The first example of alkynylation of propargylic alcohols with alkynylsilanes catalyzed by molecular iodine

Article abstract of DOI:10.1016/j.tetlet.2008.01.017

Aryl propargyl alcohols undergo smooth alkynylation with alkynylsilanes in the presence of 10 mol % of iodine under mild and neutral conditions to produce 1,4-diynes in excellent yields with high selectivity. The use of readily available molecular iodine

Full text of DOI:10.1016/j.tetlet.2008.01.017

Available online at www.sciencedirect.com
Tetrahedron Letters 49 (2008) 2031–2033
The first example of alkynylation of propargylic alcohols
with alkynylsilanes catalyzed by molecular iodine
J. S. Yadav *, B. V. Subba Reddy, N. Thrimurtulu, N. Mallikarjuna Reddy, A. R. Prasad
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 29 October 2007; revised 19 December 2007; accepted 2 January 2008
Available online 8 January 2008
Abstract
Aryl propargyl alcohols undergo smooth alkynylation with alkynylsilanes in the presence of 10 mol % of iodine under mild and
neutral conditions to produce 1,4-diynes in excellent yields with high selectivity. The use of readily available molecular iodine makes
this method simple, convenient, cost-effective and practical.
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords: Aryl propargyl alcohols; Alkynylation; Molecular iodine; 1,4-Diynes
The stereoselective addition of allylsilanes to aldehydes,
referred to as the Sakurai–Hosomi reaction has been
recognized as an efficient method for carbon–carbon bond
formation and has been applied extensively in organic
synthesis, especially in natural products synthesis.1,2 Lewis
acid catalyzed carbon–carbon bond forming reactions are
of great significance in organic synthesis because of their
high reactivity, selectivity and mild reaction conditions.3
Aryl propargylic methanols are well-known carbon elec-
trophiles capable of reacting with various nucleophiles
and their ability to undergo nucleophilic substitution
reactions contributes largely to their synthetic value.4,5
However, there have been no reports on the direct nucleo-
philic substitution of aryl propargylic alcohols with
alkynyltrimethylsilane.
Molecular iodine has received considerable attention in
organic synthesis because of its high tolerance to air and
moisture, low-cost, nontoxic nature and ready availability,
affording the corresponding products with high selectivity
in excellent yields. The mild Lewis acidity associated with
iodine has led to its use in organic synthesis using catalytic
to stoichiometric amounts.6
In continuation of our interest on the use of molecular
iodine for various transformations,7 we herein report for
the first time, a direct and metal-free nucleophilic substitu-
tion of aryl propargyl alcohols with alkynylsilanes using
molecular iodine as a novel catalyst. As a preliminary
study, 1,3-diphenyl-2-propyn-1-ol (1) was treated with
phenyl(trimethylsilyl)acetylene (2) in the presence of
10 mol % of molecular iodine. The reaction went to com-
pletion at room temperature in 3 h and the product, 1,4-
diyne 3a was obtained in 96% yield (Scheme 1).
Other alkynylsilanes such as 1,4-bis(trimethylsilyl)-
butadiyne and bis(trimethylsilyl)acetylene also reacted well
with 1,3-diphenyl-2-propyn-1-ol under the influence of
molecular iodine (Table 1, entries b and c). The remarkable
catalytic activity of iodine provided the incentive for
further study of reactions with various other propargyl
alcohols. Aryl propargyl methanols such as 3-phenyl-1-
(thien-2-yl)prop-2-yn-1-ol, and 1-(2,5-dimethoxyphenyl)-
Ph
OH
10 mol % I2
Me3Si
Ph
+
Ph
Ph
CH2Cl2, r.t.
1
2
3a
*
Corresponding author. Tel.: +91 40 27193535; fax: +91 40 27160512.
Scheme 1. Preparation of product 3a.
E-mail address: yadavpub@iict.res.in (J. S. Yadav).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.01.017

2032
J. S. Yadav et al. / Tetrahedron Letters 49 (2008) 2031–2033
Table 1
Iodine-catalyzed alkynylation of propargylic alcohols
Entry
a
Propargyl alcoho
TMS–alkyne
Producta
Time (h)
3.0
Yieldb (%)
96
Ph
OH
TMS
TMS
Ph
Ph
Ph
Ph
Ph
Ph
OH
Ph
b
c
3.5
3.0
1.5
90
93
97
TMS
Ph
Ph
Ph
Ph
Ph
Ph
OH
TMS
TMS
TMS
Ph
Ph
Ph
Ph
Ph
OH
S
d
Ph
S
S
Ph
Ph
Ph
S
OH
Ph
e
f
TMS
TMS
TMS
2.0
3.0
2.0
96
95
93
TMS
Ph
S
S
OH
OH
Ph
TMS
Ph
S
Ph
Ph
S
MeO
OMe
OMe
Ph
g
Ph
MeO
Ph
MeO
OMe
MeO
OH
OMe
Ph
h
2.5
90
TMS
TMS
Ph
Ph
MeO
OMe
Ph
OH
OH
i
j
TMS
TMS
2.5
3.5
90
88
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
TMS
Ph
Ph
Ph
Ph
Ph
Ph
OH
Ph
k
TMS
TMS
3.0
4.0
90
80
TMS
Ph
Ph
Ph
Ph
OH
l
CH
Ph
Ph
H
a
All products were characterized by 1H NMR, IR and mass spectrometry.
Yield refers to pure products after chromatography.
b

J. S. Yadav et al. / Tetrahedron Letters 49 (2008) 2031–2033
2033
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Ph
OH
10 mol % I2
CH2Cl2, r.t.
3. Kobayashi, S. Eur. J. Org. Chem. 1999, 15–27.
TMS
Ph
+
Ph
4. (a) Nicholas, K. M.; Mulvaney, M.; Bayer, M. J. Am. Chem. Soc. 1980,
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8. General procedure: To a stirred solution of 3-phenyl-1-thien-2-ylprop-
2-yn-1-ol (1 mmol) and phenyl(trimethylsilyl)acetylene (1 mmol) in
dichloromethane (10 mL), iodine (10 mol %) was added at 0 °C and the
mixture was stirred for the appropriate time at this temperature. After
complete conversion as indicated by TLC, the reaction mixture was
quenched with water (10 mL) and extracted with dichloromethane
(3 Â 15 mL). The combined extracts were washed with a 15% solution
of aqueous sodium thiosulfate, dried over anhydrous Na2SO4 concen-
trated in vacuo and purified by column chromatography on silica
gel (Merck 60–120 mesh, ethyl acetate–hexane, 1:9) to afford pure
2-(3-phenyl-1-phenylethynylprop-2-ynyl)thiophene. Spectral data for
selected products:
Ph
3i
Scheme 2. Preparation of 3i.
3-phenylprop-2-yn-1-ol underwent smooth coupling with
alkynylsilanes to produce the corresponding 1,4-diynes in
excellent yields (Table 1, entries d–h). In addition, doubly
activated (E)-1,5-diphenyl-1-penten-4-yn-3-ol also under-
went facile nucleophilic substitution with alkynylsilanes
to furnish the respective 1,4-enediynes (Scheme 2, Table
1, entries i–l).
In all the cases, the reactions proceeded smoothly at
room temperature under the influence of 10 mol % of
iodine. This method is compatible with aryl alkyl ethers,
alkynes and alkenes present in the molecule. It should be
noted that alkynylation of all the substrates led exclusively
to the formation of propargylic products and no traces of
allenic side products were detected. As a solvent, dichloro-
methane gave the best results compared to THF, 1,4-diox-
ane and acetonitrile. All the products were characterized by
1H, 13C NMR, IR and mass spectrometry. The scope and
generality of this process are illustrated in Table 1.8
However, in the absence of iodine, the reaction did not
proceed even after a long reaction time. Interestingly, the
use of a catalytic amount of TMSI was found to be an
equally effective catalyst for this conversion. However,
the use of alkynyltri-n-butyltin in place of the alkynylsilane
did not yield the desired product under these reaction con-
ditions, perhaps because iodine does not interact with allyl-
tri-n-butyltin. Thus, the combination of allyltrimethylsilane
and iodine is a useful system for alkynylation of propargyl
alcohols.9 No additives or activators are required for the
activation of the –OH group. The advantages of this
method are the ready availability of alcohols and no salt
formation.
2-(1,5-Diphenylpenta-1,4-diyn-3-yl)thiophene (d): Liquid, IR (KBr): m
3063, 2922, 2853, 1734, 1632, 1441, 1233, 1073, 1031, 839, 755, 695,
.
599 cmÀ1 1H NMR (300 MHz, CDCl3,): d 7.60 (q, 2H, J = 1.6 Hz),
7.27–7.40 (m, 10H), 7.10 (t, 1H, J = 4.5 Hz), 5.80 (s, 1H). 13C NMR
(proton decoupled, 75 MHz, CDCl3): d 132.0, 131.7, 128.8, 128.6,
128.4, 127.1, 126.9, 126.6, 126.4, 125.8, 125.3, 100.1, 99.8, 52.5. EIMS:
m/z: (M+H+): 299. ESI-HRMS calcd for C13H9S (M+À101): 197.0424.
Found: 197.0419.
In summary, we have described a novel and an efficient
protocol for the alkynylation of aryl propargyl alcohols
using molecular iodine as the catalyst. In addition to its
efficiency, simplicity and mild reaction conditions, this
method provides excellent yields of 1,4-diynes with high
selectivity, which makes it a useful and attractive process
for the direct substitution of propargyl alcohols with
alkynylsilanes.
1,4-Dimethoxy-2-(1,5-diphenylpenta-1,4-diyn-3-yl)benzene (g): Liquid,
IR (KBr): m 2924, 2854, 1723, 1602, 1496, 1457, 1235, 1046, 751 cmÀ1
.
1H NMR (300 MHz, CDCl3): d 3.77 (s, 3H), 3.88 (s, 3H), 5.66 (s, 1H),
6.56 (s, 1H), 6.85–6.75 (m, 3H), 7.63–7.09 (m, 9H). 13C NMR (proton
decoupled, 75 MHz, CDCl3): d 127.7, 127.5, 127.1, 126.5, 123.5, 123.1,
122.8, 113.9, 112.8, 112.1, 57.7, 56.5, 55.6. ESIMS: m/z: (M+): 352.
ESI-HRMS calcd for C25H21O2 (M+H+): 353.0943. Found: 353.0931.
1,5-Diphenyl-3-(2-phenylethynyl)pent-1-ene-4-yne (i): Liquid, IR
(KBr): m 3023, 2923, 2854, 2167, 1630, 1485, 1440, 1283, 1096, 1026,
950, 855, 756, 694, 648, 610 cmÀ1. 1H NMR (300 MHz, CDCl3): d 5.20
(d, 1H, J = 9.8 Hz), 6.40–6.60 (m, 2H), 7.10–7.55 (m, 15H). 13C NMR
(proton decoupled, 75 MHz, CDCl3 + DMSO): d 167.1, 151.5, 99.0,
33.2, 30.5, 30.3, 28.3, 27.4, 23.7, 21.3, 12.9. EIMS m/z: (M+H+): 319.
ESI-HRMS calcd for C17H13 (M+À101): 217.1017. Found: 217.1018.
9. (a) Sakurai, H.; Sasaki, K.; Hosomi, A. Tetrahedron Lett. 1981, 22,
745–748; (b) Jung, M. E.; Blumenkopf, T. A. Tetrahedron Lett. 1978,
19, 3657–3660.
Acknowledgement
N.T. and N.M.R. thank CSIR, New Delhi, for the
award of the fellowships.
References and notes
1. (a) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207–2293; (b)
Marshall, J. A. CHEMTRACTS 1992, 5, 75–98.