ORGANIC
LETTERS
2
006
Vol. 8, No. 26
031-6034
Copper-Catalyzed Amidation of Allylic
and Benzylic C H Bonds
6
s
Guillaume Pelletier and David A. Powell*
Merck Frosst Centre for Therapeutic Research, 16711 Trans Canada Highway,
Kirkland, Qu e´ bec H9H 3L1, Canada
Received October 11, 2006
ABSTRACT
A copper-catalyzed amidation of allylic and benzylic C−H bonds with both primary and secondary sulfonamides is described. The reaction is
applicable to the coupling of a diverse set of hydrocarbon species with aryl, heteroaryl, and alkyl sulfonamides and is tolerant of a variety of
functional groups. Mechanistic insight has been gained through the isolation of a benzylic acetate intermediate, which was demonstrated to
undergo facile conversion to the substituted sulfonamide product under copper catalysis.
2
The formation of C-N bonds is of fundamental importance
in organic synthesis, owing to the high prevalence of
nitrogen-containing molecules of natural and pharmaceutical
attractive and efficient alternative. Considerable achieve-
ments have been made within the past several years in order
to effect amidation via a C-H activation strategy, particularly
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3-7
relevance. The vast majority of techniques for the introduc-
with regards to allylic and benzylic C-H bonds.
For example, C-H amidation methodologies that proceed
through transition metal-nitrene (imido) intermediates have
been demonstrated with a variety of metal catalysts, including
tion of C-N bonds rely on functional group interconversions
for their synthesis. In contrast, the formation of new C-N
bonds directly from C-H bonds represents an extremely
8
(
5) Representative intermolecular metal-nitrene-type amidations: (a)
(
1) Modern Amination Reactions; Ricci, A., Ed.; Wiley-VCH: Weinheim,
Germany, 2000.
2) For a recent review of oxidative functionalization of C-H bonds,
see: Dick, A. R.; Sanford, M. S. Tetrahedron 2006, 62, 2439-2463.
3) For some recent reviews of C-H bond amidations, see: (a) Davies,
Fructos, M. R.; Trofimenko, S.; D ´ı az-Requejo, M. M.; P e´ rez, P. J. J. Am.
Chem. Soc. 2006, 128, 11784-11791. (b) Thu, H.-Y.; Yu, W.-Y.; Che,
C.-M. J. Am. Chem. Soc. 2006, 128, 9048-9049. (c) Leung, S. K.-Y.; Tsui,
W.-M.; Huang, J.-S.; Che, C.-M.; Liang, J.-L.; Zhu, N. J. Am. Chem. Soc.
2005, 127, 16629-16640. (d) Yamawaki, M.; Tsutsui, H.; Kitagaki, S.;
Anada, M.; Hashimoto, S. Tetrahedron Lett. 2002, 43, 9561-9564. (e)
Kohmura, Y.; Katsuki, T. Tetrahedron Lett. 2001, 42, 3339-3342. (f) Yang,
J.; Weinberg, R.; Breslow, R. Chem. Commun. 2000, 531-532. (g) Au,
S.-M.; Huang, J.-S.; Che, C.-M.; Yu, W.-Y. J. Org. Chem. 2000, 65, 7858-
7864. (h) Yu, X.-Q.; Huang, J.-S.; Zhou, X.-G.; Che, C.-M. Org. Lett. 2000,
2, 2233-2236. (i) N a¨ geli, I.; Baud, C.; Bernardinelli, G.; Jacquier, Y.;
Moran, M.; M u¨ ller, P. HelV. Chim. Acta 1997, 80, 1087-1105. (j) Mahy,
J. P.; Bedi, G.; Battioni, P.; Mansuy, D. Tetrahedron Lett. 1988, 29, 1927-
1930. (k) Breslow, R.; Gellman, S. H. J. Chem. Soc., Chem. Commun. 1982,
1400-1401.
(6) (a) Kohmura, Y.; Kawasaki, K.-i.; Katsuki, T. Synlett 1997, 1456-
1458. (b) Smith, K.; Hupp, C. D.; Allen, K. L.; Slough, G. A. Organome-
tallics 2005, 24, 1747-1755. (c) Clark, J. S.; Roche, C. Chem. Commun.
2005, 5175-5177.
(7) For other strategies for the amination of allylic and benzylic C-H
bonds, see: (a) Adam, W.; Krebs, O. Chem. ReV. 2003, 103, 4131-4146.
(b) Johannsen, M.; Jørgensen, K. A. Chem. ReV. 1998, 98, 1689-1708.
(8) Review: (a) M u¨ ller, P.; Fruit, C. Chem. ReV. 2003, 103, 2905-2919.
(b) Dauban, P.; Dodd, R. H. Synlett 2003, 1571-1586.
(
(
H. M. L.; Long, M. S. Angew. Chem., Int. Ed. 2005, 44, 3518-3520. (b)
Du, Bois, J. Chemtracts 2005, 18, 1-13. (c) Espino, C. G.; Du Bois, J. In
Modern Rhodium-Catalyzed Organic Reactions; Evans, P. A., Ed; Wiley-
VCH: Weinheim, 2005; pp 379-416. (d) Halfen, J. A. Curr. Org. Chem.
2
005, 9, 657-669.
4) Representative intramolecular metal-nitrene-type amidations: (a) Kim,
M.; Mulcahy, J. V.; Espino, C. G.; Du Bois, J. Org. Lett. 2006, 8, 1073-
(
1
1
2
4
076. (b) Lebel, H.; Huard, K.; Lectard, S. J. Am. Chem. Soc. 2005, 127,
4198-14199. (c) Zhang, J.; Chan, P. W. H.; Che, C.-M. Tetrahedron Lett.
005, 46, 5403-5408. (d) Cui, Y.; He, C. Angew. Chem., Int. Ed. 2004,
3, 4210-4212. (e) Espino, C. G.; Fiori, K. W.; Kim, M.; Du Bois, J. J.
Am. Chem. Soc. 2004, 126, 15378-15379. (f) Liang, J.-L.; Yuan, S.-X.;
Huang, J.-S.; Che, C.-M. J. Org. Chem. 2004, 69, 3610-3619. (g) Fruit,
C.; M u¨ ller, P. HelV. Chim. Acta 2004, 87, 1607-1615. (h) Liang, J.-L.;
Yuan, S.-X.; Huang, J.-S.; Yu, W.-Y.; Che, C.-M. Angew. Chem., Int. Ed.
2
002, 41, 3465-3468. (i) Espino, C. G.; Wehn, P. M.; Chow, J.; Du Bois,
J. J. Am. Chem. Soc. 2001, 123, 6935-6936. (j) Espino, C. G.; Du Bois, J.
Angew. Chem., Int. Ed. 2001, 40, 598-600. (k) Breslow, R.; Gellman, S.
H. J. Am. Chem. Soc. 1983, 105, 6728-6729.
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0.1021/ol062514u CCC: $33.50
© 2006 American Chemical Society
Published on Web 11/18/2006