The Journal of Organic Chemistry
Article
1
5
1
0.7, 6.3 Hz, 1H), 5.54 (q, J = 6.3 Hz, 1H), 5.34 (d, J = 17.4 Hz, 1H),
(CH), 117.1 (CH ), 75.0 (CH), 33.5 (CH × 2), 32.5 (CH ), 23.8
2
2
2
+
81
+
.22 (d, J = 10.7 Hz, 1H), 3.70 (t, J = 6.5 Hz, 2H), 1.92−1.81 (m, 2H),
(CH ); HRMS (EI ) m/z calcd for C H BrO [M] 298.0391,
2
14 17
2
13
79
+
.75−1.63 (m, 2H); C NMR (75 MHz, CDCl ) δ 166.0 (C), 136.3
found 298.0391; C H BrO [M] 296.0412, found 296.0411.
3
14 17 2
(
CH), 133.0 (CH), 130.5 (C), 129.7 (CH), 128.4 (CH), 117.0 (CH ),
3-(6-Bromo-2-methylhex-1-enyl) Benzoate (6c). Compound 5c
(0.51 mmol, 0.12 g) was treated according to method E to give the
colorless oil 6c (0.11 g, 70%, purification by column chromatography
2
+
7
5.0 (CH), 62.5 (CH ), 30.7 (CH ), 28.3 (CH ); HRMS (ESI ): m/z
2 2 2
+
calcd for C H O [M + H] : 221.1178, found 221.1172.
13
17
3
−1 1
5
-(1-Hydroxylhept-6-enyl) Benzoate (5b). Compound 4b (3.28
with eluent EtOAc/hexanes 4/96): IR (neat) 1716 (CO) cm ; H
mmol, 1.22 g) was treated according to method D to give the pale
NMR (300 MHz, CDCl ) δ 8.06 (d, J = 8.4 Hz, 2H), 7.57 (t, J = 7.1
3
yellow oil 5b (0.24 g, 97%, over two steps): IR (neat) 3382 (OH),
Hz, 1H), 7.45 (t, J = 7.7 Hz, 2H), 5.46 (br s, 1H), 5.06 (s, 1H), 4.95
−1
1
13
1
715 (CO) cm ; H NMR (300 MHz, CDCl ) δ 8.06 (d, J = 7.8
(s, 1H), 3.45 (t, J = 3.0 Hz, 2H), 2.10−1.90 (m, 4H), 1.82 (s, 3H);
C
3
Hz, 2H), 7.56 (t, J = 7.4 Hz, 1H), 7.46 (t, J = 7.7 Hz, 2H), 5.90 (ddd, J
NMR (75 MHz, CDCl ) δ 165.8 (C), 142.6 (C), 133.0 (CH), 129.6
3
=
17.3, 10.5, 6.3 Hz, 1H), 5.51 (q, J = 6.3 Hz, 1H), 5.33 (d, J = 17.3
(CH), 128.4 (CH), 113.1 (CH ), 76.6 (CH), 33.3 (CH ), 31.2 (CH ),
2
2
2
+
81
Hz, 1H), 5.21 (d, J = 10.5 Hz, 1H), 3.66 (t, J = 6.6 Hz, 2H), 1.92−1.69
28.5 (CH ), 18.2 (CH ); HRMS (EI ) m/z calcd for C H BrO2
2
3
14 17
13
+
79
+
(
m, 2H), 1.62 (q, J = 6.7 Hz, 2H), 1.56−1.42 (m, 2H); C NMR (75
[M] 298.0391, found 298.0391; C H BrO [M] 296.0412, found
14 17 2
MHz, CDCl ) δ 165.9 (C), 136.3 (CH), 132.9 (CH), 130.4 (C), 129.5
296.0406.
3
(
3
CH), 128.3 (CH), 116.7 (CH ), 75.1 (CH), 62.5 (CH ), 34.0 (CH ),
3-(7-Bromo-2-methylhept-1-enyl) Benzoate (6d). Compound 5d
(2.09 mmol, 0.52 g) was treated according to method E to give the
colorless oil 6d (0.55 g, 85%, purification by column chromatography
2
2
2
+
2.3 (CH ), 21.3 (CH ); HRMS (ESI ) m/z calcd for C H O Na
2 2 14 18 3
+
[
M + Na] 257.1148, found 257.1145.
-(1-hydroxyl-5-methylhex-5-enyl) Benzoate (5c). Compound 4c
0.88 mmol, 0.31 g) was treated according to method D to give the
−1 1
4
with eluent EtOAc/hexanes 3/97): IR (neat) 1716 (CO) cm ; H
(
NMR (300 MHz, CDCl ) δ 8.06 (d, J = 7.8 Hz, 2H), 7.57 (t, J = 7.4
3
colorless oil 5c (0.12 g, 61%): IR (neat) 3401 (OH), 1713 (CO)
Hz, 1H), 7.45 (t, J = 7.5 Hz, 2H), 5.43 (t, J = 6.5 Hz, 1H, CHOBz),
5.05 (s, 1H), 4.95 (s, 1H), 3.41 (t, J = 6.8 Hz, 2H), 1.92 (quintet, J =
−1 1
cm ; H NMR (300 MHz, CDCl ) δ 8.06 (d, J = 7.8 Hz, 2H), 7.57 (t,
3
J = 7.1 Hz, 1H), 7.44 (t, J = 7.5 Hz, 2H), 5.46 (t, J = 6.5 Hz, 1H), 5.05
7.3 Hz, 2H), 1.85−1.70 (m, overlapped with one s at 1.80, CH , 5H),
3
13
(
1
s, 1H), 4.94 (s, 1H), 3.70 (t, J = 6.3 Hz, 2H), 1.94−1.83 (m, 2H),
1.59−1.43 (m, 2H); C NMR (75 MHz, CDCl ) δ 165.8 (C), 142.8
3
13
.81 (s, 3H), 1.72−1.59 (m, 2H), 1.45 (br s, 1H, OH); C NMR (75
(C), 132.9 (CH), 130.4 (C), 129.6 (CH), 128.4 (CH), 113.1 (CH ),
2
MHz, CDCl ) δ 165.8 (C), 142.9 (C), 132.9 (CH), 130.5 (C), 129.6
77.4 (CH), 33.4 (CH ), 32.4 (CH ), 31.7 (CH ), 23.9 (CH ), 18.2
3
2
2
2
2
+
81
+
(
2
CH), 128.4 (CH), 112.9 (CH ), 77.6 (CH), 62.5 (CH ), 29.1 (CH ),
(CH ); HRMS (EI ) m/z calcd for C H BrO [M] 312.0548,
2
2
2
3 15 19 2
+
79
+
8.5 (CH ), 18.2 (CH ); HRMS (ESI ) m/z calcd for C H O Na
found 312.0544; C H BrO [M] 310.0568, found 310.0573.
15 19 2
2
3
14 18
3
+
[
M + Na] 257.1154, found 257.1147.
-(1-Hydroxyl-6-methylhept-6-enyl) Benzoate (5d). Compound
d (2.20 mmol, 0.85 g) was treated according to method D to give the
6-Benzoyloxy-2-hexanone (8c). A solution of 6c (0.36 mmol,
5
0.11 g) in CH Cl (5 mL) was cooled to −78 °C, and then a stream of
2
2
4
ozone was bubbled into the reaction solution. Once the solution
turned blue, ozone was bubbled for around 10 min, and then the
ozone generator was turned off. Oxygen was continuously bubbled
into the solution for another 5 min in order to disperse ozone
remaining in the solution. While the solution turned from blue to
colorless, excess dimethyl sulfoxide (0.9 mL) was added at the same
temperature. The reaction mixture was warmed to room temperature
and stirred for 5 h and then diluted with CH Cl (60 mL). The
colorless oil 5d (0.28 g, 51%): IR (neat) 3379 (OH), 1716 (CO)
−1 1
cm ; H NMR (300 MHz, CDCl ) δ 8.06 (d, J = 6.6 Hz, 2H), 7.55
3
(
tt, J = 7.2, 1.5 Hz, 1H), 7.44 (t, J = 7.4 Hz, 2H), 5,43 (t, J = 6.6 Hz,
1
H), 5.04 (s, 1H) 4.93 (s, 1H), 3.64 (t, J = 6.6 Hz, 2H), 1.92−1.69 (m,
overlapped with one s at 1.80, 5H), 1.68−1.55 (m, 2H), 1.53−1.35
(
(
m, 2H); 13C NMR (75 MHz, CDCl ) δ 165.8 (C), 143.0 (C), 132.9
CH), 130.5 (C), 129.5 (CH), 128.3 (CH), 112.9 (CH ), 77.7 (CH),
3
2
2
2
6
2.6 (CH ), 32.5 (CH ), 32.4 (CH ), 21.6 (CH ), 18.2 (CH ); HRMS
organic layer was washed with water (20 mL) and brine (20 mL),
filtered, and concentrated to give 7c, which was used for the next step
without purification.
2
2
2
2
3
+
+
(
ESI ) m/z calcd for C H O Na [M + Na] 271.1305, found
15 20 3
2
71.1301.
General Procedure E. To the solution of compound 5a−d (1
equiv) and triphenylphosphine (1.75 equiv) in CH Cl was added
To a refluxing solution of the radical precursor 7c (0.22 mmol, 0.07
g) in benzene (3.7 mL) at 88 °C was added dropwise a solution of
AIBN (0.040 mmol, 0.007 g) and tributyltin hydride (0.33 mmol, 0.09
mL) in benzene (3.6 mL) over 1 h. The resulting solution was stirred
at same temperature for 30 min. The solution was cooled and directly
concentrated to give a crude product. To a solution of this crude
product in THF (2.2 mL) was added triethylamine (0.06 mL). The
reaction mixture was stirred for 3 h and then concentrated to give a
crude product, which was purified by column chromatography (silica
gel/KF 9/1; EtOAc/hexanes 2/8) to give the colorless oil 8c (44 mg,
2
2
slowly a solution of tetrabromomethane (1.5 equiv) in CH Cl . The
2
2
reaction mixture was stirred at room temperature for 5 h. The reaction
solution was directly concentrated to give a crude product, which was
purified by column chromatography to give 6a−d.
3
-(6-Bromohex-1-enyl) Benzoate (6a). Compound 5a (1.29 mmol,
0
.30 g) was treated according to method E to give the colorless oil 6a
(
0.35 g, 96%, purification by column chromatography with eluent
−1 1
EtOAc/hexanes 5/95): IR (neat) 1716 (CO) cm ; H NMR (300
−1 1
MHz, CDCl ) δ 8.06 (d, J = 7.2 Hz, 2H), 7.57 (t, J = 7.5 Hz, 1H), 7.45
90%, over two steps): IR (neat) 1713 (CO) cm ; H NMR (300
3
(
t, J = 7.5 Hz, 2H), 5.90 (ddd, J = 17.1, 10.7, 6.3 Hz, 1H), 5.54 (m,
MHz, CDCl ) δ 8.03 (d, J = 7.8 Hz, 2H), 7.56 (t, J = 7.1 Hz, 1H), 7.34
3
1
5
1
H), 5.35 (d, J = 17.1 Hz, 1H), 5.24 (d, J = 10.7 Hz, 1H), 3.54 (t, J =
(t, J = 8.1 Hz, 2H), 4.32 (t, J = 6.0 Hz, 2H), 2.52 (t, J = 6.8 Hz, 2H),
13
13
.9 Hz, 2H), 2.09−1.87 (m, 4H); C NMR (75 MHz, CDCl ) δ
2.15 (s, 3H), 1.83−1.72 (m, 4H); C NMR (75 MHz, CDCl ) δ
3
3
65.8 (C), 136.1 (CH), 133.1 (CH), 130.4 (C), 129.7 (CH), 128.5
208.4 (C), 166.6 (C), 132.9 (CH), 130.3 (C), 129.5 (CH), 128.3
(CH), 64.5 (CH ), 43.0 (CH ), 29.9 (CH ), 28.1 (CH ), 20.2 (CH );
(
CH), 117.2 (CH ), 74.3 (CH), 33.3 (CH ), 33.0 (CH ), 28.5 (CH );
2 2 2 2
2
2
3
2
2
+
79
+
+
+
HRMS (FAB ) m/z calcd for C H O Br [M] 282.0255, found
HRMS (ESI ) m/z calcd for C H O K [M + K] 259.0737, found
13
15
2
13 16 3
81
+
2
82.0259; C H O Br [M] 284.0235, found 284.0234. Anal. Calcd
259.0739.
1
3
15
2
for C H O Br: C, 55.140; H, 5.340. Found: C, 55.662; H, 5.427.
7-Benzoyloxy-2-heptanone (8d). A solution of 6d (1.77 mmol,
13
15
2
3-(7-Bromohept-1-enyl) Benzoate (6b). Compound 5b (2.67
0.55 g) in CH Cl (18 mL) was cooled to −78 °C, and then a stream
2
2
mmol, 0.63 g) was treated according to method E to give the
of ozone was bubbled into the reaction solution. Once the solution
turned blue, ozone was bubbled for around 10 min, and then the
ozone generator was turned off. Oxygen was continuously bubbled
into the solution for another 5 min in order to disperse ozone
remaining in the solution. While the solution turned from blue to
colorless, excess dimethyl sulfoxide (4.5 mL) was added at the same
temperature. The reaction mixture was warmed to room temperature
and stirred for 5 h and then diluted with CH Cl (120 mL). The
colorless oil 6b (0.65 g, 82%, purification by column chromatography
−1 1
with eluent EtOAc/hexanes 5/95): IR (neat) 1715 (CO) cm ; H
NMR (300 MHz, CDCl ) δ 8.06 (d, J = 7.8 Hz, 2H), 7.57 (t, J = 6.9
3
Hz, 1H), 7.45 (t, J = 7.1 Hz, 2H), 5.90 (ddd, J = 17.0, 10.6, 6.3 Hz,
1
1
1
H), 5.50 (q, J = 6.3 Hz, 1H), 5.34 (d, J = 17.0 Hz, 1H), 5.23 (d, J =
0.6 Hz, 1H), 3.41 (t, J = 6.6 Hz, 2H), 1.92 (quintet, J = 7.2 Hz, 2H),
13
.86−1.69 (m, 2H), 1.66−1.50 (m, 2H); C NMR (75 MHz, CDCl3)
2
2
δ 165.9 (C), 136.3 (CH), 133.0 (CH), 130.5 (C), 129.7 (CH), 128.5
organic layer was washed with water (40 mL) and brine (40 mL),
F
J. Org. Chem. XXXX, XXX, XXX−XXX