Job/Unit: O20075
/KAP1
Date: 02-05-12 18:25:12
Pages: 18
Enantioselective Complexation Gas Chromatography
dried with sodium sulfate and the solvent was evaporated under
reduced pressure. Drying in vacuo at elevated temperatures over a
period of three days yielded analytically pure 9 (2.75 g, 9.0 mmol,
1215, 1185, 1165, 1118, 1097, 1067, 1023, 958, 920, 897, 886, 855,
813, 780, 743, 724 cm–1. C17H19F7O3 (404.32): calcd. C 50.50, H
4.74; found C 51.05 H 5.01.
1
94%) as a colorless, viscous oil. H NMR (500.13 MHz, CDCl3):
(1S,4R)-10-Thiocamphor (6): (1S)-10-Camphorsulfonic acid
(50.0 g, 0.215 mol) and thionyl chloride (51.21 g, 0.430 mol,
31.3 mL) were placed in a three-necked flask equipped with a con-
denser under an argon atmosphere, and an exhaust line for direct
gas discharge into the fume hood. The reaction mixture was heated
at 80 °C for 4–5 h until the evolution of hydrochloric acid and sul-
fur dioxide ceased. Thionyl chloride was then removed under re-
duced pressure in vacuo at elevated temperature. To the crude 10-
camphorsulfonic acid was added triphenylphosphane (169.2 g,
0.645 mol) together with a 1:4 mixture of H2O and dioxane
(1500 mL) and the suspension was stirred at reflux temperature for
4 h. The suspension was allowed to cool to room temperature, H2O
(600 mL) was added, and the mixture was extracted with pentane
(4ϫ100 mL). The organic layers were combined, washed with H2O
(8ϫ100 mL), followed by brine (2ϫ25 mL) and dried with sodium
sulfate. Evaporation of the solvent under reduced pressure and high
vacuum yielded pure 6 (42.1 g, 0.228, 94%) as colorless crystals;
m.p. 55–57 °C. 1H NMR (300.51 MHz, CDCl3): δ = 2.88 (d, J =
6.8 Hz, 1 H, CH2SH), 2.83 (d, J = 6.8 Hz, 1 H, CH2SH), 2.39–2.30
(m, 2 H), 2.08–2.05 (m, 1 H), 2.03–1.83 (m, 4 H), 1.72–1.65 (m, 1
H), 1.41–1.35 (m, 1 H), 1.01 (s, 3 H, CH3), 0.90 (s, 3 H, CH3) ppm.
13C NMR (75.56 MHz, CDCl3): δ = 19.8, 20.3, 21.4, 26.6, 27.0,
43.2, 43.6, 47.8, 60.6, 217.8 ppm. MS (EI): m/z (%) = 55 (18), 67
(30), 81 (47), 95 (42), 109 (50), 123 (37), 141 (34), 151(23) [M –
(SH)]+, 169 (5) [M – (CH3)]+, 184 (100) [M]+. C10H16OS (184.30):
calcd. C 65.17, H 8.75; found C 65.40, H 8.76.
δ = 11.4 (br. s, 1 H, OH), 5.93–5.86 (m, 1 H, -OCH2CH-), 5.28
2
(dd, J = 17.4, J = 1.6 Hz, 1 H, methylene-CH2trans), 5.18 (dd, J =
10.5, 2J = 1.5 Hz, 1 H, methylene-CH2cis), 4.00 (d, J = 5.4 Hz, 2
2
2
H, -OCH2CH-), 3.65 (d, J = 10.4 Hz, 1 H, -CCH2O-), 3.63 (d, J
= 10.5 Hz, 1 H, -CCH2O-), 2.85–2.82 [m, 1 H, CHC(CH3)2], 2.16–
2.08 (m, 2 H), 1.50–1.39 (m, 2 H), 1.07 (s, 3 H, CH3), 0.97 (s, 3 H,
CH3) ppm. 13C NMR (125.76 MHz, CDCl3): δ = 19.4, 21.5, 25.7,
26.5, 47.9, 49.2, 61.6, 65.4, 72.6, 116.1, 116.7, 117.8 (q, J = 2.5 Hz,
CCCF3), 119.4 (q, J = 276.6 Hz, CF3), 134.7, 148.5 (q, J = 37.2 Hz,
CCF3), 212.2 ppm. 19F NMR (282.76 MHz, CDCl3):
δ =
–70.2 ppm. MS (EI): m/z (%) = 177 (21), 191 (17), 205 (17), 233
(100) [M – (C4H7O)]+, 247 (15) [M – (C3H5O)]+, 263 (6) [M –
(C3H5)]+, 304 (7) [M]+. HRMS (EI): m/z = calcd. for C15H19F3O3
[M]+ 304.1286; found 301.1288. ATR-FTIR: ν = 2963, 2874, 1702,
˜
1648, 1703, 1648, 1507, 1476, 1454, 1419, 1393, 1374, 1363, 1348,
1313, 1293, 1266, 1222, 1188, 1140, 1067, 1004, 989, 924, 891, 854,
816, 809, 753, 717 cm–1. C15H19F3O3 (304.31): calcd. C 59.20, H
6.29; found C 59.24, H 6.44.
(1R,4S)-10-(Allyloxy)-3-(heptafluorobutanoyl)camphor (10): To a
suspension of lithium hydride (160 mg, 20.1 mmol) in anhydrous
THF (50 mL) in a three-necked flask under argon equipped with
a reflux condenser, was added dropwise a solution of 8 (2.000 g,
9.6 mmol) in anhydrous THF (30 mL) at 0 °C. The mixture was
stirred for 15 min at this temperature, then allowed to warm to
room temperature and stirred for a further 15 min. The mixture
was then heated at reflux temperature for 10 h until the the solution
became pale-orange. The mixture was cooled to room temperature
and ethyl heptafluorobutyrate (5.346 g, 22.1 mmol, 3.83 mL) dis-
solved in anhydrous THF (40 mL) was added dropwise over a
period of 30 min. After stirring for 20 min, the mixture was heated
at reflux temperature for 14–18 h. Progress of the reaction was
monitored by GC analysis of pH neutral samples. After completion
of the reaction, concd. hydrochloric acid (10 mL) was added, fol-
lowed by addition of H2O (500 mL) while stirring. The mixture
was extracted with Et2O (3ϫ100 mL) and the organic layers were
combined, washed with H2O (2ϫ200 mL) and brine (2ϫ200 mL).
The organic phase was dried with sodium sulfate and the solvent
was evaporated under reduced pressure. Drying in vacuo at elevated
temperatures over a period of three days, followed by distillation
at 120 °C under high vacuum (small-sized distillation apparatus
equipped with a short connecting tube) yielded pure 10 (2.898 g,
7.2 mmol, 75%) as a colorless, viscous oil. 1H NMR (500.13 MHz,
CDCl3): δ = 11.69 (br. s, 1 H, OH), 5.93–5.86 (m, 1 H, OCH2CH),
(1S,4R)-10-(Allylthio)camphor (11): To a suspension of sodium hy-
dride (2.74 g, 114 mmol) in anhydrous THF (250 mL) was slowly
added a solution of 6 (20.00 g, 109 mol) in anhydrous THF (50 mL)
at 0 °C. After 30 min, the mixture was allowed to warm to room
temperature and then heated at reflux temperature for 30 min. The
reddish mixture was then cooled to 0 °C and allyl bromide (13.39 g,
111 mmol, 9.58 mL), dissolved in anhydrous THF (50 mL), was
added dropwise. The reaction mixture was stirred for 30 min at
room temperature and then heated to 50 °C and maintained at this
temperature for 2 h. The mixture was cooled to 0 °C, quenched
with small amounts of EtOH (15 mL), and H2O (400 mL) was
added. The solution was extracted with pentane (4ϫ100 mL) and
the organic layers were combined, washed with H2O (2ϫ50 mL)
and brine (2ϫ50 mL), and dried with sodium sulfate. Evaporation
of the solvent under reduced pressure, followed by high vacuum,
yielded analytically pure (1R,4R)-10-(allyloxy)camphor (19.74 g,
88 mmol, 81%) as a colorless oil. 1H NMR (500.13 MHz, CDCl3):
δ = 5.84–5.75 (m, 1 H, -SCH2CH-), 5.15–5.09 (m, 2 H, methylene-
2
5.28 (dd, J = 17.3, J = 1.5 Hz, 1 H, methylene-CH2trans), 5.18 (dd,
2
CH2), 3.20–3.12 (m, 2 H), 2.74 (d, J = 13.1 Hz, 1 H, -CCH2S-),
2
J = 10.5, J = 1.5 Hz, 1 H, methylene-CH2cis), 4.00 (d, J = 5.2 Hz,
2.47 (d, 2J = 13.0 Hz, 1 H, -CCH2S-), 2.39–2.34 (m, 1 H), 2.08–
1.96 (m, 3 H), 1.86 (d, J = 18.4 Hz, 1 H), 1.53–1.48 (m, 1 H), 1.39–
1.35 (m, 1 H), 1.04 (s, 3 H, CH3), 0.90 (s, 3 H, CH3) ppm. 13C
NMR (125.76 MHz, CDCl3): δ = 20.20, 20.2, 26.8, 26.9, 27.7, 37.0,
43.1, 43.5, 47.8, 60.9, 117.1, 134.4, 217.5 ppm. MS (EI): m/z (%) =
55 (28), 67 (30), 81 (39), 95 (14), 109 (39), 123 (20), 151 (16) [M –
(C3H5S)]+, 168 (13), 183 (62) [M – (C3H5)]+, 224 (100) [M]+.
HRMS (EI): m/z = calcd. for C13H20OS [M]+ 224.1325; found
2
2
2 H, OCH2CH), 3.66 (d, J = 10.7 Hz, 1 H, -CCH2O-), 3.63 (d, J
= 10.7 Hz, 1 H, -CCH2O-), 2.82–2.79 [m, 1 H, CHC(CH3)2], 2.15–
2.09 (m, 2 H), 1.49–1.42 (m, 2 H), 1.07 (s, 3 H, CH3), 0.96 (s, 3 H,
CH3) ppm. 13C NMR (125.76 MHz, CDCl3): δ = 19.4, 21.4, 25.6,
26.4, 48.2, 49.3, 61.5, 65.4, 72.6, 116.7, 120.6, 134.7, 148.7 (dd, J
=
29.5, J =
29.7 Hz, CCF2CF2CF3), 212.0 ppm. 19F NMR
(282.76 MHz, CDCl3): δ = –127.3 to –127.4 (m, CF2CF2CF3),
–119.4 (qdd, J = 8.8, 2.0, 283.4 Hz, CF2CF2CF3), –117.9 (qd, J =
224.1237. ATR-FTIR: ν = 3080, 2958, 2887, 1725, 1634, 1469,
˜
8.8, 283.4 Hz, CF2CF2CF3), –119.4 (t,
J
=
8.8 Hz,
1453, 1416, 1389, 1372, 1317, 1298, 1281, 1227, 1197, 1159, 1128,
1101, 1062, 1049, 1026, 989, 964, 914, 866, 851, 754 cm–1.
C13H20OS (224.36): calcd. C 69.59, H 8.97; found C 69.54, H 8.97.
CF2CF2CF3) ppm. MS (EI): m/z (%) = 177 (7), 235 (5), 291 (9),
305 (10), 333 (100) [M – (C4H7O)]+, 347 (14) [M – (C3H5O)]+,
363 (4) [M – (C3H5)]+, 404 (16) [M]+. HRMS (EI): m/z calcd. for
C H F O [M]+ 404.1222; found 404.1212. ATR-FTIR: ν = 2963,
(1S,4S)-10-(Allylthio)-3-(heptafluorobutanoyl)camphor (12): Lith-
˜
17 19
7
3
2874, 1699, 1642, 1479, 1454, 1422, 1393, 1374, 1345, 1315, 1292,
ium hydride (149 mg, 18.7 mmol) in anhydrous THF (60 mL) was
Eur. J. Org. Chem. 0000, 0–0
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