Iridium-Catalyzed Ring Cleavage Reaction of Cyclobutanone O-Benzoyloximes Providing Nitriles.

TLDR: 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.

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.

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SUPPORTING INFORMATION
Iridium-Catalyzed Ring Cleavage Reaction of Cyclobutanone O-Benzoyloximes Providing Nitriles
Takahiro Nishimura,* Tomoki Yoshinaka, Yoshiki Nishiguchi, Yasunari Maeda, and Sakae Uemura*
Department of Energy and Hydrocarbon Chemistry, Graduate School of Engineering
Kyoto University, Nishikyo-ku, Kyoto 615-8510, Japan
E-mail: takahiro@scl.kyoto-u.ac.jp
General Methods.
1
H NMR spectra were obtained in CDCl
3
at 270, 300, or 400 MHz with Me
4
Si as
an internal standard.
13
C NMR spectra were obtained at 67.8, 75.5, or 100 MHz. Elemental analyses were
performed at the Microanalytical Center of Kyoto University.
Materials. All commercially available organic and inorganic compounds were used without further
purification except for the solvent, which was distilled by the known method before use. Cyclobutanone
O-benzoyloximes were prepared according to the reported procedures from the corresponding
cyclobutanones.
S1
Cyclobutanones were produced by the reduction of
α
,
α
-dichlorocyclobutanones
synthesized from the corresponding alkenes by the reported procedure
S2
in the presence of Zn-powder and
AcOH.
S3
3-Methyl-3-phenylcyclobutanone O-benzoyloxime (1a). White solid; mp 81.0–81.5 °C;
1
H NMR
(270 MHz, CDCl
3
)
δ
1.59 (s, 3H), 3.15–3.37 (m, 2H), 3.38–3.58 (m, 2H), 7.23–7.34 (m, 3H), 7.37 (t, J =
6.9 Hz, 2H), 7.47 (t, J = 6.9 Hz, 2H), 7.59 (t, J = 6.9 Hz, 1H), 8.07 (d, J = 7.3 Hz, 2H);
13
C NMR (67.8
MHz, CDCl
3
)
δ
30.9, 38.0, 44.8, 125.0, 126.3, 128.4, 128.5, 128.9, 129.5, 133.1, 147.8, 163.8, 165.0.
Anal. Calcd for C
18
H
17
NO
2
: C, 77.40; H, 6.13; N, 5.01. Found: C, 77.27; H, 6.14; N, 4.99.
Benzoic acid 3-phenylcarboxyimino-1-methylcyclobutylmethyl ester (1c). White solid; mp
59.1–59.3 °C;
1
H NMR (270 MHz, CDCl
3
)
δ
1.44 (s, 3H), 2.92 (d, J = 18.8 Hz, 2H), 3.22 (d, J = 18.8 Hz,
2H), 4.34 (s, 2H), 7.38–7.64 (m, 6H), 8.04 (d, J = 7.3 Hz, 4H);
13
C NMR (67.8 MHz, CDCl
3
)
δ
23.8, 33.7,
40.8, 70.3, 128.4, 128.8, 129.5, 133.2, 163.7, 164.2, 166.2. Anal. Calcd for C
20
H
19
NO
4
: C, 71.20; H, 5.68;
N, 4.15. Found: C, 71.26; H, 5.81; N, 4.09.
S–1

2-Benzyloxymethyl-3,3-dimethylcyclobutanone O-benzoyloxime (4a, E/Z mixture). Colorless oil;
1
H NMR (300 MHz, CDCl
3
)
δ
1.23 (s, 2.1H), 1.27 (s, 0.9H), 1.33 (s, 0.9H), 1.36 (s, 2.1H), 2.70–2.85 (m,
2H), 3.30–3.36 (m, 1H), 3.71–3.98 (m, 2H), 4.48–4.55 (m, 2H), 7.22–7.50 (m, 7H), 7.53–7.65 (m, 1H),
7.90–8.04 (m, 2H).
13
C NMR (67.8 MHz, CDCl
3
)
δ
22.6, 22.7, 29.9, 30.1, 33.0, 33.7, 43.5, 43.8, 54.1,
55.3, 66.3, 66.9, 73.1, 73.2, 127.5, 127.6, 127.6, 128.3, 128.4, 128.4, 128.8, 129.0, 129.4, 129.5, 133.0,
133.1, 137.8, 138.0, 163.8, 166.0, 166.9. Anal. Calcd for C
21
H
23
NO
3
: C, 74.75; H, 6.87; N, 4.15. Found:
C; 74.73, H; 6.95, N; 4.11.
1-Phenylbicyclo[3.2.0]heptan-6-one O-benzoyloxime (4b, E/Z mixture). Colorless oil;
1
H NMR
(270 MHz, CDCl
3
)
δ
1.76–2.46 (m, 6H), 3.05–3.19 (m, 1H), 3.43 (d, J = 18.1 Hz, 2H) 3.85–3.92 (m,
1H), 7.20–7.62 (m, 8H), 8.03–8.08 (m, 2H);
13
C NMR (75.5 MHz, CDCl
3
)
δ
26.3, 26.4, 30.8, 32.7,
41.8, 41.9, 42.4, 42.4, 48.2, 49.0, 55.6, 55.9, 125.5, 126.3, 128.5, 128.5, 128.6, 129.1, 129.1, 129.6,
133.2, 133.3, 146.6, 146.6, 163.9, 168.9, 169.6. Anal. Calcd for C
20
H
19
NO
2
: C, 78.66; H, 6.27; N,
4.59. Found: C; 78.96, H; 6.36, N; 4.48.
Typical Procedure for the Synthesis of 3-Methyl-3-phenylbutyronitrile. A mixture of [IrCl(cod)]
2
(0.0024 mmol), BnBPA (0.0050 mmol), K
2
CO
3
(0.10 mmol), 9,10-dihydroanthracene (0.12 mmol), and
DMF (0.30 mL) in a 20-mL Schlenk tube was stirred at room temperature under N
2
. After 15 min,
3-methyl-3-phenylcyclobutanone O-benzoyloxime (1a) (0.10 mmol) in DMF (0.20 mL) was added, and
the resulting mixture was stirred at 50 °C for 48 h. The reaction mixture was cooled down to room
temperature, and then filtered through a pad of Florisil. The filtrate was concentrated under vacuum to
leave a colorless oil, which was subjected to column chromatography on SiO
2
with EtOAc-hexane (3/97)
as eluent.
3-Benzyl-3-methyl-4-phenylbutyronitrile (2b). Colorless oil;
1
H NMR (300 MHz, CDCl
3
)
δ
0.95 (s,
3H), 2.04 (s, 2H), 2.74 (d, J = 13.5 Hz, 2H), 2.83 (d, J = 13.5 Hz, 2H), 7.15–7.37 (m, 10H);
13
C NMR
(75.5 MHz, CDCl
3
)
δ
23.6, 26.4, 38.0, 46.0, 118.8, 126.7, 128.3, 130.5, 136.7. HRMS (FAB): calcd for
C
18
H
20
N (M+H
+
), 250.1596; found, 250.1596. Anal. Calcd for C
18
H
19
N: C, 86.70; H, 7.68; N, 5.62.
Found: C, 86.16; H, 7.70; N, 5.44.
Benzoic acid 3-cyano-2,2-dimethylpropyl ester (2c). Colorless oil;
1
H NMR (300 MHz, CDCl
3
)
δ
S–2

1.22 (s, 6H), 2.46 (s, 2H), 4.16 (s, 2H), 7.43–7.51 (m, 2H), 7.55–7.63 (m, 1H), 8.02–8.07 (m, 2H);
13
C
NMR (75.5 MHz, CDCl
3
)
δ
24.2, 27.9, 34.2, 55.7, 117.7, 128.5, 129.6, 129.7, 133.3, 166.1. HRMS
(FAB): calcd for C
14
H
16
NO
2
(M+H
+
), 218.1181; found, 218.1183. Anal. Calcd for C
13
H
15
NO
2
: C, 71.87;
H, 6.96; N, 6.45. Found: C, 71.79; H, 7.00; N, 6.21.
5-Benzyloxy-3,3-dimethylpentanenitrile (5a). Colorless oil;
1
H NMR (300 MHz, CDCl
3
)
δ
1.10 (s,
6H), 1.71 (t, J = 6.2 Hz, 2H), 2.34 (s, 2H), 3.56 (t, J = 6.2 Hz, 2H), 4.49 (s, 2H), 7.25–7.40 (m, 5H);
13
C
NMR (75.5 MHz, CDCl
3
)
δ
27.2, 30.8, 32.5, 40.4, 66.8, 73.1, 118.6, 127.6, 127.6, 128.4, 138.2. Anal.
Calcd for C
14
H
19
NO: C, 77.38; H, 8.81; N, 6.45. Found: C, 77.51; H, 8.82; N, 6.30.
1-Phenylcyclopentylacetonitrile (5b). Yellow oil;
1
H NMR (400 MHz, CDCl
3
)
δ
1.77–1.83 (m, 4H),
2.05–2.09 (m, 4H), 2.58 (s, 2H), 7.23–7.42 (m, 5H);
13
C NMR (67.8 MHz, CDCl
3
)
δ
23.1, 30.4, 37.2,
49.2, 118.3, 126.4, 126.8, 128.5, 145.5. HRMS (FAB): calcd for C
13
H
15
N (M+H
+
), 186.1283; found,
186.1288.
Typical Procedure for the Reaction of 3-Methyl-3-phenylcyclobutanone O-Benzoyloxime (1a)
with Diphenyldisulfide. A mixture of [IrCl(cod)]
2
(0.0125 mmol), BnBPA (0.025 mmol), K
2
CO
3
(0.50
mmol), and ethylene carbonate (0.50 mL) in a 20-mL Schlenk tube was stirred at 50 °C under N
2
. After
15 min, 3-methyl-3-phenylcyclobutanone O-benzoyloxime (1a) (0.50 mmol) and diphenyl disulfide (0.75
mmol) in ethylene carbonate (0.50 mL) were added, and the resulting mixture was stirred at 50 °C for 24
h. The reaction mixture was cooled down to room temperature, and then filtered through a pad of Florisil.
The filtrate was concentrated under vacuum to leave a yellow oil, which was subjected to column
chromatography on SiO
2
with EtOAc-hexane (3/97) as eluent.
3-Methyl-3-phenyl-4-(phenylthio)butyronitrile (6). Yellow oil;
1
H NMR (300 MHz, CDCl
3
)
δ
1.56
(s, 3H), 2.77 (d, J = 16.5 Hz, 1H), 2.85 (d, J = 16.5 Hz, 1H), 3.30 (d, J = 13.0 Hz, 1H), 3.31 (d, J = 13.0
Hz, 1H), 7.06–7.32 (m, 10H);
13
C NMR (75.5 MHz, CDCl
3
)
δ
25.4, 29.5, 41.7, 47.0, 117.7, 125.6, 126.6,
127.4, 128.7, 129.0, 130.3, 136.3, 142.8. HRMS (FAB); calcd for C
17
H
17
NS (M
+
), 267.1082; found,
287.1083. Anal. Calcd for C
17
H
17
NS: C, 76.36; H, 6.41; N, 5.24. Found: C, 76.31; H, 6.38; N, 5.24.
3-Methyl-3-phenyl-4-(phenylseleno)butyronitrile (7). Yellow oil;
1
H NMR (400 MHz, CDCl
3
)
δ
1.62 (s, 3H), 2.82 (d, J = 16.6 Hz, 1H), 2.91 (d, J = 16.6 Hz, 1H), 3.33 (d, J = 12.7 Hz, 1H), 3.40 (d, J =
S–3

S–4
12.7 Hz, 1H), 7.18–7.35 (m, 8H), 7.42–7.44 (m, 2H);
13
C NMR (75.5 MHz, CDCl
3
)
δ
25.7, 30.0, 41.5,
41.7, 117.7, 125.5, 127.2, 127.3, 128.6, 129.0, 130.3, 133.2, 142.9. Anal. Calcd for C
17
H
17
NSe: C, 64.97;
H, 5.45; N, 4.46. Found: C, 65.05; H, 5.50; N, 4.28.
3-Methyl-3-phenyl-4-(phenyltellro)butyronitrile (8). Yellow oil;
1
H NMR (400 MHz, CDCl
3
)
δ
1.67
(s, 3H), 2.85 (d, J = 16.1), 2.91 (d, J = 16.6), 3.33 (d, J = 12.2), 3.49 (d, J = 12.2), 7.14–7.35 (m, 10H),
7.64–7.66 (m, 2H);
13
C NMR (100 MHz, CDCl
3
)
δ
25.2, 26.8, 31.4, 41.3, 117.9, 125.3, 127.3, 127.9,
128.7, 129.2, 138.9, 143.5. Anal. Calcd for C
17
H
17
NTe: C, 56.26; H, 4.72; N, 3.86. Found: C, 56.34; H,
4.78; N, 3.79.
References
(S1) Nishimura, T.; Uemura, S. J. Am. Chem. Soc. 2000, 122, 12049.
(S2) Ramnauth, J.; Lee-Ruff, E. Can. J. Chem. 1999, 77, 1245.
(S3) Aljancic-Solaja, I.; Rey, M.; Dreiding, A. S. Helv. Chim. Acta 1987, 70, 1302.

Frequently asked questions

Q1. What are the contributions mentioned in the paper "Supporting information iridium-catalyzed ring cleavage reaction of cyclobutanone o-benzoyloximes providing nitriles" ?

O-benzoyloximes were prepared according to the reported procedures from the corresponding cyclobutanones. Cyclobutanones were produced by the reduction of α, α-dichlorocyclobutanones synthesized from the corresponding alkenes by the reported procedure in the presence of Zn-powder and AcOH.