4244
J. Am. Chem. Soc. 1998, 120, 4244-4245
Table 1. Iridium Hydride Complex-Catalyzed Addition of Nitriles
to CN Triple Bonds of Nitriles
Iridium Hydride Complex Catalyzed Addition of
Nitriles to Carbon-Nitrogen Triple Bonds of Nitriles
Hikaru Takaya, Takeshi Naota, and Shun-Ichi Murahashi*
Department of Chemistry
Graduate School of Engineering Science
Osaka UniVersity, Machikaneyama
Toyonaka, Osaka 560-8531, Japan
ReceiVed December 3, 1997
Addition of carbon nucleophiles to CN triple bonds of nitriles
is one of the most attractive transformations of nitriles.1 However,
the reported methods are limited to strong base promoted
intramolecular cyclization reactions of dinitriles (Thorpe-Ziegler
reaction) because of the low reactivity of nitriles.2 Development
of a catalytic method which proceeds under neutral conditions
has been waiting to be explored in view of both synthetic and
environmental aspects. As a line of our study on the development
of redox Lewis acids and bases for exploring environmentally
friendly processes,3 we have found that low-valent ruthenium and
rhodium hydride complexes are effective catalysts for the activa-
tion of both R-C-H bonds4 and the CN triple bond5 of nitriles.
Metal-coordinated nitriles 1 undergo either R-C-H activation to
give R-metalated nitriles 2, which react with electrophiles, or
direct reaction with nucleophiles as shown in Scheme 1. These
Scheme 1
a A mixture of nucleophile (1.0 mmol), nitrile (2.0 mmol), and
IrH(CO)(PPh3)3 (3) (3 mol %) in dry THF (0.25 mL) was stirred at
120 °C for 12 h under argon. b A mixture of dinitrile (1.0 mmol) and
IrH5(P-i-Pr3)2 (10) (3 mol %) in dry toluene (0.5 mL) was stirred at
140 °C for 12 h under argon. c A mixture of nitrile (3.0 mmol) and 10
(3 mol %) in dry toluene (0.5 mL) was stirred at 140 °C for 12 h under
argon. d Isolated yield based on the starting nitrile. e Reaction temper-
ature, 30 °C. f Catalyst, 10 mol %.
Herein, we wish to report the novel chemo- and stereoselective
iridium-catalyzed addition of nitriles (eq 1).
principles have led us to find a novel catalytic carbon-carbon
bond formation of nitriles that proceeds by simultaneous activation
of both R-C-H bonds and CN triple bonds of nitriles. Addition
of nitriles to CN triple bonds of nitriles can be performed under
neutral condition by iridium hydride complex catalysts to give
cyanoenamines, which are versatile synthetic intermediates,
although RuH2(PPh3)4, which is the excellent catalyst for the
reaction of nitriles with carbonyl compounds, is ineffective.
Iridium hydride complex IrH(CO)(PPh3)3 (3) has proved to be
an efficient catalyst for catalytic carbon-carbon bond formation
of nitriles. The representative results of the present reaction are
shown in Table 1. In the presence of 3 (3 mol %), activated
nitriles undergo dimerization to give the corresponding cyano-
enamines stereoselectively. Typically, the dimerization of ethyl
cyanoacetate proceeds efficiently under neutral conditions to give
(Z)-cyanoenamine 4 in excellent yield (entry 1). Selective
formation of the Z enamine is due to the strong hydrogen bonding
of the hydrogen of the enamine with the oxygen of the carbonyl
moiety. The cyanoenamines thus obtained are useful precursors
for synthesis of heterocyclic compounds. Typically, treatment
of 4 with sulfuric acid gives 4-amino-3-ethoxycarbonyl-2,6-dioxo-
1,2,5,6-tetrahydropyridine (96%), which is an important building
block for antitumor alkaloids. Other low-valent iridium com-
plexes such as Ir(CO)2(acac)-PR3 and Ir4(CO)12-PR3 and rhodium
hydride complexes such as RhH(CO)(PPh3)3 and RhH(PPh3)4 are
also effective for the present carbon-carbon bond formation. The
effectiveness of the present reaction is illustrated by cross-coupling
reactions of nitriles. When cyanohydrin derivatives are used as
acceptors,2d the cross-coupling reaction of activated nitriles
proceeds highly efficiently (entry 2). Generally, cross-coupling
(1) (a) Larock, R. C. In ComprehensiVe Organic Transformations: A Guide
to Functional Group Preparations; VCH Publishers: New York, 1989. (b)
Patai, S. In The Chemistry of Functional Groups: The Chemistry of the Cyano
Group; Rappoport, Z., Ed.; Wiley: London, 1970.
(2) (a) Davis, B. R.; Garratt, P. J. In ComprehensiVe Organic Synthesis;
Trost, B. M., Fleming, I., Heathcock, C. H., Eds.; Pergamon Press: Oxford,
1991; Vol. 2, Chapter 3.6, pp 848-863. (b) Schaefer, J. P.; Bloomfield, J. J.
Org. React. 1967, 15, 1. (c) Taylor, E. C.; McKillop, A. In AdVances in
Organic Chemistry Vol. 7: The Chemistry of Cyclic Enaminonitriles and
o-Aminonitriles; Taylor, E. C., Ed.; Wiley: New York, 1970. Cross-Thorpe
reaction see: (d) Hiyama, T.; Kobayashi, K. Tetrahedron Lett. 1983, 24, 3509.
Hiyama, T.; Kobayashi, K.; Nishide, K. Bull. Chem. Soc. Jpn. 1987, 60, 2127.
(3) (a) Murahashi, S.-I.; Naota, T. Bull. Chem. Soc. Jpn. 1996, 69, 1805.
(b) Murahashi, S.-I.; Naota, T. Chemtracts-Org. Chem. 1994, 7, 281.
(4) (a) Naota, T.; Taki, H.; Mizuno, M.; Murahashi, S.-I. J. Am. Chem.
Soc. 1989, 111, 5954. (b) Murahashi, S.-I.; Naota, T.; Taki, H.; Mizuno, M.;
Takaya, H.; Komiya, S.; Mizuho, Y.; Oyasato, N.; Hiraoka, M.; Hirano, H.;
Fukuoka, A. J. Am. Chem. Soc. 1995, 117, 12436. (c) Go´mez-Bengoa, E.;
Cuerva, J. M.; Mateo, C.; Echavarren, A. M. J. Am. Chem. Soc. 1996, 118,
8553. See also, the R-C-H activation of amines: (d) Murahashi, S.-I.; Hirano,
T.; Yano, T. J. Am. Chem. Soc. 1978, 100, 348. Murahashi, S.-I.; Watanabe,
T. J. Am. Chem. Soc. 1979, 101, 7429.
(5) (a) Murahashi, S.-I.; Naota, T.; Saito, E. J. Am. Chem. Soc. 1986, 108,
7846. (b) Naota, T.; Shichijo, Y.; Murahashi, S.-I. J. Chem. Soc., Chem.
Commun. 1994, 1359.
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Published on Web 04/18/1998