Iridium-catalyzed ring cleavage reaction of cyclobutanone O-benzoyloximes providing nitriles

Article abstract of DOI:10.1021/ol0507120

(Chemical Equation Presented) Iridium-catalyzed ring cleavage reaction of cyclobutanone O-benzoyloximes in the presence of 9,10-dihydroanthracene and potassium carbonate proceeds to give saturated nitriles via C-C bond fission at the sterically more hinde

Full text of DOI:10.1021/ol0507120

ORGANIC
LETTERS
2005
Vol. 7, No. 12
2425-2427
Iridium-Catalyzed Ring Cleavage
Reaction of Cyclobutanone
O-Benzoyloximes Providing Nitriles
Takahiro Nishimura,* Tomoaki Yoshinaka, Yoshiki Nishiguchi,
Yasunari Maeda, and Sakae Uemura*
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering,
Kyoto UniVersity, Nishikyo-ku, Kyoto 606-8510, Japan
takahiro@scl.kyoto-u.ac.jp
Received April 4, 2005
ABSTRACT
Iridium-catalyzed ring cleavage reaction of cyclobutanone O-benzoyloximes in the presence of 9,10-dihydroanthracene and potassium carbonate
proceeds to give saturated nitriles via C C bond fission at the sterically more hindered site.
−
The cleavage of C-C bonds by transition metal complexes
is a very attractive field in organometallic chemistry.1 Its
catalytic reaction is of interest particularly due to its ability
to provide useful synthetic tools for various unique trans-
formations.2
saturated nitriles where the bond fission occurred at the
sterically more hindered site.
(2) See for examples: Rhodium-catalyzed reactions: (a) Wender, P. A.;
Correa, A. G.; Sato, Y.; Sun, R. J. Am. Chem. Soc. 2000, 122, 7815. (b)
Murakami, M.; Itahashi, T.; Ito, Y. J. Am. Chem. Soc. 2002, 124, 13976.
Ruthenium-catalyzed reactions: (c) Trost, B. M.; Toste, F. D.; Shen, H. J.
Am. Chem. Soc. 2000, 122, 2379. Nickel-catalyzed reaction: (d) Miller, J.
A. Tetrahedron Lett. 2001, 42, 6991. (e) Kondo, T.; Kaneko, Y.; Taguchi,
Y.; Nakamura, A.; Okada, T.; Shiotsuki, M.; Ura, Y.; Wada, K.; Mitsudo,
T. J. Am. Chem. Soc. 2002, 124, 6824. Palladium-catalyzed reactions: (f)
Nakamura, I.; Saito, S.; Yamamoto, Y. J. Am. Chem. Soc. 2000, 122, 2661.
(g) Suginome, M.; Matsuda, T.; Ito, Y. J. Am. Chem. Soc. 2000, 122, 11015.
(h) Lautens, M.; Piguel, S. Angew. Chem., Int. Ed. 2000, 39, 1045. (i) Park,
S.-B.; Cha, J. K. Org. Lett. 2000, 2, 147. (j) Okumoto, H.; Jinnai, T.;
Shimizu, H.; Harada, Y.; Mishima, H.; Suzuki, A. Synlett 2000, 629. (k)
Satoh, T.; Jones, W. D. Organometallics 2001, 20, 2916. (l) Camacho, D.
H.; Nakamura, I.; Saito, S.; Yamamoto, Y. J. Org. Chem. 2001, 66, 270
(m) Nu¨ske, H.; Noltemeyer, M.; de Meijere, A. Angew. Chem., Int. Ed.
2001, 40, 3411. (n) Trost, B. M.; Yasukata, T. J. Am. Chem. Soc. 2001,
123, 7162. (o) Terao, Y.; Wakui, H.; Satoh, T.; Miura, M.; Nomura, M. J.
Am. Chem. Soc. 2001, 123, 10407. (p) Knoke, M.; de Meijere, A. Synlett
2003, 195. (q) Ma, S.; Zhang, J. Angew. Chem., Int. Ed. 2003, 42, 184. (r)
Chiba, S.; Kitamura, M.; Saku, O.; Narasaka, K. Bull. Chem. Soc. Jpn.
2004, 77, 785.
Recently, we have disclosed some transition metal-
catalyzed C-C bond cleavage reactions3-5 such as oxidative
transformation3 and arylation4 of tert-cyclobutanols via
â-carbon elimination of a palladium-alcoholate intermediate.
Furthermore, it was found that the Pd-catalyzed C-C bond
cleavage of cyclobutanone O-acyloximes afforded unsatur-
ated nitriles where C-C bond fission occurred at the
sterically less hindered site (Scheme 1).5,6 In sharp contrast,
we have now found that the use of an iridium complex in
place of a palladium complex resulted in a formation of
(1) For reviews of C-C bond cleavage reactions, see: (a) Bishop, K.
C., III. Chem. ReV. 1976, 76, 461. (b) Crabtree, R. H. Chem. ReV. 1985,
85, 245. (c) Jennings, P. W.; Johnson, L. L. Chem. ReV. 1994, 94, 2241.
(d) Rybtchinski, B.; Milstein, D. Angew. Chem., Int. Ed. 1999, 38, 870. (e)
Murakami, M.; Ito, Y. In ActiVation of UnreactiVe Bonds and Organic
Synthesis; Murai, S., Ed.; Springer: New York, 1999; pp 97-129.
(3) (a) Nishimura, T.; Ohe, K.; Uemura, S. J. Am. Chem. Soc. 1999,
121, 2645. (b) Nishimura, T.; Ohe, K.; Uemura, S. J. Org. Chem. 2001,
66, 1455.
10.1021/ol0507120 CCC: $30.25
© 2005 American Chemical Society
Published on Web 05/13/2005

as a hydrogen donor increased the yield of 2a (entry 2).
Hoping to improve the yield of the product, we added several
ligands8 to the reaction, but a signifcant effect was not
observed (entries 3-7). The presence of 9,10-dihydroan-
thracene was important for the efficient reaction even in the
reaction in the presence of ligand (entry 8). IrCl(CO)(PPh3)2
also worked well as a catalyst (entry 9). At a lower
temperature (50 °C), the yield of 2a was much improved
(entries 10-13), where the addition of BnBPA9 as a ligand
was slightly effective, giving 2a in 91% yield (entry 10).
Certainly, no reaction occurred in the absence of the catalyst.
Scheme 1. Palladium-Catalyzed Ring-Opening Reaction of
Cyclobutanone O-Benzoyloximes
Scheme 2
Treatment of 3-methyl-3-phenylcyclobutanone O-benzo-
yloxime (1a) in DMF (N,N-dimethylformamide) in the
presence of [Ir(cod)Cl]2 at 100 °C for 3 h under nitrogen
gave the ring-opening product 2a (a saturated nitrile) as well
as cyclobutanone 3, where the process for 2a should involve
the reduction step (Table 1, entry 1).7 The reaction in DMF-
Among the solvents examined such as toluene, NMP (N-
methyl-2-pyrrolidone), DMAc (dimethylacetamide), ethylene
carbonate, and benzene, DMF was revealed to be the solvent
of choice.
Table 1. Iridium-Catalyzed Ring-Opening Reaction of 1aa
GLC yield (%)
The presence of a base was also essential for efficient
reaction, where K2CO3 was more effective than other bases
such as Na2CO3, Cs2CO3, KOAc, and organic bases. When
the reaction was carried out under air, it did not proceed at
entry
ligand (mol %)
temp (°C) time (h)
2a
3
1b
2
3
4
5
6
7
8b
9
10
11
12
13
100
100
100
100
100
100
100
100
100
50
3
3
3
3
3
3
3
3
3
48
48
48
48
39
58
60
55
55
62
62
44
62
91
89
85
84
29
4
3
6
29
4
4
33
4
3
3
(R)-(+)-BINAP (5)
PPh3 (10)
bpy (5)
Table 2. Reactions of Various Cyclobutanone
O-Benzoyloximesa
TPA (5)
BnBPA (5)
BnBPA (5)
c
BnBPA (5)
(R)-(+)-BINAP (5)
TPA (5)
50
50
50
4
4
c
a Reaction conditions: 1a (0.1 mmol), [Ir(cod)Cl]2 (2.5 mol %), ligand,
9,10-dihydroanthracene (1.2 equiv.), K2CO3 (1.0 equiv), DMF (1.0 mL) at
100 °C for 3 h. b In the absence of 9,10-dihydroanthracene. c IrCl(CO)-
(PPh3)2 (5 mol %) was used.
d6 showed the deuterium incorporation at the newly formed
methyl group of 2a. The addition of 9,10-dihydroanthracene
(4) (a) Nishimura, T.; Uemura, S. J. Am. Chem. Soc. 1999, 121, 11010.
(b) Nishimura, T.; Matsumura, S.; Maeda, Y.; Uemura, S. Tetrahedron Lett.
2002, 43, 3037. (c) Nishimura, T.; Matsumura, S.; Maeda, Y.; Uemura, S.
Chem. Commun. 2002, 50. (d) Nishimura, T.; Matsumura, S.; Maeda, Y.;
Uemura, S. J. Am. Chem. Soc. 2003, 125, 8862.
a Reaction conditions: 1 (0.50 mmol), [Ir(cod)Cl]2 (2.5 mol %), BnBPA
(5.0 mol %), K2CO3 (1.0 equiv), 9,10-dihydroanthracene (1.2 equiv), DMF
(1.0 mL, 0.5 M) at 50 °C. b 1 (0.3 mmol).
(5) (a) Nishimura, T.; Uemura, S. J. Am. Chem. Soc. 2000, 122, 12049.
(b) Nishimura, T.; Nishiguchi, Y.; Maeda, Y.; Uemura, S. J. Org. Chem.
2004, 69, 5342.
(6) An alkylideneaminopalladium species was suggested, see: (a) Tsutsui,
H.; Kitamura, M.; Narasaka, K. Bull. Chem. Soc. Jpn. 2002, 75, 1451. (b)
Zaman, S.; Kitamura, M.; Narasaka, K. Bull. Chem. Soc. Jpn. 2003, 76,
1055.
(7) Reaction of cyclobutanone oximes with tributyltin hydride or under
photolysis was reported by Zard et al.; see for example: (a) Boivin, J.;
Fouquet, E.; Zard, S. Z. Tetrahedron 1994, 50, 1757. (b) Boivin, J.; Fouquet,
E.; Schiano, A.-M.; Zard, S. Z. Tetrahedron 1994, 50, 1769. (c) Callier-
Dublanchet, A.-C.; Quiclet-Sire, B.; Zard, S. Z. Tetrahedron Lett. 1997,
38, 2463.
all. On the other hand, the reaction under an inert atmosphere
occurred smoothly even in the dark.
(8) Abbreviations for the ligands are as follows: (R)-(+)-2,2′-bis-
(diphenylphosphino)-1,1-binaphthyl ((R)-(+)-BINAP), triphenylphosphine
(PPh3), 2,2′-bipyridine (bpy), N,N,N-tris(2-pyridylmethyl)amine (TPA),
N-benzyl-N,N-bis(2-pyridylmethyl)amine (BnBPA).
(9) de Bruin, B.; Brands, J. A.; Donners, J. J. J. M.; Donners, M. P. J.;
de Gelder, R.; Smits, J. M. M.; Gal, A. W.; Spek, A. L. Chem. Eur. J.
1999, 5, 2921.
2426
Org. Lett., Vol. 7, No. 12, 2005

The results of the reactions of several cyclobutanone
O-benzoyloximes are shown in Table 2. The reaction of 3,3-
disubstituted cyclobutanone O-benzoyloximes (1a-d) gave
the corresponding nitriles in good yields (Table 2, entries
1-4). 3-Monosubstituted cyclobutanone O-benzoyloxime
such as 1e also gave the corresponding nitrile in a moderate
yield (entry 5).
the other hand, when the reaction was carried out in the
presence of several diphenyl dichalcogenides, which are
known to react with a carbon radical forming a carbon-
chalcogen bond,11 a saturated nitrile containing a ben-
zenechalogeno moiety was produced (Scheme 5). Thus,
Scheme 5. Reaction of 1a with Diphenyl Dichalcogenides
Next, the reaction of 2,3,3-trisubstituted cyclobutanone
O-benzoyloximes was carried out (Scheme 3). The reaction
Scheme 3
treatment of 1a with diphenyl disulfide in DMF in the
absence of 9,10-dihydroanthracene gave 2a and 6 in 19 and
59% yield, respectively. To avoid hydrogen transfer from
the solvent, the same reaction was tested in several solvents.
As a result, the reaction in ethylene carbonate instead of DMF
improved the yield of 6 to 65% without any formation of
2a. The reaction of 1a with diphenyl diselenide afforded 7
in much higher yield. On the other hand, the yield of the
corresponding telluride 8 was lower in the reaction with
diphenyl ditelluride. These results suggest the presence of a
carbon radical in this catalytic reaction system as shown in
Scheme 4.
In summary, we demonstrated that the iridium-catalyzed
ring cleavage reaction of cyclobutanone O-benzoyloximes
proceeded via an iminyl radical to afford the saturated
nitriles. The carbon radical, which may be formed from the
aminyl radical, can be trapped by diphenyl dichalcogenides
to produce nitriles containing a benzenechalcogeno moiety.
of 4a gave the corresponding saturated nitrile 5a. Similarly,
bicyclic 4b afforded 5b in a good yield. It is noteworthy
that the C-C bond at the sterically more hindered site was
selectively cleaved in this iridium-catalyzed reaction in
contrast to the palladium-catalyzed system. Considering the
known C-C bond fission of a cyclobutane ring via a
cyclobutylideneaminyl radical initiated by tributyltin hydride
or photolysis,7 we propose a similar radical pathway for this
reaction, which affords a more stable secondary carbon
radical via a homolytic cleavage of the C-C bond (Scheme
4). Contrary to the palladium case, there is no evidence for
intervention of an organoiridium intermediate.
Scheme 4. Ring Opening via a Cyclobutylideneaminyl
Note Added after ASAP Publication. Errors were found
in the TOC and Abstract graphics in the version published
ASAP May 13, 2005; the corrected version was published
ASAP May 20, 2005.
Radical
Supporting Information Available: Standard experi-
mental procedure and characterization data for the new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
OL0507120
(10) The smaller influence of radical inhibitors in this reaction system
is probably due to the large cage effect of the solvent, which can prevent
the trap of the radical species by the inhibitors, especially when the solvent
has a high viscosity.
(11) For an example, see: Ogawa, A.; Obayashi, R.; Ine, H.; Tsuboi,
Y.; Sonoda, N.; Hirao, T. J. Org. Chem. 1998, 63, 881.
To obtain more information about the reaction pathway,
the effect of radical inhibitors such as galvinoxyl and BHT
(2,6-di-tert-butyl-4-methylphenol) was investigated, but they
did not show any significant effects on the reaction.10 On
Org. Lett., Vol. 7, No. 12, 2005
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