R,â-Unsaturated Nitriles
J . Org. Chem., Vol. 67, No. 11, 2002 3671
13C NMR δ 13.8, 22.4, 25.2, 25.9, 28.8, 31.5, 36.4, 67.4, 117.8;
MS m/e 154 (M - H).
28.5, 28.6, 31.4, 31.8, 33.2, 99.4, 99.6, 115.9, 117.5, 155.1, 156.0;
MS m/e 138 (M + H).
3-[(1S,5S)-6,6-Dim eth ylbicyclo[3.1.1]h ep t-2-en -2-yl]-3-
h yd r oxyp r op a n en itr ile (8b). The general procedure was
employed with (-)-myrtenal (2b) (57 mg, 0.38 mmol) to afford,
after radial chromatography, 63 mg (87%) of 8b as an oily
mixture of two diastereomers: IR (film) 3458, 3034, 2252, 1653
(2E)-3-((1S,5S)-6,6-Dim eth ylbicyclo[3.1.1]h ep t-2-en -2-
yl)p r op -2-en en itr ile (1b). The general procedure was em-
ployed with 8b (34 mg, 0.18 mmol) but adding the MeMgCl to
a cold (-78 °C), THF solution of 8b and maintaining the
temperature at -78 °C for 4 h prior to warming to room
temperature for 12 h. This modification afforded, after radial
chromatography, 26 mg (84%) of 1b as an oil with 1H NMR
and IR data identical to that reported previously:33 13C NMR
δ 20.7, 26.1, 31.0, 32.5, 37.9, 40.5, 40.6, 92.3, 119.0, 135.1,
145.3, 150.7; MS m/e 174 (M + H).
1
cm-1; H NMR δ 0.81, 0.82 (s, 3H each), 1.14 (d, J ) 8. Hz,
1H), 1.28 (s, 3H), 2.00-2.59 (m, 8H), 4.30 (t, J ) 6 Hz, 1H),
5.56-5.62 (m, 1H); 13C NMR δ 21.1 (co-incident), 23.9 and 24.0,
25.9 (co-incident), 30.9 (coincident), 31.5 and 31.6, 37.7 and
37.8, 40.6 and 40.7, 41.6 and 41.8, 69.8 and 70.0, 117.5
(coincident), 120.0 and 120.1, 146.9 and 147.1; MS m/e 192
(M + H) for each isomer.
2-(1,3,3-Tr im eth ylbicyclo[2.2.1]h ep t-2-ylid en ea ceton i-
tr ile (1c). The general procedure was employed with 8c (87
mg, 0.45 mmol) but refluxing the solution for 2 h immediately
following the addition of MeMgCl. This modification afforded,
after radial chromatography, 61 mg (77%) of (E)-1c and 11
mg (14%) of (Z)-1c as oils. (E)-1c: IR (film): 3050, 2213, 1631
cm-1;1H NMR δ 1.17 (s, 3H), 1.26 (s, 3H), 1.34 (s, 3H), 1.54-
1.66 (m, 4H), 1.72 (dd, J ) 8.7, 2.5 Hz, 1H), 1.75 (dd, J ) 9.2,
2.5 Hz, 1H), 1.89 (br s, 1H), 4.94 (s, 1H); 13C NMR δ 17.8, 23.4,
25.0, 25.5, 34.9, 43.4, 44.6, 48.1, 52.2, 84.3, 117.5, 186.6; MS
(1R,2R,4S)-2-(2-Hyd r oxy-1,3,3-tr im eth ylbicyclo[2.2.1]-
h ep t-2-yl)a cetoen itr ile (8c) a n d (1R,2S,4S) -2-(2-Hyd r oxy-
1,3,3-tr im eth ylbicyclo[2.2.1]h ep t-2-yl)a cetoen itr ile (8e).
The general procedure was employed with (-)-fenchone (2c)
(150 mg, 0.99 mmol) to afford, after radial chromatography,
177 mg (93%) of 8c and 8e in a 5.8:1 ratio.29 Repetitive
chromatography afforded an enriched sample of 8e, as a 1:1
mixture of diastereomers, and pure 8c as a white crystalline
1
solid (mp 84-86 °C): IR (NaCl) 3464, 2253 cm-1; H NMR δ
176 (M + H). (Z)-1c: IR (film): 3040, 2211, 1631 cm-1 1H
;
1.05 (s, 3H), 1.07 (s, 3H), 1.18 (s, 3H), 1.05-1.60 (m, 4H), 1.65-
1.79 (m, 2H), 1.88-2.01 (m, 2H), 2.50 (s, 2H); 13C NMR δ 17.3,
21.7, 24.8, 25.8, 26.7, 29.9, 40.8, 44.2, 49.4, 52.3, 79.9, 119.3;
MS m/e 194 (M + H). Comparing spectra of pure 8c with the
enriched mixture reveals 8e to exhibit: 1H NMR δ 1.02 (s, 3H),
NMR δ 1.05 (s, 3H), 1.08 (s, 3H), 1.17-1.42 (m, 3H), 1.59 (s,
3H), 1.60-1.83 (m, 3H), 1.88 (br s, 1H), 4.94 (s, 1H); 13C NMR
δ 18.7, 25.0, 25.8, 28.6, 35.2, 45.3, 46.0, 46.6, 52.7, 85.0, 117.4,
185.7; MS m/e 176 (M + H). An analogous elimination using
a 5:1 ratio of 8c:8e (76 mg, 0.39 mmol) afforded 59 mg (86%)
of (E)-1c and (Z)-1c in a 5:1 ratio.
1.07 (s, 3H), 1.09 (s, 3H), 1.05-2.01 (m, 8H), 2.50 (s, 2H); 13
C
NMR δ 15.8, 22.2, 23.4, 24.8, 25.4, 30.8, 40.9, 45.0, 46.7, 52.7,
80.3, 119.0; MS m/e 194 (M + H).
(2E)-3,4,4-Tr im eth ylp en t-2-en en itr ile (1d ). The general
procedure was employed with 8d (105 mg, 0.74 mmol) using
Et2O, rather than EtOAc, to extract the aqueous phase to
afford, after radial chromatography (1 mm plate, 1:9 Et2O:
pentane), 74 mg (81%) of 1d 34 as a volatile oil: IR (film) 2219,
(()-3-Hyd r oxy-3,4,4-tr im eth ylp en ta n en itr ile (8d ). The
general procedure was employed with 3,3-dimethylbutan-2-
one (200 mg, 2.00 mmol) to afford, after radial chromatogra-
phy, 236 mg (84%) of 8d as a white crystalline solid (mp 38-
1
1613 cm-1; H NMR δ 1.09 (s, 9H), 2.06 (d, J ) 0.7 Hz, 3H),
1
40 °C): IR (NaCl) 3484, 2249 cm-1; H NMR δ 0.98 (s, 9H),
5.17 (br s, 1H); 13C NMR δ 17.8, 28.3, 37.4, 93.4, 117.8, 172.8;
MS m/e 124 (M + H).
1.40 (s, 3H), 1.77 (s, 1H), 2.59 (ABq, J ) 16, ∆νAB ) 62 Hz,
2H); 13C NMR δ 22.7, 25.1, 27.5, 37.6, 74.9, 118.6; MS m/e 142
(M + H).
2-[5-Met h yl-2-(p r op a n -2-ylid en e)cycloh exylid en e]-1-
ca r bon itr ile (1f). The general procedure was employed with
8f (80 mg, 0.42 mmol) to afford, after radial chromatography,
43 mg (59%) of (E)-1f and 20 mg (28%) of (Z)-1f as oils. (E)-1f:
IR (film) 3050, 2213, 1605 cm-1; 1H NMR δ 1.11-1.35 (m, 1H),
1.38 (d, J ) 6.0 Hz, 3H), 1.46-1.65 (m, 2H), 2.08 (s, 3H), 2.11
(s, 3H), 2.13-2.40 (m, 2H), 2.98 (dt, J ) 13.8, 4 Hz, 1H), 3.14-
3.21 (m, 1H), 5.18 (s, 1H); 13C NMR δ 20.3, 21.5, 21.9, 30.1,
34.0, 34.5, 42.5, 94.5, 117.3, 128.2, 132.2, 165.7; MS m/e 176
2-[(5S)-1-H yd r oxy-5-m et h yl-2-(m et h ylet h ylid en e)cy-
cloh exyl]a ceton itr ile (8f). The general procedure was em-
ployed with (+)-pulegone (150 mg, 0.99 mmol) to afford, after
radial chromatography, 169 mg (89%) of 8f as an oily mixture
of diastereomers, spectroscopically identical to material previ-
ously reported.30
Gen er a l P r oced u r e for th e MgO Elim in a tion of Hy-
d r oxyn itr iles. A THF solution of MeMgCl (2.1 equiv) was
added to a room temperature, THF solution (0.1 M) of the
appropriate â-hydroxynitrile (1 equiv). After 12 h, saturated,
aqueous NH4Cl was added, and the aqueous phase was
extracted with EtOAc. The organic extracts were combined,
dried (Na2SO4), concentrated, and purified by radial chroma-
tography (1 mm plate, 1:9 EtOAc:hexanes) to afford the
corresponding unsaturated nitrile.
Non -2-en en itr ile (1a ). The general procedure was em-
ployed with 8a (68 mg, 0.44 mmol) but adding the MeMgCl to
a cold (-78 °C), THF solution of 8a and maintaining the
temperature at -78 °C for 12 h prior to warming to room
temperature for 12 h. This modification afforded, after radial
chromatography, 43 mg (71%) of (E)-1a 31 and (Z)-1a 32 as a 1:1
mixture of oils. Repetitive radial chromatography provided
pure samples of each isomer: (Z)-1a : IR (film) 3064, 2220,
1620 cm-1; 1H NMR δ 1.20-1.30 (m, 3H), 1.55-1.90 (m, 8H),
2.65-2.78 (m, 2H), 5.54-5.60 (m, 1H), 6.71 (dt, J ) 10.9, 7.7
Hz, 1H); 13C NMR of a 1:1 mixture δ 13.9, 22.4, 27.5, 28.1,
1
(M + H). (Z)-1f: IR (film) 3040, 2213, 1611 cm-1; H NMR δ
1.34 (d, J ) 6.3 Hz, 3H), 2.07 (d, J ) 1.4 Hz, 3H), 2.11 (s, 3H),
2.00-2.20 (m, 5H), 2.60-2.71 (m, 1H), 3.02-3.18 (m, 1H), 5.38
(s, 1H); MS m/e 176 (M + H).
6-(4-Ch lor o-1,1-d im eth ylbu tyl)cycloh ex-1-en eca r bon i-
tr ile (1g). The general procedure was employed with 8g22 (21
mg, 86 mmol) to afford, after radial chromatography, 18 mg
(92%) of 1g as a colorless oil: IR (film) 2959, 2855, 2210, 1615
cm-1; 1H NMR δ 1.01 (s, 3H), 1.07 (s, 3H), 1.44-1.90 (m, 9H),
2.09-2.27 (m, 2H), 3.49 (dt, J ) 13.7, 6.9 Hz, 1H), 3.57 (dt, J
) 13, 6 Hz, 1H), 6.81-6.84 (m, 1H); 13C NMR δ 20.4, 24.1,
25.7, 26.0, 27.5, 36.4, 37.9, 43.4, 45.6, 114.7, 121.5, 150.4; MS
m/e 226 (M + H).
6-(4-Ch lor obu tyl)cycloh ex-1-en eca r bon itr ile (1h ). The
general procedure was employed with 8h 22 (11 mg, 51 mmol)
but refluxing the solution for 2 h immediately following the
addition of MeMgCl. This modification afforded, after radial
chromatography, 9 mg (90%) of 1h as a colorless oil spectro-
(31) E-1a exhibited spectral data identical to that reported previ-
ously: Ro¨ttlander, M.; Boymond, L.; Cahiez, G.; Knochel, P. J . Org.
Chem. 1999, 64, 1080.
(27) For general experimental procedures, see: Fleming, F. F.;
Hussain, Z.; Weaver, D.; Norman, R. E. J . Org. Chem. 1997, 62, 1305.
(28) â-hydroxynitrile 8a has been prepared previously and partial
1H NMR data reported: Barhdadi, R.; Gal, J .; Heintz, M.; Troupel,
M.; Pe´richon, J . Tetrahedron 1993, 49, 5091.
(29) Nucleophilic additions to fenchone generate predominantly the
endo-alcohol corresponding to 8c: Gosselin, P.; J oulain, D.; Laurin,
P.; Rouessac, F. Tetrahedron Lett. 1990, 31, 3151.
(32) Nitrile Z-1a has been reported previously although the 1H NMR
data appears to be incorrectly referenced and is therefore shifted
compared to the stated values: Crowe, W. E.; Goldberg, D. R. J . Am.
Chem. Soc. 1995, 117, 5162.
(33) 1H NMR data for nitrile 1b has been reported previously.13a
(34) Nitrile 1d has been prepared previously although no spectral
data were reported: Palomo, C.; Aizpurua, J . M.; Garcia, J . M.; Ganboa,
I.; Cossio, F. P.; Lecea, B.; Lo´pez, C. J . Org. Chem. 1990, 55, 2498.
(30) Trost, B. M.; Florez, J .; J ebaratnam, D. J . J . Am. Chem. Soc.
1987, 109, 613.