Radical Reactions of Epoxyketones and Epoxynitriles
(
3H, s), 1.80-2.60 (12H, m), 3.44 (1H, d, J ) 10.5 Hz), 3.52 (1H,
H, C13
H
20NO
2
), calcd 222.1483. Anal. Calcd for C13
2
H19NO : C,
d, J ) 10.7 Hz)*, 3.73 (1H, d, J ) 10.7 Hz)*, 3.76 (1H, d, J )
70.56; H, 8.65; N, 6.33. Found: C, 70.67; H, 8.64; N, 6.34.
2-(Hydroxymethyl)-2-methyl-5-(pent-4-enyl)hexanedinitrile 42
(32 mg, 31%) was obtained as a mixture of isomers in a ratio of
3
1:1: IR, ν 3461, 2242, 1644, 1073 cm ; H NMR (CDCl ) δ 1.35
1
5
2
3
6
1
0.5 Hz), 5.22 (2H, d, J ) 15.3 Hz), 5.25 (2H, d, J ) 24.1 Hz),
.80 (2H, m) ppm; 13C NMR (CDCl
9.2 (CH ), 29.9 (CH ), 30.1 (CH )*, 30.2 (CH
)*, 48.3 (C), 49.3 (C)*, 51.3 (C)*, 51.4 (C), 66.6 (CH
)*, 118.5 (C)*, 119.2 (C), 120.7 (CH ), 120.9 (CH
) δ 19.8 (CH
)*, 20.7 (CH
)*, 36.7 (CH
),
),
),
3
3
3
2
2
-
1 1
2
2
2
2
8.6 (CH
7.6 (CH
2
(3H, s), 1.36 (3H, s), 1.50-2.20 (12H, m), 2.58 (2H, m), 3.64 (4H,
m), 5.00 (2H, d, J ) 9.2 Hz), 5.03 (2H, d, J ) 17.2 Hz), 5.78 (2H,
2
2
2
)*,
m) ppm; 13C NMR (CDCl
) δ 20.5 (CH
), 21.0 (CH
), 26.2 (2CH
30.6 (CH)*, 130.7 (CH), 212.9 (C) 213.2 (C)* ppm; MS EI, m/z
3
3
3
2
),
+
(
relative intensity) 192 (M - 1, 3), 150 (14), 136 (16), 122 (19),
27.5 (CH
(CH), 32.9 (2CH
67.6 (CH ), 68.0 (CH
(2CH) ppm; MS EI, m/z (relative intensity) 205 (M - 15, 3), 190
(3), 189 (12), 175 (16), 161 (20), 134 (14), 122 (74), 109 (85), 94
2
), 27.7 (CH
), 33.1 (CH
), 115.4 (2CH
2
2
), 31.2 (CH
2
), 31.3 (CH
2
), 31.5 (CH), 31.6
+
9
4 (32), 67 (26), 57 (100); HRMS (ESI) 194.1132 (M + H, C11
NO ), calcd 194.1176. Anal. Calcd for C11 : C, 68.37; H,
.82; N, 7.25. Found: C, 68.42; H, 7.84; N, 7.28.
A mixture of isomers of 5-allyl-2-(hydroxymethyl)-2-methyl-
hexanedinitrile 34 (30 mg, 30%) was obtained in a ratio 1.5:1, as
a viscous liquid: IR, ν 3455, 2242, 1060 cm-1; 1H NMR (CDCl
δ 1.34 (3H, s), 1.36 (3H, s), 1.75-2.10 (8H, m), 2.40 (4H, m),
.66 (2H, m), 3.63 (4H, m), 5.20 (1H, d, J ) 11.3 Hz), 5.22 (1H,
H
16
-
2
2
), 33.2 (CH
2
), 39.1 (C), 39.3 (C),
2
H15NO
2
2
2
), 121.3 (2C), 122.4 (2C), 137.4
+
7
+
(95), 81 (63), 69 (100), 54 (97); HRMS (ESI) 221.1693 (M + H,
C H N O), calcd 221.1649. Anal. Calcd for C13H N O: C, 70.87;
13 21 2 20 2
3
)
H, 9.15; N, 12.72. Found: C, 70.77; H, 9.21; N, 12.79.
Reaction of 43 with Cp TiCl. According to GP 1, reaction of
43 (200 mg, 1.41 mmol) with Cp TiCl followed by flash chroma-
tography (hexane/ethyl acetate 70:30) furnished 1,2,2-trimethylcy-
clopentane-1,3-diol 46, minor isomer (75 mg, 37%), major isomer
(99 mg, 49%).
2
2
13
d, J ) 16.6 Hz), 5.81 (2H, m) ppm; C NMR (CDCl
3
) δ 20.5
), 31.4 (CH), 31.5
)*, 36.1 (CH ), 39.1
), 119.3 (2CH ), 120.8 (2C),
22.4 (2C), 132.4 (2CH) ppm; MS EI, m/z (relative intensity) 177
2
(CH
(CH)*, 33.0 (CH
(C)*, 39.2 (C), 67.5 (CH
3
)*, 21.0 (CH
), 33.1 (CH
)*, 67.9 (CH
3
), 26.9 (CH
2
)*, 27.1 (CH
2
2
2
)*, 35.9 (CH
2
2
2
2
2
Data for minor isomer, colorless oil: IR, ν 3381, 1036 cm-1;
1
(
1
(
+
1
M - 15, 3), 175 (12), 161 (31), 147 (49), 134 (40), 122 (19),
H NMR (CDCl ) δ 0.76 (3H, s), 1.03 (3H, s), 1.14 (3H, s), 1.88
3
08 (17), 94 (62), 81 (89), 68 (100), 54 (92); HRMS (ESI) 193.1375
(3H, m), 2.09 (1H, m), 2.96 (1H, br s), 3.73 (1H, d, J ) 5.9 Hz)
+
13
M
+ H, C11
H
17
N
2
O), calcd 193.1336. Anal. Calcd for
ppm; C NMR (CDCl ) δ 15.8 (CH ), 21.5 (CH ), 23.8 (CH ),
3
3
3
3
C
11
H
16
N
2
O: C, 68.72; H, 8.39; N, 14.57. Found: C, 68.97; H, 8.32;
2 2
30.7 (CH ), 37.8 (CH ), 48.2 (C), 82.8 (CH), 83.3 (C) ppm; MS
+
N, 14.53.
Reaction of 35 with Cp
5 (120 mg, 0.73 mmol) with Cp
EI, m/z (relative intensity) 126 (M - 18, 14), 111 (59), 93 (71),
+
2
TiCl. According to GP 1, reaction of
TiCl followed by flash chroma-
69 (80), 55 (89), 43 (100); HRMS (ESI) 167.1053 (M + Na,
3
2
8 16 2 8 16 2
C H O Na), calcd 167.1047. Anal. Calcd for C H O : C, 66.63;
tography (hexane/diethyl ether 70:30) furnished 5-allyl-2-(hy-
H, 11.18. Found: C, 66.87; H, 11.07.
droxymethyl)-2-methylcyclopentanone 36, major isomer (58 mg,
Data for major isomer, white solid: mp 85-89 °C; IR, ν 3391,
-
1 1
48%) and minor isomer (49 mg, 40%).
1055 cm ; H NMR (CDCl
(3H, s), 1.4-2.2 (5H, m), 4.17 (1H, t, J ) 8.5 Hz) ppm; C NMR
(CDCl ) δ 17.4 (CH ), 18.8 (CH ), 23.3 (CH ), 29.0 (CH ), 35.9
(CH ), 47.3 (C), 79.4 (CH), 81.7 (C) ppm; MS EI, m/z (relative
intensity) 126 (M - 18, 13), 108 (92), 93 (40), 83 (39), 71 (100),
3
) δ 0.77 (3H, s), 0.95 (3H, s), 1.17
13
Data for major isomer, as a viscous liquid: IR, ν 3444, 1730
-
1 1
cm ; H NMR (CDCl
3
) δ 1.09 (3H, s), 1.65 (2H, m), 2.07 (3H,
3
3
3
3
2
m), 2.41 (2H, m), 3.47 (1H, d, J ) 10.8 Hz), 3.55 (1H, d, J ) 10.8
2
+
Hz), 5.02 (1H, d, J ) 7.6 Hz), 5.07 (1H, d, J ) 13.0 Hz), 5.74
1H, m) ppm; 13C NMR (CDCl
) δ 20.3 (CH
), 47.9 (CH), 50.1 (C), 67.1 (CH
35.6 (CH), 224.3 (C) ppm; MS EI, m/z (relative intensity) 168
), 25.0 (CH
), 31.6
+
(
(
3
3
2
55 (55); HRMS (ESI) 167.1043 (M + Na, C
8
H
16
O
2
Na), calcd
CH
2
), 33.7 (CH
2
2
), 116.6 (CH
2
),
167.1047. Anal. Calcd for C
C, 66.98; H, 11.13.
8 16 2
H O : C, 66.63; H, 11.18. Found:
1
(
+
M , 5), 122 (14), 107 (12), 100 (23), 81 (53), 67 (100), 57 (96);
Reaction of 47 with Cp
47 (150 mg, 0.82 mmol) with Cp
2
TiCl. According to GP 1, reaction of
TiCl followed by flash chroma-
+
HRMS (ESI) 169.1245 (M + H, C10
Calcd for C10 : C, 71.39; H, 9.59. Found: C, 71.45; H, 9.53.
Data for minor isomer, as a viscous liquid: IR, ν 3444, 1737
17 2
H O ), calcd 169.1223. Anal.
2
H O
16 2
tography (hexane/ethyl acetate 70:30) furnished of 1-but-3-enyl-
2,2-dimethylcyclopentane-1,3-diol 51, minor isomer (30 mg, 20%)
and major isomer (96 mg, 63%)
-
1 1
3
cm ; H NMR (CDCl ) δ 0.98 (3H, s), 1.64 (2H, m), 1.96 (1H,
m), 2.12 (2H, m), 2.26 (1H, m), 2.50 (1H, m), 3.48 (1H, d, J )
Data for minor isomer, colorless oil: 1H NMR (CDCl
3
) δ 0.79
1
5
0.8 Hz), 3.65 (1H, d, J ) 10.8 Hz), 5.02 (1H, d, J ) 9.2 Hz),
(3H, s), 1.07 (3H, s), 1.48 (1H, m), 1.61 (1H, s), 1.81 (2H, m),
1.97 (1H, m), 2.12 (2H, m), 2.31 (1H, m), 3.75 (1H, br s), 4.96
(1H, d, J ) 10 Hz), 5.05 (1H, d, J ) 16.2 Hz), 5.87 (1H, m) ppm;
13
.06 (1H, d, J ) 12.3 Hz), 5.73 (1H, m) ppm; C NMR (CDCl
), 24.9 (CH ), 30.7 (CH ), 34.1 (CH ), 49.6 (CH), 50.5
C), 67.4 (CH ), 116.5 (CH ), 135.5 (CH), 224.0 (C) ppm; MS EI,
m/z (relative intensity) 168 (M , 5), 122 (17), 107 (12), 100 (30),
1 (49), 67 (100), 57 (96); HRMS (ESI) 169.1228 (M+ + H,
), calcd 169.1223. Anal. Calcd for C10 : C, 71.39;
H, 9.59. Found: C, 71.35; H, 9.57.
Reaction of 37 with Cp TiCl. According to GP 1, reaction of
7 (100 mg, 0.47 mmol) with Cp TiCl followed by flash chroma-
tography (70:30 hexane/ethyl acetate) furnished 3-(hydroxymethyl)-
3
)
δ 18.9 (CH
3
2
2
2
1
3
(
2
2
C NMR (CDCl
(CH ), 34.4 (CH ), 35.6 (CH
20 2
(CH ), 139.3 (C) ppm; HRMS (ESI) 207.1345 (M + Na, C11H O -
3
) δ 16.0 (CH
3 3 2
), 23.7 (CH ), 28.4 (CH ), 30.8
+
2
2
2
), 48.8 (C), 83.5 (CH), 85.4 (C), 114.4
+
8
2
C
10
H
17
O
2
H O
16 2
20 2
Na), calcd 207.1355. Anal. Calcd for C11H O : C, 71.70; H, 10.94.
Found: C, 71.87; H, 10.96.
1
2
Data for major isomer, white solid: mp 88-89 °C; H NMR
3
2
(CDCl
m), 2.12 (2H, m), 2.21 (1H, m), 4.20 (1H, dd, J ) 8.2 Hz, J
8.3 Hz), 4.96 (1H, d, J ) 10.1 Hz), 5.04 (1H, d, J ) 17.2 Hz),
5.86 (1H, m) ppm; 13C NMR (CDCl
) δ 16.9 (CH ), 18.8 (CH ),
27.80 (CH ), 28.7 (CH ), 33.5 (CH ), 35.2 (CH ), 47.8 (C), 79.3
(CH), 83.5 (C), 114.5 (CH ), 139.2 (C) ppm; HRMS (ESI) 207.1318
Na), calcd 207.1355. Anal. Calcd for
: C, 71.70; H, 10.94. Found: C, 71.63; H, 11.07.
Reaction of 54 with Cp TiCl. According to GP 1, reaction of
51 (125 mg, 0.55 mmol) with Cp TiCl followed by flash chroma-
3
) δ 0.78 (3H, s), 1.09 (3H, s), 1.2-1.7 (4H, m), 1.84 (1H,
1
)
3
6
2
1
1
5
2
3
3
6
1
-methyl-2-oxo-1-(pent-4-enyl)cyclopentanecarbonitrile 40 (64 mg,
2
2%), as a mixture of isomers in a ratio of 2:1: IR, ν 3487, 3078,
3
3
3
-
1 1
242, 1748 cm ; H NMR (CDCl
3
) δ 1.09 (3H, s)*, 1.15 (3H, s),
2
2
2
2
.50-2.50 (20H, m), 3.46 (1H, d, J ) 10.5 Hz), 3.55 (1H, d, J )
2
+
0.7 Hz)*, 3.75 (1H, d, J ) 10.7 Hz)*, 3.78 (1H, d, J ) 10.5 Hz),
(M + Na, C11
20 2
H O
.04 (4H, m), 5.78 (2H, m) ppm; 13C NMR (CDCl
) δ 20.1 (CH
)*,
)*,
)*,
3
3
11 20 2
C H O
0.9 (CH
1.0 (CH
3
), 24.0 (CH
), 31.2 (CH
2
), 24.2 (CH
2
)*, 29.6 (CH
), 33.1 (CH
2
), 30.2 (CH
), 33.1 (CH
2
2
2
2
)*, 32.2 (CH
2
2
2
2
4.1 (CH
7.7 (CH
2
)*, 48.6 (C), 49.7 (C)*, 51.1 (C)*, 51.2 (C), 67.0 (CH
2
),
tography (hexane/diethyl ether 60:40) furnished a diastereomeric
mixture of ethyl 2-hydroxy-3-hydroxymethyl-1,2,3-trimethylcyclo-
pentanecarboxylate 57 (82 mg, 65%) in a ratio of 7:3, as a viscous
2
)*, 115.4 (CH ), 115.6 (CH )*, 118.6 (C)*, 119.4 (C),
2
2
37.2 (CH)*, 137.3 (CH), 213.3 (C) 213.71 (C)* ppm; MS EI, m/z
+
-1 1
(relative intensity) 206 (M - 15, 2), 154 (40), 122 (19), 110 (18),
3
liquid: IR, ν 3426, 1720, 1033 cm ; H NMR (CDCl ) δ (major)
+
94 (25), 80 (23), 72 (39), 57 (100); HRMS (ESI) 222.1456 (M +
0.88 (3H, s), 1.19 (3H, s), 1.24 (3H, t, J ) 7.0 Hz), 1.24 (3H, s),
J. Org. Chem, Vol. 72, No. 26, 2007 9981