4498
J . Org. Chem. 1996, 61, 4498-4499
Sch em e 1
A Nick el(0)-Ca ta lyzed P r ocess for th e
Tr a n sfor m a tion of En yn es to Bicyclic
Cyclop en ten on es
Minghui Zhang and Stephen L. Buchwald*
Department of Chemistry, Massachusetts Institute of
Technology, Cambridge, Massachusetts 02139
Received February 28, 1996
The coupling of an alkyne, an alkene, and carbon
monoxide mediated by transition metal complexes to
yield a cyclopentenone1 has attracted a great deal of
interest in the past few years. In particular, the conver-
sion of an enyne to a bicyclic enone2 has been ac-
complished using a number of metal carbonyl complexes,
including Co2(CO)8 (the Pauson-Khand reaction),3 Fe-
(CO)4(acetone) under CO pressure,4 W(CO)6(THF),5 and
Cp2Mo2(CO)4.6 Metallocene equivalents generated from
Cp2ZrCl27 and Cp2TiCl28 in combination with CO can also
be utilized to effect the transformation. In the latter
procedures, the initially formed metallacycles are con-
verted to enone products by carbonylation. In general,
these reactions require stoichiometric amounts of transi-
tion metal complexes. When an isocyanide is used in lieu
of CO, the reaction yields an iminocyclopentene. This
process has been accomplished using metallocene re-
agents,8 as well as Ni(COD)2/Bu3P.9 Our recent success
using a titanocene catalyst for this transformation10 and
recent reports of catalytic Pauson-Khand reactions11
prompted us to search for a catalytic variant of the Ni-
mediated process. Here we wish to describe a method
for the conversion of an enyne and a trialkylsilyl isocya-
nide to an iminocyclopentene catalyzed by a Ni(0) com-
plex generated in situ from Ni(COD)2 and a bulky bis-
ketimine ligand.
yield (Scheme 1). As our ultimate goal is to develop an
asymmetric catalyst for this process, the successful
employment of a bidentate ligand is significant. The
increased efficiency of the reaction with the more electron-
rich ligand DCyPE relative to DPPP prompted us to
investigate the use of highly electron-donating bidentate
nitrogen ligands.12 For example, the reaction of an
equimolar mixture of 1, 2, Ni(COD)2, and 2,2′-bipyridine
(Bipy) at 80 °C for 8 h gave 3 in 80% yield, and the
analogous reaction of 1, 2, Ni(COD)2, and rac-diimine 4
at room temperature for 8 h gave 3 in 80% yield (Scheme
1).
Attempts to convert 1 to iminocyclopentenes such as
3 with a variety of isocyanides in the presence of as much
as 25 mol % of Ni(COD)2/4 were unsuccessful. However,
we observed that after an initial stoichiometric reaction
involving 1, 2, and Ni(COD)2/4 addition of a second
equivalent of 1 and 2 to the same reaction vessel followed
by heating to 65 °C led to the consumption of the
substrates with concomitant production of iminocyclo-
pentene 3. After five such cycles, 3 was obtained in 70%
yield [350% based on Ni(COD)2]. These results suggested
that the failure of the catalytic coupling of 1 with 2 to
form 3 was due to the formation of nickel-isocyanide
complexes, which prevent the coordination, and hence,
cyclization, of the enyne.8,10
We have previously shown that trialkylsilyl cyanides
serve as an effective isocyanide source for the titanocene-
catalyzed conversion of enynes to iminocyclopentenes.10
Trialkylsilyl cyanides generate a sufficient yet relatively
low equilibrium concentration of the trialkylsilyl isocya-
nide isomer (K ≈ 0.01)13 to effect the desired coupling
reaction while avoiding the formation of inactive Ti-
isocyanide complexes.10 Similarly, trialkylsilyl cyanides
were also coupled with 1 employing a catalytic amount
of Ni(COD)2/4. For example, reaction of 1 with tert-
butyldimethylsilyl cyanide (TBDMSCN) in the presence
of 5 mol % of Ni(COD)2/4 at 130 °C for 36 h followed by
acidic hydrolysis of the initially formed intermediate gave
cyclopentenone 5 in 60% yield. The reaction proceeded
at lower temperature (120 °C) and approximately the
same rate using the bulkier bis-ketimine ligand, N,N′-
bis(diphenylmethylene)ethylenediamine (BDPEDA, 6). In
addition, when the larger (triisopropyl)silyl cyanide (TIP-
SCN) was used, cyclization occurred at 110 °C (Scheme
2). In all cases, moderately high dilution ([Ni] ≈ 10-3
M) was required to suppress the formation of nickel-
isocyanide complexes. Of interest is that the amounts
While the stoichiometric Ni(COD)2-mediated reaction
of an enyne and an isocyanide to produce an iminocyclo-
pentene required 2 equiv of Bu3P, the use of a bidentate
phosphine ligand such as Ph2P(CH2)3PPh2 (DPPP) was
reported to completely inhibit the cyclization.9 However,
we found that the reaction of an equimolar mixture of
Ni(COD)2, enyne 1, 2,6-dimethylphenyl isocyanide, 2, and
chelating ligand Cy2P(CH2)2PCy2 (DCyPE) at 65 °C for 8
h formed the corresponding iminocyclopentene 3 in 40%
(1) For leading references, see: Trost, B. M. Science (Washington,
D.C.) 1991, 254, 1471.
(2) For
a recent review, see: Schore, N. E. In Comprehensive
Organometallic Chemistry II; Abel, E. W., Stone, F. G., Wilkinson, G.,
Eds.; Elsevier: New York, 1995; Vol. 12, p 703.
(3) Pauson, P. L.; Khand, I. U. Ann. N.Y. Acad. Sci. 1977, 295, 2.
(4) Pearson, A. J .; Dubbert, R. A. J . Chem. Soc., Chem. Commun.
1991, 202.
(5) (a) Hoye, T. R.; Suriano, J . A. J . Am. Chem. Soc. 1993, 115, 1154.
(b) Hoye, T. R.; Suriano, J . A. Organometallics 1992, 11, 2044.
(6) Mukai, C.; Uchiyama, M.; Hanaoka, M. J . Chem. Soc., Chem.
Commun. 1992, 1014.
(7) Negishi, E.-I. In Comprehensive Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: New York, 1991; Vol. 5, p 1037 and
references therein.
(8) (a) Grossman, R. B.; Buchwald, S. L. J . Org. Chem. 1992, 57,
5803. (b) Grossman, R. B. Ph. D. Dissertation, Massachusetts Institute
of Technology, 1992.
(9) (a) Tamao, K.; Kobayashi, K.; Ito, Y. J . Am. Chem. Soc. 1988,
110, 1286. (b) Tamao, K.; Kobayashi, K.; Ito, Y. Synlett 1992, 539.
(10) (a) Berk, S. C.; Grossman, R. B.; Buchwald, S. L. J . Am. Chem.
Soc. 1993, 115, 4912. (b) Berk, S. C.; Grossman, R. B.; Buchwald, S.
L. J . Am. Chem. Soc. 1994, 116, 8593. (c) Berk. S. C. Ph. D.
Dissertation, Massachusetts Institute of Technology, 1994.
(11) (a) J eong, N.; Hwang, S. H.; Lee, Y.; Chung, Y. K. J . Am. Chem.
Soc. 1994, 116, 3159. (b) Lee, B. Y.; Chung, Y. K.; J eong, N.; Lee, Y.;
Hwang, S. H. J . Am. Chem. Soc. 1994, 116, 8793.
(12) Togni, A.; Venanzi, L. M. Angew. Chem., Int. Ed. Engl. 1994,
33, 497.
(13) Rasmussen, J . K.; Heilmann, S. M.; Krepski, L. R. In Advances
in Silicon Chemistry; Larson, G. L., Ed.; J AI: Greenwich, 1991; Vol.
1, p 67 and references therein.
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