5294
S. Kamijo et al. / Tetrahedron 68 (2012) 5290e5296
27.9, 37.7, 41.4, 49.2, 55.7, 64.2, 111.1, 111.8, 128.4, 129.5, 130.2, 133.0,
166.5; HRMS (ESI) calcd for C16H16O2N2Cl2Na [MþNa]þ 361.0481,
found 361.0482.
12.0, 5.0 Hz), 1.57 (3H, m), 1.60 (3H, m), 1.75e1.82 (1H, m),
2.04e2.13 (2H, m), 2.24e2.30 (1H, m), 2.32e2.41 (1H, m), 3.03 (2H,
s), 5.96 (1H, dd, J¼2.6, 2.6 Hz); 13C NMR (100 MHz, CDCl3)
d 24.5,
27.7, 29.96, 29.98, 30.5, 42.9, 45.5, 49.6, 73.5, 112.2, 112.3, 128.3,
132.3; HRMS (ESI) calcd for C14H20ON2Cl2Na [MþMeOHþNa]þ
325.0845, found 325.0841.
4.2.12. 5,7-Dichloro-7-cyanoheptyl benzoate (3ac). Ratio of diaster-
eomers¼ca. 1:1; colorless oil; IR (neat) 2250, 1717, 1601, 1451, 1277,
714, 687 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 1.58e1.90 (6H, m),
2.36e2.57 (2H, m) 4.05e4.15 (1H, m), 4.35 (2H, t, J¼6.1 Hz),
4.74e4.84 (1H, m), 7.45 (2H, dd, J¼8.0, 8.0 Hz), 7.56 (1H, t, J¼8.0 Hz),
8.03 (2H, d, J¼8.0 Hz); 13C NMR (100 MHz, CDCl3) detectable signals:
4.2.19. 2,2,4-Trichloro-6-phenylhexanenitrile (3na). Colorless oil; IR
(neat) 2248, 1603, 1496, 1454, 779, 749, 700 cmꢂ1
;
1H NMR
(400 MHz, CDCl3)
d
2.09e2.22 (2H, m), 2.81 (1H, ddd, J¼12.0, 7.5,
d
22.7, 22.9, 28.1, 37.4, 37.7, 39.8, 40.2, 44.3, 45.0, 57.7, 58.4, 64.3, 64.4,
6.0 Hz), 2.89 (1H, dd, J¼13.0, 3.5 Hz), 2.94 (1H, ddd, J¼12.0, 7.5,
4.5 Hz), 3.04 (1H, dd, J¼13.0, 7.0 Hz), 4.18 (1H, dddd, J¼7.0, 7.0, 3.5,
3.5 Hz), 7.20e7.25 (3H, m), 7.29e7.34 (2H, m); 13C NMR (100 MHz,
116.2, 116.7, 128.4, 129.5, 130.2, 133.0, 166.5; HRMS (ESI) calcd for
C15H17O2NCl2Na [MþNa]þ 336.0529, found 336.0533.
CDCl3)
d 32.0, 39.9, 55.0, 55.9, 66.3, 115.1, 126.4, 128.4, 128.6, 139.8;
4.2.13. 5,7-Dichloro-7-cyano-9-phenylnonyl benzoate (3ad). Ratio
of diastereomers¼ca. 1:1; colorless oil; IR (neat) 2250, 1718, 1601,
HRMS (ESI) calcd for C12H12NCl3Na [MþNa]þ 297.9928, found
297.9930.
1452, 1314, 1276, 749, 713, 702 cmꢂ1 1H NMR (400 MHz, CDCl3)
;
d
1.60e2.05 (6H, m), 2.25e2.70 (4H, m), 2.93e3.10 (2H, m)
4.2.20. 2-Chloro-2-(2-chloro-4-phenylbutyl)malononitrile
4.25e4.40 (3H, m), 7.17e7.25 (3H, m), 7.30e7.40 (2H, m), 7.44 (2H,
dd, J¼7.8, 7.8 Hz), 7.58 (1H, t, J¼7.8 Hz), 8.04 (2H, d, J¼7.8 Hz); 13C
(3nb). Colorless oil; IR (neat) 2250, 1603, 1496, 1454, 751,
701 cmꢂ1
;
1H NMR (400 MHz, CDCl3)
d
2.15 (2H, ddd, J¼6.8, 5.5,
NMR (100 MHz, CDCl3) detectable signals:
d
22.57, 22.58, 27.96,
5.5 Hz), 2.72 (1H, dd, J¼13.0, 2.9 Hz), 2.81 (1H, dt, J¼12.0, 2.9 Hz),
2.91 (1H, dd, J¼13.0, 8.0 Hz), 2.95 (1H, dt, J¼12.0, 5.5 Hz), 4.17 (1H,
dtd, J¼8.0, 5.5, 2.9 Hz), 7.19e7.23 (3H, m), 7.30e7.34 (2H, m); 13C
27.98, 31.2, 31.5, 38.1, 38.6, 43.6, 45.0, 49.5, 50.1, 56.8, 57.3, 58.8,
59.0, 64.3, 64.4, 117.8, 118.3, 126.60, 126.63, 128.31, 128.32, 128.4,
128.7,129.5,130.21,130.23,132.86,132.88,139.0,139.1,166.5; HRMS
(ESI) calcd for C23H25O2NCl2Na [MþNa]þ 440.1155, found 440.1155.
NMR (100 MHz, CDCl3)
d 31.9, 39.8, 41.4, 49.2, 55.2, 111.1, 111.8,
126.6, 128.4, 128.7, 139.4; HRMS (ESI) calcd for C13H12N2Cl2Na
[MþNa]þ 289.0270, found 289.0257.
4.2.14. 3,5,5-Trichloro-5-cyano-3-methylpentyl benzoate (3kb). Co-
lorless oil; IR (neat) 2252,1719,1601,1451,1274,1114, 807, 712 cmꢂ1
;
4.2.21. 2,4-Dichloro-6-phenylhexanenitrile (3nc). Ratio of diaster-
eomers¼ca. 1:1; colorless oil; IR (neat) 2250, 1602, 1496, 1454, 751,
1H NMR (400 MHz, CDCl3)
d
1.93 (3H, s), 2.41 (1H, dt, J¼15.0, 6.0 Hz),
2.48 (1H, dt, J¼15.0, 6.0 Hz), 2.99 (1H, d, J¼15.0 Hz), 3.10 (1H, d,
J¼15.0 Hz), 4.61 (2H, t, J¼6.0 Hz), 7.46 (2H, dd, J¼7.5, 7.5 Hz), 7.59
(1H, t, J¼7.5 Hz), 8.02 (2H, d, J¼7.5 Hz); 13C NMR (100 MHz, CDCl3)
700 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 2.07e2.13 (2H, m),
2.37e2.51 (2H, m), 2.75e2.83 (1H, m), 2.89e2.95 (1H, m),
4.04e4.11 (1H, m), 4.76e4.83 (1H, m), 7.19e7.23 (3H, m), 7.30e7.34
d
30.1, 39.8, 43.4, 54.2, 60.7, 66.1, 111.7, 112.0, 128.5 (overlap of two
(2H, m); 13C NMR (100 MHz, CDCl3)
d 32.3, 32.4, 39.5, 39.7, 39.8,
carbon signals in the phenyl group), 129.5 (overlap of three carbon
signals in the phenyl group), 133.3, 166.2; HRMS (ESI) calcd for
C15H14O2N2Cl2Na [MþNa]þ 347.03252, found 347.0322.
40.2, 44.3, 44.9, 57.2, 58.0, 116.1, 116.7, 126.3, 126.4, 128.36, 128.38,
128.6, 128.7, 139.9, 140.0; HRMS (ESI) calcd for C12H13NCl2Na
[MþNa]þ 264.0317, found 264.0316.
4.2.15. trans-1-Chloro-2-(dichlorocyanomethyl)cyclohexane (trans-
4.2.22. 2,4-Dichloro-2-phenethyl-6-phenylhexanenitrile (3nd). Ra-
tio of diastereomers¼ca. 1:1; colorless oil; IR (neat) 2242, 1603,
3lb). Colorless oil; IR (neat) 2250, 741 cmꢂ1 1H NMR (400 MHz,
;
CDCl3)
d
1.34e1.46 (3H, m), 1.76e1.89 (2H, m), 1.92e1.97 (1H, m),
1496, 1454, 1496, 1454, 749, 700 cmꢂ1 1H NMR (400 MHz, CDCl3)
;
2.33e2.43 (2H, m), 2.52 (1H, ddd, J¼11.5, 10.0, 3.8 Hz), 4.00 (1H,
d
2.08e2.72 (6H, m), 2.76e2.86 (1H, m), 2.89e3.10 (3H, m),
4.14e4.30 (1H, m), 7.17e7.28 (6H, m), 7.30e7.36 (4H, m); 13C NMR
(100 MHz, CDCl3) detectable signals: 31.2, 31.5, 32.1, 32.2, 40.1,
ddd, J¼11.1, 10.0, 4.0 Hz); 13C NMR (100 MHz, CDCl3)
d 24.4, 25.3,
28.3, 37.4, 47.8, 52.7, 58.5, 111.5, 112.0; HRMS (ESI) calcd for
d
C9H10N2Cl2Na [MþNa]þ 239.0113, found 239.0115.
40.7, 43.6, 45.0, 49.5, 50.1, 56.3, 56.9, 58.7, 58.9, 117.9, 118.4, 126.31,
126.32, 126.6, 126.7, 128.40, 128.44, 128.49, 128.58, 128.59, 128.72,
139.0, 139.1, 140.1, 140.2; HRMS (ESI) calcd for C20H21NCl2Na
[MþNa]þ 368.0943, found 368.0942.
4.2.16. cis-1-Chloro-2-(dichlorocyanomethyl)cyclohexane (cis-3lb).
Colorless oil; IR (neat) 2251, 691 cmꢂ1 1H NMR (400 MHz, CDCl3)
;
d
1.32e1.42 (1H, m), 1.60e1.69 (1H, m), 1.74e1.87 (2H, m), 1.95e2.11
(3H, m), 2.16e2.25 (1H, m), 2.42 (1H, ddd, J¼11.5, 4.0, 3.0 Hz), 4.75
4.3. Procedure for the reduction of 3na to 3nc
(1H, m); 13C NMR (100 MHz, CDCl3)
d 18.7, 22.3, 24.8, 34.3, 47.2,
52.0, 57.1, 110.7, 111.5; HRMS (ESI) calcd for C9H10N2Cl2Na [MþNa]þ
To a solution of compound 3na (29.2 mg, 0.10 mmol) in toluene
(1.0 mL) was added n-Bu3P (37.5 mL, 0.15 mmol). The reaction
239.0113, found 239.0112.
mixture was stirred at room temperature for 15 min under Ar. After
the consumption of the starting material on TLC, the mixture was
diluted with H2O and extracted with AcOEt (ꢃ3). The organic layer
was washed with brine, dried over Na2SO4, and concentrated. The
residue was purified with a flash column chromatography (SiO2;
hexane/Et2O 30:1e10:1) to give compound 3nc in 76% yield
(18.3 mg).
4.2.17. 2,2-Dichloro-4-((1R,5S)-6,6-dimethylbicyclo[3.1.1]hept-2-en-
2-yl)butanenitrile (3mb). Colorless oil; IR (neat) 2250, 1643,
858 cmꢂ1 1H NMR (400 MHz, CDCl3)
; d 0.90 (3H, s), 1.22 (1H, d,
J¼7.5 Hz), 1.31 (3H, m), 2.11e2.15 (1H, m), 2.29e2.43 (3H, m), 2.49
(1H, dt, J¼7.5, 4.9 Hz), 3.01 (1H, dd, J¼11.0, 0.8 Hz), 3.04 (1H, dd,
J¼11.0, 0.8 Hz), 5.80e5.83 (1H, m); 13C NMR (100 MHz, CDCl3)
d
21.3, 25.9, 31.7, 32.0, 38.2, 39.9, 42.8, 46.4, 49.1, 112.0, 112.1, 129.2,
138.1; HRMS (ESI) calcd for C14H19ON2ClNa [MþMeOHþNa]þ
4.4. Procedure for the transformation of 3nc to 4
289.1078, found 289.1077.
To a solution of compound 3nc (24.2 mg, 0.10 mmol) in acetone
(5.0 mL) was added NaI (74.9 mg, 0.50 mmol). The reaction mixture
was refluxed for 72 h under Ar. After the consumption of the
starting material on TLC, the mixture was diluted with H2O and
4.2.18. (S)-2,2-Dichloro-4-(4-(2-chloropropan-2-yl)cyclohex-1-en-1-
yl)butanenitrile (3mb0). Colorless oil; IR (neat) 2250, 1662,
858 cmꢂ1; 1H NMR (400 MHz, CDCl3)
d
1.43 (1H, dddd, J¼12.0, 12.0,