Medicinal Chemistry Research
to afford 82 mg (54%) of 10 as a colorless oil. [α] = +18.5
afford 134 mg (0.87 mmol, 87%) of 13 as a colorless oil.
[α] = +26.4 (c 0.5, CHCl ); FT-IR (KBr): 3450, 3012,
D
−
1
(
c 0.4, CHCl ); FT-IR (KBr): 3260, 2910, 1710, 1210 cm ;
3
D
3
−1
1
1
H NMR (400 MHz, CDCl ) δ 5.65 (dqd, J = 10.7, 6.9,
2958, 2886, 1717, 1471 cm ; H NMR (400 MHz, CDCl )
3
3
1
2
2
1
.2 Hz, 1H), 5.20 (ddq, J = 11.0, 9.3, 1.8 Hz, 1H), 4.97 (s,
H), 4.70 (td, J = 6.4, 3.1 Hz, 1H), 3.42 – 3.30 (m, 1H),
.74 – 2.53 (m, 2H), 2.45 – 2.28 (m, 2H), 2.22 (tddd, J =
3.8, 7.3, 4.7, 1.4 Hz, 2H), 1.68 (dd, J = 6.9, 1.8 Hz, 3H);
δ 5.60 (ddddd, J = 10.8, 8.1, 6.8, 5.6, 1.3 Hz, 1H), 5.42
(ddq, J = 11.0, 9.2, 1.8 Hz, 1H), 4.02 (dt, J = 4.7, 2.7 Hz,
1H), 2.99 – 2.89 (m, 1H), 2.71 – 2.54 (m, 2H), 2.29 – 2.17
(m, 2H), 2.12 (ddt, J = 14.7, 5.9, 4.4 Hz, 1H), 2.03 (d,
J = 9.6 Hz, 1H), 1.91 (tdd, J = 13.8, 5.2, 2.6 Hz, 1H), 1.62
1
3
C NMR (101 MHz, CDCl ) δ 208.6, 128.7, 128.1, 81.1,
3
1
3
4
2.9, 40.1, 37.1, 28.8, 13.3. HRMS calculated for
(dt, J = 6.9, 1.5 Hz, 3H); C NMR (101 MHz, CDCl ) δ
3
+
+
.
C H NO SNa 256.0620 Found 256.0617 (MNa ).
211.3, 129.3, 126.9, 68.3, 42.4, 40.8, 36.0, 32.4, 13.4;
9
15
4
+
HRMS calculated for C H O Na 177.0892 Found
177.0894 (MNa ).
9
14
2
+
(
1R,2R)-4-oxo-2-((Z)-prop-1-en-1-yl)cyclohexyl 3,5-
dinitrobenzoate (12)
(
1R,2R)-4-oxo-2-((Z)-prop-1-en-1-yl)cyclohexyl sulfamate
A mixture of 9 (0.4 g, 2.59 mmol), PPh (3.4 g, 12.98 mmol, 5
(14)
3
equiv.) and 3,5-dinitro-benzoic acid (2.75 g, 12.98 mmol, 5
equiv.) in dry toluene (40 mL) was stirred at room temperature
Formic acid (61 µL, 1.62 mmol, 2.5 equiv.) was added to
neat chlorosulfonyl isocyanate (140 µL, 1.62 mmol, 2.5
equiv.) at 0 °C and the mixture was stirred for 5 minutes.
Vigorous gas evolution was observed during the addition,
and the mixture turned into a white solid after 5–10 min.
Anhydrous acetonitrile (2 mL) was added to the solid. The
resulting solution was stirred at room temperature for 12 h.
After 12 h, the reaction mixture was cooled to 0 °C, and
alcohol 13 (100 mg, 0.65 mmol) dissolved in 0.5 mL of
DMA was added dropwise using a syringe. The resulting
solution was stirred at room temperature for 5 h. The
reaction was quenched with ice water (10 mL) and trans-
ferred to a separatory funnel. The organic layer was sepa-
rated, and then the aqueous layer was extracted with ethyl
acetate (2 × 10 mL). The combined organic layers were
washed with brine solution (2 × 10 mL), dried over anhy-
drous Na SO , filtered, and the solvent was removed in
for 30 min under N atmosphere. After 30 min, diethyl azo-
2
dicarboxylate (2 mL, 12.74 mmol, 5 equiv.) was added drop-
wise to the reaction mixture at 0 °C. The resulting mixture was
stirred at room temperature for 24 h under N atmosphere.
2
After 24 h, the reaction mixture was concentrated under
reduced pressure. The residue was taken in 20% EtOAc/hex-
anes (200 mL) and filtered through a celite pad. The filtrate
was concentrated under reduced pressure. The resulting resi-
due was purified through silica gel column chromatography
(hexane/ethyl acetate = 85:15) to afford 588 mg (1.69 mmol,
6
5%) of 12 as a white solid. [α] = −91.0 (c 0.5, CHCl ); FT-
D
3
−1
1
IR (KBr): 3110, 3023, 1712, 1719, 1460 cm ; H NMR
(
400 MHz, CDCl ): δ 9.26 (t, J = 2.1 Hz, 1H), 9.14 (d,
3
J = 2.2 Hz, 2H), 5.68 – 5.59 (m, 1H), 5.52 (dt, J = 5.8, 3.1 Hz,
1
4
8
H), 5.37 (ddt, J = 12.7, 9.3, 1.8 Hz, 1H), 3.30 (tt, J = 9.4,
.5 Hz, 1H), 2.69 – 2.52 (m, 3H), 2.47 (dddd, J = 14.8, 13.3,
.1, 3.5 Hz, 2H), 2.17 (ddt, J = 16.3, 9.6, 3.9 Hz, 1H), 1.65
2
4
vacuo. The residue was purified through silica gel column
chromatography (hexane/ethyl acetate = 1:1) to afford
13
(dd, J = 6.9, 1.8 Hz, 3H); C NMR (126 MHz, CDCl3):
δ 208.2, 162.1, 148.9, 133.9, 129.4, 127.9, 127.3, 122.8, 74.2,
82 mg (0.35 mmol, 54%) of 14 as a colorless oil. [α] =
D
.
4
3.3, 38.6, 36.5, 28.9, 13.4; HRMS calculated for
−38.2 (c 0.5, CHCl ); FT-IR (KBr): 3264, 2926, 1708,
3
+
+
−1
1
C H N O Na 371.0855 Found 371.0855 (MNa ).
1180 cm ; H NMR (400 MHz, CDCl ) δ 5.63 (dq,
16
16
2
7
3
J = 10.7, 6.9 Hz, 1H), 5.45 (ddq, J = 10.8, 9.0, 1.8 Hz,
1H), 4.94 (d, J = 6.8 Hz, 2H), 4.83 (d, J = 2.4 Hz, 1H),
3.13 – 3.01 (m, 1H), 2.78 – 2.49 (m, 3H), 2.33 (dddd,
J = 29.9, 14.8, 4.9, 2.3 Hz, 2H), 2.00 (dddd, J = 14.8, 12.9,
(
(
3R,4R)-4-hydroxy-3-((Z)-prop-1-en-1-yl)cyclohexan-1-one
13)
1
3
A mixture of 12 (0.350 g, 1 mmol) and K CO (207 mg,
6.2, 2.3 Hz, 1H), 1.65 (dd, J = 6.9, 1.8 Hz, 3H); C NMR
2
3
1
.5 mmol, 1.5 equiv.) in dry methanol (10 mL) was stirred
(101 MHz, CDCl ) δ 209.0, 128.1, 127.2, 80.3, 42.4, 39.5,
3
.
+
at room temperature for 1 h. After 1 h, the solvent was
evaporated under reduced pressure. The resulting residue
was dissolved in DCM and extracted with 1 N HCl (30 mL).
The organic layer was separated, and the aqueous layer was
extracted with DCM (2 × 40 mL). The combined organic
layers were washed with brine solution (2 × 20 mL), dried
over anhydrous Na SO , filtered, and the solvent was
35.6, 30.0,13.3; HRMS calculated for C H NO SNa
9 15 4
+
256.0620 Found 256.0618 (MNa ).
(1R,2R)-4-oxo-2-((Z)-prop-1-en-1-yl)cyclohexyl(4-
methoxyphenyl)sulfamate (16)
A mixture of 13 (0.1 g, 0.649 mmol) and (4-methox-
2
4
removed in vacuo. The residue was purified through silica
gel column chromatography (hexane/ethyl acetate = 1:1) to
yphenyl)sulfamoyl chloride (214 mg, 0.973 mmol, 1.5
equiv.) in dry DCM (3 mL) was added NEt (0.135 mL,
3