2518 J . Org. Chem., Vol. 64, No. 7, 1999
Notes
(m, 5H), 2.96 (q, J ) 7.2 Hz, 4H), 3.27 (s, 3H); 13C NMR (100
MHz) δ 13.9 (CH3), 45.4 (CH2), 25.3 (CH2), 26.7 (CH2), 33.4 (CH),
55.0 (CH3), 84.5 (C); MS m/z (relative intensity) 183 (M+, 49),
168 (100), 152 (50); HR-MS calcd for C11H21N1O1, 183.1623.
Found, 183.1617. Anal. Calcd for C11H21N1O1: C, 72.08; H, 11.55;
N, 7.64. Found: C, 72.04; H, 11.34; N, 7.60.
7-en d o-H yd r oxy-7-exo-m or p h olin ob icyclo[4.1.0]h e p -
ta n e (8): mp 130-132 °C (rodlike crystals from Et2O) (lit.3b mp
128 °C). The IR, 1H NMR, and 13C NMR spectra of 8 agreed
with those reported in the literature.3b
Acid -Ca ta lyzed Alcoh olysis of N,O-Aceta l 2e a n d 2g.
Gen er a l P r oced u r e. To a solution of N,O-acetal 2 (10 mmol)
in absolute alcohol (20 mL) was added a few drop of concentrated
H2SO4 with stirring at room temperature. After 2 h, a small
amount of K2CO3 (10 mg) was added to the reaction mixture,
and the alcohol was removed by evaporation. The residue was
treated with saturated aqueous NaHCO3 (10 mL), and the oily
layer was extracted with Et2O (20 mL × 3), dried (K2CO3), and
distilled in vacuo.
6-en d o-Meth ylp h en yla m in o-6-exo-m eth oxybicyclo[3.1.0]-
h exa n e (2b): bp 120 °C (3 mmHg); IR ν 1101 cm-1; 1H NMR δ
0.7-2.1 (m, 8H), 3.10 (s, 3H), 3.23 (s, 3H), 6.6-7.4 (m, 5H); 13
C
NMR δ 38.6 (CH3), 113.3 (CH), 117.7 (CH), 128.7 (CH), 147.2
(C) 23.5 (CH2), 26.4 (CH2), 27.0 (CH2), 30.6 (CH), 34.7 (CH), 53.6
(CH3), 80.3 (C); MS m/z (relative intensity) 217 (M+, 59), 184
(100). Anal. Calcd for C14H19N1O1: C, 77.38; H, 8.81; N, 6.41.
Found: C, 77.63; H, 8.97; N, 6.43.
1-Meth oxy-6-m or p h olin ocycloh exen e (9): yield 78%; bp
63-64 °C (0.05 mmHg) [lit.5b bp 62-64 °C (0.04 mmHg)]. The
6-exo-Meth oxy-6-en d o-p yr r olid in obicyclo[3.1.0]h exa n e
1
IR, H NMR, and 13C NMR spectra of this fraction agreed with
1
(2c): bp 68-71 °C (4 mmHg); IR ν 1082 cm-1; H NMR δ 1.4-
those reported in the literature.5b Distillation at
a higher
2.0 (m, 12H), 2.9-3.2 (m, 4H), 3.30 (s, 3H); 13C NMR δ 25.4
(CH2), 47.8 (CH2), 25.8 (CH2), 26.6 (CH2), 32.3 (CH), 55.4 (CH3),
79.4 (C); MS m/z (relative intensity) 181 (M+, 70), 166 (90), 150
(100). Anal. Calcd for C11H19N1O1: C, 72.88; H, 10.57; N, 7.73.
Found: C, 72.77; H, 10.52; N, 7.79.
temperature gave a mixture of allylic and vinylic methoxy-
enamines (10).7 For example, a fraction at 100-102 °C (3 mmHg)
consisted of two regioisomers 9/10, in a ratio of 7:3. Allylic
methoxyenamine 9: 13C NMR δ 48.7 (CH2), 67.0 (CH2), 17.5
(CH2), 24.6 (CH2), 26.4 (CH2), 55.3 (CH3), 71.3 (CH), 104.0 (CH),
145.4 (C). Vinylic methoxy enamine 10: 13C NMR δ 50.1 (CH2),
67.7 (CH2), 23.0 (CH2), 23.2 (CH2), 24.4 (CH2), 26.2 (CH2), 56.3
(CH3), 128.1 (C), 143.1 (C).
6-exo-Met h oxy-6-en d o-p ip er id in ob icyclo[3.1.0]h exa n e
(2d ): bp 80-82 °C (4 mmHg); IR ν 1080 cm-1; 1H NMR δ 1.2-
1.8 (m, 14H), 2.6-3.4 (m, 4H), 3.35 (s, 3H); 13C NMR δ 25.3
(CH2), 26.6 (CH2), 51.0 (CH2), 26.8 (CH2), 32.9 (CH), 56.3 (CH3),
83.9 (C); MS m/z (relative intensity) 195 (M+, 33), 180 (54), 164
(100). Anal. Calcd for C12H21N1O1: C, 73.79; H, 10.84; N, 7.17.
Found: C, 73.70; H, 10.84; N, 7.08.
6-exo-Me t h oxy-6-en d o-m or p h olin ob icyclo[3.1.0]h e x-
a n e (2e): bp 95-97 °C (4 mmHg) [lit.5b bp 77-79 (0.04)]. The
IR, 1H NMR, and 13C NMR spectra of 2e agreed with those
reported in the literature.5b
1-Eth oxy-6-m or p h olin ocycloh exen e (11): yield 76%; bp
1
58-59 °C (0.07 mmHg); IR ν 1647, 1123 cm-1; H NMR δ 1.21
(t, J ) 7 Hz, 3H), 1.4-2.3 (m, 6H), 2.7-3.0 (m, 4H), 3.6-4.0 (m,
7H), 4.77 (t, J ) 4 Hz, 1H); 13C NMR δ 48.6 (CH2), 67.0 (CH2),
15.9 (CH3), 17.6 (CH2), 24.6 (CH2), 27.2 (CH2), 63.2 (CH2), 72.0
(CH), 103.8 (CH), 145.3 (C). Anal. Calcd for C12H21N1O2: C,
68.21; H, 10.02; N, 6.63. Found: C, 67.87; H, 9.85; N, 6.51.
7-exo-E t h oxy-7-en d o-m or p h olin ob icyclo[4.1.0]h ep t a n e
(13): yield 78%; bp 100 °C (3 mmHg) (Kugelrohr); mp 57-58
7-exo-Me t h oxy-7-en d o-p yr r olid in ob icyclo[4.1.0]h e p -
1
ta n e (2f): bp 84-87 °C (4 mmHg). The IR and H NMR spectra
1
°C (leaflets from n-hexane); IR ν 1113 cm-1; H NMR δ 1.11 (t,
agreed with those reported in the literature.2b 13C NMR δ 25.0
(CH2), 47.8 (CH2), 19.9 (CH2), 21.7 (CH2), 22.1 (CH), 55.7 (CH3),
79.5 (C); MS m/z (relative intensity) 195 (M+, 7), 163 (53), 70
(100). Anal. Calcd for C12H21N1O1: C, 73.79; H, 10.84; N, 7.17.
Found: C, 73.76; H, 10.87; N, 7.27.
J ) 7 Hz, 3H), 1.1-2.1 (m, 10H), 3.63 (q?, 2H), 2.76 (HA, 2H),
3.06 (HB, 2H), 3.53 (HX, 2H), 3.79 (HY, 2H) (ABXY system); 13
C
NMR δ 49.8 (CH2), 67.6 (CH2), 16.2 (CH3), 19.5 (CH2), 21.5 (CH2),
21.9 (CH), 64.4 (CH2), 81.6 (C). Anal. Calcd for C13H23N1O2: C,
69.29; H, 10.29; N, 6.22. Found: C, 69.31; H, 10.27; N, 6.16.
Acetolysis of N,O-Aceta l 2e. To a stirred solution of 2e (1.97
g, 10 mmol) in Et2O (20 mL) was added AcOH (1.32 g, 22 mmol),
and the mixture was allowed to stand overnight at room
temperature. Excess AcOH was quenched with NaHCO3 (0.5 g,
6 mmol), and the solid was removed by filtration. Distillation of
the filtrate gave 1.87 g of acetoxyenamine 12 in a yield of 88%.
1-Acet oxy-6-m or p h olin ocycloh exen e (12): bp 110 °C (3
mmHg) (Kugelrohr); IR ν 1730 cm-1; 1H NMR δ 1.5-2.0 (m, 4H),
2.07 (s, 3H), 2.0-2.3 (m, 2H), 2.5-3.1 (m, 4H), 3.68 (t, J ) 4.7
Hz, 4H), 4.94 (t, J ) 4.0 Hz, 1H), 5.52 (m, 1H); 13C NMR δ 48.8
(CH2), 67.0 (CH2), 17.6 (CH2), 21.3 (CH3), 24.4 (CH2), 29.3 (CH2),
65.7 (CH), 106.7 (CH), 143.7 (C), 170.4 (CO); MS m/z (relative
intensity) 225 (M+, 34), 166 (83), 165 (100). Anal. Calcd for
C12H19N1O3: C, 63.97; H, 8.50; N, 6.22. Found: C, 64.00; H, 8.54;
N, 6.06.
Tr a n sfor m a tion of N,O-Aceta ls 2 in to Am in on itr iles 3.
Gen er a l P r oced u r e. To a stirred solution of N,O-acetal 2 (10
mmol) and Me3SiCN (1.44 g, 15 mmol) in CH2Cl2 (25 mL) was
added dropwise a solution of BF3‚Et2O (2.13 g, 15 mmol) within
10 min at dry ice temperature. Stirring was continued for 2 h,
and the mixture was then allowed to stand until it was warmed
to 0 °C. The reaction mixture was poured into cold water (30
mL), and the organic layer was washed with water, washed with
saturated aqueous NaHCO3, dried (Na2SO4), and evaporated.
The product 3 was isolated by distillation or column chroma-
tography on silica gel by eluting with a mixture of Et2O-hexane.
Product yields are shown in Table 2.
7-exo-Me t h oxy-7-en d o-m or p h olin ob icyclo[4.1.0]h e p -
ta n e (2g): mp 54-55.5 °C (prisms from n-pentane, - 50 °C),
bp 103-107 °C (4 mmHg) [lit.3b mp 49 °C, bp 57-62 °C (0.007).
The IR, 1H NMR, and 13C NMR spectra of 2g agreed with those
reported in the literature.3b
Acid Hyd r olysis of N,O-Aceta ls 2e a n d 2g. A heteroge-
neous mixture of N,O-acetal 2e (1.97 g, 10 mmol) in CH2Cl2 (10
mL) and 3 N H2SO4 (10 mL) was stirred at room temperature
for 5 h. After the reaction was complete, the organic layer was
separated, and the water layer was shaken with CH2Cl2 (20 mL
× 3). The combined CH2Cl2 layers were washed with brine, dried
(Na2SO4), and concentrated. The residue was subjected to
column chromatography on silica gel with Et2O to give 2-hy-
droxycyclohexanone 5 (0.96 g, 84% yield). 5: bp 83-86 °C (14
mmHg); IR ν 3400, 1710 cm-1. The hydroxy ketone 5 dimerized
and solidified upon standing overnight. Dimer of 5 (6): mp 110-
113 °C (lit.14 mp 114-118 °C); IR (KBr) ν 3350 cm-1, no (CO).
This was identified by direct comparison with an authentic
sample.14
Similar treatment of 2e (1.97 g, 10 mmol) with concentrated
HCl (10 mL) in CH2Cl2 (10 mL) gave 2-chlorocyclohexanone 4
(1.12 g, 85% yield). 4: bp 85-89 °C (14 mmHg) [lit.15 bp 90-91
°C (14-15 mmHg)]. This was identified by comparison to an
authentic sample prepared as described in the literature.15
A solution of N,O-acetal 2g (8.77 g, 45 mmol) in CH2Cl2 (50
mL) was occasionally shaken with 3 N H2SO4 (40 mL) for 2 h.
After the CH2Cl2 layer was removed, the aqueous layer was
washed with CH2Cl2 (20 mL) and added dropwise to 3 N NaOH
(60 mL) with stirring at ice-bath temperature. The white solid
was collected by filtration and washed with small portions of
cold water. Almost pure N,O-semiacetal 8 was obtained (6.47 g
80% yield).
6-exo-Cya n o-6-en d o-d iet h yla m in ob icyclo[3.1.0]h exa n e
(3a ): IR ν 2214 cm-1; 1H NMR (400 MHz) δ 1.10 (t, J ) 7.2 Hz,
6H), 1.5-1.8 (m, 2H), 1.8-2.0 (m, 6H), 2.68 (dq, J ) 7.2, 2.8 Hz,
4H); 13C NMR (100 MHz) δ 12.9 (CH3), 47.4 (CH2), 24.8 (CH2),
26.4 (CH2), 34.1 (CH), 42.3 (C), 120.0 (CN, 3J CH ) 4.5 Hz);16 MS
(14) Sheehan, J . C.; Neill, R. C. O.; White, M. A. J . Am. Chem. Soc.
1950, 72, 3376.
(15) Newman, M. S.; Farbman, M. D.; Hipsher, H. Org. Synth. 1955,
3, 188.
(16) Vilsmaier, E.; Stamm, T.; Dauth, W.; Tezlaff, C.; Barth, S. Bull.
Soc. Chim. Belg. 1992, 101, 37. According to their report, values of
3J CH of 4.5 Hz (3a ) and 4.5-3.1 Hz (3b) are accordance with the syn-
position of the bridgehead hydrogen atoms and the cyano group.