(S)-3,5-Dimethyl-2-isopropyl-2-cyclohexen-1-one (4). A stirred solution of 2 (3.00 g, 19.7 mmol) in absolute Et O
2
(30 mL, -78°C, Ar) was treated dropwise with LiMe in absolute THF (34 mL, 1.75 N). The reaction mixture was stirred as the
temperature was increased gradually over 1 h to ambient and then for another 2 h at room temperature, cooled to 5°C, treated
with saturated NH Cl solution, stirred for 1.5 h, and extracted with Et O (3 × 30 mL). The extract was washed with saturated
4
2
NaCl solution, dried over Na SO , and evaporated to afford 3 (2.83 g, 85%).
2
-1
4
IR spectrum (ν, cm ): 916, 994 (H–C=); 1162 (C–O); 1654 (C=C); 3460 (OH). Compound 3 was used without further
purification in the next step.
A suspension of PCC (7.93 g, 36.7 mmol) in dry CH Cl (20 mL, 5-10°C, Ar) was stirred vigorously and treated with
2
2
3 (2.80 g, 16.7 mmol) in dry CH Cl (5 mL). The reaction mixture was stirred for 2 h at room temperature, treated with Et O
2
2
2
(30 mL), stirred for another 15 min, and filtered through a layer of Al O . The solid was washed with Et O. The filtrate was
2
3
2
evaporated. The solid was chromatographed over SiO (PE eluent) to afford 4 (2.02 g, 62% based on 2). The chemical purity
2
21
according to GC was 96%, R 0.67 (PE:EA, 2:1), [α]
+119.0° (c 7.1, CHCl ).
3
f
-1
D
IR spectrum (ν, cm ): 1618 (C=C), 1666 (C=O).
PMR spectrum (δ, ppm, J/Hz): 0.98 (d, 3H, J = 5.8, CH C-5), 1.12 and 1.15 [both d, 6H, J = 7.1, (CH ) C], 1.92 (s,
3
3 2
3H, CH C-3), 1.93-2.11 (m, 3H, H -4, H-5, H -6), 2.27 (d, 1H, J = 13.8, H -6), 2.38 (d, 1H, J = 12.7, H -4), 2.95 (h, 1H,
3
J = 7.1, HCC-2).
13
a
a
e
e
C NMR spectrum (δ, ppm): 20.38 (CH C-5), 20.90 and 21.15 [(CH ) C], 21.26 (HCC-2), 27.10 (CH C-3), 29.41
3
3 2
3
(C-5), 42.26 (C-4), 47.24 (C-6), 139.75 (C-2), 153.38 (C-3), 199.31 (C-1).
Methyl (S)-3-Methyl-5-oxohexanoate (5). An O /O mixture (produced byan ozonator at 40 mmol O /h) was passed
3
2
3
through a solution of 4 (1.40 g, 8.5 mmol) in a mixture of dry MeOH (10 mL) and CH Cl (10 mL) at 5°C until the starting
2
2
material completely dissolved (TLC monitoring). The reaction mixture was purged with Ar, treated with TsOH (0.08 g) and
dry MeOH (15 mL), stirred for 48 h at room temperature, treated with NaHCO (0.84 g), evaporated in vacuum, diluted with
3
Et O (100 mL), washed with saturated NaCl solution until the pH was 7, dried over Na SO , evaporated, and chromatographed
2
2
4
21
over SiO to afford 5 (1.00 g, 78%). The chemical puritywas 99% according toGC, R 0.54 (PE:t-BuOMe, 2:1), [α]
+2.57°
f
2
D
(c 1.29, CHCl ).
3
-1
IR spectrum (ν, cm ): 1264 (C–O–C); 1714, 1738 (C=O).
PMR spectrum (δ, ppm, J/Hz): 0.98 (d, 3H, J = 6.5, CH C-3), 2.14 (s, 3H, H-6), 2.17-2.57 (m, 5H, H-2, H-3, H-4), 3.66
3
(s, 3H, CH O).
3
(R)-3-Methyl-γ-butyrolactone (1). A suspension of m-chloroperbenzoic acid (1.10 g, 6.3 mmol) in CHCl (30 mL)
3
at room temperature was treated dropwise with 5 (1.00 g, 42 mmol) in CHCl (20 mL). The reaction mixture was stirred at
3
room temperature for 48 h, diluted with Et O, washed successively with Na SO solution (5%) and saturated NaHCO and
2
2
3
3
NaCl, dried over MgSO , and evaporated.
4
The solid (0.60 g) was treated with KOH (0.71 g, 12.6 mmol) dissolved in MeOH (5 mL), stirred at room temperature
for 48 h, and boiled for 4 h. The MeOH was evaporated. The mixture was treated with HCl (6 N) until the pH was 3-4,
extracted with t-BuOMe, dried over Na SO , and evaporated. The solid was chromatographed over SiO to afford 1 (0.43 g,
2
4
2
20
68%), R 0.43 (PE:t-BuOMe, 2:1), [α]
+25° (c 4, MeOH) (similar to the reported values [1]). The IR and NMR spectra
f
D
agreed with those previously reported [6].
REFERENCES
1.
2.
3.
4.
5.
6.
Jpn. Pat. No. 60-174535 (1987); Ref. Zh. Khim., 11O51P (1988).
D. G. Wenzel and C. M. Smith, J. Am. Pharm. Assoc., 47, 269 (1958).
T. Mukaiyama, K. Fujimoto, T. Hirose, and T. Takeda, Chem. Lett., 6, 635 (1980).
W. Treibs and H. Albrecht, J. Prakt. Chem., 13, 291 (1961).
A. J. Gordon and R. A. Ford, A Chemist's Companion, Wiley-Interscience, New York (1972).
E. I. Troyanskii, I. V. Svitan ko, and G. I. Nikishin, Izv. Akad. Nauk, Ser. Khim., 2318 (1982).
483