Iodine as novel reagent for the 1,2-addition of trimethylsilyl cyanide to ketones including α,β-unsaturated ketones

Article abstract of DOI:10.1016/S0040-4039(02)02321-3

Molecular iodine is found to catalyze efficiently the addition of trimethylsilyl cyanide to a range of simple and functionalized ketones under very mild and convenient conditions to afford the corresponding cyanohydrin trimethylsilyl ethers in excellent y

Full text of DOI:10.1016/S0040-4039(02)02321-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 9703–9706
Iodine as novel reagent for the 1,2-addition of trimethylsilyl
cyanide to ketones including a,b-unsaturated ketones
J. S. Yadav,* B. V. S. Reddy, M. Sridhar Reddy and A. R. Prasad
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 9 August 2002; revised 2 October 2002; accepted 11 October 2002
Abstract—Molecular iodine is found to catalyze efficiently the addition of trimethylsilyl cyanide to a range of simple and
functionalized ketones under very mild and convenient conditions to afford the corresponding cyanohydrin trimethylsilyl ethers
in excellent yields in a short reaction period with high selectivity. a,b-Unsaturated ketones selectively afford the corresponding
1,2-adducts without the formation of 1,4-adducts under similar reaction conditions. © 2002 Elsevier Science Ltd. All rights
reserved.
a-Cyanohydrins or cyanohydrin trimethylsilyl ethers
are useful precursors for the synthesis of a-hydroxy-
acids, a-hydroxyaldehydes, b-aminoalcohols, a-
sterically hindered ketones. Thus, there is still a need to
develop a simple, convenient and efficient method for
the cyanation of both aliphatic and aromatic ketones
using inexpensive and readily available reagents. Owing
to its unique catalytic properties, iodine has been exten-
sively used as a catalyst for a plethora of organic
transformations. However, there are no examples of
the cyanation of ketones with trimethylsilyl cyanide
using molecular iodine as the catalyst.
1
cyanoketones and many other types of compounds.
They are generally prepared by the nucleophilic addi-
2
tion of cyanide to carbonyl compounds. Among vari-
ous cyanating agents such as potassium or sodium
cyanide and HCN, the use of trimethylsilyl cyanide is
safe and a more effective cyanide anion source for
nucleophilic addition to carbonyl compounds under
8
3
mild conditions. Generally, in the absence of a cata-
In continuation of our interest on the catalytic applica-
tions of elemental iodine for various organic transfor-
lyst, no reaction is observed between TMSCN and
carbonyl compounds. Consequently, several activators
or promoters both in stoichiometric and catalytic
amounts have been reported for the cyanation of car-
9
mations, we report herein a mild and convenient
method for the cyanation of both cyclic and acyclic
ketones with trimethylsilyl cyanide using elemental
iodine as an efficient catalyst (Scheme 1).
4,5
bonyl compounds with trimethylsilyl cyanide.
Recently, lanthanide triflates were also reported to be
efficient catalysts in promoting cyanation reactions of
6
The treatment of benzophenone with trimethylsilyl cya-
nide in the presence of 5 mol% of elemental iodine in
carbonyl compounds. However, only few methods
have been reported for the cyanation of substituted and
7
dichloromethane
afforded
the
corresponding
functionalized ketones. Furthermore, many of these
methods involve the use of expensive reagents, strongly
acidic conditions and extended reaction times. In addi-
tion, some of these methods are limited to simple
aliphatic ketones and are not applicable to aryl or
trimethylsilylated cyanohydrin in 93% yield. Similarly,
various ketones such as 2-phenyl-4-chromanone, ace-
tophenone, a-methylcyclohexanone, tetralone, 2-
acetylthiophene, and a-azido- and a-bromo-ketones
Scheme 1.
Keywords: ketones; trimethylsiyl cyanide; iodine; a-cyanohydrins.
*
Corresponding author. Fax: 91-40-7160512; e-mail: yadav@iict.ap.nic.in
0
040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02321-3

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J. S. Yada6 et al. / Tetrahedron Letters 43 (2002) 9703–9706
Table 1. Iodine-catalyzed preparation of cyanohydrin trimethylsilyl ethers

J. S. Yada6 et al. / Tetrahedron Letters 43 (2002) 9703–9706
9705
Scheme 2.
were converted efficiently to the corresponding a-cyano
2. (a) Kurtz, P. Ann. Chem. 1951, 23, 572; (b) Lapworth, A.
J. Chem. Soc. 1903, 83, 995; (c) Greenlee, W. J.;
Hangauer, D. G. Tetrahedron Lett. 1983, 24, 4559; (d)
Kawasaki, Y.; Fujii, A.; Nakano, Y.; Sakaguchi, S.; Ishii,
Y. J. Org. Chem. 1999, 64, 4214.
1
0
silyl ethers using this procedure. Enones such as 2- ben-
zylidenecyclohexanone, 2-benzylidenecyclopentanone, 2-
cyclohexen-1-one, benzylideneacetone, 4-phenyl-3-
buten-2-one also reacted smoothly with trimethylsilyl
cyanide in the presence of 5 mol% iodine to afford the
corresponding 1,2-adducts in excellent yields (Scheme 2).
3. (a) Groutas, W. C.; Felker, D. Synthesis 1980, 861; (b)
Fujii, A.; Sakaguchi, S.; Ishii, Y. J. Org. Chem. 2000, 65,
6
209.
In case of a,b-unsaturated ketones, no 1,4-adduct was
observed under these reaction conditions. In all cases, the
reactions proceeded efficiently at ambient temperatures
and were complete within 20–40 min. Dichloromethane
is the solvent of choice giving the best results. This method
is equally effective for the cyanation of both cyclic and
acyclic ketones. The scope and generality of this process
is illustrated with respect to various ketones including
alkyl, aryl, and a,b-unsaturated ketones and the results
are presented in Table 1. All products were characterized
4. (a) Matsubara, S.; Takai, T.; Utimoto, K. Chem. Lett.
1991, 1447; (b) Curini, M.; Epifanio, F.; Marcotullio, M.
C.; Rosati, O.; Rossi, M. Synlett 1999, 315.
5. (a) Gassman, P. G.; Talley, J. J. Tetrahedron Lett. 1978,
19, 3773; (b) Whitesell, J. K.; Apodaca, R. Tetrahedron
Lett. 1996, 37, 2525; (c) Jenner, G. Tetrahedron Lett.
1999, 40, 491; (d) Ward, D. E.; Hrapchak, M.; Sales, M.
Org. Lett. 2000, 2, 57.
6
. (a) Yang, Y.; Wang, D. Synlett 1997, 861; (b) Yang, Y.;
Wang, D. Synlett 1997, 1379; (c) Saravanan, P.; Anand,
R. V.; Singh, V. R. Tetrahedron Lett. 1998, 39, 3823.
. (a) Bandini, M.; Cozzi, P. G.; Melchiorre, P.; Umani-
Ronchi, A. Tetrahedron Lett. 2001, 42, 3041; (b) Golin-
ski, M.; Brock, C. P.; Watt, D. S. J. Org. Chem. 1993, 58,
1
by H NMR, IR, and mass spectroscopy and also by
1
1
comparison with authentic compounds. However, in the
absence of a catalyst, the reaction did not yield any
product even after a long reaction time. In most cases the
yields are excellent, sometimes quantitative, making this
methodausefulsyntheticprotocolforthestraightforward
preparation of silylated cyanohydrins. Among catalysts
7
1
59; (c) Hamashima, Y.; Kanai, M.; Shibasaki, M. J.
Am. Chem. Soc. 2000, 122, 7412.
8
. (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.
such as CAN, DDQ, NBS, HI, IBX and Mn(OAc)3,
molecular iodine was found to be more efficient in terms
of conversion and reaction time.
9
. (a) Yadav, J. S.; Reddy, B. V. S.; Hashim, S. R. J. Chem.
Soc., Perkin Trans. 1 2000, 3025; (b) Yadav, J. S.; Reddy,
B. V. S.; Sabitha, G.; Reddy, G. S. K. K. Synthesis 2000,
In summary, the paper describes a simple and efficient
method for the cyanation of various functionalized and
hindered ketones with TMSCN using the cheap and
readily available elemental iodine as the catalyst. This
method is effective for the cyanation of both aliphatic as
well as aromatic ketones. In addition to its efficiency,
operational simplicity and mild reaction conditions, this
method provides high yields of products within a short
time, which makes it a useful entry for the synthesis of
trimethylsilyl ethers of cyanohydrins.
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.
1
0. General procedure: To a stirred solution of the ketone (1
mmol), and iodine (5 mol%) in dichloromethane (10 mL),
TMSCN (1.2 mmol) was added slowly dropwise at 0°C
and the mixtures were allowed to stir at room tempera-
ture 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 Na SO , and concentrated in vacuo. The
Acknowledgements
B.V.S.R. and M.S.R. thank CSIR, New Delhi, for the
award of the fellowships.
2
4
resulting product was purified by column chromatogra-
phy on silica gel (Merck, 100–200 mesh, ethyl acetate–
hexane, 1:9) to afford the pure trimethylsilyl derivative of
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9
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J. S. Yada6 et al. / Tetrahedron Letters 43 (2002) 9703–9706
1
1
9
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