9240 J . Org. Chem., Vol. 61, No. 26, 1996
Gleiter et al.
Red u ction of 7-Meth yl-3,8-d ioxa p en ta cyclo[4.4.1.02,4
.
1112, 1069 cm-1; UV/vis (CH3CN) λmax [nm] (log ꢀ) ) 196 (3.16),
222 (2.04). Anal. Calcd for C10H14O2 (166.1): C, 72.26; H, 8.49.
Found: C, 72.01; H, 8.59.
05,9.07,10]u n d eca n e (26) w ith Li/EDA. To a 1-L three-necked
flask fitted with a reflux condenser and a magnetic stirring
bar were added at rt with vigorous stirring 12 g (73 mmol) of
oxetane 26 and 50 mL of anhydrous ethylenediamine (EDA),
followed by 0.8 g (117 mmol) of lithium powder. The reduction
is exothermic, and an ice bath was necessary to keep the
temperature at 40 °C, where it was maintained for 30 min.
Then an additional 3.2 g (467 mmol) of lithium powder was
added. The reaction mixture was stirred for an additional 1
h at rt. Many colors were observed during the reduction, but
the reduction was complete when a blue-purple color persisted.
The reaction mixture was cooled, and 100 mL of diethyl ether
and 150 mL of water were added to destroy excess reagent.
The aqueous layer was extracted for 2 h with ether. The
combined organic layers were dried with MgSO4 and concen-
trated to give a brown oily residue. Purificaton by silica gel
chromatography with diethyl ether as eluent gave a mixture
of products. Additional purification of this mixture by silica
gel column chromatography yielded 28 (0.85 g, 7%) as a
colorless oil and 27 (1.03 g, 8%), 29 (3.52 g, 29%), and 30 (5.64
g, 46%) as white solids. 27 and 30 were recrystallized from
CHCl3.
9-Met h ylt r icyclo[4.3.0.03,8]n on a n e-2,5-d iol (30): mp )
155 °C; Rf (SiO2, ethyl acetate, p-methoxybenzaldehyde) )
0.29; 1H NMR (300 MHz, DMSO-d6) δ 0.75-0.78 (d, 2J ) 11.5
3
2
Hz, 1H), 0.88-0.90 (d, J ) 6.9 Hz, 3H), 1.36-1.42 (dd, J )
3
2
3
13.5 Hz, J ) 3.5 Hz, 1H), 1.56-1.63 (dd, J ) 11.5 Hz, J )
7.9 Hz, 1H), 1.67 (m, 1H), 1.76-1.77 (m, 2H), 1.83-1.90 (ddd,
2J ) 13.5 Hz, J 1 ) 7.4 Hz, J 2 ) 1.7 Hz, 1H), 1.93-1.97 (m,
3
3
3
3
1H), 2.77-2.83 (q, J ) 6.9 Hz, 1H), 3.80-3.84 (dd, J ) 3.4
3
3
Hz, 1H), 4.25 (m, 1H), 4.44 (d, J ) 3.6 Hz, 1H), 4.75 (d, J )
2.9 Hz, 1H); 13C NMR (75.47 MHz, DMSO-d6) δ 14.94 (q), 28.08
(t), 36.29 (t), 37.95 (d), 38.16 (d), 38.85 (d), 42.10 (d), 48.31
(d), 70.63 (d), 73.91 (d); MS: m/z 150 (5) [M+ - H2O], 135 (5)
[M+ - H2O, CH3], 121 (13), 106 (12) [C8H10+], 96 (23), 95 (34),
94 (17), 93 (44) [C7H9+], 92 (13), 91 (24), 81 (36), 80 (100)
[C6H8+], 79 (60) [C6H7+], 78 (13), 77 (23), 72 (57), 71 (60), 67
(20), 57 (16), 55 (21), 53 (12); HRMS calcd for C10H14O1 [M+
-
H2O] 150.1045, found 150.1050; IR (KBr) 3330, 2943, 1361,
1081, 1066, 1002, 990, 964 cm-1; UV/vis (CH3CN) λmax [nm]
(log ꢀ) ) 194 (2.48).
9-Meth ylen etr icyclo[4.3.0.03,8]n on a n -4-on e (31). To a
stirred solution of oxalyl chloride (3.0 mL, 33.3 mmol) in dry
CH2Cl2 (270 mL) was added dry DMSO (5.0 mL, 66.6 mmol)
at -60 °C. After the solution was stirred for 2 min at -60 °C,
1.4 g (8.32 mmol) of 27 in 60 mL of dry CH2Cl2 was added.
The mixture was stirred for 15 min at -60 °C, treated with
triethylamine (23.4 mL, 155.5 mmol) and then allowed to
warm up to rt before being poured into cold water (150 mL).
The aqueous layer was extracted twice with CH2Cl2. The
combined CH2Cl2 solutions were washed three times with cold
aqueous HCl (2%) and twice with H2O, saturated aqueous
NaHCO3, and brine, the solution was dried with MgSO4, and
the solvent was evaporated. The residue was purified by silica
gel column chromatography with pentane/ether (4:1) as eluent
yielding 494 mg (40%) of 31 as a white solid: mp ) 42 °C; Rf
(SiO2, pentane/ether, 1:1, p-methoxybenzaldehyde) ) 0.48; 1H
9-Met h ylt r icyclo[4.3.0.03,8]n on a n e-4,9-d iol (27): mp )
160 °C; Rf (SiO2, ethyl acetate, p-methoxybenzaldehyde) )
0.37; 1H NMR (300 MHz, DMSO-d6) δ 0.77-0.81 (d, 2J ) 11.0
Hz, 1H), 1.27 (s, 3H), 1.35-1.47 (dt, J 1 ) 13.4 Hz, J 2 ) 3.9
Hz, 2H), 1.50-1.52 (m, 1H), 1.60-1.61 (m, 1H), 1.72-1.75 (d,
J ) 9.6 Hz, 1H), 1.88-2.00 (m, 3H), 2.16-2.21 (dd, J 1 ) 9.6
Hz, J 2 ) 7.4 Hz, 1H), 3.88-3.93 (td, J 1 ) 7.2 Hz, J 2 ) 3.6 Hz,
1H), 4.44 (s, 1H), 4.69-4.70 (d, 3J 1 ) 3.3 Hz, 1H); 13C NMR
(75.47 MHz, DMSO-d6) δ 25.55 (q), 28.70 (t), 31.31 (t), 32.08
(d), 37.55 (t), 38.15 (d), 44.54 (d), 44.58 (d), 71.09 (d), 83.38
(s); MS: m/z 168 (0.04) [M+], 150 (11) [M+ - H2O], 132 (8)
[M+ - 2H2O], 117 (12) [C9H9], 109 (22), 107 (35), 106 (17), 95
(17), 93 (17), 92 (50), 91 (31), 81 (43), 80 (100) [C6H8], 79 (65)
[C6H7], 78 (13), 77 (17), 72 (14), 71 (37), 67 (11), 53 (12); HRMS
calcd for C10H16O2 168.1150, found 168.1149; IR (KBr) 3315,
2956, 2936, 1294, 1112, 1105, 1070 cm-1; UV/vis (CH3CN) λmax
[nm] (log ꢀ) ) 194 (2.62).
2
3
NMR (300 MHz, CDCl3) δ 1.17-1.24 (dt, J ) 12.2 Hz, J )
1.4 Hz, 2H), 1.64-1.75 (dd, J 1 ) 5.2 Hz, J 2 ) 1.8 Hz, 2H),
5-Meth yl-4-oxa tetr a cyclo[4.3.1.02,5.03,7]d eca n -9-ol (28):
Rf (SiO2, ethyl acetate, p-methoxybenzaldehyde) ) 0.40; 1H
1.84-1.88 (dd, J ) 12.2 Hz, J ) 1.8 Hz, 1H), 2.03-2.10 (dd,
3 2
2
3
2J ) 17.1 Hz, J ) 3.4 Hz, 1H), 2.51-2.71 (m, J 1 ) 17.1 Hz,
2J 2 ) 12.6 Hz, 4H), 4.55 (s, 1H), 4.60 (s, 1H); 13C NMR (50.32
MHz, CDCl3) δ 28.63 (d), 33.21 (t), 39.99 (d), 40.08 (t), 42.25
(d), 42.38 (t), 47.58 (d), 95.64 (t), 160.17 (s), 215.26 (s); MS
m/z 148 (18) [M+], 133 (5) [M+ - CH3], 120 (18) [M+ - CO],
106 (11), 105 (26) [M+ - CO - CH3], 104 (18), 92 (30), 91 (61)
[M+ - C3H5O], 80 (14), 79 (100) [C6H7+], 78 (75), 77 (52), 69
(24), 65 (13), 55 (18), 53 (12), 51 (16); IR (neat film) 2964, 1731,
1681, 1261, 1075, 1020, 784, 759 cm-1; UV/vis (n-pentane) λmax
[nm] (log ꢀ) ) 198 (2.86), 294 (2.52), 306 (2.67), 320 (2.64), 334
(2.27), 352 (2.12). Anal. Calcd for C10H12O (148.2): C, 81.04;
H, 8.16. Found: C, 81.09; H 8.15.
NMR (300 MHz, CDCl3) δ 1.10-1.17 (ddd, 2J ) 11.7 Hz, 3J 1
)
5.9 Hz, 3J 2 ) 2.0 Hz, 1H), 1.32-1.45 (m, 2H), 1.41 (s, 3H),
1.56 (s, 1H), 1.87-1.90 (m, 1H), 1.95-1.99 (d, 2J ) 11.8 Hz,
1H), 2.10-2.12 (m, 1H), 2.18-2.22 (m, 1H), 2.39-2.44 (m, 1H),
4.55-4.57 (dd, 3J 1 ) 1.8 Hz, 3J 2 ) 5.4 Hz, 1H), 4.84-4.87 (dd,
3J 1 ) 4.9 Hz, 3J 2 ) 3.6 Hz, 1H); 13C NMR (75.47 MHz, CDCl3)
δ 23.72 (q), 25.87 (t), 32.05 (t), 36.17 (d), 38.57 (d), 47.48 (d),
56.35 (d), 78.98 (d), 81.48 (s), 84.04 (d); MS m/z 166 (19) [M+],
148 (4) [M+ - H2O], 123 (38) [C8H11O+], 122 (12) [C8H10O+],
112 (10) [C6H8O2+], 107 (10) [C7H7O+], 105 (22) [C8H9+], 95
(14), 94 (10) [C6H6O+], 93 (11) [C7H9+], 91 (17), 87 (20), 81 (14),
80 (76), 79 (96) [C6H7+], 78 (18), 77 (18), 73 (14), 69 (14), 67
(13), 43 (100); HRMS calcd for C10H14O2 166.0994, found
166.1008; IR (KBr) 3393, 3359, 2978, 2959, 1377, 1304, 1146,
1127, 1079, 1018, 960, 946, 903, 890 cm-1; UV/vis (CHCl3) λmax
[nm] (log ꢀ) ) 244 (1.70).
(9-Meth ylen tr icyclo[4.3.0.03,8]n on -4-en eyl)tosylh yd r a -
zon e (32). To a magnetically stirred solution of 499 mg (3.37
mmol) of ketone 31 in 20 mL of anhydrous ethanol was added
648 mg (3.48 mmol) of p-toluenesulfonohydrazide. The reac-
tion mixture was stirred for 3 days at rt. The light brown
needles were collected by filtration and dried. The liquid was
evaporated. Purification of the residue by silica gel column
chromatography (elution with pentane/ether, 3:1) gave further
product. The yield of tosylhydrazone 32 was 928 mg (87%):
mp 181 °C; Rf (SiO2, pentane/ether, 1:1, p-methoxybenzalde-
hyde) ) 0.21; 1H NMR (300 MHz, CDCl3) δ 0.91-0.95 (d, 2J )
9-Meth ylen etr icyclo[4.3.0.03,8]n on a n e-2,5-d iol (29): mp
) 144 °C; Rf (SiO2, ethyl acetate, p-methoxybenzaldehyde) )
0.32; 1H NMR (200 MHz, DMSO-d6) δ 1.04-1.11 (dd, 2J ) 10.9
3
2
Hz, J ) 1.6 Hz, 1H), 1.16-1.26 (m, 1H), 1.43-1.52 (dd, J )
13.7 Hz, 3J ) 3.6 Hz, 1H), 1.75-1.76 (m, 1H), 1.85-1.96 (ddd,
2J ) 13.7 Hz, J 1 ) 7.3 Hz, J 2 ) 1.9 Hz, 1H), 2.02-2.05 (m,
3
3
2
1H), 2.22-2.25 (m, 1H), 2.30-2.33 (m, 1H), 3.81-3.86 (dm,
11.2 Hz, 1H), 1.47-1.51 (d, J ) 11.2 Hz, 1H), 1.52-1.58 (m,
3J ) 5.2 Hz, 2H), 4.25-4.29 (dd, J 1 ) 2.2 Hz, J 2 ) 5.2 Hz,
1H), 1.64-1.77 (m, 2H), 2.15-2.21 (md, 2J ) 15.7 Hz, 2H),
2.28-2.33 (dd, 2J ) 16.3 Hz, 3J ) 3.3 Hz, 1H), 2.41 (s, 3H),
2.43-2.47 (d, 2J ) 11.8 Hz, 1H), 2.56-2.58 (d, 3J ) 5.8 Hz,
3
3
1H), 4.47 (s, 1H), 4.62 (s, 1H), 4.87 (d, J ) 3.0 Hz, 1H); 13C
3
NMR (50.32 MHz, DMSO-d6) δ 31.99 (t), 35.64 (t), 38.47 (d),
38.73 (d), 41.51 (d), 48.34 (d), 69.85 (d), 71.97 (d), 97.85 (t),
160.20 (s); MS: m/z 166 (1) [M+], 148 (7) [M+ - H2O], 120 (15)
[C9H12+], 119 (13) [C9H11+], 117 (15) [C9H9+], 105 (30) [C7H5O1+],
104 (19) [C8H8+], 94 (10) [C7H10+], 93 (50) [C7H9+], 92 (34)
[C7H8+], 91 (52) [C7H7+], 81 (32), 80 (100) [C6H8+], 79 (71)
[C6H7+], 78 (33) [C6H6+], 77 (32) [C6H5+], 69 (10), 67 (11), 65
(10), 57 (19), 55 (11), 53 (12); HRMS calcd for C10H14O2
166.0994, found 166.0968; IR (KBr) 3412, 2956, 2937, 1631,
3
1H), 2.65-2.69 (t, J ) 5.7 Hz, 1H), 4.46 (s, 1H), 4.49 (s, 1H),
7.26-7.31 (dd, J 1 ) 8.3 Hz, J 2 ) 6.9 Hz, 2H), 7.81-7.84 (d, J 1
) 8.3 Hz, 2H); 13C NMR (75.47 MHz, CDCl3) δ 21.57 (q), 28.60
(d), 31.15 (t), 34.80 (t), 39.39 (t), 40.48 (d), 40.57 (d), 42.82 (d),
95.10 (t), 127.94 (d), 129.55 (d), 135.69 (s), 143.88 (s), 160.59
(s), 166.00 (s); MS m/z 316 (0.2), 175 (23), 161 (20), 144 (13),
133 (20), 132 (10), 131 (17), 119 (10), 117 (32), 115 (11), 107
(11), 105 (30), 104 (12), 103 (24), 99 (11), 97 (16), 95 (16), 93