used for ozonolytic transformations of conjugated enones, an equimolar amount was sufficient for the complete transformation
of 2. Deoxygenation of 3 according to Huang–Minlon that was accompanied by saponification of the ester gave (3S)-
methylundecanoic acid (4), which was converted by the standard method through alcohol 5 to bromide 6 or immediately to
bromide 7.
Thus, we demonstrated new synthetic capabilities of accessible (R)-4-menthen-3-one that included chemoselective
transformations that did not affect the asymmetric center.
EXPERIMENTAL
IR spectra in thin layers were recorded on a Prestige-21 IR instrument (Shimadzu). NMR spectra in CDCl were
3
1
13
recorded on a Bruker AM-300 spectrometer (300.13 MHz operating frequency for H; 75.47, C). The internal standards
were CDCl resonances in the PMR spectrum of impurity protons in the deuterated solvent (ꢃ 7.27 ppm); in the C NMR
13
3
spectrum, the average resonance of CDCl (ꢃ 77.00 ppm). Chromatography was carried out on Chrom-5 [column length 1.2
3
m; stationary phase silicone SE-30 (5%) + OV-225 (3%) on Chromaton N-AW-DMCS (0.16–0.20 mm); operating temperature
50–200°C] and GC-9A [Shimadzu, quartz capillary column length 25 m, stationary phase DB-1 (0.25 ꢄm), operating temperature
80–280°C] instruments with He carrier gas. Optical rotation was measured on a Perkin–Elmer 241-MC polarimeter. Column
chromatography was performed over silica gel L (60–200 ꢄm, Lancaster, England). TLC used Sorbfil plates (Krasnodar).
Mass spectra were obtained on a Shimadzu JCMS 2010 EV under APCI conditions at electron energy 20 eV in positive- and
negative-ion modes. The nebulizer gas (N ) flow rate was 0.05 L/min with MeOH:H O (50:50) mobile phase at flow rate
2
2
0.03 mL/min.
(5S)-Methyl-2-isopropyl-3-hexyl-2-cyclohexen-1-one (2). A stirred solution of 1 (5.00 g, 32.9 mmol) in anhydrous
hexane (40 mL, –78°C, Ar) was treated dropwise with a solution of n-C H Li prepared from Li (1.84 g, 263.2 mg-atom) and
6
13
n-C H Br (21.71 g, 131.6 mmol) in anhydrous hexane (80 mL, ꢂ, Ar). The mixture was stirred for 6 h at –78°C. Then, the
6
13
temperature was raised to 5°C. Saturated NH Cl solution (100 mL) was added. Stirring was continued for 1.5 h. The mixture
4
was extracted with Et O (3 ꢅ 100 mL). The combined extracts were washed with saturated NaCl solution (until the pH was 7),
2
–1
dried over MgSO , and evaporated. The crude product [7.69 g; IR spectrum (KBr, , cm ): 3439 (O–H), 1654 (C=C)] was
4
used without further purification in the next step by adding it in anhydrous CH Cl (40 mL) with vigorous stirring to a
2
2
suspension of PCC (14.06 g, 65.1 mmol) in anhydrous CH Cl (65 mL, 5 –10°C, Ar). The mixture was stirred for 2 h at room
2
2
temperature, treated with Et O (60 mL), stirred for another 15 min, filtered through a thin layer of Al O , and washed with
2
2 3
Et O. The filtrate was evaporated. The solid (7.52 g) was chromatographed over a column of SiO (PE) to afford 2 (5.86 g,
2
2
21
75%), the chemical purity of which according to GC was 99%, R 0.68 (PE:MTBE, 3:1), [ꢆ] +31.6° (c 0.6, CH Cl ).
IR spectrum (KBr, , cm ): 1612 (C=C), 1666 (C=O).
f
D
2
2
–1
+
+
Mass spectrum (m/z, I , %): 237 (100) [M + H] , 473 (0.6) [2M + H] , 321 (10.4), 153 (4.6).
rel
PMR spectrum (300.13 MHz, CDCl , ꢃ, ppm, J/Hz): 0.85 (3H, t, J = 6.6, H-6ꢇ), 0.92 (3H, d, J = 6.8, CH -5), 1.12
3
3
(3H, d, J = 6.5, H-2ꢈ), 1.15 (3H, d, J = 6.5, H-3ꢈ), 1.15–1.34 (6H, m, H-3ꢇ, H-4ꢇ, H-5ꢇ), 1.30–1.42 (2H, m, H-2ꢇ), 1.88 (1H, dd,
2
3
2
3
J = 12.6, J = 3.3, H -6), 1.98 (1H, dd, J = 12.6, J = 4.1, H -6), 2.03–2.14 (1H, m, H-5), 2.06–2.20 (2H, m, H-1ꢇ), 2.18 (1H,
a
e
2
3
2
3
dd, J = 12.5, J = 4.3, H -4), 2.32 (1H, dd, J = 12.5, J = 2.6, H -4), 2.8 (1H, h, J = 6.5, H-1ꢈ).
a
e
13
C NMR spectrum (75.47 MHz, CDCl , ꢃ): 13.97 (q, C-6ꢇ), 20.99 (q, C-2ꢈ), 21.16 (q, C-3ꢈ, CH -5), 22.52 (t,
3
3
C-5ꢇ), 27.31 (d, C-1ꢈ), 28.15 (t, C-4ꢇ), 29.83 (d, C-5), 30.04 (t, C-3ꢇ), 31.62 (t, C-2ꢇ), 34.99 (t, C-1ꢇ), 40.14 (t, C-4), 47.51 (t,
C-6), 139.34 (s, C-2), 157.33 (s, C-3), 199.54 (s, C-1).
(3S)-Methyl-5-oxoundecanoic Acid Methyl Ester (3). A solution of 2 (5.80 g, 24.5 mmol) in anhydrous MeOH
(25 mL) and anhydrous CH Cl (25 mL) at 0°C was purged with an O /O mixture (ozonator production 35 mmol O /h) until
2
2
3
2
3
the starting compound disappeared (TLC monitoring). The mixture was purged with Ar before adding TsOH (0.25 g) and
anhydrous MeOH (40 mL), stirring at room temperature for 48 h, adding NaHCO (3.0 g), and evaporating in vacuo. The
3
solid was treated with Et O (200 mL), washed with saturated NaCl solution (until the pH was 7), dried over MgSO , and
2
4
evaporated. The solid was chromatographed over a column of SiO (PE) to isolate 3 (4.82 g, 86%), the chemical purity of
2
21
–1
which according to GC was 99%, R 0.53 (PE:MTBE, 3:1), [ꢆ] +3.2° (c 0.3, CH Cl ). IR spectrum (KBr, , cm ): 1712
f
D
2
2
(C=O), 1735 (COOMe).
+
+
–
Mass spectrum (m/z, I , %): 229 (100) [M + H] , 246 (12.3) [M + H O] , 197 (77.1) [M – OCH ] , 169 (25.0)
rel
2
3
–
–
–
[M – CO CH ] , 227 (76.0) [M – H] , 196 (100) [M – H – OCH ] .
2
3
3
371