One-Pot Amidation of Olefins through
Pd-Catalyzed Coupling of Alkylboranes and
†
Carbamoyl Chlorides
Yoshizumi Yasui, Sayo Tsuchida, Hideto Miyabe, and
Yoshiji Takemoto*
Graduate School of Pharmaceutical Sciences, Kyoto UniVersity,
Yoshida, Sakyo-ku, Kyoto 606-8501, Japan
FIGURE 1. Strategy for amide formation.
ReceiVed April 6, 2007
6
7,8
CN) of alkynes and alkenes followed such transformations.
Expanding these methods to intermolecular reactions is an
ongoing task, with the difficulties of finding an effective catalyst
and controlling the regiochemical course of the reaction.9
The direct amidation of organometallic reagents with forma-
mide derivatives is also an attractive method owing to its
simplicity and reliability (Figure 1, path c); however, the
organometallic reagents used for such an approach have been
limited mainly to magnesium or lithium reagents.11 It would
be useful to develop the amidation of less reactive metallic
reagents, to allow the presence of various functional groups.1
In this paper, we report a one-pot amidation of olefins through
hydroboration, and subsequent coupling of the resulting alkyl-
boranes with carbamoyl chlorides (X ) Cl), which allows
olefins to be precursors for amide synthesis (path d f path c).
For the hydroboration, 9-BBN-H was chosen as a reagent due
,10
2,13
1
A one-pot synthesis of C -elongated amides starting from
olefins and carbamoyl chlorides has been developed. Alkyl-
boranes, generated by hydroboration of terminal olefins with
9-BBN-H, underwent smooth coupling with carbamoyl
chlorides in the presence of palladium catalyst and Cs CO
2
3
.
(
6) (a) Kobayashi, Y.; Kamisaki, H.; Yanada, R.; Takemoto, Y. Org.
Amides have a fundamental importance in organic chemistry
due to their biological significance and synthetic utility. Gener-
ally, amides are formed through condensation of amines and
Lett. 2006, 8, 2711. (b) Kobayashi, Y.; Kamisaki, H.; Takeda, H.; Yasui,
Y.; Yanada, R.; Takemoto, Y. Tetrahedron 2007, 63, 2978.
(7) For related intramolecular amidation of formamide derivatives, see:
(
a) Toyofuku, M.; Fujiwara, S.; Shin-ike, T.; Kuniyasu, H.; Kambe, N. J.
Am. Chem. Soc. 2005, 127, 9706. (b) Anwar, U.; Fielding, M. R.; Grigg,
R.; Sridharan, V.; Urch, C. J. J. Organomet. Chem. 2006, 691, 1476.
1
carboxylic acids (Figure 1, path a). However, this method is
not always efficient, especially when the availability of the
carboxylic acid is limited. Therefore alternative methods have
been developed for the synthesis of a broad range of amides.
Recent examples include oxidative coupling of alkynes with
(8) Intramolecular carbonylative amidation of unsaturated amines is an
equivalent transformation, see: (a) Gabriele, B.; Salerno, G.; Costa, M.;
Chiusoli, G. P. J. Organomet. Chem. 2003, 687, 219 and references cited
therein. (b) Ye, F.; Alper, H. AdV. Synth. Catal. 2006, 348, 1855.
(9) Similar problems were reported on the related intermolecular hy-
droamidation, see: (a) Tsuji, Y.; Yoshii, S.; Ohsumi, T.; Kondo, T.;
Watanabe, Y. J. Organomet. Chem. 1987, 331, 379. (b) Kondo, T.; Okada,
T.; Mitsudo, T. Organometallics 1999, 18, 4123. (c) Ko, S.; Han, H.; Chang,
S. Org. Lett. 2003, 5, 2687.
2
3
amines, hydrative condensation of alkynes and sulfonyl azides,
and iridium-catalyzed conversion of alcohols to amides via
4
oximes. The transition-metal-catalyzed amidation of multiple
C-C bonds with formamide derivatives (X-CO-NR′2) is a
unique strategy, which enables the use of the corresponding one-
carbon-less olefins and acetylenes as the amide precursors
(10) A few regioselective intermolecular amidations are known. For
carbamoylstannation, see: (a) Hua, R.; Onozawa, S.; Tanaka, M. Organo-
metallics 2000, 19, 3269. For carbonylative selenoamidation, see: (b)
Knapton, D. J.; Meyer, T. Y. J. Org. Chem. 2005, 70, 785. For carbonylative
radical amidation, see: (c) Uenoyama, Y.; Fukuyama, T.; Nobuta, O.;
Matsubara, H.; Ryu, I. Angew. Chem., Int. Ed. 2005, 44, 1075.
(
Figure 1, path b). Our recent studies showed that rhodium-
5
catalyzed intramolecular hydroamidation (X ) H) of alkynes
and palladium-catalyzed intramolecular cyanoamidation (X )
(11) (a) Blicke, F. F.; Zinnes, H. J. Am. Chem. Soc. 1955, 77, 4849. (b)
Mills, R. J.; Taylor, N. J.; Snieckus, V. J. Org. Chem. 1989, 54, 4372. (c)
Lemoucheux, L.; Rouden, J.; Lasne, M.-C. Tetrahedron Lett. 2000, 41, 9997.
(d) Nagao, Y.; Miyamoto, S.; Miyamoto, M.; Takeshige, H.; Hayashi, K.;
Sano, S.; Shiro, M.; Yamaguchi, K.; Sei, Y. J. Am. Chem. Soc. 2006, 128,
9722. For amidation of Cu, K, Ti, and Zn reagents, see: (e) Lemoucheux,
L.; Seitz, T.; Rouden, J.; Lasne, M.-C. Org. Lett. 2004, 6, 3703 and
references cited therein.
(12) For amidation of aryl- and vinyltin reagents, see: (a) Balas, L.;
Jousseaume, B.; Shin, H.; Verlhac, J.-B.; Wallian, F. Organometallics 1991,
10, 366. (b) Murakami, M.; Hoshino, Y.; Ito, H.; Ito, Y. Chem. Lett. 1998,
163.
†
Dedicated to the memory of Professor Yoshihiko Ito.
1) (a) Sewald, N.; Jakubke, H.-D. Peptides: Chemistry and Biology;
(
Wiley-VCH Verlag GmbH: Weinheim, Germany, 2002. (b) Montalbetti,
C. A. G. N.; Falque, V. Tetrahedron 2005, 61, 10827.
(
2) Chan, W.-K.; Ho, C.-M.; Wong, M.-K.; Che, C.-M. J. Am. Chem.
Soc. 2006, 128, 14796.
3) (a) Cho, S. H.; Yoo, E. J.; Bae, I.; Chang, S. J. Am. Chem. Soc.
005, 127, 16046. (b) Cassidy, M. P.; Raushel, J.; Fokin, V. V. Angew.
Chem., Int. Ed. 2006, 45, 3154.
(
2
(
4) Owston, N. A.; Parker, A. J.; Williams, J. M. J. Org. Lett. 2007, 9,
7
3.
(
(13) Amidation of arylboron reagents was recently reported, see: (a)
Duan, Y.-Z.; Deng, M.-Z. Synlett 2005, 355. (b) Lys e´ n, M.; Kelleher, S.;
Begtrup, M.; Kristensen, J. L. J. Org. Chem. 2005, 70, 5342.
5) Kobayashi, Y.; Kamisaki, H.; Yanada, K.; Yanada, R.; Takemoto,
Y. Tetrahedron Lett. 2005, 46, 7549.
10.1021/jo070724u CCC: $37.00 © 2007 American Chemical Society
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J. Org. Chem. 2007, 72, 5898-5900
Published on Web 06/20/2007