J. Am. Chem. Soc. 2000, 122, 12049-12050
12049
Table 1. Palladium-Catalyzed Reaction of 3-Phenylcyclobutanone
O-Acyloximes
Palladium(0)-Catalyzed Ring Cleavage of
Cyclobutanone Oximes Leading to Nitriles via
â-Carbon Elimination
Takahiro Nishimura and Sakae Uemura*
Department of Energy and Hydrocarbon Chemistry
Graduate School of Engineering, Kyoto UniVersity
Sakyo-ku, Kyoto 606-8501, Japan
GLC yield (%)
entry
substrate
ligand
2
3
ReceiVed August 28, 2000
1
2
3
4
5
6c
7
8
1a
1a
1a
1a
1a
1a
1b
1c
dppe
dppp
dppb
dppf
(R)-(+)-BINAP
(R)-(+)-BINAP
(R)-(+)-BINAP
(R)-(+)-BINAP
3
3
1
3
6
3
15
4
10
17
8
24
76
38
We have recently disclosed a novel Pd catalytic system
involving â-carbon elimination from an intermediate palladium-
(II)-alcoholate to afford ketones, the driving force of which is
the release of the ring strain of cyclobutane skeleton (eq 1).1,2 To
66
84 (80)d
a Reaction conditions: 1 (0.50 mmol), Pd2(dba)3‚CHCl3 (0.0125
mmol), ligand (0.0375 mmol), K2CO3 (0.50 mmol), THF (5 mL), 90
°C (bath temp.), under N2. b Based on 1 employed. c THF (2 mL).
d Isolated yield.
utilize this â-carbon elimination in palladium catalysis for other
organic transformations, we envisaged constructing a new Pd(0)
catalytic system using cyclobutanone O-acyloximes. As shown
in eq 2, we assumed â-carbon elimination from an intermediate
a bidentate phosphine ligand. The results are summarized in Table
1. As we expected, ring-opening reaction occurred to give
isomeric phenylbutenenitriles 2 and 3, the latter being the major
product. As a phosphine ligand, (R)-(+)-2,2′-bis(diphenylphos-
phino)-1,1′-binaphthyl (BINAP)8 was found to be most effective
to give 3 in 76% yield (entry 5). In this reaction the concentration
of the substrate affected the product yield which decreased using
a higher concentration of 1a (entry 6). Among various organic
and inorganic bases examined, K2CO3 was revealed to be the base
of choice. Other solvents such as toluene and N,N-dimethylfor-
mamide (DMF) were not effective. When Pd(PPh3)4 was used as
a catalyst, the yield of the products was low (3% of 2 and 13%
of 3, respectively).9 When the substrate having different acyl
groups such as 3-phenylcyclobutanone O-trimethylacetyloxime
(1b) and 3-phenylcyclobutanone O-benzoyloxime (1c) was em-
ployed, the oxime 1c gave 3 in a higher yield than the case of 1a
and 1b (entry 8). When 1c was treated in the absence of Pd2-
(dba)3‚CHCl3, no reaction occurred and 1c was recovered intact.10
The formation of the products 2 and 3 from 1c can be explained
as follows; first, the oxidative addition of the N-O bond of
O-benzoyloxime 1c to the Pd(0)-BINAP complex occurs to give
a cyclobutaniminopalladium(II) intermediate (A), followed by the
formation of an alkylpalladium species (B) via â-carbon elimina-
tion. Next, successive â-hydrogen elimination from the alkyl-
palladium species proceeds to give 2, followed by the isomer-
ization of 2 to more stable 3 and the reproduction of Pd(0) species
by reductive elimination. Similarly, O-benzoyloxime 4 gave
nitriles 5 (as an E/Z mixture), while the oxime 6 afforded nitriles
cyclobutaniminopalladium(II) complex (A) might give a γ-cy-
anoalkylpalladium species (B), since the oxidative addition of the
N-O bond of ketone O-acyloximes to Pd(0) species giving
alkaniminopalladium(II) complexes was quite recently proposed
in the synthesis of five-membered nitrogen heterocycles.3,4 In this
paper we describe our successful results on the palladium(0)-
catalyzed reaction of cyclobutanone O-acyloximes leading to
various nitriles.5,6
First, a tetrahydrofuran (THF) solution of 3-phenylcyclo-
butanone O-acetyloxime 1a7 was heated under reflux in the
presence of a catalytic amount of Pd2(dba)3‚CHCl3, a base, and
(1) Palladium(II)-catalyzed oxidative ring cleavage of tert-cyclobutanols,
see: (a) Nishimura, T.; Ohe, K.; Uemura, S. J. Am. Chem. Soc. 1999, 121,
2645. Palladium(0)-catalyzed arylation of tert-cyclobutanols, see: (b) Nish-
imura, T.; Uemura, S. J. Am. Chem. Soc. 1999, 121, 11010.
(2) For examples of the dealkylation reaction of tert-alcoholates via
â-carbon elimination catalyzed by the late transition metal, see: (a) Harayama,
H.; Kuroki, T.; Kimura, M.; Tanaka, S.; Tamaru, Y. Angew. Chem., Int. Ed.
Engl. 1997, 36, 2352. (b) Kondo, T.; Kodoi, K.; Nishinaga, E.; Okada, T.;
Morisaki, Y.; Watanabe, Y.; Mitsudo, T. J. Am. Chem. Soc. 1998, 120, 5587.
(c) Park, S.-B.; Cha, J. K. Org. Lett. 2000, 2, 147. (d) Okumoto, H.; Jinnai,
T.; Shimizu, H.; Harada, Y.; Mishima, H.; Suzuki, A. Synlett 2000, 629.
(3) Tsutsui, H.; Narasaka, K. Chem. Lett. 1999, 45.
(4) For examples of the oxidative addition of oximes to metal, see: (a)
Deeming, A. J.; Owen, D. W.; Powell, N. I. J. Organomet. Chem. 1990, 398,
299. (b) Ferreira, C. M. P.; Guedes da Silva, M. F. C.; Kukushkin, V. Y.;
Frau´to da Silva, J. J. R.; Pombeiro, A. J. L. J. Chem. Soc., Dalton Trans.
1998, 325.
(5) Ring opening reaction of cyclobutaniminyl radical to afford nitriles has
been reported, see: (a) Boivin, J.; Fouquet, E.; Zard, S. Z. Tetrahedron Lett.
1991, 32, 4299. (b) Boivin, J.; Fouquet, E.; Zard, S. Z. J. Am. Chem. Soc.
1991, 113, 1055. (c) Boivin, J.; Fouquet, E.; Zard, S. Z. Tetrahedron 1994,
50, 1757. (d) Zard, S. Z. Synlett 1996, 1148. (e) Callier-Dublanchet, A.-C.;
Quiclet-Sire, B.; Zard S. Z. Tetrahedron Lett. 1997, 38, 2463.
1
7 and 8 in 71% yield (7:8 ) 64:36 estimated by H NMR,
(7) Cyclobutanone O-acyloximes were prepared by the reaction of cy-
clobutanone oximes with acid anhydride or acyl halide in the presence of
triethylamine in CH2Cl2. Cyclobutanone oximes were easily prepared by the
treatment of cyclobutanones with NH2OH‚HCl and NaOAc in an aqueous
ethanol. Cyclobutanones were prepared by the reduction of R,R-dichloro-
cyclobutanones in the presence of Zn-powder and AcOH, which were
synthesized by the reported procedure. See: Krepski, L. R.; Hassner, A. J.
Org. Chem. 1978, 43, 2879.
(8) dppe, dppp, dppb, and dppf stand for 1,2-bis(diphenylphosphino)ethane,
1,3-bis(diphenylphosphino)propane, 1,4-bis(diphenylphosphino)butane, and
1,1′-bis(diphenylphosphino)ferrocene, respectively.
(9) The intramolecular cyclization of γ,δ-unsaturated ketone O-pentafluo-
robenzolyoximes reported by Tsutsui and Narasaka (ref 3) was successful in
the presence of Pd(PPh3)4 and Et3N in DMF. In our case, however, such
combination was not effective.
(10) In the presence of Pd2(dba)3‚CHCl3, but in the absence of a phosphine
ligand, the product yield was only 5%.
(6) For examples of palladium-induced Beckmann fission of oximes to give
nitriles, see: (a) Maeda, K.; Moritani, I.; Hosokawa, T.; Murahashi, S.-I. J.
Chem. Soc., Chem. Commun. 1975, 689. (b) Leusink, A. J.; Meerbeek, T. G.;
Noltes, J. G. Recl. TraV. Chim. Pays-Bas 1976, 95, 123.
10.1021/ja005558l CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/14/2000