Elemental iodine-catalyzed coupling of alkynylsilanes with acid chlorides: A facile synthesis of α,β-acetylenic ketones

Article abstract of DOI:10.1055/s-2003-41014

Alkynylsilanes undergo coupling smoothly with acid chlorides in the presence of molecular iodine under mild reaction conditions to afford the corresponding α, β-acetylenic ketones in excellent yields in a short reaction time with high selectivity.

Full text of DOI:10.1055/s-2003-41014

1722
LETTER
Elemental Iodine-Catalyzed Coupling of Alkynylsilanes with Acid Chlorides:
A Facile Synthesis of a,b-Acetylenic Ketones
E
lemental
.
Iodine-Catal
S
yzedCoupling
.
of
A
lkynyl
Y
silanes adav,* B. V. S. Reddy, M. Sridhar Reddy
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad-500 007
Fax +91(40)27160512; E-mail: yadav@iict.ap.nic.in
Received 6 January 2003
Abstract: Alkynylsilanes undergo coupling smoothly with acid
chlorides in the presence of molecular iodine under mild reaction
conditions to afford the corresponding a,b-acetylenic ketones in ex-
cellent yields in a short reaction time with high selectivity.
Key words: alkynylsilanes, iodine, acid chlorides, a,b-acetylenic
ketones
Scheme 1
Thus, treatment of p-anisyl chloride with phenyl (trimeth-
ylsilyl)acetylene in the presence of 5 mol% of iodine at
ambient temperature led to the formation of 1-(4-meth-
oxyphenyl)-3-phenyl-2-propyn-1-one in 90% yield. In a
similar fashion, various acid chlorides reacted smoothly
with a range of alkynyltrimethylsilanes to give the corre-
sponding alkynyl ketones in excellent yields (Table 1). In
case of equimolar quantities of bis(trimethylsilyl)acety-
lene and acid chlorides, mono-ketoalkynes (entries l–n)
were obtained in high yields. However, the use of 2 equiv-
alents of acid chlorides and 1 equivalent of bis(trimethyl-
silyl)acetylene, 1,4-diketoalkynes were formed under
similar conditions (Scheme 2).
a,b-Acetylenic carbonyl compounds are important pre-
cursors for various heterocyclic compounds and impor-
tant frame-works in DNA cleaving agents.1 They are also
useful intermediates for the synthesis of nucleosides, non-
proteinogenic amino-acids, pheromones and drugs.2 They
are generally prepared by acylation of silver or copper(I)
acetylides with acid halides.3 Alternatively, they can also
be synthesized either by coupling of alkynylsilanes with
acid chlorides in the presence of aluminium chloride or by
coupling of acyl chlorides with (1-alkynyl)tributylstan-
nanes in the presence of palladium(II) or palladium(0)
complexes.4 Other methods include the oxidation of pro-
pargyl alcohols into the corresponding alkynyl ketones.5
However, many of these methods involve the use of heavy
metal salts or toxic tin compounds and expensive reagents
and also require high temperature reaction conditions.
Furthermore, some of these methods have limited synthet-
ic scope due to low conversions and the lack of selectivity
with other functionalities.6 Thus, there is still scope to de-
velop a simple, convenient and practical method for the
synthesis of alkynyl ketones using inexpensive and readi-
ly available reagents. Owing to its unique catalytic prop-
erties, iodine has been extensively used as a catalyst for a
plethora of organic transformations.7 However, there are
no examples of the coupling of alkynylsilanes with acid
halides using molecular iodine as the catalyst.
Scheme 2
In all cases, the reactions proceeded efficiently at room
temperature with high conversions. Dichloromethane is
the choice of solvent giving the best results. This method
is equally effective for the alkynylation of both aromatic
and aliphatic acid chlorides. All products were character-
ized by NMR, IR, and mass spectroscopy. However, in
the absence of catalyst, the reaction did not proceed even
after a long reaction time. In most cases the yields are ex-
cellent, some times quantitative, making this method a
useful synthetic protocol for the straightforward prepara-
tion of alkynylketones. There are several advantages in
the use of iodine as catalyst for this transformation, which
include high yields of products, cleaner reaction profiles,
short reaction times and easy availability of the catalyst at
low cost. In addition, the reaction conditions are amenable
to scale-up. Among various catalysts such as scandium
triflate, ytterbium triflate, cerium triflate and indium trif-
late employed for this transformation, molecular iodine
was found to be the most effective catalyst in terms of
yields and reaction rates. However, the products were
In continuation of our interest on the catalytic applications
of elemental iodine for various organic transformations,8
we report herein a mild and convenient method for the
synthesis of alkynyl ketones from alkynylsilanes and acid
halides using elemental iodine as an efficient catalyst
(Scheme 1).
Synlett 2003, No. 11, Print: 02 09 2003. Web: 11 08 2003.
Art Id.1437-2096,E;2003,0,11,1722,1724,ftx,en;D00303ST.pdf.
DOI: 10.1055/s-2003-41014
© Georg Thieme Verlag Stuttgart · New York

LETTER
Elemental Iodine-Catalyzed Coupling of Alkynylsilanes
1723
obtained in low to moderate yields (45–55%) when TMSI additives or stringent reaction conditions. The scope and
was employed as catalyst for this reaction. Since the reac- generality of this process is illustrated with respect to var-
tion also succeeded with TMSI, we assume that the reac- ious alkynylsilanes and a range of acid chlorides including
tion probably proceeds by a catalytic amount of TMSI t-butyl, alkyl, aryl and cyclopropyl derivatives and the re-
formed in situ by the interaction of molecular iodine with sults are presented in the Table 1.
alkynyl silanes. In addition, this method avoids the use of
either acidic or basic conditions and does not require any
Table 1 Iodine-Catalyzed Preparation of a,b-Acetylenic Ketones9
Entry
Alkynylsilane
1
Producta
3
Reaction Time
(min)
Yieldb (%)
90
a
30
b
c
“
“
“
35
45
35
89
87
89
d
e
f
30
45
50
40
88
90
87
89
“
“
g
h
i
“
35
45
90
87
j
k
l
30
20
25
85
81
83
m
“
Synlett 2003, No. 11, 1722–1724 © Thieme Stuttgart · New York

1724
J. S.Yadav et al.
LETTER
Table 1 Iodine-Catalyzed Preparation of a,b-Acetylenic Ketones9 (continued)
Entry
Alkynylsilane
1
Producta
3
Reaction Time
(min)
Yieldb (%)
n
“
25
79
87
o
“
60
p
“
70
90
a All products were characterized by 1H NMR, IR and mass spectroscopy.
b Isolated and unoptimized yields
(5) Maeda, Y.; Kakiuchi, N.; Matsumura, S.; Nishimura, T.;
Kawamura, T.; Uemura, S. J. Org. Chem. 2002, 67, 6718;
and references cited therein.
(6) (a) Schimdt, U.; Schwochau, M. Chem. Ber. 1964, 97, 1649.
(b) Tohda, Y.; Sonogashira, K.; Hagihara, N. Synthesis
1977, 777. (c) Birkofer, L.; Ritter, A.; Uhlenbrauck, H.
Chem. Ber. 1963, 96, 3280.
(7) (a) Deka, N.; Kalita, D. J.; Borah, R.; Sharma, J. C. J. Org.
Chem. 1997, 62, 1563. (b) Vaino, A. R.; Szarek, W. A.
Synlett 1995, 1157. (c) Lipshutz, B. H.; Keith, J.
Tetrahedron Lett. 1998, 39, 2495.
(8) (a) Yadav, J. S.; Reddy, B. V. S.; Hashim, S. R. J. Chem.
Soc., Perkin Trans. 1 2000, 3082. (b) Yadav, J. S.; Reddy,
B. V. S.; Sabitha, G.; Reddy, G. S. K. K. Synthesis 2000,
1532. (c) Kumar, H. M. S.; Reddy, B. V. S.; Reddy, E. J.;
Yadav, J. S. Chem. Lett. 1999, 857. (d) Yadav, J. S.; Reddy,
B. V. S.; Rao, C. V.; Chand, P. K.; Prasad, A. R. Synlett
2001, 1638.
In summary, this paper describes a simple, convenient and
efficient protocol for the synthesis of alkynylketones from
acid chlorides and alkynylsilanes using cheap and readily
available elemental iodine as the catalyst under extremely
mild reaction conditions. This method is effective for the
alkynylation of both aliphatic as well as aromatic acid
chlorides. In addition to its efficiency and operational
simplicity, this method provides high yields of products
within a short time, which makes it a useful and attractive
process for the synthesis of alkynylketones.
Acknowledgement
BVS and MSR thank CSIR, New Delhi for the award of the fel-
lowships.
(9) General procedure: To a stirred solution of the alkynylsilane
(1 mmol), and iodine (5 mol%) in dichloromethane (10 mL),
acyl chloride (1.2 mmol) was added slowly in a dropwise
manner at 0 °C and the mixture was allowed to stir at room
temperature for the appropriate time (Table 1). After
complete conversion as indicated by TLC, the reaction
mixture was quenched with water (15 mL) and extracted
with dichloromethane (2 × 15 mL). The combined extracts
were washed with 15% solution of sodium thiosulphate,
dried over anhydrous Na2SO4, and concentrated in vacuo.
The resulting product was purified by column
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Synlett 2003, No. 11, 1722–1724 © Thieme Stuttgart · New York