Methyltriphenylphosphonium iodide catalyzes the addition of trimethylsilyl cyanide to aldehydes

Article abstract of DOI:10.1016/S0040-4039(03)01391-1

Methyltriphenylphosphonium iodide catalyzes the formation of cyanohydrin trimethylsilyl ethers of aliphatic, aromatic and heterocyclic aldehydes.

Full text of DOI:10.1016/S0040-4039(03)01391-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6157–6159
Methyltriphenylphosphonium iodide catalyzes the addition of
trimethylsilyl cyanide to aldehydes
Rube´n Co´rdoba and Joaqu´ın Plumet*
Universidad Complutense, Facultad de Qu´ımica, Departamento de Qu´ımica Orga´nica, E-28040 Madrid, Spain
Received 7 February 2003; revised 7 March 2003; accepted 3 June 2003
Abstract—Methyltriphenylphosphonium iodide catalyzes the formation of cyanohydrin trimethylsilyl ethers of aliphatic, aromatic
and heterocyclic aldehydes.
© 2003 Elsevier Ltd. All rights reserved.
Cyanohydrin trimethylsilyl ethers are versatile interme-
diates such as in the synthesis of a-hydroxy acids and
b-aminoalcohols.1 For the synthesis of O-TMS
cyanohydrins a plethora of catalytic agents including
Zn(II), Ti(IV), Cu(II), Ce(IV), Al(III), In(III) and
Sm(III) salts have been used, among others.2 Several of
these methodologies were adapted to the preparation of
non-racemic cyanohydrins.3 Searching for new non-
metallic catalysts for this reaction without lack of
efficiency, phosphonium salts were used as new cata-
lytic reagents. To the best of our knowledge, the use of
phosphines for the trimethylsylil cyanation of aldehydes
has been reported in one unique paper applied on an
isolated case.4 Thus, the reaction of 3-phenylpropanal
with TMSCN at 0°C gave 96% of the O-TMS cyanohy-
drin in the presence of 10 mol% of Bu3P and gave 27%
in the presence of Ph3P. On the other hand, phospho-
rus(V) reagents did not promote the cyanosilylation.5
No data on the use of phosphonium salts as catalysts
for these reactions has been so far reported. In this
paper we wish to describe our findings in this field.
Table 1. Synthesis of cyanohydrins by reaction of alde-
hydes and TMSCN
Entry
Substrate (R)
Isolated yield (%)
1
2
3a
4
5
6
7
8
9
C6H5
70
85
81
97
73
92
92
86
86
PMeO-C6H4
PNO2-C6H4
2-Furyl
3-Furyl
2-Pyridyl
3-Pyridyl
1-Naphthyl
Isopropyl
a The reaction mixture was achieved from −78 to 5°C during 24 h.
N-protected cyanohydrin for o-hydoxybenzaldehyde
and 2-pirrolcarboxaldehyde, respectively, and a mixture
of N-protected and NH cyanohydrin for 3-indolcarbox-
aldehyde (Scheme 1).
The reaction of aromatic and aliphatic aldehydes (1.0
equiv.) with TMSCN (1.0 equiv.) in the presence of 0.1
equiv. of methyltriphenylphosphonium iodide salt, took
place at room temperature to give good yields of the
expected cyanohydrins.6 The results are quoted in Table
1.
In the case of a,b-unsaturated aldehydes, the reaction
takes place as well. For instance, in the case of acroleyn
and cinnamaldehyde, excellent yields of the expected
O-TMS cyanohydrins were obtained in 1 h of reaction
(Scheme 2).
In the case of aldehydes with OH or NH groups, the
reaction with 2.0 equiv. of TMSCN gave the O- or
In summary, the use of methyltriphenylphosphonium
iodide as a catalytic reagent for cyanosilylation of
aldehydes has been described in this report. The experi-
mental method is very simple and, in some cases, pure
Keywords: trimethylsilyl cyanide; cyanohydrins; phosphonium salts.
* Corresponding author. Tel./fax: (34) 91 394 41 00; e-mail:
plumety@quim.ucm.es
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01391-1

6158
R. Co´rdoba, J. Plumet / Tetrahedron Letters 44 (2003) 6157–6159
Scheme 1.
2002, 3243–3249.
3. For reviews, see Ref. 1 and: (a) North, M. Synlett 1993,
807–820; (b) Effenberger, F. Angew. Chem., Int. Ed. 1994,
33, 1555–1564; (c) Schmidt, M.; Griengl, H. Top. Curr.
Chem. 1999, 200, 193–226. For more recent references, see:
(d) Belokon, Y.; Flego, M.; Ikounikov, N.; Moskalenko,
M.; North, M.; Orizu, C.; Tararov, V.; Tasinazzo, M. J.
Chem. Soc., Perkin 1 1997, 1293–1295; (e) Choi, M. C. K.;
Chan, S. S.; Matsumoto, K. Tetrahedron Lett. 1997, 38,
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Mol. Catal. 1998, 132, L1–L4; (h) Belokon, Y. N.;
Caveda-Cepas, S.; Green, B.; Ikonnikov, N. S.; Krustalev,
V. N.; Larichev, V. S.; Moskalenko, M. A.; North, M.;
Orizu, C.; Tararov, V. I.; Tasinazzo, M.; Timofeeva, G. I.;
Yashkina, L. V. J. Am. Chem. Soc. 1999, 121, 3968–3973;
(i) Belokon, Y. N.; Green, B.; Ikonnikov, N. S.; North,
M.; Tararov, V. I. Tetrahedron Lett. 1999, 40, 8147–8150;
(j) Flores-Lo´pez, L. Z.; Parrahake, M.; Somanathan, R.;
Walsh, P. J. Organometallics 2000, 19, 2153–2160; (k)
Holmes, I. P.; Kagan, H. B. Tetrahedron Lett. 2000, 41,
7453–7456; (l) Holmes, I. P.; Kagan, H. B. Tetrahedron
Lett. 2000, 41, 7457–7460; (m) Ward, D. E.; Sales, M.;
Hrapchak, M. J. Can. J. Chem. 2001, 79, 1775–1785; (n)
Belokon, Y. N.; Gutnov, A. V.; Moskalenko, M. A.;
Yashkina, L. V.; Lesovoy, D. E.; Ikonnikov, N. S.;
Larichev, V. S.; North, M. Chem. Commun. 2002, 244–245
(this paper relates to the catalytic asymmetric synthesis of
O-acetyl cyanohydrins); (o) Aspinall, H. C.; Greeves, N. J.
Organomet. Chem. 2002, 647, 151–157; (p) Liang, S.; Bu,
X. R. J. Org. Chem. 2002, 67, 2702–2704; (q) Choi, M. C.
K.; Chan, S. S.; Chan M. K.; Jim, J. C.; Matsumoto, K.
Heterocycles 2002, 58, 645–654; (r) Shen, Y. C.; Feng, X.
M.; Zhang, G. L.; Jiang, Y. Z. Synlett 2002, 1353–1355; (s)
Belokon, Y. N.; Carta, P.; Gutnov, A. V.; Maleev, V.;
Moskalenko, M. A.; Yashkina, L. V.; Ikonnikov, N. S.;
Voskoboev, N. U.; Khrustaler, V. N.; North, M. Helv.
Chim. Acta 2002, 85, 3301–3312 (this paper relates to the
catalytic asymmetric synthesis of O-acetyl cyanohydrins);
(t) Casas, J.; Na´jera, C.; Sansano, J. M.; Saa´, J. M. Org.
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Scheme 2.
O-TMS cyanohydrins are isolated by successive washes
of the reaction crude with water. On the other hand,
the use of chiral phosphonium salts, in order to achieve
the enantioselective synthesis of these useful com-
pounds, is now under active research in our laboratory.
Acknowledgements
We thank Professor Marcial Moreno (Universidad
Auto´noma de Barcelona) for valuable suggestions.
Financial support of this work by the Ministerio de
Educacio´n, Cultura y Deporte, Project BQU 2000-0653
is gratefully acknowledged.
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R. Co´rdoba, J. Plumet / Tetrahedron Letters 44 (2003) 6157–6159
6159
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under argon and at room temperature, the carbonyl com-
pound (0.742 mmol) followed by TMSCN (0.093 mL, 0.742
mmol). The reaction was allowed to progress for 24–72 h.
Water (6 mL) was added and the mixture was extracted with
CH2Cl2. Drying of the combined organic phases with MgSO4
was followed by evaporation of the solvent in vacuo. The
products were purified by chromatography on silica gel (ethyl
6. Typical experimental procedure: To a solution of the phos-
phonium salt (30 mg, 0.074 mmol) in dry CH2Cl2 was added,
1
acetate/hexane), and characterized by H and 13C NMR.