Vinylcyclobutanols: A Composite Functional Group?
J. Am. Chem. Soc., Vol. 118, No. 50, 1996 12553
42a: IR (CDCl ):
): 1727, 1450 cm-1. 1H NMR (300 MHz, CDCl
quenched by addition to saturated aqueous sodium bicarbonate solution
3
3
(
80 mL) and ether (25 mL). The organic layers were dried (MgSO
4
)
δ 3.29 (s, 3H), 3.25 (dt, J ) 9.3, 3.9 Hz, 1H), 2.26 (m, 2H), 2.11 (m,
13
and evaporated in Vacuo. Purification of the yellow residue by silica
gel chromatography (4:1 pentane/ether) gave 36 (148 mg, 86%) as a
2H), 1.87 (m, 4H), 1.75 (d, J ) 4.1 Hz, 2H), 1.70-1.16 (m, 10H).
C
NMR (75.5 MHz, CDCl ): δ 223.6, 85.7, 56.9, 52.7, 50.7, 43.1, 36.6,
3
4
.6:1 diastereomeric mixture by GC.
36.1, 34.9, 34.7, 33.7, 33.5, 31.7, 24.0, 18.8. HRMS: Calcd for
): 1729, 1459 cm 1. 1H NMR (300 MHz, CDCl
-
):
+
3
6a: IR (CDCl
3
3
C
C
15
H
H
24
O
O
2
(M ): 236.1776. Found: 236.1787. Anal. Calcd for
δ 3.52 (tt, J ) 8.6, 2.1 Hz, 1H), 3.27 (s, 3H), 2.26 (m, 2H), 2.03 (m,
15
24
2
: C, 76.23; H, 10.24. Found: C, 76.46; H, 10.09.
1
3
-1
1H NMR (300 MHz, CDCl
1
7
H), 1.96-1.25 (m, 13H). C NMR (75.5 MHz, CDCl
3
): δ 223.8,
42b: IR (CDCl
3
): 1726, 1452 cm
.
3
):
8.0, 56.0, 49.1, 40.6, 38.4, 36.7, 35.6, 34.5, 25.8, 23.4, 18.3. HRMS:
δ 3.54 (m, 1H), 3.34 (s, 3H), 2.32 (m, 1H), 2.19-1.53 (m, 16H), 1.46
+
13
Calcd for C12
for C12
H O
20 2
(M ): 196.1463. Found: 196.1474. Anal. Calcd
(dt, J ) 14.8, 5.0 Hz, 1H), 1.32 (m, 1H), 1.16 (m, 1H). C NMR
H O
20 2
: C, 73.43; H, 10.27. Found: C, 73.19; H, 10.13.
3
(75.5 MHz, CDCl ): δ 222.9, 81.0, 57.5, 51.1, 49.0, 38.1, 36.6, 36.1,
-
1
1H NMR (300 MHz,
3
6b: IR (CDCl
3
): 1729, 1463, 1455 cm
.
36.0, 35.4, 31.6, 30.2, 28.1, 24.2, 18.9. HRMS: Calcd for C15
H
24
O
2
+
CDCl
3
): δ 3.23 (s, 3H), 3.14 (tt, J ) 9.6, 2.9 Hz, 1H), 2.20 (m, 2H),
(M ): 236.1776. Found: 236.1787. Anal. Calcd for C15
24
H O
2
: C,
2
.00-1.12 (m, 14H).
-Iodospiro[4.6]undecan-1-one (37). Following the procedure for
formation of 35, 36a (18 mg, 0.09 mmol) and trimethylsilyl iodide (2
17.0 µL, 0.24 mmol total) in 0.5 mL of acetonitrile gave 37 (20 mg,
4%) after flash chromatography (8:1 pentane/ether). IR (CDCl ):
): δ 4.69 (tt, J )
0.5, 2.5 Hz, 1H), 2.56 (m, 2H), 2.27 (m, 2H), 2.09 (m, 2H), 1.94-
76.23; H, 10.24. Found: C, 76.47; H, 9.99.
-
1
1H NMR (300 MHz, CDCl
7
42c: IR (CDCl
3
): 1728, 1455 cm
.
3
):
δ 3.30 (s, 3H), 2.94 (ddd, J ) 9.6, 7.8, 5.8 Hz, 1H), 2.28 (m, 2H),
2.00 (m, 2H), 1.92-1.71 (m, 8H), 1.67-1.26 (m, 9H). 13C NMR (75.5
×
7
1
1
1
3
3
MHz, CDCl
3
): δ 222.5, 83.9, 56.2, 52.5, 43.5, 38.7, 36.3, 36.1, 34.6,
-
1
1
+
730, 1457, 1406 cm
.
H NMR (400 MHz, CDCl
3
32.8, 31.0, 29.7, 28.4, 22.8, 18.7. HRMS: Calcd for C15
236.1776. Found: 236.1770.
H
24
O
2
(M ):
1
3
.35 (m, 10H). C NMR (100 MHz, CDCl
3
): δ 222.5, 49.0, 44.8,
Deoxygenation of Cyclopentanones 42. Of 42a. A solution of
42a (10 mg, 0.04 mmol) and p-toluenesulfonylhydrazine (9.8 mg, 0.05
mmol) in 100 µL of absolute ethanol was heated to reflux. Solvents
were removed in vacuo after 24 h. The residue was then taken up in
1:1 DMF-sulfolane (200 µL), and sodium cyanoborohydride (10.6 mg,
0.168 mmol) and p-toluenesulfonic acid (2.1 mg, 0.01 mmol) were
added. The reaction was then heated to 110 °C. After 2 h, the reaction
was cooled, taken up in water (2 mL), and extracted with hexane (2 ×
8.4, 36.8, 34.2, 30.9, 28.9, 23.2, 18.6. HRMS: Calcd for C11
H
17
O
+
(M - I) : 165.1279. Found: 165.1278.
Cyclization of trans-2-(2-(1′-Hydroxycyclobutyl)-2-propen-1-yl)-
1
-(dimethoxymethyl)cyclohexane (14). Following the standard pro-
tocol, 14 (67 mg, 0.25 mmol), 2,6-di-tert-butylpyridine (39.3 µL, 0.175
mmol), and trimethylsilyl triflate (48.2 µL, 0.250 mmol) in 7.5 mL of
methylene chloride gave 32 mg (54%) of 40a and 18 mg (30%) of
4
0b after flash chromatography (10:1 pentane/ether).
2 mL), and the latter was dried (MgSO
4
). Following evaporation, the
-
1
1H NMR (300 MHz,
residue was chromatographed with 10:1 pentane/ether to yield 43a (6.2
3
40a: IR (CDCl ): 1728, 1602, 1450 cm .
-1
1
mg, 66%). IR (CDCl
CDCl ): δ 3.32 (s, 3H), 3.01 (ddd, J ) 9.6, 6.0, 4.5 Hz, 1H), 2.04 (m,
H), 1.85-1.16 (m, 21H). 13C NMR (100 MHz, CDCl
): δ 86.0, 56.5,
52.4, 44.2, 43.7, 43.4, 41.1, 40.2, 38.9, 34.9, 32.5, 31.3, 24.2, 24.0,
3.5.
Of 42b. Following the above protocol, 42b (10 mg, 0.04 mmol)
gave 6.4 mg (68%) of 43b after flash chromatography. IR (CDCl ):
): δ 3.41 (td, J ) 6.0,
3
): 1712, 1602, 1452 cm . H NMR (300 MHz,
CDCl
3
): δ 3.39 (ddd, J ) 11.0, 9.8, 4.6 Hz, 1H), 3.34 (s, 3H), 2.30
m, 2H), 2.13 (m, 1H), 2.07 (ddd, J ) 13.0, 4.5, 2.1 Hz, 1H), 1.93 (m,
(
2
3
1
3
H), 1.80-1.43 (m, 6H), 1.33-1.10 (m, 2H), 1.11 (dd, J ) 12.9, 11.0
1
Hz, 1H), 1.06-0.82 (m, 5H). H NMR (300 MHz, C
6
D
6
): δ 3.65
ddd, J ) 10.8, 9.8, 4.4 Hz, 1H), 3.24 (s, 3H), 2.43 (m, 1H), 1.99
ddd, J ) 12.8, 4.5, 2.0 Hz, 1H), 1.89 (m, 2H), 1.75 (m, 1H), 1.62 (m,
2
(
(
2
H), 1.48-1.28 (m, 7H), 1.21 (m, 2H), 1.04 (dd, J ) 12.9, 11.0 Hz,
H), 0.96 (m, 1H), 0.79 (m, 1H), 0.65 (dd, J ) 13.2, 12.6 Hz, 1H). 13
): δ 222.4, 79.8, 57.1, 48.7, 48.5, 40.2, 39.9,
3
-1
1
1
C
1602, 1450 cm
3.3 Hz, 1H), 3.34 (s, 3H), 1.90-1.11 (m, 22H). C NMR (100 MHz,
CDCl ): δ 80.2, 57.6, 49.9, 44.8, 44.0, 41.9, 39.9, 39.0, 37.8, 35.3,
. H NMR (300 MHz, CDCl
3
13
NMR (75.5 MHz, CDCl
3
3
8.0, 37.4, 35.6, 33.7, 28.7, 26.1, 26.06, 18.6. HRMS: Calcd for
3
+
C
15
H
4
O
24 2
(M ): 236.1776. Found: 236.1804.
32.2, 29.5, 24.7, 24.3, 24.2.
0b: IR (CDCl
300 MHz, CDCl ): δ 3.22 (s, 3H), 3.16 (ddd, J ) 2.7, 2.7, 2.7 Hz,
H), 2.49 (m, 2H), 2.21-1.14 (m, 15H), 1.02-0.75 (m, 3H). 1H NMR
300 MHz, C ): δ 3.00 (s, 3H), 2.86 (ddd, 2.7, 2.7, 2.7 Hz, 1H),
.57 (tdt, J ) 23.3, 11.7, 3.6 Hz, 1H), 2.18 (m, 2H), 1.93-1.01 (m,
3
): 1732, 1602, 1462, 1450, 1378 cm-1
.
1H NMR
2-Methoxybicyclo[6.3.0]undecane-4-spiro-1′-cyclopentan-2′-one
(46). To a solution of 31 (280 mg, 0.991 mmol) and 2,6-di-tert-
butylpyridine (222.6 µL, 0.991 mmol) in 99 mL of dichloromethane
at -78 °C was added titanium(IV) chloride (1.00 M in dichloromethane,
1.98 mL, 1.98 mmol) dropwise. The reaction was then allowed to warm
to room temperature slowly. After 6 h, methanol (1 mL) was added.
After another 30 min, the reaction was diluted with hexane (50 mL)
and washed with 1 M aqueous hydrochloric acid solution (1 × 100
mL), saturated aqueous sodium bicarbonate solution (1 × 100 mL),
(
1
(
2
1
7
2
2
3
6 6
D
1
3
4H), 0.97-0.63 (m, 3H). C NMR (75.5 MHz, CDCl ): δ 219.8,
3
9.7, 77.2, 57.2, 46.8, 46.6, 39.8, 35.7, 34.6, 31.5, 29.7, 28.8, 26.7,
6.0, 16.7. HRMS: Calcd for C15
36.1784.
+
H
24
O
2
(M ): 236.1776. Found:
and brine (1 × 100 mL) and dried (Na
2 4
SO ). Following solvent
Cyclization of cis-2-(2-(1′-hydroxycyclobutyl)-2-propen-1-yl)-1-
dimethoxymethyl)cyclohexane (15). Following the standard protocol,
5 (25 mg, 0.093 mmol), 2,6-di-tert-butylpyridine (14.6 µL, 0.065
removal in vacuo, the residue was chromatographed (10:1 pentane/
ether then 1.5 ether/pentane) to yield 47.3 mg (19%) of a white
crystalline solid as a single diastereomer, 46b (minor), and 125.7 mg
(
1
mmol) and trimethylsilyl triflate (18.0 µL, 0.093 mmol) in 9.3 mL of
methylene chloride gave 18 mg (82%) of 41 after flash chromatography
(
51%) of a mixture of two diastereomers, 46a (major) and 46c (trace),
for a total yield of 70%.
46a: IR (CDCl
): 1725, 1604, 1458 cm-1
CDCl ): δ 3.31 (s, 3H), 3.07 (ddd, J ) 10.5, 4.7, 2.0 Hz, 1H), 2.39-
0.86 (m, 22H). C NMR (75.5 MHz, CDCl ): δ 222.6, 77.2, 56.9,
-
1
(
10:1 pentane/ether). IR (CDCl
3
): 1726, 1467, 1450, 1407, 1374 cm
): δ 3.82 (dt, J ) 12.0, 4.8 Hz, 1H), 3.32
s, 3H), 2.29 (td, J ) 7.6, 2.7 Hz, 2H), 2.09 (m, 2H), 1.91 (dt, J )
4.8, 7.0 Hz, 2H), 1.80 (d, J ) 6.5 Hz, 1H), 1.77 (m, 2H), 1.68 (ddd,
.
1
.
1H NMR (300 MHz,
H NMR (300 MHz, CDCl
(
1
3
3
3
13
3
1
J ) 13.2, 4.7, 1.4 Hz, 1H), 1.59-1.16 (m, 10H). H NMR (300 MHz,
): δ 4.08 (dt, J ) 12.0, 4.9 Hz, 1H), 3.17 (s, 3H), 2.32 (m, 1H),
49.6, 49.3, 41.9, 37.9, 36.8, 36.6, 35.7, 33.0, 31.5, 29.7, 23.9, 21.9,
+
C
6
D
6
18.5. HRMS: Calcd for C16
H O
26 2
(M ): 250.1932. Found: 250.1934.
2
1
1
3
.04 (m, 1H), 1.87 (m, 2H), 1.71 (ddd, J ) 13.3, 4.6, 1.6 Hz, 2H),
Anal. Calcd for C16
10.54.
26 2
H O : C, 76.75; H, 10.47. Found: C, 77.00; H,
.65 (m, 1H), 1.50-1.11 (m, 12H), 1.06 (ddd, J ) 13.8, 4.1, 1.7 Hz,
1
3
H). C NMR (75.5 MHz, CDCl
8.0, 37.9, 32.5, 31.5, 31.1, 29.6, 26.1, 20.9, 18.6, 17.8. HRMS: Calcd
3
): δ 222.2, 77.2, 55.6, 48.4, 40.4,
46b: mp 71-72 °C (recrystallized from hexane). IR (CDCl
3
): 1727,
): δ 3.37 (dt, J
) 10.2, 4.3 Hz, 1H), 3.31 (s, 3H), 2.4 -2.18 (m, 4H), 2.01-1.08 (m,
18H). 13C NMR (75.5 MHz, CDCl
): δ 222.9, 80.2, 58.2, 50.3, 46.0,
40.2, 38.8, 38.0, 37.4, 36.9, 34.2, 33.1, 31.0, 25.8, 22.6, 18.6. Anal.
Calcd for C16 : C, 76.75; H, 10.47. Found: C, 76.87; H, 10.25.
-
1
1
1602, 1465, 1452 cm . H NMR (300 MHz, CDCl
3
+
for C15
H O
24 2
(M ): 236.1776. Found: 236.1782.
Cyclization of trans-1-(dimethoxymethyl)-2-(1′-hydroxymethyl)-
-((1′-hydroxycyclobutyl)-3-buten-1-yl) cyclopentane (25). Follow-
3
2
ing the standard procedure, 25 (121 mg, 0.451 mmol), 2,6-di-tert-
26 2
H O
butylpyridine (71 µL, 0.32 mmol), and trimethylsilyl triflate (87 µL,
Deoxygenation of Cyclopentanones (46a-c). Of 46a + c: A
mixture of 46a and 46c (20 mg, 0.08 mmol) was deoxygenated as before
using p-toluenesulfonylhydrazine (17.9 mg, 0.096 mmol) in 200 µL of
ethanol followed by sodium cyanoborohydride (20 mg, 0.32 mmol)
0
.45 mmol) in 45 mL of methylene chloride gave 100 mg (93%) of 42
after flash chromatography (10:1 then 6:1 pentane/ether) as a 3.9:3.4:1
ratio of diastereomers.