Studies on tetrahydrofuran-based highly O-functionalized alkynes: Applications to synthesis of tetrahydrofuranyl-polyynes and C-nucleoside analogues

Article abstract of DOI:10.1002/ejoc.201001442

The enantiomerically pure tetrahydrofuranylalkynes 17-20 were synthesized by using various methods. By utilizing these alkynes, an efficient CuI-catalysed sp-sp carbon homo-coupling protocol in dry DMF without other additives (like amine or base, phosphan

Full text of DOI:10.1002/ejoc.201001442

FULL PAPER
DOI: 10.1002/ejoc.201001442
Studies on Tetrahydrofuran-Based Highly O-Functionalized Alkynes:
Applications to Synthesis of Tetrahydrofuranyl-Polyynes and C-Nucleoside
Analogues
P. Venkat Reddy,[a] Vikas Bajpai,[b] Brijesh Kumar,[b] and Arun K. Shaw*[a]
Keywords: Alkynes / C-C coupling / C-Nucleosides
The enantiomerically pure tetrahydrofuranylalkynes 17–20
were synthesized by using various methods. By utilizing
these alkynes, an efficient CuI-catalysed sp-sp carbon homo-
coupling protocol in dry DMF without other additives (like
amine or base, phosphane and palladium catalyst) has been
developed. The method has been applied to the synthesis of
symmetrical butadiynyl (32–37), octatetraynyl (47) and do-
decahexaynyl (49) polyynes. The unsymmetrically substi-
tuted diynes 39, 40 and 41 and triynes 43 and 44 were syn-
thesized by coupling reaction between the newly synthe-
sized bromoalkyne/diynes 38/42 and commercially available
(trialkylsilyl)acetylenes. Syntheses of the 1,2,3-triazolyl-C-
nucleoside analogue 51 and of the ethynyl- and butadiynyl-
bridged 1,2,3-triazolyl-C-nucleoside analogues 52 and 53
were performed by 1,3-dipolar cycloaddition reaction
(“click“ chemistry) of their respective alkyne precursors.
Polyynes are also useful for the construction of
carbon-rich materials such as novel dehydrobenzoannul-
enes, molecular rods, molecular wires, switches, nanoarchi-
tectures, macromolecules, acetylenic cyclophanes and fuller-
enes.[10e,14a,14f,24–26] In addition, conjugated diynes play an
important role in the properties of many functional materi-
als, such as nonlinear optical materials, electrical conduc-
tive plastics, liquid crystals.[14e,27,28] Syntheses of alkyne
polymers[29] and dendrimers[30] have also been reported.
The homo-coupling reaction is the one of the most impor-
tant reactions for the construction of conjugated 1,3-diynes
and polyynes.
Homo-coupling of terminal alkynes was pioneered by
Glaser in 1869.[31] CuI-catalyzed oxidative homo-coupling
reaction of terminal alkynes represents one of the most at-
tractive route to synthesize symmetrical diynes.[1c,1d] While
Mori and co-workers have reported the oxidative dimeriza-
tion of TMS-protected alkyne in the presence of CuCl in
DMF at 60 °C,[32a,32b] Cu(OAc)2-catalyzed homo-coupling
reaction of potassium alkynyltrifluroborates reported by
Stefani is a simple and efficient strategy to obtain 1,3-di-
ynes.[32c] Recently, the effect of different bases and amines
on the yields of the CuCl-catalyzed homo-couplings of ter-
minal alkynes with oxygen as an oxidant in acetonitrile has
been shown by Beifuss et al.[33] Li and co-workers reported
phosphane-free palladium(II)-catalyzed homo-coupling re-
action in the presence of CuI and a base,[34] whereas Zhang
et al. developed an efficient protocol for homo-coupling of
alkynes using PdCl2(PPh3)2, CuI, ethyl bromoacetate and
amine (DIPEA or DABCO) as the catalytic system.[35] Fair-
lamb and co-workers also reported [PdCl2(PPh3)2], CuI-
and PPh3-catalyzed homo-coupling of alkynes in the pres-
Introduction
Terminal alkynes are useful and versatile building blocks
in organic synthesis.[1] The most commonly used methods
for the synthesis of terminal alkyne derivatives from alde-
hydes are Corey–Fuchs reaction,[2] Fritsch–Buttenberg–
Wiechell rearrangement,[3] Colvin rearrangement,[4] dehy-
drohalogenation of halovinyl compounds,[5] Bestmann–
Ohira reagent[6] and Gilbert–Seyferth reagent.[7] Among the
alkynes, those substituted with tetrahydrofuran (THF) are
paramount building blocks for the synthesis of biologically
important compounds like unnatural C-nucleosides and
natural products.[8] Recent development with transition
metal-catalyzed carbon-carbon coupling reactions such as
Sonogashira coupling,[9] Hay’s coupling,[10] coupling of vin-
ylic tellurides,[11] synthesis of oligoynes[1a,3c,12] and enyne
metathesis[13] have proven the utility of acetylenic func-
tional group in organic chemistry.
Conjugated diyne and polyyne segments found in both
natural and unnatural products constitute a very structur-
ally diverse and useful building blocks in organic synthe-
sis.[1,14] They exhibit a wide range of biological activities
such as anti-inflammatory,[15] antitumor,[16] antifungal,[17]
antibacterial,[18] antiviral,[19] antiplasmodial,[19] antimicro-
bial,[20] anticancer,[21] anti HIV,[22] and antiangiogenic.[23]
[a] Division of Medicinal and Process Chemistry, Central Drug
Research Institute (CDRI), CSIR,
Lucknow 226001, India
E-mail: akshaw55@yahoo.com
[b] Sophisticated Analytical Instrument Facility, Central Drug
Research Institute (CDRI), CSIR,
Lucknow 226001, India
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201001442.
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ence of Et3N/MeCN solvent mixture.[36] Jai and co-workers
disclosed the homo-coupling reaction in the presence of
Copper(I) iodide, Na2CO3 as catalytic system in DMF.[37]
Zhang et al. described CuI/NBS/DIPEA system as promot-
ing system for homo-coupling reaction of alkynes.[38] In all
the above examples palladium reagent or a amine/base was
commonly used. However, owing to foul smell and pungent
flavor of the amines, prices of palladium reagents and air-
sensitive nature of phosphane ligands, the development of
an effective procedure for homo-coupling of alkynes in ab-
sence of any other additives like amine (base), phosphane,
and palladium reagents would be significant. Recently, Ra-
divoy and co-workers disclosed a copper nanoparticle-me-
diated one-pot direct homo-coupling of terminal alkynes.[39]
A few years ago we disclosed the synthesis of enantio-
merically pure 2,3,4-trisubstituted THF building blocks[40]
and later showed their synthetic utility towards the synthe-
ses of marine cytotoxic natural products oxybiotin, jaspine
B, and other important stereochemically pure building
blocks like furanoid glycals and γ-azido-tetrahydrofuran
carboxylic acid monomers.[41–42] In continuation of our
above studies and also with the growing interest in alkynes
and polyynes bearing THFs[8,43] in the field of synthetic and
medicinal chemistry, we became also interested to investi-
gate the synthesis of stereochemically pure functionalized
THF terminal alkynes (C-alkynyl glycosides),[44] symmetri-
cal and unsymmetrical polyynes by utilizing the highly
functionalized enantiomerically pure trisubstituted THF
building blocks 1–4 (Figure 1).
Results and Discussion
Synthesis of Enantiopure THF Alkynes
Synthesis of Alkynes via Chlorovinyl Compounds (Method
A)
The THF building blocks 1–4 were synthesized by using
our previous reported method.[40a] The chlorovinyl com-
pounds were obtained from THF derivatives 1–4 by their
sequential
hydrolysis–oxidation
Wittig
olefination
(SHOWO).[41,45] Hydrolysis–oxidation of domains by
1.2 equiv. of H5IO6 afforded the aldehydes 5–8 quantita-
tively. These aldehydes were subjected to Wittig olefination
with (chloromethyl)triphenylphosphonium chloride in the
presence of potassium tert-butoxide in dry tetrahydrofuran
at –40 to 0 °C to provide the chlorovinyl derivatives as a
mixture of Z/E isomers (see Table S1 in the Supporting In-
formation) in 66–75% yields for two steps. Remarkably in
the case of domain 1 only the Z-isomer 9 was formed, while
the remaining three domains 2–4 furnished a diastereomeric
mixture of E and Z isomers. Notably, out of these geometri-
cal isomers only Z-isomers underwent dehydrohalogena-
tion[5a–5b] on treatment with potassium tert-butoxide to fur-
nish terminal alkynes by E2 elimination (see Table S2 in
1
the Supporting Information). The H NMR spectrum of
compound 17 showed a doublet at δ = 2.46 (d, J = 2.2 Hz,
1 H) for the alkyne proton and its 13C NMR spectrum
showed peaks at 76.7 and 79.5 for alkyne CH and qC
respectively. The ESI-MS displayed peak at m/z 241 [M +
Na]+ and it’s HRMS showed peak at 218.0944 [M]+.
Since, the E-isomer did not form the required alkynes
and therefore, the overall yields of alkynes 17, 18, 19 and 20
from their respective precursors 1, 2, 3 and 4 via chlorovinyl
compounds 9, 11, 13, and 15 were 53, 31, 28 and 24%,
respectively.
Figure 1. Structures of enantiomerically pure trisubstituted THF
building blocks.
Synthesis of Alkynes via Dibromoalkenes (Method B)
To increase the yields of all the above THF terminal al-
Thus, keeping this interest in our mind, herein we would kynes, we tried to obtain them from their respective dibro-
like to report the following: (i) synthesis of highly O-func- moalkenes (21–24, see Table S3 in the Supporting Infor-
tionalized enantiopure tetrahydrofuran (THF) terminal al- mation) that could be obtained from THFs 1–4 via the al-
kynes (C-alkynyl glycosides) by using various methods, (ii) dehydes 5–8. Thus, each of these aldehydes (5–8) was
the homo-coupling of these alkynes in the presence of CuI in treated with dibromomethylenephosphorane (Ramirez pro-
dry DMF without using other additives to afford symmetrical cedure)[46] which was generated in situ from the correspond-
conjugated 1,3-butadiynes and polyynes, (iii) the synthesis ing dibromomethyltriphenylphosphonium bromide in the
of unsymmetrical diynes and triynes from cross-coupling presence of zinc in refluxing 1,4-dioxane to form 1,1-dibro-
reaction under Sonogashira condition [in the presence of moalkenes in 65–93% yields for two steps. The 1,1-dibro-
PdCl2(PPh3)2, CuI, Et3N, tetrahydrofuran as solvent, under moalkenes were then further treated with LDA (1.8 m solu-
H2 atmosphere], (iv) the synthesis of 1,2,3-triazolyl-C-nu- tion in tetrahydrofuran) at –78 °C to afford the desired
cleoside analogues from THF terminal alkynes by “click“ THF terminal alkynes 17–20 in 60–75% yield (see Table S3
chemistry. To the best of our knowledge the direct homo- in the Supporting Information). The overall yields of the
coupling of terminal alkynes under mild conditions pro- alkynes 17, 18, 19 and 20 from their respective domains 1,
moted by CuI only in dry DMF as an organic solvent with- 2, 3 and 4 via dibromoalkenes 21–24 were 51, 43, 37 and
out using any other additive(s) like amine, base, palladium 55% which were better than the previous method (method
catalyst, ligand has not yet been reported so far.
A).
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Tetrahydrofuran-Based Highly O-Functionalized Alkynes
Synthesis of Alkynes by Using the Bestmann–Ohira
Reagent (Method C)
THF terminal alkynes for the synthesis of natural product
jaspine B and its other stereoisomers. In order to achieve
our goal, THF-alkyne 18 was chosen as the precursor. It
was subjected to undergo alkylation at room temperature
with 1-bromododecane at the terminal carbon of the alkyne
18 in the presence of (i) CuI (0.05 equiv.), CsCO3 (1 equiv.),
NaI (1 equiv.) as catalytic system in dry DMF (2 mL).[47]
But instead of getting the desired compound, the homo-
coupled product 32 was obtained in 86% yield in 40 h.
Since, enantiomerically pure symmetrical and unsymmetri-
cal polyynes are important class of compounds and chiral
building blocks as well; we changed our plan of work and
tried to concentrate our study on oxidative coupling of
THF terminal alkynes. Next we examined the reaction in
the presence of (ii) CuI (0.05 equiv.), CsCO3 (1 equiv.) in
dry DMF (2 mL) and also in the presence of (iii) CuI
(0.05 equiv.) alone in dry DMF (2 mL) without using both
NaI and CsCO3 to see whether either of these reagents or
both have any role in homo-coupling of 18. To our surprise,
in both the above-mentioned procedures (Table 2 entries 2–
3) the homo-coupling took place smoothly at room tem-
perature within 43 h to furnish the symmetrical 1,3-diyne
32 in 80% and 86% yields, respectively. Here, formation
of the desired homo-coupled product 32 from the reaction
condition (iii) led to argue that CsCO3 and NaI did not
participate in the reaction in the presence of dry DMF sol-
vent.
To further increase the yield of the alkynes, we chose
Bestmann–Ohira reagent[6] (dimethyl 1-diazo-2-oxopropyl-
phosphonate) that allows the preparation of alkynes di-
rectly from aldehydes in good yields under a mild condition
without requiring low temperatures, inert-gas atmosphere
and a strong base. Thus, the aldehydes 5–8 were treated
with the Bestmann–Ohira reagent 25 in the presence of po-
tassium carbonate in methanol to obtain the desired al-
kynes 17–20 in 60–75% yields for two steps (Table 1).
Table 1. Synthesis of alkynes with Bestmann–Ohira reagent.
Table 2. Optimisation of homo-coupling of THF-alkyne.
To examine the influence of the free 4-OH group in
THFs 1–4 towards their transformation to obtain THF ter-
minal alkynes, we carried out the reaction on dibenzylated
THF aldehydes 28 (2,3-syn) and 29 (2,3-trans), respectively,
with Bestmann–Ohira reagent. The benzyl-protected THF
building blocks 26[40] and 27[40] prepared from 1 and 3,
respectively, were treated with H5IO6 to obtain the alde-
hydes 28 and 29 quantitatively. These aldehydes as such on
treatment with Bestmann–Ohira reagent 25 afforded the
terminal alkynes 30 and 31, respectively, each in 80% yields
for two steps (see Scheme S1 in the Supporting Infor-
mation). From the above study it was concluded that
among the three methods (methods A–C) used for the syn-
thesis of the targeted enantiomerically pure THF terminal
alkynes 17–20 from their respective THF building blocks
1–4, the sequential synthesis of alkynes using the Best-
mann–Ohira reagent (method C) was the most efficient
method to furnish the desired alkynes 17, 18, 19 and 20 in
an overall yields 75, 70, 68 and 60%, respectively, from their
corresponding precursors.
The reaction was also carried out in the presence of (iv)
CuI (0.05 equiv.) in tetrahydrofuran without using any base
or free amine and (v) CuI (0.05 equiv.) and base Et3N
(1 equiv.) in tetrahydrofuran. While the former reaction
condition failed to furnish the desired symmetrical 1,3-buta-
Applications of THF Terminal Alkynes
Homo-Coupling of Stereochemically Pure THF Terminal
Alkynes
Having the enantiopure THF terminal alkynes in hand, diyne 32, there was no improvement in the yield of sym-
the homo-coupling of each of these alkynes was under- metrical 1,3-butadiyne from the latter reaction condition
taken. Actually, initially we were interested to use these (Table 2, entries 4–5). Thus, the usage of CuI and DMF
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turned out to be the best reaction condition for carrying Synthesis of Unsymmetrical Polyynes
out homo-coupling reaction of alkyne 18 since it did not
Synthesis of the Unsymmetrical 1,3-Butadiynes 39–41
require any other additive(s). However, it is worth men-
tioning that freshly distilled DMF from CaH2 is not pure
enough and the amine is still present there. Therefore, re-
sults shown in Table 2 and the literature precedent[32a,32b]
on CuI-catalyzed oxidative dimerization of TMS-protected
alkyne in dry DMF at 60 °C clearly indicate that both oxy-
gen and amine contained in DMF are likely to be sufficient
to let the homo-coupling reaction go to completion. The
optimized reaction condition (Table 2, entry 3) was used for
homo-coupling of all the isomers of the tetrahydrofuran-
bearing terminal alkynes 17, 19, 20, 30 and 31 to afford
their corresponding symmetrical 1,3-butadiynes 33–37 in
80–86% yields. The results are summarized in Table 3.
After completion of the synthesis of stereochemically
pure symmetrical 1,3-butadiynes from their corresponding
THF-alkynes, we focused towards the synthesis of unsym-
metrical diynes from 38 and triynes from bromoalkyne 42
by their cross-coupling reaction under Sonogashira condi-
tion [in the presence of PdCl2(PPh3)2, CuI, Et3N, solvent
THF].[48] This reaction was carried out in the presence of
H2 atmosphere just to avoid the homo-coupling of TMS-
acetylene or the substrate acetylene.[8d] The bromoalkyne
38 was obtained from THF-alkyne 17 or 1,1-dibromoalkene
21. While the bromoalkyne 38 was obtained in 88% yield
by treating THF-alkyne 17 in acetone with N-bromosuc-
cinimide (NBS, 1.1 equiv. with respect to alkyne) in the
presence of silver nitrate (0.1 equiv.) as a catalyst at room
temperature,[49] treatment of 1,1-dibromoalkene 21 with
5 equiv. of TBAF·3H2O in DMF yielded 1-bromo-1-alkyne
38 in 80% yield (Scheme 1).[5a]
Table 3. Synthesis of symmetrical 1,3-butadiynes 33–37.
Scheme 1. Reagents and conditions: (i) NBS (1.1 equiv.), AgNO3
(0.1 equiv.), acetone, room temp., 1.5 h; (ii) TBAF·3H2O (5 equiv.),
DMF (2 mL), 60 °C, 2h; (iii) CuI (0.1 equiv.), [PdCl2(PPh3)2]
(0.1 equiv.), Et3N (2 equiv.), TMS alkyne (1.3 equiv.) or TIPS al-
kyne (1.3 equiv.) or TES alkyne (1.3 equiv.), H2 atmosphere, THF
(5 mL), room temp., 2 h.
The cross-coupling reaction between (trimethylsilyl)-
acetylene (1 equiv.) and bromoalkyne 38 (1 equiv.) under
Sonogashira condition produced the cross-coupling product
39 in 82% yield, along with some unidentified side prod-
ucts. However, when the same reaction was conducted with
1.3 equiv. of trimethylsilylacetylene the desired compound
39 was obtained as the sole product in 88% yield. Thus,
with the optimized reaction condition in hand to obtain
unsymmetrical 1,3-butadiynes, the cross-coupling of bro-
moalkyne 38 with triisopropylsilyl- (TIPS) and triethylsilyl-
acetylenes (TES), in succession, catalyzed by CuI
(0.1 equiv.), [PdCl2(PPh3)2] (0.1 equiv.), Et3N (2 equiv.) in
dry tetrahydrofuran (5 mL) and in the presence of hydrogen
atmosphere led to the facile formation of unsymmetrical
TIPS-diyne 40 and TES-diyne 41 in 78 and 81% yields,
respectively.
Synthesis of the Unsymmetrical 1,3,5-Hexatriynes 43 and
44
In situ one pot desilylative bromination of compound 40
or 41 with silver fluoride (AgF) and NBS in acetonitrile at
room temperature led to the desired bromodiyne 42 in 76%
from 40 and in 80% yield from 41.[48] The TIPS-triyne 43
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Tetrahydrofuran-Based Highly O-Functionalized Alkynes
and TES-triyne 44 were then shaped in 70% and 75% yields
from bromodiyne 42 by treatment with commercially avail-
able TIPS- and TES-acetylenes under Sonogashira condi-
tion as described above (Scheme 2).
Scheme 4. Reagents and conditions: a) CuI (1 equiv.), DMF
(2 mL), 60 °C, 6 h; b) (i) TBAF (1.0 m solution in THF, 1.2 equiv.),
tetrahydrofuran (5 mL), 0 °C, 5 min; (ii) CuI (0.05 equiv.), dry
DMF (2 mL), room temp., 24 h; c) Cu(OAc)2 (3 equiv.), Py:Et2O
(3:1), TBAF (1.0 m solution in THF, 1.2 equiv.), room temp., 2 h.
Scheme 2. Reagents and conditions: (i) NBS (1.2 equiv.), AgF
(1.2 equiv.), CH3CN (5 mL), room temp., 1.5 h; (ii) CuI
(0.1 equiv.), [PdCl2(PPh3)2] (0.1 equiv.), Et3N (2 equiv.), TIPS-
alkyne (1.3 equiv.) or TES-alkyne (1.3 equiv.), H2 atmosphere, dry
tetrahydrofuran, room temp., 2 h.
Synthesis of Symmetrical Polyynes
the better substrate compared to 40 and 41 for oxidative
homo-coupling to produce the tetrayne 47 in 80% yield in
the presence of CuI (1 equiv.) in dry DMF at 60 °C (condi-
tion a, Scheme 4).
The cross-coupling reaction between bromodiyne 42 and
the alkyne 17 under Sonogashira condition (as described in
Scheme 2) afforded the symmetrical triyne 45, along with
the homo-coupling product 33 in an almost 1:1 ratio (1H
NMR) as an inseparable mixture (see Supporting Infor-
mation and Scheme 3).
Synthesis of the Symmetrical Hexayne 49
Here, the oxidative dimerization of the THF-triynes 43
and 44 by a literature method[50] to obtain hexayne 49
(Scheme 5) was more challenging. Desilylation of TIPS-
triyne 43 or TES-triyne 44 with a fluoride source (TBAF)
and subsequent treatment of the in situ generated terminal
triyne 48 with Cu(OAc)2 in pyridine/ether (3:1) for 2 h at
room temperature furnished the hexayne 49 in low yield
(15%) probably due to decomposition of intermediate ter-
minal triyne 48.[12,51] Therefore, we decided to modify the
synthesis of 49 as follows. When the desilylation of 43 was
carried out at –78 °C, the reaction was completed within
5 min (monitored by TLC). The reaction mixture contain-
ing the terminal triyne was diluted with saturated ammo-
Scheme 3. Reagents and conditions: (i) CuI (0.1 equiv.),
[PdCl2(PPh3)2] (0.1 equiv.), Et3N (2 equiv.), H2 atmosphere, tetra-
hydrofuran (2 mL), room temp., 2 h.
Synthesis of the Symmetrical Tetrayne 47
In order to show the efficiency of our above-described nium chloride solution and extracted with diethyl ether
homo-coupling method (Table 2 and Table 3) to obtain (3ϫ5 mL). The combined organic layers were dried with
symmetrical polyynes (47 and 49), the symmetrical tetrayne Na2SO4 and concentrated to obtain crude product as a
47 was synthesized in 70% yield from TES-diyne 41. The black insoluble material formed probably due to decompo-
deprotection of the triethylsilyl (TES) group in 41 with sition of the crude product during the process of solvent
TBAF at 0 °C furnished the intermediate terminal diyne 46 evaporation. So to overcome this problem, a modified
that was then treated with CuI in dry DMF to furnish the workup procedure was adopted. 3 mL of dry DMF was
symmetrical tetrayne 47 in 70% yield after two reaction added to the organic phase and the solution was then con-
steps (condition b, Scheme 4) and chromatographic purifi- centrated at low temperature (below 10 °C) with the care to
cation.
avoid complete evaporation of the solvent to dryness, which
In order to make a comparative study to obtain tetrayne probably resulted in the decomposition of the intermediate
47 from another alternative route, the TES-diyne 41 was terminal triyne 48. Once the diethyl ether was evaporated,
subjected to undergo in situ one-pot desilylation/oxidative the intermediate 48 in DMF was stirred with CuI
dimerization in the presence of Cu(OAc)2 (3 equiv.) and (0.05 equiv.) for 24 h. The reaction mixture was worked up
TBAF (1.0 m solution in THF, 1.2 equiv.) in pyridine/ether and purified by column chromatography to obtain the
(3:1) for 2 h at room temperature to give the tetrayne prod- hexayne 49 in 60% yield for two steps (Scheme 5).
uct 47 in 65% yield[50] (condition c, Scheme 4) that was less
The UV spectra of compounds 47 and 49 revealed the
by 5% of its yield synthesized from 41 via the intermediate expected bathochromic shift upon increasing the number of
46 (condition b, Scheme 4). Similarly, TIPS-diyne 40 gave conjugated triple bonds. The tetrayne 47 absorbed at
47 in 68% yield when it was subjected to undergo in situ 245 nm and hexayne 49 absorbed at 296 nm. It is very
one-pot desilylation/oxidative dimerization (condition c, clearly resolved vibronic fine structure for the higher po-
Scheme 4). However, TMS-diyne 39 was turned out to be lyyne 49.[1e,12]
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azide 50 to give the corresponding ethynyl-bridged 1,2,3-
triazolyl-C-nucleoside analogue 52 in 52% yield for two
steps (Scheme 6).
After successfully carrying out the synthesis of ethynyl-
bridged 1,2,3-triazolyl-C-nucleoside analogue 52, we syn-
thesized 1Ј,3Ј-butadiynyl-bridged 1,2,3-triazolyl-C-nucleo-
side analogue 53. TIPS-triyne 43 was desilylated with
TBAF in tetrahydrofuran within 5 min at –78 °C. The reac-
tion mixture was diluted with saturated ammonium chlo-
ride solution and extracted with diethyl ether followed by
addition of 3 mL of tBuOH to the organic phase. The re-
sulting solution was then concentrated at low temperature
(below 10 °C) with the care to avoid complete evaporation
of the solvent to dryness (as described in Scheme 5). Once
the diethyl ether was removed from the organic phase, the
residue containing the terminal triyne 48 in tBuOH was
then stirred with azide 50, (+)-sodium l-ascorbate and
water at room temperature for 10 h to obtain the 1Ј,3Ј-buta-
diynyl-bridged 1,2,3-triazolyl-C-nucleoside analogue 53 in
50% yield for two steps (Scheme 6).
Scheme 5. Reagents and conditions: (i) TBAF (1.0 m solution in
THF, 1.2 equiv.), tetrahydrofuran, –78 °C, 5 min, (ii) CuI
(0.05 equiv.), dry DMF (2 mL), room temp., 24 h.
Syntheses of the 1,2,3-Triazolyl-C-nucleoside Analogue 51
and the Ethynyl- and Butadiynyl-Bridged 1,2,3-Triazolyl-C-
nucleoside Analogues 52 and 53
Nowadays C-nucleosides are attracting much attention
because of their broad applications in medicinal chemistry
and chemical biology.[52] Several naturally occurring C-nu-
cleosides are known to exhibit extensive biological activities
like antiviral and antitumor activity.[53–56] The interesting
biological activities exhibited by 1,2,3-triazolyl-nucleo-
sides[57] or other C-nucleosides like ethynyl-bridged cytosine
C-nucleoside reported by Diederichsen and co-workers[58]
encouraged us to explore the potential of enantiopure
THF-alkynes and polyynes described herein. Based on the
above-mentioned literature reports, we synthesized 1,2,3-tri-
azolyl-C-nucleoside 51[59] and alkynyl-bridged 1,2,3-triaz-
olyl-C-nucleosides analogues 52 and 53.
The straightforward synthesis of C-nucleoside analogues
51–53 were completed from THF-alkynes 17, 46 and 48
respectively. The alkyne 17 was subjected to 1,3-dipolar cy-
cloaddition reaction[60] with the enantiopure THF-azide 50
(1 equiv.)[41b,42b] to obtain triazolyl-C-nucleoside analogue
51 in 71% yield (Scheme 6).
Conclusions
In summary, herein we have described the synthesis of
highly O-functionalized alkynes (C-alkynyl glycosides) 17–
20 bearing tetrahydrofuran building blocks from their re-
spective THF domains 1–4 via chlorovinyl compounds 9,
11, 13, and 15, respectively (method A), dibromoalkenes
21–24 (method B) and by the reaction of enantiopure O-
functionalized tetrahydrofurancarbaldehydes 5–8 with Best-
mann–Ohira reagent (method C). Among the three meth-
ods (methods A–C) described, the method C was an ef-
ficient and practical procedure for the synthesis of enantio-
merically pure 2,3,4-trisubstituted THF-alkynes 17–20. By
using these alkynes, CuI catalysed sp-sp carbon homo-cou-
pling protocol in dry DMF has been developed efficiently
in the absence of other additives like, amine or base, phos-
phane and palladium catalyst. This new methodology has
been applied to the synthesis of the symmetrical 1,3-buta-
diynes 32–37, the 1,3,5,7-octatetrayne 47, and the
1,3,5,7,9,11-dodecahexayne 49. Whilst the synthesis of 49
from the TIPS-triyne 43 was possible in 2 h but in a very
low yield by adopting the literature method that involves in
situ one-pot desilylation/oxidative dimerization in the pres-
ence of Cu(OAc)2 (3 equiv.) and TBAF (1.2 equiv.) in pyr-
idine/ether (3:1), its synthesis by treatment of the terminal
triyne intermediate 48 (obtained from desilylation of TIPS-
triyne 49) with CuI in dry DMF by our modified method
afforded the hexayne 49 in 60% yield. The unsymmetrical
1,3-butadiynes 39, 40, 41 and 1,3,5-hexatriynes 43, 44 have
Scheme 6. Synthesis of 1,2,3-triazolyl-C-nucleoside analogues 51,
52, and 53. Reagents and conditions: a) CuSO4·5H2O (0.2 equiv.),
(+)-sodium l-scorbate (0.4 equiv.), tBuOH/H2O (1:1), room temp.,
10 h.
Next we turned our attention to synthesize the ethynyl- also been synthesized by cross-coupling reaction reaction
and butadiynyl-bridged 1,2,3-triazolyl-C-nucleoside ana- between the newly synthesized bromoalkyne/diynes 38/42
logues 52 and 53 by trapping[51] of terminal butadiyne 46, and commercial trialkylsilyl-acetylenes under Sonogashira
and hexatriyne 48, respectively.
condition. The synthetic utility of THF terminal alkyne 17,
TIPS-diyne 40 was desilylated with TBAF in THF at diyne 46 and triyne 48 has also been exemplified by treating
0 °C to afford the intermediate terminal diyne 46 which was each of them with enantiopure THF azide 50 under 1,3-
directly used for 1,3-dipolar cycloaddition reaction with dipolar cycloaddition reaction condition to obtain the re-
1580
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 1575–1586

Tetrahydrofuran-Based Highly O-Functionalized Alkynes
H, 4-H, 4Ј-H), 4.05 (dd, J = 4.3, 9.9 Hz, 2 H, 6b-H, 6Јb-H), 3.93
(dd, J = 1.9, 9.9 Hz, 2 H, 6a-H, 6Јa-H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 137.4 (ArqC), 128.9 (ArC), 128.5 (ArC), 128.2 (ArC),
90.8 (C-4, C-4Ј), 77.7 (C-2, C-2Ј), 76.6 (C-5, C-5Ј), 74.6 (C-6, C-
6Ј), 73.4 (C-3, C-3Ј), 72.7 (CH2Ph), 71.2 (C-1, C-1Ј) ppm. IR (neat):
spective 1,2,3-triazolyl-C-nucleoside analogue 51, ethynyl-
bridged 52, and butadiynyl-bridged 1,2,3-triazolyl-C-nu-
cleoside analogue 53. Further utilization of THF-alkynes
and polyynes described in this paper towards target-
oriented synthesis of natural products, natural product like
molecules of biological significance and diversity oriented
synthesis of this class of C-nucleoside analogues and evalu-
ation of their various biological activities is underway in
our laboratory.
ν = 3423, 3020, 2361, 1638, 1426, 1261 1045, 761. Mass (ESI-MS):
˜
m/z 434; found 452 [M + NH4] and 457 [M + Na]+; DART-HRMS:
calcd. for C26H27O6 [M
+
H]+: 435.1807; found 435.1791.
C26H26O6 (434.49): calcd. C 67.66, H 6.33; found C 67.44, H 6.32.
Compound 33: Oil, 40 mg, 80% yield. [α]2D9 = –361.8 (c = 0.15,
CHCl3); column chromatography chloroform/methanol, 99:1; Rf =
1
0.28 (n-hexane/ethyl acetate, 1:1). H NMR (300 MHz, CDCl3): δ
Experimental Section
= 7.29–7.38 (m, 10 H, ArH), 4.87 (d, J = 4.6 Hz, 2 H, 3-H, 3Ј-H),
4.76 (d, J = 11.9 Hz, 2 H, CH2Ph), 4.62 (d, J = 11.9 Hz, 2 H,
CH2Ph), 4.36 (m, 2 H, 5-H, 5Ј-H), 4.19 (dd, J = 4.6, 9.7 Hz, 2 H,
6b-H, 6Јb-H), 3.94 (dd, J = 2.2, 4.3 Hz, 2 H, 4-H, 4Ј-H), 3.70 (dd,
J = 1.7, 9.8 Hz, 2 H, 6a-H, 6Јa-H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 137.7 (ArqC), 128.9 (ArC), 128.4 (ArC), 128.3 (ArC),
85.6 (C-4, C-4Ј), 76.0 (C-5, C-5Ј), 75.3 (C-2, C-2Ј), 73.6 (C-6, C-
6Ј), 73.3 (CH2Ph), 72.5 (C-1, C-1Ј), 71.7 (C-3, C-3Ј) ppm. IR (neat):
General Remarks: DMF was dried with calcium hydride overnight
and distilled. CH2Cl2 was dried with anhydrous calcium chloride
overnight and distilled from phosphorus pentoxide. Tetra-
hydrofuran was freshly distilled from sodium/benzophenone. All
the products were characterized by 1 H, 13C, IR, ESI-MS, EI-
HRMS or DART-HRMS. Analytical TLC was performed using
2.5ϫ5 cm plates coated with a 0.25 mm thickness of silica gel (60
F-254),visualization was accomplished with CeSO4 (1% in 2 m
H2SO4) or 10% H2SO4/EtOH and subsequent charring over a hot
plate. Column chromatography was performed using silica gel (60–
120, 100–200, 230–400 mesh). NMR spectra were recorded on
Bruker Avance DPX 200FT, Bruker Robotics, Bruker DRX 300
Spectrometers at 200, 300 MHz (1H) and 50, 75, MHz (13C). Ex-
periments were recorded in CDCl3 or CDCl3/CCl4 mixture at
25 °C, otherwise mentioned. IR spectra were recorded on Perkin–
Elmer 881 and FTIR-8210 PC Shimadzu Spectrophotometers.
Mass spectra were taken on a JEOLJMS-600H high-resolution
spectrometer in the electron-impact (EI) mode at 70 eV, JMS-
100 TLC (AccuTof) atmospheric pressure ionization time-of-flight
mass spectrometer (Jeol, Tokyo, Japan) fitted with a DART ion
source operated in positive-ion mode. Optical rotations were deter-
mined on an Autopol III polarimeter (Rudolph Research) using a
1 dm cell and chloroform as solvent; concentrations mentioned are
in g/100 mL.
ν = 3418, 3020, 2360, 1633, 1426, 1216, 1045, 761. Mass (ESI-
˜
MS): m/z 434; found 452 [M + NH4]+; DART-HRMS: calcd. for
C26H27O6 [M + H]+: 435.1807; found 435.1800. C26H26O6 (434.49):
calcd. C 68.60, H 6.26; found C 68.88, H 6.58.
Compound 34: Oil, 41 mg, 83% yield. [α]2D6 = –99.6 (c = 0.34,
CHCl3); column chromatography chloroform/methanol, 99:1; Rf =
1
0.31 (n-hexane/ethyl acetate, 1:1). H NMR (300 MHz, CDCl3): δ
= 7.32–7.42 (m, 10 H, ArH), 4.78 (d, J = 11.6 Hz, 2 H, CH2Ph),
4.68 (d, J = 11.6 Hz, 2 H, CH2Ph), 4.61 (d, J = 5.4 Hz, 2 H, 3-H,
3Ј-H), 4.30–4.31 (m, 2 H, 5-H, 5Ј-H), 4.05–4.09 (m, 4 H, 4-H, 4Ј-
H, 6b-H, 6Јb-H), 3.82 (dd, J = 3.2, 9.8 Hz, 2 H, 6a-H, 6Јa-H), 2.67
(br. s, 2 H, 2ϫ OH) ppm. 13C NMR (75 MHz, CDCl3): δ = 136.9
(ArqC), 129.1 (ArC), 128.9 (ArC), 128.4 (ArC), 84.2 (C-4, C-4Ј),
77.8 (C-2, C-2Ј), 73.7 (CH2Ph, C-6, C-6Ј), 71.3 (C-3, C-3Ј), 70.8
(C-5, C-5Ј), 70.8 (C-1, C-1Ј) ppm. IR (neat): ν = 3411, 3019, 2927,
˜
2361, 1456, 1216, 1092, 1055, 928, 761. Mass (ESI-MS): m/z 434;
found 452 [M + NH4]+; DART-HRMS: calcd. for C26H27O6 [M +
H]+: 435.1807; found 435.1808.
(i) General Procedure for the Preparation of Alkynes with Bestmann–
Ohira Reagent: To a stirred solution of aldehyde (1 equiv.) in
MeOH was added K2CO3 (3 equiv.) and freshly prepared Best-
mann–Ohira reagent (dimethyl 1-diazo-2-oxopropylphosphonate)
(3 equiv.). The stirring was continued till the completion of the re-
action (1–2 h, TLC monitoring). The reaction mixture was diluted
with water and extracted with Et2O (3ϫ10 mL). The combined
organic layers were washed with brine (2ϫ10 mL), dried with
Na2SO4 and concentrated under vacuum. The crude product was
purified by column chromatography on silica gel to give the pure
alkyne.
Compound 35: Oil, 42 mg, 84% yield. [α]2D9 = +260.6 (c = 0.27,
CHCl3); column chromatography n-hexane/chloroform, 1:9; Rf =
1
0.27 (n-hexane/ethyl acetate, 1:1). H NMR (300 MHz, CDCl3): δ
= 7.31–7.40 (m, 10 H, ArH), 4.85 (d, J = 11.5 Hz, 2 H, CH2Ph),
4.79 (d, J = 6.03 Hz, 2 H, 3-H, 3Ј-H), 4.67 (d, J = 11.5 Hz, 2 H,
CH2Ph), 4.26–4.30 (m, 2 H, 5-H, 5Ј-H), 3.97–4.07 (m, 4 H, 4-H,
4Ј-H, 6b-H, 6Јb-H), 3.91 (dd, J = 4.1, 9.7 Hz, 2 H, 6a-H, 6Јa-H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 136.7 (ArqC), 128.7 (ArC),
128.4 (ArC), 128.3 (ArC), 78.8 (C-4, C-4Ј), 75.7 (C-2, C-2Ј), 73.4
(C-6, C-6Ј), 73.4 (CH2Ph), 72.2 (C-1, C-1Ј), 70.2 (C-3, C-3Ј), 69.9
(C-5, C-5Ј) ppm. IR (neat): ν = 3424, 2930, 2361, 1636, 1455, 1304,
˜
(ii) General Procedure for the Synthesis of Symmetrical 1,3-Buta-
diynes: To a stirred solution of alkyne (1 equiv.) in dry DMF
(2 mL) was added a 5 mol-% of CuI (with respect to alkyne) at
room temperature. After stirring for 40–43h, reaction mixture was
diluted with saturated ammonium chloride solution and extracted
with diethyl ether (3ϫ5 mL). The combined organic layers were
dried with Na2SO4, concentrated under reduced pressure and puri-
fied by column chromatography to obtained pure symmetrical 1,3-
butadiynes.
1095, 1046. Mass (ESI-MS): m/z 434; found 435 [M + H]+ and
452 [M + NH4]+; DART-HRMS: calcd. for C26H27O6 [M + H]+:
435.18076; found 435.17984. C26H26O6 (434.49): calcd. C 68.60, H
6.26; found C 68.81, H 6.20.
Compound 36: Oil, 43 mg, 86% yield. [α]2D6 = –101.5 (c = 0.44,
CHCl3); column chromatography n-hexane/ethyl acetate, 93:7; Rf =
0.37 (n-hexane/ethyl acetate, 9:1). 1H NMR (300 MHz, CDCl3,
CCl4): δ = 7.27–7.36 (m, 20 H, ArH), 4.80 (d, J = 4.6 Hz, 2 H, 3-
H, 3Ј-H), 4.73 (d, J = 12.0 Hz, 2 H, CH2Ph), 4.59 (d, J = 12.0 Hz,
Compound 32: Solid, m.p. 124–126 °C; 43 mg, 86% yield. [α]2D8
=
+308.0 (c = 0.27, CHCl3), eluent for column chromatography 2 H, CH2Ph), 4.47 (br. s, 4 H, 2ϫ CH2Ph), 4.10–4.19 (m, 4 H, 5-
(CHCl3); Rf
=
0.31 (n-hexane/ethyl acetate, 1:1). 1H NMR
H, 5Ј-H, 6b-H, 6Јb-H), 4.04–4.05 (m, 2 H, 4-H, 4Ј-H), 3.79–3.83
(300 MHz, CDCl3): δ = 7.33–7.41 (m, 10 H, ArH), 4.58–4.67 (m, (m, 2 H, 6a-H, 6Јa-H) ppm. 13C NMR (75 MHz, CDCl3, CCl4): δ
6 H, 3-H, 3Ј-H, 2ϫ CH2Ph), 4.32 (brs 2 H, 5-H, 5Ј-H), 4.11 (s, 2 = 138.0 (ArqC), 137.9 (ArqC), 128.9 (ArC), 128.5 (ArC), 128.4
Eur. J. Org. Chem. 2011, 1575–1586
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1581

P. V. Reddy, V. Bajpai, B. Kumar, A. K. Shaw
FULL PAPER
(ArC), 128.3 (ArC), 128.1 (ArC), 83.9 (C-4, C-4Ј), 83.2 (C-5, C-
Na2SO4, and concentrated in vacuo. The resulting residue was puri-
5Ј), 75.4 (C-2, C-2Ј), 73.2 (CH2Ph), 72.6 (C-1, C-1Ј), 72.0 (CH2Ph), fied by column chromatography to give pure (trialkylsilyl)diynes.
71.9 (C-3, C-3Ј), 71.5 (C-6, C-6Ј) ppm. IR (neat): ν = 3019, 2928,
˜
Compound 39: Oil, 65 mg, 88% yield. [α]2D5 = –247.9 (c = 0.48,
CHCl3); eluent for column chromatography n-hexane/ethyl acetate,
93:7; Rf = 0.63 (n-hexane/ethyl acetate, 1:1). H NMR (300 MHz,
CDCl3, CCl4): δ = 7.27–7.37 (m, 5 H, ArH), 4.81 (d, J = 4.9 Hz,
5-H), 4.76 (d, J = 11.9 Hz, CH2Ph), 4.61 (d, J = 11.9 Hz, CH2Ph),
4.32–4.33 (m, 1 H, 7-H), 4.14 (dd, J = 4.8, 9.7 Hz, 1 H, 8b-H),
3.89–3.91 (m, 1 H, 6-H), 3.65 (dd, J = 2.0, 9.7 Hz, 1 H, 8a-H), 0.22
(s, 9 H, 3ϫ CH3) ppm. 13C NMR (75 MHz, CDCl3, CCl4): δ =
137.9 (ArqC), 128.9 (ArC), 128.5 (ArC), 128.5 (ArC), 88.2 (C-4),
87.9 (C-3), 85.8 (C-6), 76.1 (C-7), 73.5 (3 C, C-8, C-1, C-2), 73.4
2358, 1648, 1458, 1216, 1053, 759. Mass (ESI-MS): m/z 614; found
632 [M + NH4]+.
1
Compound 37: Oil, 42 mg, 85% yield. [α]2D6 = –105.3 (c = 0.20,
CHCl3); column chromatography n-hexane/ethyl acetate, 93:7; Rf =
0.37 (n-hexane/ethyl acetate, 9:1). 1H NMR (300 MHz, CDCl3,
CCl4): δ = 7.32–7.37 (m, 20 H, ArH), 4.55–4.72 (m, 10 H, 4ϫ
CH2Ph, 3-H, 3Ј-H), 4.11–4.14 (m, 2 H, 5-H, 5Ј-H), 4.03–4.07 (m,
4 H, 4-H, 4Ј-H, 6b-H, 6Јb-H), 3.89 (qt, J = 4.7 Hz, 2 H, 6a-H, 6Јa-
H) ppm. 13C NMR (50 MHz, CDCl3, CCl4): δ = 138.2 (ArqC),
137.8 (ArqC), 128.9 (ArC), 128.8 (ArC), 128.4 (ArC), 128.3 (ArC),
128.3 (ArC), 128.2 (ArC), 83.4 (C-4, C-4Ј), 78.2 (C-2, C-2Ј), 77.7
(C-5, C-5Ј), 73.1 (CH2Ph), 72.7 (CH2Ph), 71.6 (C-3, C-3Ј), 71.1 (C-
(CH Ph), 71.7 (C-5), 0.12 [3 C, Si(CH ) ] ppm. IR (neat): ν = 3444,
˜
2
3 3
3021, 2359, 1523, 1427, 1216, 1043, 928, 762. Mass (ESI-MS): m/z
314; found 332 [M + NH4]+. HRMS (EI): calcd. for C18H22O3Si
[M]+: 314.1338; found 314.1352.
1, C-1Ј), 70.9 (C-6, C-6Ј) ppm. IR (neat): ν = 3020, 2359, 1595,
˜
1427, 1216, 1046, 928, 761. Mass (ESI-MS): m/z 614; found 632
[M + NH4]+. HRMS (EI): calcd. for C40H39O6 [M + H]+: 615.2747;
found 615.2736.
Compound 40: Oil, 73 mg, 78% yield. [α]2D5 = –191.1 (c = 0.50,
CHCl3); eluent for column chromatography n-hexane/ethyl acetate,
1
23:2; Rf = 0.61 (n-hexane/ethyl acetate, 1:1). H NMR (300 MHz,
(iii) Synthesis of the Bromoalkyne 38 from Alkyne 17: To a stirred
solution of alkyne 17 (50 mg, 0.22 mmol) in acetone (5 mL) were
added NBS (44 mg, 0.25 mmol) and silver(I) nitrate (3.5 mg,
0.02 mmol). The resulting solution was stirred for 1.5 h at room
temperature. After completion of the reaction (monitored by TLC),
the solution was filtered through a pad of celite and the filtrate was
concentrated in vacuo. The crude residue was diluted with diethyl
ether and washed with water. The combined organic layers were
dried with Na2SO4, concentrated under reduced pressure and puri-
fied by silica gel column chromatography to give bromoalkyne 38
(60 mg, 88%) as a semi solid.
CDCl3, CCl4): δ = 7.29–7.40 (m, 5 H, ArH), 4.85 (d, J = 4.8 Hz,
5-H), 4.79 (d, J = 11.6 Hz, CH2Ph), 4.65 (d, J = 11.6 Hz, CH2Ph),
4.36–4.37 (m, 1 H, 7-H), 4.18 (dd, J = 4.6, 9.7 Hz, 1 H, 8b-H), 3.94
(qt, J = 2.3 Hz, 1 H, 6-H), 3.69 (dd, J = 2.0, 9.7 Hz, 1 H, 8a-H),
1.32 [3 H, CH(CH3)2]3, 1.12 (s, 18 H, 6ϫ CH3) ppm. 13C NMR
(75 MHz, CDCl3, CCl4): δ = 137.9 (ArqC), 128.9 (ArC), 128.5
(ArC), 128.4 (ArC), 89.8 (C-4), 85.9 (C-6), 85.1 (C-3), 76.1 (C-7),
73.8 (C-2), 73.6 (C-8), 73.4 (CH2Ph), 72.4 (C-1), 71.8 (C-5), 19.1 [6
C, {CH(CH3)2}3], 11.7 {3 C, [CH(CH3)2]3} ppm. IR (neat): 3443,
3021, 2358, 1645, 1520, 1216, 1043, 927, 760. Mass (ESI-MS): m/z
398; found 416 [M + NH4]+. HRMS (EI): calcd. for C24H34O3Si
[M]+: 398.2277; found 398.2291.
(iv) Preparation of Bromoalkyne 38 from 1,1-Dibromoalkene 21: To
a stirred solution of 1,1-dibromoalkene 21 (25 mg, 0.06 mmol) in
of DMF (2 mL) was added TBAF·3H2O (104 mg, 0.33 mmol). The
reaction mixture was heated at 60 °C for 2h. After that it was co-
oled to room temperature. To this a saturated ammonium chloride
solution was added and extracted with diethyl ether (3ϫ5 mL).
The combined organic layers were dried with Na2SO4, and concen-
trated under reduced pressure. The residue was purified by column
chromatography to give the 1-bromoalkyne 38 in 80% yield
(16 mg).
Compound 38: Semisolid, 60 mg, 88% yield. [α]2D5 = –105.8 (c =
0.46, CHCl3); eluent for column chromatography n-hexane/ethyl
acetate, 22:3; Rf = 0.60 (n-hexane/ethyl acetate, 1:1). 1H NMR
(300 MHz, CDCl3, CCl4): δ = 7.30–7.38 (m, 5 H, ArH); 4.80 (d, J
= 4.7 Hz, 1 H, 3-H), 4.76 (d, J = 11.8 Hz, 1 H, CH2Ph), 4.59 (d, J
= 11.8 Hz, 1 H, CH2Ph), 4.34 (br. s, 1 H, 5-H), 4.17 (dd, J = 4.6,
9.6 Hz, 1 H, 6b-H), 3.90 (dd, J = 2.3, 4.4 Hz, 1 H, 4-H), 3.68 (dd,
J = 1.7, 9.7 Hz, 1 H, 6a-H) ppm. 13C NMR (75 MHz, CDCl3,
CCl4): δ = 137.9 (ArqC), 128.9 (ArC), 128.4 (ArC), 128.3 (ArC),
85.7 (C-4), 76.1 (C-2), 75.9 (C-5), 73.5 (C-6), 73.3 (CH2Ph), 72.1
Compound 41: Oil, 68 mg, 81% yield. [α]2D5 = –41.6 (c = 0.40,
CHCl3); eluent for column chromatography n-hexane/ethyl acetate,
1
23:2; Rf = 0.62 (n-hexane/ethyl acetate, 1:1). H NMR (300 MHz,
CDCl3, CCl4): δ = 7.32–7.44 (m, 5 H, ArH), 4.88 (d, J = 4.8 Hz,
5-H), 4.79 (d, J = 11.7 Hz, 1 H, CH2Ph), 4.66 (d, J = 11.7 Hz, 1
H, CH2Ph), 4.39–4.41 (m, 1 H, 7-H), 4.20 (dd, J = 4.7, 9.8 Hz, 1
H, 8b-H), 3.97 (qt, J = 2.4 Hz, 1 H, 6-H), 3.73 (dd, J = 2.1, 9.8 Hz,
1 H, 8a-H), 1.03 (t, 9 H, 3ϫ CH2CH3), 0.65 (qt, J = 7.8 Hz, 6 H,
3ϫ CH2CH3) ppm. 13C NMR (50 MHz, CDCl3, CCl4): δ = 137.8
(ArqC), 128.9 (ArC), 128.5 (ArC), 128.4 (ArC), 88.8 (C-4), 86.3
(C-3), 85.8 (C-6), 76.0 (C-7), 73.8 (C-2), 73.6 (C-8), 73.4 (CH2Ph),
72.7 (C-1), 71.8 (C-5), 7.7 (3 C, 3ϫ CH2CH3), 4.6 (3 C, 3ϫ
CH CH ) ppm. IR (neat): ν = 3409, 2957, 2924, 2364, 2103, 1633,
˜
2
3
1460, 1219, 1014, 760 cm–1. Mass (ESI-MS): m/z 356; found 341
[M – CH3]+. DART-HRMS: calcd. for C21H28O3Si [M]+: 356.1807;
found 356.18264.
Compound 43: Oil, 68 mg, 70% yield, [α]2D5 = –116.9 (c = 0.40,
CHCl3); eluent for column chromatography n-hexane/ethyl acetate,
23:2; Rf = 0.5 (n-hexane/ethyl acetate, 1:1). 1H NMR (200 MHz,
CDCl3, CCl4): δ = 7.31–7.40 (m, 5 H, ArH), 4.85 (d, J = 4.7 Hz,
7-H), 4.76 (d, J = 11.9 Hz, CH2Ph), 4.64 (d, J = 11.9 Hz, CH2Ph),
4.35–4.39 (m, 1 H, 9-H), 4.18 (dd, J = 4.6, 9.8 Hz, 1 H, 10b-H),
3.95 (qt, J = 2.3 Hz, 1 H, 8-H), 3.72 (dd, J = 1.9, 9.8 Hz, 1 H, 10a-
H), 1.26 {3 H, [CH(CH3)2]3}, 1.09 (s, 18 H, 6ϫ CH3) ppm. 13C
(C-3), 48.4 (C-1) ppm. IR (neat): ν = 3449, 3020, 2928, 2361, 1216,
˜
1053, 760. Mass (ESI-MS): m/z 296; found 296 [M]+. HRMS (EI):
calcd. for C13H12BrO3 [M – H]+: 294.9970; found 294.9969.
(v) General Procedure for the Cross Coupling of Bromoalkyne with
(Trialkylsilyl)alkynes: To a degassed solution of bromoalkyne 38
(0.23 mmol, 1 equiv.), (trialkylsilyl)alkyne (0.29 mmol, 1.3 equiv.),
Pd(PPh3)2Cl2 (0.023 mmol, 0.1 equiv.) and CuI (0.023 mmol, NMR (75 MHz, CDCl3, CCl4): δ = 137.7 (ArqC), 128.9 (ArC),
0.1 equiv.) in tetrahydrofuran (5 mL) was added Et3N (0.46 mmol,
2 equiv.) in the presence of H2 atmosphere (balloon). The reaction
mixture was stirred for 1.5–2 h at room temperature and then
quenched with saturated NH4Cl solution and extracted with diethyl
ether (3ϫ5 mL). The combined organic layers were dried with
128.5 (ArC), 128.3 (ArC), 89.9 (C-6), 85.9 (C-5), 85.8 (C-8), 75.9
(C-9), 73.7 (2 C, C-10, C-4), 73.4 (CH2Ph), 73.3 (C-3), 71.8 (C-7),
64.7 (C-2), 60.6 (C-1), 18.9 {6 C, [CH(CH3)2]3}, 11.6 {3 C,
[CH(CH ) ] } ppm. IR (neat): ν = 3417, 3021, 2946, 2359, 1728,
˜
3 2 3
1521, 1216, 1045, 928, 760 cm–1. Mass (ESI-MS): m/z 422; found
1582
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© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 1575–1586

Tetrahydrofuran-Based Highly O-Functionalized Alkynes
405 [M – OH]+. HRMS (EI): calcd. for C26H34O3Si [M]+: 422.2277;
found 422.2285.
sponding TIPS- or TES-alkyne (0.16 mmol, 1 equiv.) in pyridine/
ether (3:1) was added a solution of TBAF (0.19 mmol, 1.2 equiv.,
1.0 m solution in THF) at room temperature. The blue solution
became emerald green once addition began. After complete ad-
dition, the reaction mixture was stirred for 2 h. The solution was
poured into ether and HCl (1 m). The organic phase was washed
excessively with HCl (1 m) until all pyridine was removed and then
organic phase was dried with Na2SO4 and concentrated. The crude
was purified by column chromatography to yield the pure dimer
product.
Compound 44: Oil, 66 mg, 75% yield. [α]2D5 = –41.6 (c = 0.40,
CHCl3); eluent for column chromatography n-hexane/ethyl acetate,
1
23:2; Rf = 0.62 (n-hexane/ethyl acetate, 1:1). H NMR (300 MHz,
CDCl3, CCl4): δ = 7.33–7.41 (m, 5 H, ArH), 4.87 (d, J = 4.7 Hz,
5-H), 4.77 (d, J = 11.9 Hz, CH2Ph), 4.66 (d, J = 11.9 Hz, CH2Ph),
4.38–4.39 (m, 1 H, 7-H), 4.20 (dd, J = 4.6, 9.8 Hz, 1 H, 8b-H),
3.95–3.98 (m, 1 H, 6-H), 3.73 (d, J = 9.0 Hz, 1 H, 8a-H), 1.02 (t,
J = 7.9 Hz, 9 H, 3ϫ CH3), 0.66 (qt, J = 7.8 Hz, 6 H, 3ϫ CH2)
ppm. 13C NMR (50 MHz, CDCl3, CCl4): δ = 137.7 (ArqC), 128.9
(ArC), 128.5 (ArC), 128.4 (ArC), 89.2 (C-6), 86.6 (C-5), 85.8 (C-
8), 75.9 (C-9), 73.9 (C-4), 73.8 (C-10, CH2), 73.4 (CH2Ph), 73.3 (C-
3), 71.8 (C-5), 64.4 (C-2), 60.9 (C-1), 7.7 (3 C, 3ϫ CH2CH3), 4.5
(vii) Desilylation and Dimerization of 41: To a stirred solution of
TES-diyne 41 (57 mg, 0.16 mmol, 1 equiv.) in tetrahydrofuran at
0 °C was added TBAF (0.19 mmol, 1.2 equiv., 1.0 m solution in
THF) slowly by a syringe. After five min, reaction mixture was
diluted with saturated ammonium chloride solution and extracted
with diethyl ether (3ϫ10 mL). The combined organic layers were
dried with Na2SO4, concentrated to obtain the crude product 46.
To this crude compound 46 in DMF was added CuI (0.05 equiv.)
and the resulting mixture was stirred for 24 h. The reaction mixture
was diluted with saturated ammonium chloride solution and ex-
tracted with diethyl ether (3ϫ5 mL). The combined organic layers
dried with anhydrous Na2SO4 and concentrated under reduced
pressure. The residue was purified by column chromatography to
give tetrayne product 47 (27 mg) in 70% yield.
(3 C, 3ϫ CH CH ) ppm. IR (neat): ν = 3449, 2926, 2368, 2103,
˜
2
3
1710, 1636, 1460, 1217, 1103, 1014, 761 cm–1. Mass (ESI-MS): m/z
380; found 351 [M – C2H5]+; DART-HRMS: calcd. for C23H29O3Si
[M + H]+: 381.1886; found 381.1880.
Compounds 45 and 33: Oil, 41 mg, 57% yield, eluent for column
chromatography chloroform/methanol, 99:1; Rf = 0.28 (n-hexane/
ethyl acetate, 1:1). 1H NMR (300 MHz, CDCl3): δ = 7.29–7.38 (m,
10 H), 4.87 (d, J = 4.6 Hz, 2 H), 4.62–4.79 (m, 4 H), 4.37 (br. s, 2
H), 4.19 (dd, J = 4.5, 9.8 Hz, 2 H), 3.94–3.97 (m, 2 H), 3.71–3.74
(m, 2 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 137.7 (ArqC);
137.6 (ArqC), 129.0 (ArC), 128.9 (ArC), 128.5 (ArC), 128.4 (ArC),
128.3 (ArC), 85.7 (C-5, C-5Ј of compound 45), 85.6 (C-4, C-4Ј of
compound 33), 75.9 (C-5, C-5Ј of compound 33), 75.8 (C-6, C-6Ј
of compound 45), 75.3 (C-2, C-2Ј of compound 33), 74.5 (qC of
compound 45), 73.8 (C-7, C-7Ј of compound 45), 73.6 (C-6, C-6Ј
of compound 33), 73.4 (CH2Ph of compound 45), 73.3 (CH2Ph
of compound 33), 73.1 (qC of compound 45), 72.5 (C-1, C-1Ј of
compound 33), 71.9 (C-4, C-4Ј of compound 45), 71.7 (C-3, C-3Ј
Compound 47: Semisolid, 27 mg, 70% yield. [α]2D9 = –410 (c = 0.16,
CHCl3), eluent for column chromatography chloroform/methanol,
1
99:1; Rf = 0.21 (n-hexane/ethyl acetate, 1:1). H NMR (300 MHz,
CDCl3): δ = 7.29–7.38 (m, 10 H, ArH), 4.87 (d, J = 4.5 Hz, 2 H,
5-H, 5Ј-H), 4.74 (d, J = 11.8 Hz, 2 H, CH2Ph), 4.65 (d, J = 11.8 Hz,
2 H, CH2Ph), 4.37 (br. s, 2 H, 7-H, 7Ј-H), 4.18 (dd, J = 4.4, 9.7 Hz,
2 H, 8b-H, 8Јb-H), 3.97 (d, J = 2.4 Hz, 2 H, 6-H, 6Ј-H), 3.73 (d, J
= 9.4 Hz, 2 H, 8a-H, 8Јa-H) ppm. 13C NMR (75 MHz, CDCl3): δ
= 137.6 (ArqC), 128.9 (ArC), 128.5 (ArC), 128.4 (ArC), 85.9 (C-6,
C-6Ј), 75.9 (C-7, C-7Ј), 74.7 (qC), 73.9 (C-8, C-8Ј), 73.5 (CH2Ph),
of compound 33), 63.4 (qC of compound 45) ppm. IR (neat): ν =
˜
3423, 2924, 2369, 2103, 1716, 1594, 1268, 1103, 1016, 753. DART-
HRMS: calcd. for C28H26O6 [M]+: 458.1729; found 458.1711.
73.2 (qC), 71.9 (C-5, C-5Ј), 64.4 (qC), 62.3 (qC) ppm. IR (neat): ν =
˜
3423, 2924, 2369, 2103, 1716, 1594, 1268, 1103, 1016, 753. DART-
HRMS: calcd. for C30H26NaO6 [M + Na]+: 505.16271; found
505.1636.
(vi) General Procedure for the Desilylative Bromination of Trialkyl-
silyl-1,3-butadiynes: To a stirred solution of trialkylsilyl-substituted
1,3-butadiynes (0.17 mmol, 1 equiv.) in acetonitrile (5 mL) taken in
a round-bottomed flask covered with a carbon paper were added
NBS (0.21 mmol, 1.2 equiv.) and AgF (0.21 mmol, 1.2 equiv.). The
reaction mixture was stirred at room temperature for 1.5 h, and
then filtered through a pad of celite. The filtrate was diluted with
diethyl ether, washed with water; the combined organic layers were
dried with Na2SO4 and concentrated under reduced pressure to
give residue which was purified by silica gel column chromatog-
raphy to give pure bromodiyne product. 43 mg from 40 and 43 mg
from 41.
(viii) Desilylation and Dimerization of 43: To a stirred solution of
TIPS triyne 43 (50 mg, 0.11, 0.1 mmol, 1 equiv.) in THF at –78 °C
was added TBAF (0.13 mL, 0.13 mmol, 1.2 equiv., 1.0 m solution
in THF) slowly by syringe. After five min reaction mixture was
diluted with saturated ammonium chloride solution and extracted
with diethyl ether. To the organic layer was added 3 mL of dry
DMF and the resulting solution was concentrated at low tempera-
ture (at 10 °C) to evaporate diethyl ether only leaving the reaction
mixture in DMF. To this crude compound in DMF was added CuI
(1.01 mg, 0.005 mmol, 0.05 equiv.) and stirred for 24 h. The reac-
tion mixture was diluted with saturated ammonium chloride solu-
tion and extracted with diethyl ether (3ϫ5 mL). The combined
organic layers dried with anhydrous Na2SO4 and concentrated un-
der reduced pressure. The residue was purified by column
chromatography to give hexayne product 19 mg in 60% yield.
Compound 42: Oil, 76% yield. [α]2D5 = –191.1 (c = 0.5, CHCl3);
eluent for column chromatography n-hexane/ethyl acetate, 22:3; Rf
1
= 0.42 (n-hexane/ethyl acetate, 1:1). H NMR (300 MHz, CDCl3,
CCl4): δ = 7.34–7.37 (m, 5 H, ArH), 4.75–4.82 (m, 3 H,CH2Ph, 5-
H), 4.65 (d, J = 11.8 Hz, 1 H, CH2Ph), 4.34 (br. s, 1 H, 7-H), 4.15–
4.19 (m, 1 H, 8b-H), 3.92–3.93 (m, 1 H, 6-H), 3.69 (d, J = 9.7 Hz,
1 H, 8a-H) ppm. 13C NMR (75 MHz, CDCl3, CCl4): δ = 137.9
(ArqC), 128.9 (ArC), 128.5 (ArC), 128.4 (ArC), 85.9 (C-6), 76.1
(C-7), 73.6 (C-8), 73.4 (2 C, C-4, CH2Ph), 71.6 (C-5), 71.1 (C-3),
Compound 49: Solid, m.p. 158–160 °C (dec.); 19 mg, 60% yield.
[α]2D9 = –277 (c = 0.05, CHCl3); eluent for column chromatography
chloroform/methanol, 99:1; Rf = 0.22 (n-hexane/ethyl acetate, 1:1).
1H NMR (300 MHz, CDCl3, CD3OD): δ = 7.23–7.30 (m, 10 H,
ArH), 4.78 (d, J = 4.5 Hz, 2 H, 7-H, 7Ј-H), 4.64 (d, J = 11.8 Hz,
2 H, CH2Ph), 4.59 (d, J = 11.9 Hz, 2 H, CH2Ph), 4.24–4.25 (m, 2
H, 9-H, 9Ј-H), 4.07 (dd, J = 4.3, 9.6 Hz, 2 H, 10b-H, 10Јb-H),
3.87–3.89 (m, 2 H, 8-H, 8Ј-H), 3.64 (dd, J = 1.3, 9.6 Hz, 2 H, 10a-
H, 10Јa-H) ppm. 13C NMR (75 MHz, CDCl3): δ = 137.5 (ArqC),
65.7 (C-2), 42.1 (C-1) ppm. IR (neat): ν = 3441, 3021, 2359, 1520,
˜
1216, 1043, 928, 761 cm–1. Mass (ESI-MS): m/z 320; found 343 [M
+
23]+ and 345 [M +2 23]+; DART-HRMS: calcd. for
+
C15H14BrO3 [M + H]+: 321.01263; found 321.0128.
(vii) General Procedure for Desilylation/Oxidative Dimerization: To
a stirred solution of Cu(OAc)2 (0.48 mmol, 3 equiv.) and corre-
Eur. J. Org. Chem. 2011, 1575–1586
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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1583

P. V. Reddy, V. Bajpai, B. Kumar, A. K. Shaw
FULL PAPER
128.8 (ArC), 128.3 (ArC), 128.2 (ArC), 85.8 (C-8), 75.3 (qC), 74.9
(CH), 73.3 (CH2), 71.8 (CH), 70.1 (CH2), 67.5 (CH2), 62.8 (CH),
(C-9), 73.9 (C-10), 73.2 (CH2Ph), 72.6 (qC), 71.8 (C-7), 64.1 (qC), 27.2 (CH ), 25.8 (CH ) ppm. IR (neat): ν = 3455, 2924, 2363, 1639,
˜
3
3
63.2 (qC), 62.9 (qC), 62.1 (qC) ppm. IR (neat): ν = 3431, 3018,
1458, 1218, 1068, 765 cm–1. Mass (ESI-MS): m/z 561; found 562
[M + H]+; DART-HRMS: m/z: calcd. for C31H36N3O7 [M + H]+:
562.2553; found 562.2578.
˜
2925, 2367, 1721, 1629, 1459, 1217, 1098, 763 cm–1. ESI-MS: m/z
530; found 553 [M + Na]+.
(ix) General Procedure for the Synthesis of 1,2,3-Triazolyl-C-nucleo-
side Analogue 51: To a stirred solution of THF-alkyne(s) (50 mg
0.23 mmol, 1 equiv.) in tert-butyl alcohol (5 mL) was added THF
azide (73 mg, 0.23 mmol, 1 equiv.). The reaction was initiated by
the addition of a solution of CuSO4·5H2O (8.5 mg, 0.05 mmol,
0.2 equiv.) and sodium ascorbate (18 mg, 0.09 mmol, 0.4 equiv.) in
distilled water. The colour suspension formed was stirred at room
temperature. After the completion of reaction, ice-cold water was
added and the aqueous layer was extracted twice with CHCl3
(2ϫ10 mL). The combined organic extracts were dried with
Na2SO4, evaporated and purified by column chromatography to
afford pure enantiomerically pure 1,2,3-triazolyl-C-nucleoside ana-
logue 51 in 71% (87 mg).
(xi) Synthesis of 1,2,3-Triazolyl-C-nucleoside Analogue 53: To a
stirred solution of TIPS triyne 43 (50 mg, 0.12 mmol, 1 equiv.) in
THF at –78 °C was added TBAF (1.0 m solution in THF, 0.14 mL,
0.14 mmol, 1.2 equiv.) slowly by a syringe. After five min, reaction
mixture was diluted with saturated ammonium chloride solution
and extracted with diethyl ether (3ϫ10 mL). The combined or-
ganic layers were dried with Na2SO4. To the organic layer was
added 5 mL of tBuOH and the resulting solution was concentrated
at low temperature (at 10 °C) to evaporate diethyl ether only leaving
the crude intermediate 48 in tBuOH alcohol. To this crude com-
pound 48 in tBuOH (5 mL) was added THF azide 50 (38 mg,
0.12 mmol, 1 equiv.). The reaction was initiated by the addition
of a solution of CuSO4·5H2O (4.4 mg, 0.02 mmol, 0.2 equiv.) and
sodium ascorbate (10 mg, 0.05 mmol, 0.4 equiv.) in distilled water.
Afterward, the colour suspension was stirred at room temperature.
On completion of the reaction, ice-cold water was added and the
aqueous layer was extracted twice with CHCl3 (2ϫ10 mL). The
combined organic extracts were dried with Na2SO4, evaporated and
purified by column chromatography to afford pure enantiomer-
ically pure 1,2,3-triazolyl-C-nucleoside analogue 53 in 50% (35 mg)
yield.
Compound 51: Oil, 87 mg, 71% yield. [α]2D8 = +16.2 (c = 0.10,
CHCl3); eluent for column chromatography chloroform/methanol,
1
49:1; Rf = 0.27 (n-hexane/ethyl acetate, 2:3). H NMR (200 MHz,
CDCl3): δ = 7.80 (s, 1 H), 7.22 (br. s, 6 H), 7.06 (br. s, 4 H), 5.45
(br. s, 2 H), 4.47 (s, 1 H), 3.79–4.39 (m, 15 H), 1.43 (s, 3 H), 1.36
(s, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 147.7 (qC of tri-
azole), 138.0 (ArqC), 137.4 (ArC), 128.9 (ArC), 128.7 (ArC), 128.7
(ArC), 128.4 (ArC), 128.2 (ArC), 128.1 (ArC), 124.0 (CH of tri-
azole), 109.6 (qC), 85.6 (CH), 83.7 (CH), 78.9 (CH), 76.7 (CH),
75.9 (CH), 74.4 (CH2), 74.3 (CH2), 73.6 (CH), 72.8 (CH2), 69.9
(CH2), 67.5 (CH2), 62.6 (1 C), 27.2 (CH3), 25.8 (CH3) ppm. IR
Compound 53: Oil, 35 mg, 50% yield. [α]2D9 = –34.9 (c = 0.30,
CHCl3); eluent for column chromatography chloroform/methanol,
1
87:3; Rf = 0.30 (n-hexane/ethyl acetate, 2:3). H NMR (300 MHz,
(neat): ν = 3420, 3205, 2930, 2883, 2364, 1708, 1653, 1456, 1222,
˜
1044, 743 cm–1. Mass (ESI-MS) m/z 537; found 538 [M + H]+,
560 [M + Na]+; DART-HRMS: calcd. for C29H36N3O7 [M + H]+:
538.2553; found 538.2536.
CDCl3): δ = 7.82 (s, 1 H, triazolyl H), 7.28–7.45 (m, 8 H, ArH),
7.06–7.09 (m, 2 H, ArH), 5.51–5.54 (m, 1 H), 4.96 (d, J = 4.6 Hz,
1 H), 4.82 (d, J = 11.9 Hz, 1 H), 4.70 (d, J = 11.9 Hz, 1 H), 4.34–
4.50 (m, 4 H), 4.18–4.27 (m, 2 H), 4.06–4.15 (m, 3 H), 3.97–4.03
(m, 3 H), 3.77 (dd, J = 1.8, 9.8 Hz, 1 H), 1.46 (s, 3 H, CH3), 1.41
(s, 3 H, CH3) ppm. 13C NMR (75 MHz, CDCl3): δ = 137.8 (ArqC),
136.7 (ArqC), 130.1 (qC of triazole), 128.9 (ArC), 128.7 (ArC),
128.6 (ArC), 128.4 (CH of triazole), 128.3 (ArC), 109.7 (qC), 85.7
(CH), 83.7 (CH), 79.6 (qC), 78.6 (CH), 77.5 (qC), 75.8 (CH), 74.8
(CH2), 73.8 (CH2), 73.3 (CH2), 73.3 (CH), 72.3 (qC), 71.9 (CH),
70.0 (CH2), 67.6 (qC), 67.4 (CH2), 62.8 (CH), 27.2 (CH3), 25.7
(x) Synthesis of 1,2,3-Triazolyl-C-nucleoside Analogue 52: To a
stirred solution of TIPS-diyne 40 (50 mg, 0.14 mmol, 1 equiv.) in
THF at 0 °C was added TBAF (0.17 mL, 0.17 mmol, 1.2 equiv.,
1.0 m solution in THF) slowly by a syringe. After five min, reaction
mixture was diluted with saturated ammonium chloride solution
and extracted with diethyl ether (3ϫ10 mL). The combined or-
ganic layers were dried with Na2SO4, concentrated to obtain the
crude intermediate 46. To this intermediate 46 in tBuOH (5 mL)
was added THF azide 50 (30 mg, 0.14 mmol, 1 equiv.) and the re-
sulting reaction mixture was stirred with a solution of CuSO4·5H2O
(5.0 mg, 0.028 mmol, 0.2 equiv.) and sodium ascorbate (12 mg,
0.06 mmol, 0.4 equiv.) in distilled water. The stirring of the colour
suspension was continued at room temperature. After the comple-
tion of reaction, ice-cold water was added and the aqueous layer
was extracted twice with CHCl3 (2ϫ10 mL). The combined or-
ganic extracts were dried with Na2SO4, evaporated and purified by
column chromatography to afford pure enantiomerically pure
1,2,3-triazolyl-C-nucleoside analogue 52 in 52% (37 mg) yield.
(CH ) ppm. IR (neat): ν = 3430, 3020, 2925, 2360, 1600, 1456,
˜
3
1376, 1216 cm–1. Mass (ESI-MS) m/z 585; found 586 [M + H]+.
HRMS (EI): m/z: calcd. for C33H35N3O7 [M]+: 585.2475; found
585.2449.
Supporting Information (see footnote on the first page of this arti-
cle): General procedure for the preparations of chlorovinyl com-
pounds, alkynes from chlorovinyl compounds, 1,1-dibromo-1-al-
kenes, alkynes from dibromoalkenes, experimental data for com-
pounds 5–8, 28, 29, 9, 11–24, 30, 31, Table S1, Table S2, Table S3,
1
Scheme S1, H and 13C NMR spectra for all the new compounds.
Compound 52: Oil, 37 mg, 52% yield. [α]3D0 = –19.3 (c = 0.20,
CHCl3); eluent for column chromatography chloroform/methanol,
49:1;Rf = 0.29 (n-hexane/ethyl acetate, 2:3). 1H NMR (300 MHz,
CDCl3): δ = 7.69 (s, 1 H), 7.26–7.41 (m, 8 H, ArH), 7.06–7.09 (m,
2 H, ArH), 5.47–5.54 (m, 1 H), 5.07 (d, J = 4.5 Hz, 1 H), 4.84 (d,
Acknowledgments
We are thankful to Sophisticated Analytical Facility Instrument
J = 12.0 Hz, 1 H), 4.71 (d, J = 12.0 Hz, 1 H), 4.26–4.47 (m, 5 H), (SAIF), Central Drug Research Institute (CDRI) for providing
3.97–4.21 (m, 7 H), 3.79 (dd, J = 1.9, 9.8 Hz, 1 H), 1.46 (s, 3 H),
spectroscopic data, Mr. A. K. Pandey for technical assistance and
1.41 (s, 3 H) ppm. 13C NMR (50 MHz, CDCl3): δ = 138.1 (ArqC), referees for their valuable suggestions. P. V. Reddy and V. Bajpai
136.9 (ArqC), 130.9 (qC), 128.9 (ArC), 128.6 (ArC), 128.2 (ArC), thank the Council of Scientific and Industrial Research (CSIR),
127.3 (CH of triazole), 109.7 (qC), 88.7 (qC), 85.8 (CH), 83.8 (CH), India for financial support. The CDRI communication number is
78.6 (CH), 77.7 (qC), 76.2 (CH), 74.6 (CH2), 73.8 (CH2), 73.4
8001.
1584
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Tetrahydrofuran-Based Highly O-Functionalized Alkynes
[11]
C. Raminelli, M. H. G. Prechtl, L. S. Santos, M. N. Eberlin,
J. V. Comasseto, Organometallics 2004, 23, 3990–3996.
T. N. Hoheisel, H. Frauenrath, Org. Lett. 2008, 10, 4525–4528.
a) S. I. Diver, D. A. Clark, A. A. Kulkarni, Tetrahedron 2008,
64, 6909–6919; b) K. P. Kaliappan, V. Ravikumar, J. Org.
Chem. 2007, 72, 6116–6126; c) F. Dolhem, C. Lièvre, G. De-
mailly, J. Org. Chem. 2004, 69, 3400–3407; d) J. Tsuji (Ed.),
Transition Metal Reagents and Catalysts, John Wiley & Sons
Ltd., Chichester, UK, 2000.
[1]
a) H. A. Stefani, A. S. Guarezeminib, R. Cella, Tetrahedron
2010, 66,7871–7918; b) A. L. K. Shi Shun, R. R. Tykwinski,
Angew. Chem. Int. Ed. 2006, 45, 1034–1057; c) P. Siemsen,
R. C. Livingston, F. Diederich, Angew. Chem. Int. Ed. 2000,
39, 2632–2657; d) Z. Wang, S. Campagna, K. Yang, G. Xu,
M. E. Pierce, J. M. Fortunak, P. N. Confalone, J. Org. Chem.
2000, 65, 1889–1891; e) G. Schermann, T. Grösser, F. Hampel,
A. Hirsch, Chem. Eur. J. 1997, 3, 1105–1112; f) S. Patai (Ed.),
The Chemistry of Carbon-Carbon Triple Bond, Wiley, New
York, 1978.
[12]
[13]
[14]
a) M. M. Haley, Pure Appl. Chem. 2008, 80, 519–532; b) Y.
Morisaki, T. Luu, R. R. Tykwinski, Org. Lett. 2006, 8, 689–
692; c) J. A. Marsden, M. M. Haley, J. Org. Chem. 2005, 70,
10213–10226; d) S. Eisler, A. D. Slepkov, E. Elliott, T. Luu, R.
McDonald, F. A. Hegmann, R. R. Tykwinski, J. Am. Chem.
Soc. 2005, 127, 2666–2676; e) M. B. Nielsen, F. Diederich,
Chem. Rec. 2002, 2, 189–198; f) F. Diederich, Chem. Commun.
2001, 219–227; g) S. Eisler, R. R. Tykwinski, J. Am. Chem. Soc.
2000, 122, 10736–10737.
[2]
[3]
E. J. Corey, P. L. Fuchs, Tetrahedron Lett. 1972, 13, 3769–3772.
a) T. Luu, Y. Morisaki, N. Cunningham, R. R. Tykwinski, J.
Org. Chem. 2007, 72, 9622–9629; b) H. Rezaei, S. Yamanoi, F.
Chemla, J. F. Normant, Org. Lett. 2000, 2, 419–421; c) S. Eisler,
N. Chahal, R. McDonald, R. R. Tykwinski, Chem. Eur. J.
2003, 9, 2542–2550.
[4]
[5]
a) H. B. Bang, S. Y. Han, D. H. Choi, J. W. Hwang, J.-G. Jun,
ARKIVOC 2009, 112–125; b) K. Miwa, T. Aoyama, T. Shioiri,
Synlett 1994, 107–108; c) E. W. Colvin, B. J. Hamill, J. Chem.
Soc. Perkin Trans. 1 1977, 869–874; d) E. W. Colvin, B. J. Ham-
ill, J. Chem. Soc., Chem. Commun. 1973, 151–152.
a) M. Okutani, Y. Mori, J. Org. Chem. 2009, 74, 442–444; b)
M. Beshai, B. Dhudshia, R. Mills, A. N. Thadani, Tetrahedron
Lett. 2008, 49, 6794–6796; c) M. Okutani, Y. Mori, Tetrahedron
Lett. 2007, 48, 6856–6859; d) M. A. Siddiqui, S. H. Hughes,
P. L. Boyer, H. Mitsuya, Q. N. Van, C. George, S. G. Sarafin-
anos, V. E. Marquez, J. Med. Chem. 2004, 47, 5041–5048.
a) D. Luvino, C. Amalric, M. Smietana, J.-J. Vasseur, Synlett
2007, 3037–3041; b) J. Pietruszka, A. Witt, Synthesis 2006,
4266–4268; c) E. Quesada, R. J. K. Taylor, Tetrahedron Lett.
2005, 46, 6473–6476; d) G. J. Roth, B. Liepold, S. G. Müller,
H. J. Bestmann, Synthesis 2004, 59–62; e) H. D. Dickson, S. C.
Smith, K. W. Hinkle, Tetrahedron Lett. 2004, 45, 5597–5599; f)
S. Müller, B. Liepold, G. J. Roth, H. J. Bestmann, Synlett 1996,
521–522; g) S. Ohira, Synth. Commun. 1989, 19, 561–564.
a) D. G. Brown, E. J. Velthuisen, J. R. Commerford, R. G. Bris-
bois, T. R. Hoye, J. Org. Chem. 1996, 61, 2540–2541; b) J. C.
Gilbert, U. Weerasooriya, J. Org. Chem. 1982, 47, 1837–1845;
c) D. Seyferth, R. S. Marmor, P. Hilbert, J. Org. Chem. 1971,
36, 1379–1386.
a) T. Bobula, M. Hocek, M. Kotora, Tetrahedron 2010, 66,
530–536; b) R. A. Youcef, M. D. Santos, S. Roussel, J.-P. Bal-
taze, N. Lubin-Germain, J. Uziel, J. Org. Chem. 2009, 74, 4318–
4323; c) K. P. Kaliappan, P. Kalanidhi, S. Mahapatra, Synlett
2009, 2162–2166; d) M. F. A. Adamo, R. Pergoli, Org. Lett.
2007, 9, 4443–4446; e) C. V. Ramana, A. G. Giri, S. B. Surya-
wanshi, R. G. Gonnade, Tetrahedron Lett. 2007, 48, 265–268;
f) Z. Miao, M. Xu, B. Hoffmann, B. Bernet, A. Vasella, Helv.
Chim. Acta 2005, 88,1885–1912; g) M. Takase, T. Morikawa,
H. Abe, M. Inouye, Org. Lett. 2003, 5, 625–628; h) P. Quayle,
S. Rahman, Tetrahedron Lett. 1995, 36, 8087–8088; i) R. R.
Bukownik, C. S. Wilcox, J. Org. Chem. 1988, 53, 463–471; j)
J. M. J. Tronchet, A.-P. Bonenfant, Helv. Chim. Acta 1981, 64,
1893–1901.
a) Y. Yu, G. A. Stephenson, D. Mitchell, Tetrahedron Lett.
2006, 47, 3811–3814; b) G. Altenhoff, S. Würtz, F. Glorius,
Tetrahedron Lett. 2006, 47, 2925–2928; c) E. Negishi, L. Anas-
tasia, Chem. Rev. 2003, 103, 1979–2017; d) K. Sonogashira, Y.
Tohda, N. Hahihara, Tetrahedron Lett. 1975, 16, 4467–4470.
a) S. M. E. Simpkins, M. D. Weller, L. R. Cox, Chem. Com-
mun. 2007, 4035–4037; b) L. de Quadras, E. B. Bauer, W. Mohr,
J. C. Bohling, T. B. Peters, J. M. Martin-Alvarez, F. Hampel,
J. A. Gladysz, J. Am. Chem. Soc. 2007, 129, 8296–8309; c) Q.
Zheng, J. C. Bohling, T. B. Peters, A. C. Frisch, F. Hampel,
J. A. Gladysz, Chem. Eur. J. 2006, 12, 6486–6505; d) T. Gibtner,
F. Hampel, J.-P. Gisselbrecht, A. Hirsch, Chem. Eur. J. 2002,
8, 408–432; e) A. S. Hay, J. Org. Chem. 1962, 27, 3320–3321; f)
A. S. Hay, J. Org. Chem. 1960, 25, 1275–1276.
[15]
[16]
G. Zeni, R. B. Panatieri, E. Lissner, P. H. Menezes, A. L.
Braga, H. A. Stefani, Org. Lett. 2001, 3, 819–821, and refer-
ences cited there in .
J. S. Kim, K. S. Im, J. H. Jung, Y.-L. Kim, J. Kim, C. J. Shim,
C.-O. Lee, Tetrahedron 1998, 54, 3151–3158.
A. Stütz, Angew. Chem. Int. Ed. Engl. 1987, 26, 320–328.
a) H. A. Stefani, I. M. Costa, G. Zeni, Tetrahedron Lett. 1999,
40, 9215–9217; b) G. Zheng, W. Lu, J. Cai, J. Nat. Prod. 1999,
62, 626–626, and references cited therein .
S. Kanokmedhakul, K. Kanokmedhakul, I. Kantikeaw, N.
Phonkerd, J. Nat. Prod. 2006, 69, 68–72.
[17]
[18]
[19]
[20]
[21]
[6]
N. Fusetani, T. Toyoda, N. Asai, S. Matsunaga, T. Maruyama,
J. Nat. Prod. 1996, 59, 796–797.
a) S. Morandi, F. Pellati, S. Benvenuti, F. Prati, Tetrahedron
2008, 64, 6324–6328; b) A. Ito, B. Cui, D. Chávez, H.-B. Chai,
Y. G. Shin, K. Kawanishi, L. B. S. Kardono, S. Riswan, N. R.
Farnsworth, G. A. Cordell, J. M. Pezzuto, A. D. Kinghorn, J.
Nat. Prod. 2001, 64, 246–248; c) H. Matsunaga, M. Katano,
H. Yamamoto, H. Fujito, M. Mori, K. Takata, Chem. Pharm.
Bull. 1990, 38, 3480–3482; d) Y. S. Kim, S. H. Jin, S. I. Kim,
D. R. Hahn, Arch. Pharmacol. Res. 1989, 12, 207–213.
a) L. M. Lerch, M. K. Harper, D. J. Faulkner, J. Nat. Prod.
2003, 66, 667–670; b) B. W. Gung, H. Dickson, Org. Lett. 2002,
4, 2517–2519; c) R. J. Marles, N. R. Farnsworth, D. A. Neill, J.
Nat. Prod. 1989, 52, 261–266.
[7]
[8]
[22]
[23]
[24]
S. Nakayama, Y. Uto, K. Tanimoto, Y. Okuno, Y. Sasaki, H.
Nagasawa, E. Nakata, K. Arai, K. Momose, T. Fujita, T.
Hashimoto, Y. Okamoto, Y. Asakawa, S. Goto, H. Hori, Bi-
oorg. Med. Chem. 2008, 16, 7705–7714.
a) P. F. H. Schwab, J. R. Smith, J. Michl, Chem. Rev. 2005, 105,
1197–1279; b) Y. Li, J. Zhang, W. Wang, O. Miao, X. She, X.
Pan, J. Org. Chem. 2005, 70, 3285–3287; c) J. A. Marsden, M. J.
O’Connor, M. M. Haley, Org. Lett. 2004, 6, 2385–2388; d)
V. W.-W. Yam, K. M.-C. Wong, N. Zhu, Angew. Chem. Int. Ed.
2003, 42, 1400–1403; e) M. M. Haley, M. L. Bell, S. C. Brand,
D. B. Kimhall, J. J. Pak, W. B. Wan, Tetrahedron Lett. 1997,
38, 7483–7486; f) M. M. Haley, M. L. Bell, J. J. English, C. A.
Johnson, T. J. R. Weakley, J. Am. Chem. Soc. 1997, 119, 2956–
2957; g) R. Boese, A. J. Matzger, K. P. C. Vollhardt, J. Am.
Chem. Soc. 1997, 119, 2052–2053.
[9]
[25]
[26]
a) J. Kendall, R. McDonald, M. J. Ferguson, R. R. Tykwinski,
Org. Lett. 2008, 10, 2163–2166; b) J. A. Marsden, M. M. Haley,
J. Org. Chem. 2005, 70, 10213–10226.
[10]
a) L. Gobbi, P. Seiler, F. Diederich, Helv. Chim. Acta 2001, 84,
743–777; b) L. Gobbi, P. Seiler, F. Diederich, Helv. Chim. Acta
2000, 83, 1711–1723; c) A. G. Fallis, Can. J. Chem. 1999, 77,
159–177; d) U. H. F. Bunz, Y. Rubin, Y. Tobe, Chem. Soc. Rev.
1999, 28, 107–119; e) Y. Rubin, T. C. Parker, S. J. Pastor, S.
Jalisatgi, C. Boulle, C. L. Wilkins, Angew. Chem. Int. Ed. 1998,
37, 1226–1229; f) Y. Tobe, N. Nakagawa, K. Naemura, T. Wak-
abayashi, T. Shida, Y. Achiba, J. Am. Chem. Soc. 1998, 120,
4544–4545; g) M. M. Haley, B. L. Langsdorf, Chem. Commun.
Eur. J. Org. Chem. 2011, 1575–1586
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
1585

P. V. Reddy, V. Bajpai, B. Kumar, A. K. Shaw
FULL PAPER
1997, 1121–1122; h) Y. Rubin, T. C. Parker, S. I. Khan, C. L.
Holliman, S. W. McElvany, J. Am. Chem. Soc. 1996, 118, 5308–
5309l.
[43] A. V. Subrahmanyam, K. Palanichamy, K. P. Kaliappan,
Chem. Eur. J. 2010, 16, 8545–8556.
[44] Y. Pan, T. L. Lowary, R. R. Tykwinski, Can. J. Chem. 2009,
87, 1565–1582.
[45] F. Sartillo-Piscil, M. Vargas, C. A. de Parrodi, L. Quintero, Tet-
rahedron Lett. 2003, 44, 3919–3921.
[46] a) F. Dolhem, C. Lièvre, G. Demailly, Tetrahedron Lett. 2002,
43, 1847–1849; b) P. Michel, D. Gennet, A. Rassat, Tetrahedron
Lett. 1999, 40, 8575–8578; c) P. Wolkoff, Can. J. Chem. 1975,
53, 1333–1335; d) N. B. Desai, N. Mc Kelvie, F. Ramirez, J.
Am. Chem. Soc. 1962, 84, 1745–1747.
[27]
a) W. Shi, Y. Luo, X. Luo, L. Chao, H. Zhang, J. Wang, A.
Lei, J. Am. Chem. Soc. 2008, 130, 14713–14720, and references
cited therein b) T. Luu, E. Elliott, A. D. Slepkov, S. Eisler, R.
McDonald, F. A. Hegmann, R. R. Tykwinski, Org. Lett. 2005,
7, 51–54; c) M. B. Nielsen, N. F. Utesch, N. N. P. Moonen, C.
Boudon, J.-P. Gisselbrecht, S. Concilio, S. P. Piotto, P. Seiler, P.
Günter, M. Gross, F. Diederich, Chem. Eur. J. 2002, 8, 3601–
3613.
[47] I. Vilotijevic, T. F. Jamison, Science 2007, 317, 1189–1192.
[48] S. Kim, S. Kim, T. Lee, H. Ko, D. Kim, Org. Lett. 2004, 6,
3601–3604.
[49] B. W. Gung, C. Gibeau, A. Jones, Tetrahedron: Asymmetry
2004, 15, 3973–3977.
[50] M. A. Heuft, S. K. Collins, G. P. A. Yap, A. G. Fallis, Org. Lett.
2001, 3, 2883–2886.
[28]
[29]
a) J. Y. Chang, J. H. Baik, C. B. Lee, M. J. Han, J. Am. Chem.
Soc. 1997, 119, 3197–3198; b) T. Kitamura, C. H. Lee, Y. Tani-
guchi, Y. Fujiwara, J. Am. Chem. Soc. 1997, 119, 619–620.
a) K. D. Ley, C. E. Whittle, M. D. Bartberger, K. S. Schanze, J.
Am. Chem. Soc. 1997, 119, 3423–3424; b) K. A. Bunten, A. K.
Kakkar, Macromolecules 1996, 29, 2885–2893; c) M. Takagi,
K. Kizu, Y. Miyazaki, T. Maruyama, K. Kubota, T. Yamam-
oto, Chem. Lett. 1993, 913–916.
a) G. T. Hwang, B. H. Kim, Org. Lett. 2004, 6, 2669–2672; b)
Z. Xu, M. Kahr, K. L. Walker, C. L. Wilkins, J. S. Moore, J.
Am. Chem. Soc. 1994, 116, 4537–4550.
a) C. Glaser, Ann. Chem. Pharm. 1870, 154, 137–171; b) C.
Glaser, Ber. Dtsch. Chem. Ges. 1869, 2, 422–424.
[51] T. Luu, R. McDonald, R. R. Tykwinski, Org. Lett. 2006, 8,
6035–6038.
[30]
ˇ
[52] J. Stambaský, M. Hocek, P. Kocovsky, Chem. Rev. 2009, 109,
6729–6764.
[53] J. G. Buchanan, R. H. Wightman, Top. Antibiot. Chem. 1982,
[31]
[32]
6, 229–339.
[54] K. S. Ramasamy, R. Bandaru, D. Averett, J. Org. Chem. 2000,
65, 5849–5851.
a) Y. Nishihara, K. Ikegashira, K. Hirabayashi, J.-i. Ando, A.
Mori, T. Hiyama, J. Org. Chem. 2000, 65, 1780–1787; b) K.
Ikegashira, Y. Nishihara, K. Hirabayashi, A. Mori, T. Hiyama,
[55] a) B. M. Trost, L. S. Kallander, J. Org. Chem. 1999, 64, 5427–
5435; b) A. M. Mubarak, D. M. Brown, Tetrahedron Lett.
1981, 22, 683–684.
Chem. Commun. 1997, 1039–1040; c) M. W. Paixao, M. Weber,
˜
A. L. Braga, J. B. de Azeredo, A. M. Deobald, H. A. Stefani,
[56] M. A. E. Shaban, A. Z. Nasr, Adv. Heterocycl. Chem. 1997, 68,
Tetrahedron Lett. 2008, 49, 2366–2370.
S. Adimurthy, C. C. Malakar, U. Beifuss, J. Org. Chem. 2009,
74, 5648–565.
a) J.-H. Li, Y. Liang, X.-D. Zhang, Tetrahedron 2005, 61, 1903–
1907; b) J.-H. Li, Y. Liang, Y.-X. Xie, J. Org. Chem. 2005, 70,
4393–4396.
223–432.
[33]
[34]
[57] a) C. Nájera, J. M. Sansano, Org. Biomol. Chem. 2009, 7, 4567–
4581; b) U. Pradere, V. Roy, T. R. McBrayer, R. F. Schinazi,
L. A. Agrofoglio, Tetrahedron 2008, 64, 9044–9051; c) R. Alva-
rez, S. Velázquez, A. San-Felix, S. Aquaro, E. De Clercq, C. F.
Perno, A. Karlsson, J. Balzarini, M. J. Camarasa, J. Med.
Chem. 1994, 37, 4185–4194; d) D. Häbich, W. Barth, M.
Räsner, Heterocycles 1989, 29, 2083–2088; e) R. Alonso, M. J.
Camarasa, G. Alonso, F. G. De las Heras, Eur. J. Med. Chem.
1980, 15, 105–109.
[35] A. Lei, M. Srivastava, X. Zhang, J. Org. Chem. 2002, 67, 1969–
1971.
[36] I. J. S. Fairlamb, P. S. Bäuerlein, L. R. Marrison, J. M. Dickin-
son, Chem. Commun. 2003, 632–633.
[37] D. Li, K. Yin, J. Li, X. Jai, Tetrahedron Lett. 2008, 49, 5918–
5919.
[58] D. Heinrich, T. Wagner, U. Diederichsen, Org. Lett. 2007, 9,
5311–5314.
[38] L. Li, J. Wang, G. Zhang, Q. Liu, Tetrahedron Lett. 2009, 50,
[59] a) M. A. E. Sallam, F. F. Luis, J. M. Cassady, Nucleosides Nu-
cleotides 1998, 17, 769–783; b) M. A. E. Sallam, E. I. A.
Hegazy, Carbohydr. Res. 1982, 102, 197–206; c) M. A. E. Sal-
lam, E. I. A. Hegazy, Carbohydr. Res. 1981, 95, 177–188.
[60] a) M. D. Best, Biochemistry 2009, 48, 6571–6584; b) M. Mel-
dal, C. W. Tornøe, Chem. Rev. 2008, 108, 2952–3015; c) V. V.
Rostovtsev, L. G. Green, V. V. Fokin, K. B. Sharpless, Angew.
Chem. Int. Ed. 2002, 41, 2596–2599; d) C. W. Tornøe, C. Chris-
tensen, M. Meldal, J. Org. Chem. 2002, 67, 3057–3064; e) H. C.
Kolb, M. G. Finn, K. B. Sharpless, Angew. Chem. Int. Ed.
2001, 40, 2004–2021; f) R. Huisgen, Pure Appl. Chem. 1989,
61, 613–628; g) R. Huisgen, G. Szeimies, L. Moebius, Chem.
Ber. 1967, 100, 2494–2507.
4033–4036.
[39] F. Nador, L. Fortunato, Y. Moglie, C. Vitale, G. Radivoy, Syn-
thesis 2009, 4027–4031.
[40] a) R. Sagar, L. V. R. Reddy, M. Saquib, B. Kumar, A. K. Shaw,
Tetrahedron: Asymmetry 2006, 17, 3294–3299; b) L. V. R.
Reddy, A. D. Roy, R. Roy, A. K. Shaw, Chem. Commun. 2006,
3444–3446.
[41] a) L. V. R. Reddy, G. N. Swamy, A. K. Shaw, Tetrahedron:
Asymmetry 2008, 19, 1372–1375; b) L. V. R. Reddy, P. V.
Reddy, A. K. Shaw, Tetrahedron: Asymmetry 2007, 18, 542–
546.
[42] a) P. Pal, B. Kumar, A. K. Shaw, Eur. J. Org. Chem. 2009, 2179–
2184; b) P. V. Reddy, L. V. R. Reddy, B. Kumar, R. Kumar,
P. R. Maulik, A. K. Shaw, Tetrahedron 2008, 64, 2153–2159.
Received: October 22, 2010
Published Online: January 31, 2011
1586
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 1575–1586