EXPERIMENTAL
IR spectra were recorded on a UR-20 instrument as thin layers. NMR spectra were obtained on a Bruker AM-300
1
spectrometer (working frequency 300.13 MHz for H and 75.47 MHz for 13C) in CDCl with chloroform internal standard
3
(PMR, 7.27 ppm; 13C NMR, average 77.00 ppm). Chromatography was performed on a Chrom-5 instrument [1.2 m column,
silicon SE-30 (5%) stationary phase on Chromaton N-AW-DMCS (0.16-0.20 mm), working temperature 50-300oC, He carrier
gas]. Optical rotations were measured on a Perkin—Elmer 241-MC polarimeter. TLC was carried out on SiO Silufol UV-254
2
(Czech Rep.) using petroleum ether—ethanol (2:1); chromatography, on SiO (40-100, Chemapol, Czech Rep.) using petroleum
2
16
o
ether (40-70oC). For (R)-menthenone (3), [ ]D -67.5 (c 5.3, CHCl ) (lit. -67.2o, [5]). IR and PMR spectra of 4, 5 [6], 1, and
3
7 [3] were practically identical to the published ones. Diisopropyl-(3-ethoxy-2-methyl-2-propenyl)phosphonate was graciously
supplied by E. P. Serebryakov (N. D. Zelinskii Inst. Org. Chem., Russian Acad. Sci., Moscow).
Methyl Ester of (R)-5,5-Dimethoxy-3-methylpentanoic Acid (4). An ozone—oxygen mixture (produced at 40 mmole
O /h in an ozonator) was bubbled through a solution of 3 (5.00 g, 32.9 mmole) in cyclohexane (35 mL) (or CCl ) in the presence
2
4
of absolute CH OH (2.82 mL, 65.8 mmole) at 5oC at a ratio of 1.1 mole O per mole of 3. The reaction mixture was purged
3
3
with Ar, treated with CH OH (50 mL) and TsOH (0.25 g), left at room temperature for 2 d until the peroxide disappeared
3
(starch—I test), treated with NaHCO (2.50 g), and evaporated under vacuum. The solid was dissolved in ethanol (100 mL),
2
3
washed with saturated NaCl solution (until the pH was 7), dried over Na SO , and evaporated. Yield of 4, 5.44 g (87%),
2
4
25
[ ]D -1.54o (c 4.76, CHCl ) [6].
3
13C NMR spectrum (CDCl , , ppm): 19.48 (q, H CC-3); 26.14 (d, C-3); 38.38 (t, C-4); 40.78 (t, C-2); 50.56, 51.42,
3
3
and 52.00 (all t, H CO); 102.30 (d, C-5); 172.35 (s, C-1).
3
(S)-5,5-Dimethoxy-3-methylpentan-1-ol (5). A stirred suspension of LiAlH (2.00 g, 52.6 mmole) in absolute ether
4
(60 mL) was treated (0o, Ar) with a solution of 4 (5.00 g, 26.3 mmole) in absolute ether (15 mL). The reaction mixture was
heated to ~20oC, stirred for 2 h, cooled to 0oC, treated successively with stirring with H O (4 mL) and NaOH solution (1.5 mL,
2
15%), and stirred for 2 h. The organic layer was separated. The aqueous layer was extracted with ether (3×30 mL). The
extracts were combined with the organic layer, washed with saturated NaCl solution (until the pH was 7), dried over Na SO ,
2
4
18
and evaporated. Yield of 5, 3.32 g (78%), [ ]D +5.72o (c 5.21, CHCl ) [6].
3
(S)-3,7-Dimethyloctanal (7). A solution of 5 (3.30 g, 20.4 mmole) in dry pyridine (6 mL) (0oC, Ar) was treated with
stirring with TsCl (4.28 g, 22.5 mmole). The reaction mixture was stirred (0oC, 5 h), left overnight in a refrigerator, treated
with icewater (10 g), and extracted with ether (3×30 mL). The combined extracts were treated successively with H O and
2
saturated CuSO , NaHCO , NaCl solutions; dried over Na SO ; and evaporated. Yield of 6, 6.32 g. IR spectrum (KBr,
4
3
2
4
, cm-1): 960, 1030, 1070, 1110, 1135 (C–O), 1185, 1370 (S O), 1605 (Ar). The product was used without further purification.
A solution of 6 in absolute THF (25 mL) was added dropwise (-75oC, Ar) to a stirred solution of Grignard reagent
prepared from isobutylbromide (3.84 g, 28.0 mmole) and Mg (0.74 g, 30.8 mg-at) in absolute ether (16 mL) and treated with
a solution of Li2CuCl (0.50 mL, 0.2 M) in THF. The reaction mixture was stirred (-70oC, 1 h; -10oC, 2 h; 25oC, 2 h), treated
4
with cold saturated NH Cl solution, and extracted with ether (3×50 mL). The combined extracts were washed successively with
4
saturated NaCl, NaHCO , and NaCl solutions and evaporated. The solid was dissolved in a mixture of acetone (200 mL) and
3
H O (0.7 mL), treated successively with pyridine (0.47 g) and TsOH (1.13 g), boiled for 2 h, and evaporated under vacuum.
2
The solid was dissolved in ether (150 mL); treated successively with saturated NH Cl, NaHCO , and NaCl solutions; dried over
4
3
20
Na SO ; and evaporated. Yield of 7, 2.47 g (78%), [ ]D -13.8o (c 5.1, CHCl ) [3].
2
4
3
(S)-(+)-Hydroprene (1). Aldehyde 7 (0.20 g, 1.3 mmole) and diisopropyl-(3-ethoxy-2-methyl-2-propenyl)phosphonate
(0.08 g) were reacted according to the literature [3] to give after evaporation of solvent and column chromatography (SiO ,
2
20
CH Cl ) 1 (0.23 g, 68%) as a 9:1 mixture of the (2E,4E)- and (2E,4Z)-stereoisomers, [ ]D -3.43o (c 3.1, CHCl ).
2
2
3
REFERENCES
1.
2.
V. N. Odinokov, G. Yu. Ishmuratov, R. Ya. Kharisov, E. P. Serebryakov, and G. A. Tolstikov, Izv. Akad. Nauk,
Ser. Khim., 110 (1993).
C. A. Henrick, R. J. Anderson, G. B. Staal, and G. F. Ludvick, J. Agric. Food Chem., 26, 542 (1978).
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