Deconjugation of 7-Substituted 3,4-Didehydro-2-oxepanones
J . Org. Chem., Vol. 63, No. 2, 1998 293
3,4-Did eh yd r o-7-(2-p h en eth yl)-2-oxep a n on e (6d ): 80%;
1H NMR (300 MHz) δ 7.32-7.17 (5H, m), 6.42-6.35 (1H, td,
J ) 12, 4.5 Hz), 6.02-5.96 (1H, td, J ) 12, 2 Hz), 4.32-4.24
(1H, m), 2.86-2.72 (2H, m), 2.58-2.32 (2H, m), 2.17-2.1.95
(3H, m), 1.90-1.80 (1H, m); IR (film) 1685 cm-1. Anal. Calcd
for C14H16O2: C, 77.75; H, 7.45. Found: C, 77.87; H 7.60.
3,4-Did eh yd r o-7-m eth yl-2-oxep a n on e (6a ). This mate-
rial was synthesized from 2-methylcyclohexanone by following
the above protocol for the transformation of 3b into 6b. The
material 4a 16 was obtained from 3a in 80% yield. The yield
and the spectral characteristics of the intermediate 5a are
given below. The species 5a was transformed into the known
6a 16 in 76% yield.
with EtOAc (20 mL) and H2O (2 mL). This resulted in a clear
biphasic solution to which was added enough anhyd Na2SO4
to absorb the water. Filtration and solvent removal furnished
8: 0.80 g, 80%. Absence of the broad multiplet at δ 2.0 for
the allylic CH2 in DBU indicated a complete reduction: 1H
NMR (60 MHz) δ 3.8-2.9 (1H, br m), 2.9-2.3 (7H, m), 1.9-
1.2 (10H, br m). Anal. Calcd for C9H18N2: C, 70.08; H, 11.76;
N, 18.16. Found: C, 69.76; H, 12.00; N, 18.48.
8-Meth yl-1,8-d ia za bicyclo[5.4.0]u n d eca n e (9). MeI (2.0
g, 14 mmol) was added to a stirring solution of DBU (1.52 g,
10 mmol) in dry benzene (25 mL) at rt. A white precipitate
separated out immediately. The stirring was continued for
30 min, and then the solvent was evaporated. The white solid
thus received was taken in EtOH (20 mL) and treated with,
in portions and under stirring, NaBH4 (0.38 g, 10 mmol). After
2 h, the EtOH was evaporated and the residue was dissolved
in EtOAc (20 mL) and H2O (3 mL). Enough Na2SO4 was added
to absorb H2O. Filtration and solvent removal furnished 9:
1.52 g, 90%; 1H NMR (300 MHz) δ 2.85-2.54 (7H, m), 2.47
(3H, s), 1.80-1.59 (10H, m). Anal. Calcd for C10H20N2: C,
71.38; H, 11.98; N, 16.64. Found: C, 71.15; H, 12.24; N, 16.88.
tr a n s- a n d cis-7-Ben zyl-4,5-ep oxy-2-oxep a n on es (14
a n d 15). To a stirred solution of 7b (44 mg, 0.22 mmol) in
CHCl3 (0.4 mL) at 5 °C was added PhCO3H (0.56 mL of a 0.5
M solution in CHCl3). The mixture allowed to come to rt and
stirred for 15 h. Saturated aqueous Na2SO3 (3 mL) was added,
and the contents were stirred for 30 min. The reaction was
partitioned between CHCl3 (15 mL) and H2O (5 mL). The
layers were separated, and the aqueous layer was extracted
with CHCl3 (2 × 5 mL). The combined organic extracts were
washed with 10% aqueous NaHCO3 (2 × 7 mL) and brine (7
mL). Drying, removal of solvent, and chromatography fur-
nished 14 (28 mg, 60%, mp 78-79 °C) and 15 (14 mg, 30%,
mp 86-87 °C), both as powdery solids. 14: 1H NMR (400 MHz)
δ 7.35-7.15 (5H, m), 4.30 (1H, m), 3.30 (1H, m), 3.20-3.10
(2H, m), 3.05 (1H, dd, J ) 12, 6 Hz), 2.96 (1H, dd, J ) 15, 3
Hz), 2.85 (1H, dd, J ) 12, 6 Hz), 2.45 (1H, d, J ) 15 Hz), 2.16
(1H, ddd, J ) 15, 10, 2 Hz); IR (KBr) 1720, 1590 cm-1. Anal.
Calcd for C13H14O3: C, 71.54; H, 6.47. Found: C, 71.61; H,
6.37. 15: 1H NMR (400 MHz) δ 7.35-7.20 (5H, m), 4.66 (1H,
m), 3.41 (1H, unsym d, J ) 15 Hz), 3.30 (1H, dd, J ) 15, 6
Hz), 3.2 (2H, m), 3.05 (1H, dd, J ) 15, 6 Hz), 2.78 (1H, dd, J
) 15, 6 Hz), 2.37 (1H, dd, J ) 18, 12 Hz), 2.18 (1H, ddd, J )
3-(P h en ylselen en yl)-7-m eth yl-2-oxep a n on e (5a ): 70%
(isomeric mixture); 1H NMR (60 MHz) δ 7.7-7.2 (5H, m), 5.2-
4.7 (1H, m), 4.3-4.0 (1H, bt), 1.3 (3H, d, J ) 6 Hz); IR (film)
1705 cm-1
.
3,4-Did eh yd r o-7-isop r op yl-4-m eth yl-2-oxep a n on e (6e).
Like the synthesis of 6a from 3a , the synthesis of 6e com-
menced from menthone (3e). The oxidation of 3e proceeded
in 70% yield to generate the known 4e.16 The yields and the
spectral characteristic of 5e and 6e are given below:
cis- a n d tr a n s-3-(p h en ylselen en yl)-7-isop r op yl-4-m eth -
yl-2-oxep a n on e (5e): 60%; 1H NMR (60 MHz) δ 7.6 (2H, bs),
7.3 (3H, bs), 4.6 (1H, bs), 4.3-4.0 (1H, m), 1.2 (3H, d, J ) 6.5
Hz), 1.0 (6H, 2d, J ) 6.5 Hz).
3,4-D id e h y d r o -7-is o p r o p y l-4-m e t h y l-2-o x e p a n o n e
(6e): 60%; 1H NMR (300 MHz) δ 5.86 (1H, t, J ) 1.2 Hz),
4.06-4.01 (1H, ddd, J ) 2.7 Hz), 2.54-2.44 (1H, td, J ) 18, 6
Hz), 2.33-2.22 (1H, m), 1.94 (3H, s), 1.00-0.97 (6H, 2d, J )
6.6 Hz). Anal. Calcd for C10H16O2: C, 71.38; H, 9.59. Found:
C, 71.59; H, 9.85.
Gen er a l P r oced u r e for Isom er iza tion . The lactones
6a -e (0.05 mmol) and DBU (0.076 g, 0.05 mmol) were mixed
together in CHCl3 (2 mL) [or CDCl3 (0.4 mL) if the reaction
1
was to be monitored by H NMR] and kept aside [for 3 h for
6a -d (but for the equilibration studies when the reactions were
monitored for as long as 60 h) and for 30 h for 6e] while the
progress was monitored by TLC. The workup involved dilution
with Et2O (10 mL) and washing with cold 2% aqueous HCl (2
× 5 mL), water (1 × 5 mL), and brine (1 × 5 mL). The organic
solution was dried, concentrated to furnish a residue, and
purified. The material balance was nearly quantitative.
7-Ben zyl-4,5-d id eh yd r o-2-oxep a n on e (7b ): 1H NMR
(300 MHz) δ 7.34-7.22 (5H, m), 5.69-5.61 (1H, m), 5.58-5.48
(1H, m), 4.93-4.85 (1H, m), 3.67-3.60 (1H, md), 3.13-3.06
(1H, dd, J ) 14, 6.8 Hz), 3.07-2.99 (1H, dd, J ) 16.5, 8.7 Hz),
2.88-2.81 (1H, dd, J ) 14, 6 Hz), 2.45-2.41 (2H, m); IR (film)
1720, 1650 cm-1. Anal. Calcd for C13H14O2: C, 77.20; H, 6.93.
Found: C, 77.30; H, 7.10.
7-(p -Me t h o x y b e n zy l)-4,5-d id e h y d r o -2-o x e p a n o n e
(7c): 1H NMR (300 MHz) δ 7.17 (2H, d, J ) 8.5 Hz), 6.85 (2H,
d, J ) 8.5 Hz), 5.69-5.62 (1H, td, J ) 11, 3.6 Hz), 5.52 (1H,
m), 4.88-4.79 (1H, q, J ) 6 Hz), 3.79 (3H, s), 3.07-3.00 (1H,
dd, J ) 14, 6.6 Hz), 2.82-2.75 (1H, dd, J ) 14, 6.3 Hz), 2.42-
2.40 (2H, m). Anal. Calcd for C14H16O3: C, 72.39; H, 6.94.
Found: C, 72.20; H 7.18.
15, 4, 2 Hz); IR (KBr) 1730, 1590 cm-1
13H14O3: C, 71.54; H, 6.47. Found: C, 71.64; H, 6.58.
t r a n s-3,4-D id e h y d r o -5-h y d r o x y -7-b e n zy l-2-o x e p a -
. Anal. Calcd for
C
n on e (16) a n d 7-exo-Ben zyl-2,6-d ioxa -3-oxobicyclo[3.3.0]-
octa n e (17). K2CO3 (90 mg, 0.66 mmol) was added to a
solution of 14 (48 mg, 0.22 mmol) in DMF (1.0 mL). The
mixture was stirred at rt for 2 h, and then 5 mL H2O was
added. This was extracted thoroughly with EtOAc (3 × 10
mL). The combined extracts were washed with brine (10 mL),
dried, and concentrated. The residue was chromatographed
1
to afford 16 (36 mg, 75%) and 17 (10 mg, 20%). 16: H NMR
(60 MHz) δ 7.2 (5H, s), 6.3 (1H, dd, J ) 12, 3 Hz), 5.7 (1H, dd,
J ) 12, 1 Hz), 4.9-4.2 (2H, m), 2.9 (2H, dd, J ) 14, 6 Hz),
2.3-1.9 (2H, m); IR (film) 3420, 1695, 1625, 1490 cm-1. Anal.
Calcd for C13H14O3: C, 71.54; H, 6.47. Found: C, 71.41; H,
6.29. 17: 1H NMR (300 MHz) δ 7.33-7.18 (5H, m), 5.09-
5.06 (1H, t, J ) 5 Hz), 4.82-4.79 (1H, t, J ) 5 Hz), 4.40-4.31
(1H, sextet, J ) 6 Hz), 2.95 (1H, dd, J ) 12, 6 Hz), 2.85 (1H,
dd, J ) 12, 6 Hz), 2.75 (1H, dd, J ) 18, 6 Hz), 2.65 (1H, d, J
) 18 Hz), 2.35-2.29 (1H, dd, J ) 12, 4 Hz), 1.80-1.71 (1H,
ddd, J ) 12, 9, 4 Hz); 13C NMR δ 175.7, 137.3, 129.1, 128.3,
126.4, 84.5, 78.6, 77.6, 40.5, 38.1, 36.4; IR (film) 1770, 1590
cm-1. Anal. Calcd for C13H14O3: C, 71.54; H, 6.47. Found:
C, 71.48; H, 6.60.
7-en d o-Ben zyl-2,6-d ioxa -3-oxobicyclo[3.3.0]octa n e (19).
This material was prepared from the cis-oxirane 15 (48 mg,
0.22 mmol) by treatment with K2CO3 (90 mg, 0.66 mmol) in
dry DMF for 2 h. Usual workup as above for the transforma-
tion of 14 into 16 and 17 and purification furnished 19: 46
mg, 96%. This was recrystallized from a mixture of CCl4 and
petroleum ether: mp ) 64 °C; 1H NMR (300 MHz) δ 7.33-
7.19 (5H, m), 5.04-4.99 (1H, m), 4.56-4.53 (1H, m), 4.26-
7-(2-P h en eth yl)-4,5-d id eh yd r o-2-oxep a n on e (7d ): 1H
NMR (300 MHz) δ 7.29-7.14 (5H, m), 5.66-5.47 (2H, m),
4.61-4.54 (1H, m), 2.86-2.69 (2H, m), 2.51-2.41 (1H, m),
2.32-2.26 (1H, d, J ) 18 Hz), 2.07-2.00 (1H, m), 1.86-1.77
(1H, m); IR (film) 1715 cm-1. Anal. Calcd for C14H16O2: C,
77.75; H, 7.45. Found: C, 77.94; H, 7.65.
4,5-Deh ydr o-7-isopr opyl-4-m eth yl-2-oxepan on e (7e): 1H
NMR (300 MHz) δ 5.44 (1H, bs), 4.46-4.39 (1H, ddd, J ) 2.7
Hz), 3.80 (1H, bd, J ) 16 Hz), 2.86 (1H, d, J ) 16 Hz), 2.44-
2.23 (2H, m), 1.93-1.82 (1H, m), 1.79 (3H, s), 1.00-0.96 (6H,
2d, J ) 6.6 Hz). Anal. Calcd for C10H16O2: C, 71.38; H, 9.59.
Found: C, 71.53; H, 9.83.
1,8-Diazabicyclo[5.4.0]u n decan e (8). Glacial AcOH (0.395
g, 6.5 mmol) was added to an ice-cold solution of DBU (1.0 g,
6.5 mmol) in EtOH (20 mL). To the stirred solution was then
added NaBH4 (0.25 g, 6.5 mmol) in small portions. The
reaction was stirred at rt for 2 h whereupon some white solid
separated out. The EtOH was removed and the residue taken