mu¨ller, E. Liebigs Ann. Chem. 1976, 1448–1454.
21. Osborne, J. A.; Jardine, F. H.; Young, F. H.; Wilkinson, G. J. Chem. Soc. A 1966,
1711–1732.
Acknowledgements
This project was supported by Project No. 1M0508 to the Centre
for New Antivirals and Antineoplastics, and projects
MSM0021620857 and Z40550506 from Ministry of Education of
the Czech Republic.