640
D. Soorukram, P. Knochel
PRACTICAL SYNTHETIC PROCEDURES
13C NMR (CDCl3, 75 MHz): d = 138.3, 111.0, 52.5, 40.6, 33.6,
GC (Chirasil-Dex CB, 25 mm × 0.25 mm); conditions: 60 °C (1
min), ramp of 10 °C/min to 160 °C; tR (min) = 10.991 (minor),
11.080 (major).
32.8, 32.3, 27.6, 24.4, 23.0, 14.5.
MS (EI, 70 eV): m/z (%) = 278 (M+, 16), 207 (100), 192 (2), 151 (3),
91 (3), 80 (77).
IR (film): 2956 (s), 2872 (m), 1711 (s), 1460 (m), 1369 (w), 1261
(w), 1079 cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 2.27–2.05 (m, 2 H), 2.00–1.90 (m,
1 H), 1.83–1.63 (m, 2 H), 1.62–1.40 (m, 3 H), 1.25–1.05 (m, 6 H),
1.04–0.83 (m, 4 H), 0.82–0.70 (m, 3 H), 0.66 (s, 3 H).
HRMS (EI): m/z calcd for C11H19I: 278.053; found: 278.0544.
(7R)-7-Cyclohexyl-1-iodocyclohept-1-ene (4);7 Typical Proce-
dure 2
A flame-dried round-bottomed flask equipped with a magnetic stir-
ring bar, an argon inlet, and a rubber septum was charged with a
CuCN·2LiCl solution (1.0 M in THF, 2.0 mL, 2.0 mmol, 2.0 equiv)
and cooled to –30 °C. Cyclohexylzinc iodide10 (1.0 M in THF, 2.0
mL, 2.0 mmol, 2.0 equiv) was added dropwise to the resulting solu-
tion. The mixture was stirred at –30 °C for 30 min, then (1S)-2-io-
docyclohept-2-en-1-yl pentafluorobenzoate (3; 432 mg, 1.0 mmol)
was added dropwise as a solution in NMP (1.3 mL). The mixture
was stirred at –30 to –10 °C for 16 h. A sat. aq NH4Cl solution (20
mL) was added followed by 25% aq NH3 solution. The mixture was
stirred at 25 °C until the copper salts had dissolved, and then ex-
tracted with Et2O (3 × 20 mL). The combined organic phase was
washed with brine (10 mL) and dried (Na2SO4). Purification by col-
umn chromatography (silica gel, pentane) afforded the product (R)-
4 as a colorless oil; yield: 264 mg (87%); 98% ee; [a]D20 –19.4 (c =
0.31, CH2Cl2).
13C NMR (CDCl3, 75 MHz): d = 212.2, 59.6, 39.2, 37.9, 36.9, 30.4,
27.6, 27.0, 22.7, 21.5, 21.1, 20.9, 12.4.
MS (EI, 70 eV): m/z (%) = 196 (M+, 1), 181 (12), 153 (3), 139 (4),
126 (18), 111 (100), 83 (3), 69 (7).
HRMS (EI): m/z calcd for C13H24O: 196.1827; found: 196.1831.
(2R)-2-Cyclohexylcycloheptanone (6)
[a]D20 +87 (c = 0.284, CH2Cl2).
GC (Chirasil-Dex CB, 25 mm × 0.25 mm); conditions: 60 °C (1
min), ramp of 2 °C/min to 160 °C; tR (min) = 44.308 (minor),
44.411 (major).
IR (film): 2924 (s), 2852 (s), 1702 (s), 1450 (s), 1342 (m), 1323 (m),
1166 (m), 936 cm–1 (m).
1H NMR (CDCl3, 300 MHz): d = 2.45 (dt, J = 2.88, 12.0 Hz, 1 H),
2.32–2.21 (m, 1 H), 2.19–2.07 (m, 1 H), 1.94–1.72 (m, 4 H), 1.71–
1.38 (m, 7 H), 1.38–1.00 (m, 6 H), 1.00–0.80 (m, 2 H).
13C NMR (CDCl3, 75 MHz): d = 217.5, 59.6, 43.1, 40.9, 31.7, 30.5,
30.3, 28.2, 28.1, 26.76 (2 C), 26.73, 26.0.
IR (film): 2922 (s), 2850 (s), 1446 cm–1 (s).
1H NMR (CDCl3, 300 MHz): d = 6.60–6.50 (m, 1 H), 2.58–2.48 (m,
1 H), 2.30–2.16 (m, 1 H), 2.10–2.00 (m, 1 H), 1.96–1.52 (m, 11 H),
1.48–1.10 (m, 5 H), 0.96–0.80 (m, 1 H).
MS (EI, 70 eV): m/z (%) = 194 (M+, 1), 151 (3), 123 (3), 112 (100),
97 (11), 84 (14), 67 (8).
13C NMR (CDCl3, 75 MHz): d = 141.8, 107.4, 59.6, 39.3, 32.4,
30.7, 30.4, 27.2, 26.9 (2 C), 26.71, 26.68, 25.5.
MS (EI, 70 eV): m/z (%) = 304 (M+, 32), 222 (44), 177 (13), 121 (6),
HRMS (EI): m/z calcd for C13H22O: 194.1671; found: 194.1740.
95 (100), 83 (47).
(2S)-2-Methyl-2-pentylcyclopentanone (12)7
Compound 12 was prepared on a 0.78 mmol scale (217 mg) accord-
ing to typical procedure 3; yield: 92 mg (70%); 95% ee; [a]D20 +53
(c = 0.24, CH2Cl2).
HRMS (EI): m/z calcd for C13H21I: 304.0688; found: 304.0702.
(2S)-2-Pentylcyclopentanone (9);7,9 Typical Procedure 3
A flame-dried round-bottomed flask equipped with a magnetic stir-
ring bar, an argon inlet, and a rubber septum was charged with cy-
clopentenyl iodide (8; 132 mg, 0.50 mmol, 1.0 equiv) and THF (4.0
mL). The mixture was cooled to –78 °C, and then t-BuLi (1.60 M in
pentane, 0.63 mL, 1.0 mmol, 2.0 equiv) was added dropwise. The
mixture was stirred at –78 °C for 30 min, then B(OMe)3 (0.14 mL,
1.25 mmol, 2.50 equiv) was added dropwise. The mixture was
stirred and allowed to warm to 25 °C for 24 h, then a suspension of
NaBO3·4H2O (10 equiv, 769 mg, 5.0 mmol) in H2O (6 mL) was
added at 25 °C. After stirring at 25 °C for 24 h, the mixture was
poured into H2O and extracted with Et2O (3 × 25 mL). The com-
bined organic phases were washed with brine (10 mL) and dried
(MgSO4). The solvents were evaporated and the crude product was
purified by column chromatography (silica gel, 10% Et2O–pentane)
to give the chiral ketone (S)-9 as a colorless oil; yield: 69 mg (90%);
81% ee.
GC (Chirasil-Dex CB, 25 mm × 0.25 mm); conditions: 60 °C (1
min), ramp of 5 °C/min to 160 °C; tR (min) = 14.223 (minor),
14.336 (major).
IR (film): 2958 (s), 2931 (s), 2860 (m), 1738 (s), 1461 (m), 1161
cm–1 (w).
1H NMR (CDCl3, 300 MHz): d = 2.28–2.02 (m, 2 H), 1.72 (m, 3 H),
1.70–1.58 (m, 1 H), 1.40–1.00 (m, 8 H), 0.92 (s, 3 H), 0.80 (t,
J = 6.97 Hz, 3 H).
13C NMR (CDCl3, 75 MHz): d = 224.3, 48.7, 38.1, 37.0, 36.0, 32.8,
24.3, 22.9, 22.2, 19.1, 14.4.
MS (EI, 70 eV): m/z (%) = 99 (5), 98 (100), 83 (5), 69 (7), 56 (26).
HRMS (EI): m/z calcd for C11H20O: 168.1514; found: 168.1516.
IR (film): 2959 (m), 2930 (m), 2858 (m), 1739 (s), 1454 (w), 1154
cm–1 (m).
1H NMR (CDCl3, 300 MHz): d = 2.30–1.87 (m, 6 H), 1.85–1.60 (m,
2 H), 1.55–1.38 (m, 1 H), 1.35–1.10 (m, 6 H), 0.90–0.75 (m, 3 H).
13C NMR (CDCl3, 75 MHz): d = 221.9, 49.5, 38.5, 32.1, 30.0 (2 C),
27.6, 22.9, 21.1, 14.4.
Acknowledgment
We thank the Fonds der Chemischen Industrie and the DFG for fi-
nancial support and Chemetall GmbH (Frankfurt) and BASF AG
(Ludwigshafen) for the generous gift of chemicals.
References
MS (EI, 70 eV): m/z (%) = 154 (M+, 7), 112 (1), 111 (1), 97 (13), 84
(100), 69 (4), 55 (9).
(1) (a) Fey, P.; Hartwig, W. In Stereoselective Synthesis, Vol 2;
Helmchen, G.; Hoffmann, R. W.; Mulzer, J.; Schaumann, E.,
Eds.; Thieme Verlag: Stuttgart, 1996, 969. (b) Fey, P.;
Hartwig, W. In Stereoselective Synthesis, Vol 2; Helmchen,
HRMS (EI): m/z calcd for C10H18O: 154.1358; found: 154.1362.
(2R)-3,3-Dimethyl-2-pentylcyclohexanone (5)
[a]D20 –23 (c = 0.41, Et2O).
Synthesis 2007, No. 4, 638–641 © Thieme Stuttgart · New York