2
0
milder conditions have been also reported, such as pivaloyl
tetrabutylammonium fluoride (TBAF) catalyzed hydrosi-
lylation of primary amides to amines with methyldiethox-
ysilane. Initially, benzamide was chosen as the model
substrate to identify and optimize critical reaction parameters.
To our surprise, exclusive formation toward benzonitrile took
place and no benzylamine was observed (Scheme 1).
1
3
14
15
chloride, EtOP(O)Cl
trichloroacetyl chloride. Unfortunately, the use of these
chlorides causes severe storage and handling problems as
well as significant waste generation. Therefore, there exists
considerable interest in finding ready available, easily
2
,
benzensulfonyl chloride, and
1
6
17
18
handling, and environmentally benign dehydration reagents.
Recently, we became interested in the development of new
methods for reduction of carboxylic acid derivatives in order
to avoid stoichiometric amounts of metal hydrides. Based
on this work, we started to explore different catalysts for
the hydrosilylation of amides to amines. In addition to well-
known metal catalysts, we also investigated the use of
Scheme 1. Reactions of Benzamide with Hydrosilanes
1
9
(
6) For reviews, see: (a) Sundermeier, M.; Zapf, A.; Beller, M. Eur.
J. Inorg. Chem. 2003, 3513. (b) Schareina, T.; Zapf, A.; Cott e´ , A.; M u¨ ller,
M. B. Synthesis 2008, 3351–3355. (c) M. Sundermeier, A.; Zapf, N.; Beller,
M.; Sans, J. Tetrahedron Lett. 2001, 42, 6707. (d) Ramnauth, J.; Bhardwaj,
N.; Renton, P.; Rakhit, S.; Maddaford, S. P. Synlett 2003, 2237. (e)
Sundermeier, M.; Zapf, A.; Beller, M. Angew. Chem., Int. Ed. 2003, 42,
To the best of our knowledge, this unique transformation
has only been described once before, where a triruthenium
carbonyl cluster and a bifunctional organosilane were used
for the dehydration of amides to nitriles. Hence, we studied
this reaction in more detail. Herein, we report for the first
time a general procedure for the fluoride-catalyzed dehydra-
tion of amides to nitriles.
1
661. (f) Sundermeier, M.; Mutyala, S.; Zapf, A.; Spannenberg, A.; Beller,
M. J. Organomet. Chem. 2003, 684, 50. (g) Sundermeier, M.; Zapf, A.;
Sateesh, M.; Beller, M. Chem.sEur. J. 2003, 9, 1828. (h) Chobanian, H. R.;
Fors, B. P.; Lin, L. S. Tetrahedron Lett. 2006, 47, 3303. (i) Jensen, R. S.;
Gajare, A. S.; Toyota, K.; Yoshifuji, M.; Ozawa, F. Tetrahedron Lett. 2005,
21
4
6, 8645. (j) Veauthier, J. M.; Carlson, C. N.; Collis, G. E.; Kiplinger,
J. L.; John, K. D. Synthesis 2005, 2683. (k) Cristau, H. J.; Ouali, A.;
Spindler, J. F.; Taillefer, M. Chem.sEur. J. 2005, 11, 2483. (l) Tylleman,
B.; Gomez-Aspe, R.; Gbabode, G.; Geerts, Y. H.; Sergeyev, S. Tetrahedron
As shown in Table 1, various base and standard copper
hydrosilylation catalysts were tested using (EtO) MeSiH (3.0
2
2
008, 64, 4155. (m) Ryberg, P. Org. Proc. Res. DeV. 2008, 12, 540. (n)
Iqbal, Z.; Lyubimtsev, A.; Hanack, M. Synlett 2008, 2287. (o) Challenger,
S.; Dessi, Y.; Fox, D. E.; Hesmondhalgh, L. C.; Pascal, P.; Pettman, A. J.;
Smith, J. D. Org. Proc. Res. DeV. 2008, 12, 575. (p) Wang, X.; Zhi, B.;
Baum, J.; Chen, Y.; Crockett, R.; Huang, L.; Eisenberg, S.; Ng, J.; Larsen,
R.; Martinelli, M.; Reider, P. J. Org. Chem. 2006, 71, 4021. (q) Martin,
M. T.; Liu, B.; Cooley, B. E.; Eaddy, J. F. Tetrahedron Lett. 2007, 48,
Table 1. Dehydration of Benzamide with (EtO)
Presence of Various Catalysts
2
MeSiH in the
a
2555. (r) Schareina, T.; Zapf, A.; Beller, M. Chem. Commun. 2004, 1388–
1389. (s) Schareina, T.; Zapf, A.; Beller, M. J. Organomet. Chem. 2004,
689, 4576. (t) Schareina, T.; Zapf, A.; M a¨ gerlein, W; M u¨ ller, N.; Beller,
M. Chem.sEur. J. 2007, 13, 6249. (u) Schareina, T.; Zapf, A.; M a¨ gerlein,
W.; M u¨ ller, N.; Beller, M. Synlett 2007, 555. (v) Schareina, T.; Zapf, A.;
Beller, M. Tetrahedron Lett. 2005, 46, 2585. (w) Schareina, T.; Zapf, A.;
M a¨ gerlein, W.; M u¨ ller, N.; Beller, M. Tetrahedron Lett. 2007, 48, 1087.
b
(
x) Littke, A.; Soumeillant, M.; Kaltenbach, R. F.; Cherney, R. J.; Tarby,
C. M.; Kiau, S. Org. Lett. 2007, 9, 1711.
7) (a) Kent, R. E.; McElvain, S. M. Org. Synth. 1945, 25. (b) Mowry,
entry
catalyst (mol %)
none
time (h)
yield (%)
1
2
3
4
5
6
7
8
9
a
24
0.5
21
24
19
24
24
24
24
0
99
0
41
44
2
3
0
3
(
D. T. Chem. ReV. 1948, 42, 189.
Bu
Bu
4
NF (5)
NBr (5)
(
(
(
(
(
8) Krynitsky, J. A.; Carhart, H. W. Org. Synth. 1963, IV, 436–438.
9) Reisner, D. B.; Horning, E. C. Org. Synth. 1963, IV, 144–145.
10) Rickborn, B.; Jensen, F. R. J. Org. Chem. 1962, 27, 4608.
11) Lehnert, W. Tetrahedron Lett. 1971, 19, 1501.
4
KF (5)
t
KOBu (5)
CuCl (5)
CuBr (5)
CuI (5)
12) Ellzey, S. E.; Mack, C. H.; Connick, W. J. J. Org. Chem. 1967,
3
2, 846.
(
(
13) Narsaiah, A. V.; Nagaiah, K. AdV. Synth. Catal. 2004, 346, 1271.
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CuCl
2
(5)
K. J. Chem. Commun. 2007, 3, 301.
15) Stephens, C. R.; Bianco, E. J.; Pigrim, F. J. J. Am. Chem. Soc.
955, 77, 1701.
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400.
17) Caddick, S.; Wilden, J. D.; Wadman, S. J.; Bush, H. D.; Judd, D. B.
Org. Lett. 2002, 4, 2549.
18) Recent examples of dehydration of amides: (a) Campbell, J. A.;
McDouglad, G.; McNab, H.; Rees, L. V. C.; Tyas, R. G. Synthesis 2007,
179. (b) Vaccari, D.; Davoli, P.; Bucciarelli, M.; Spaggiari, A.; Prati, F.
(
2
Reaction conditions: 1a (1.0 mmol), catalyst (5 mol %), (EtO) MeSiH
3.0 equiv), toluene (2 mL), 100 °C, argon atmosphere. Determined by
1
b
(
(
GC.
2
(
(
equiv) as the dehydrating reagent (Table 1, entries 2-9).
Notably, the reaction did not occur in the presence of the
silane alone (Table 1, entry 1). Remarkably, studies revealed
3
Lett. Org. Chem. 2007, 4, 319. (c) Vaccari, D.; Davoli, P.; Ori, C.; Spaggiari,
A.; Prati, F. Synlett 2008, 1317.
(
19) (a) Enthaler, S.; Junge, K.; Beller, M. Angew. Chem. 2008, 120,
3
363; Angew. Chem., Int. Ed. 2008, 47, 3317. (b) Shaikh, N. S.; Enthaler,
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53, 5405. (b) Drew, M. D.; Lawrence, N. J. Tetrahedron Lett. 1997, 38,
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D. L.; Sehkri, Synlett 1997, 8, 989.
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5
98.
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Org. Lett., Vol. 11, No. 11, 2009