Org. Synth. 1989, 67, 176
DOI: 10.15227/orgsyn.067.0176
SELECTIVE CYCLOPROPANATION OF (S)-(−)-PERILLYL ALCOHOL: 1-HYDROXYMETHYL-4-(1-METHYLCYCLOPROPYL)-1-CYCLOHEXENE
[1-Cyclohexene-1-methanol, 4-(1-methylcyclopropyl)-]
Submitted by Keiji Maruoka, Soichi Sakane, and Hisashi Yamamoto
1.
Checked by Hisatoyo Kato and Ryoji Noyori.
1. Procedure
A dry, 1-L, three-necked, round-bottomed flask is equipped with a gas inlet, a 50-mL pressure-equalizing dropping funnel, a rubber septum, and a Teflon-coated magnetic stirring bar. The flask is flushed with argon, after which 10.65 g (0.07 mol) of (S)-(−)-perillyl alcohol (Note 1) followed by 350 mL of dichloromethane (Note 2) is injected through the septum into the flask. The solution is stirred and 37.3 mL (0.147 mol) of triisobutylaluminum (Note 3) is added from the dropping funnel over a 20-min period at room temperature (Note 4). After the mixture is stirred at room temperature for 20 min, 7.3 mL (0.091 mol) of diiodomethane (Note 5) is added dropwise with a syringe over a 10-min period. The mixture is stirred at room temperature for 4 hr, and poured into 400 mL of ice-cold 8% aqueous sodium hydroxide. The organic layer is separated, and the aqueous layer is extracted twice with 100-mL portions of dichloromethane. The combined extracts are dried over anhydrous sodium sulfate and concentrated with a rotary evaporator at ca. 20 mm. The residual oil is distilled under reduced pressure to give 10.64–11.13 g (92–96%) of 1-hydroxymethyl-4-(1-methylcyclopropyl)-1-cyclohexene as a colorless liquid, bp 132–134°C (24 mm) (Note 6) and (Note 7).
2. Notes
1.
(S)-(−)-Perillyl alcohol is available from Aldrich Chemical Company, Inc.2.
Reagent-grade dichloromethane was dried and stored over Linde type 4A molecular sieves.
3.
Neat
triisobutylaluminum of 97.6% purity was supplied in a metal cylinder from Toso-Akzo Chemical Company, Ltd. (Japan). This reagent is also available from Aldrich Chemical Company, Inc. Since neat
triisobutylaluminum is pyrophoric and reacts violently with
oxygen and water, the used syringe should be immediately washed with
hexane.
4.
During this operation an exothermic reaction took place.
5.
Diiodomethane, available from Tokyo Kasei Kogyo Company, Ltd. (Japan), was used without any purification.
6.
The spectral properties of the product are as follows:
1H NMR (CDCl
3, 500 MHz) δ: 0.22 and 0.26 (m, 4 H, cyclopropyl C-H), 0.80–0.92, 1.24–1.30, and 1.36–1.47 (m, 3 H, cyclohexenyl C-H), 0.93 (s, 3 H, CH
3), 1.77–1.83 (m, 1 H, cyclohexenyl =C-C-H), 1.91–2.16 (m, 4 H, OH, and cyclohexenyl =C-C-H), 3.99 (brt, 2 H, CH
2-O), 5.69 (br s, 1 H, =C-C-H); IR (liquid film) cm
−1: 3330, 2830–2960, 1423–1460, 1390, 1010, 1000.
7.
Gas-chromatographic analysis of the
trimethylsilyl ether using a
25-m PEG-HT capillary column at 100°C indicated a purity of 93% (retention time: 11.2 min). Under the present conditions, neither the starting
perillyl alcohol nor the isomeric monocyclopropanation product (
1-hydroxymethyl-4-isopropenylbicyclo[4.1.0]-heptane) were detected. Dicyclopropanation products amounted to less than 5%.
3. Discussion
This procedure illustrates a new method for selective cyclopropanation of unsaturated alcohols not obtainable with ordinary cyclopropanation reactions.
2 The selectivity in this trialkylaluminum-promoted cyclopropanation is complementary to that obtained in the Simmons–Smith reaction and its modifications,
3 which give facile hydroxyl-assisted cyclopropanations with
perillyl alcohol to afford
1-hydroxymethyl-4-isopropenylbicyclo[4.1.0]heptane predominantly. A similar tendency was observed in the case of
geraniol. Thus, cyclopropanation with the
i-Bu
3Al/CH
2I
2 system takes place almost exclusively at the C(6)–C(7) olefinic site far from the hydroxyl group of
geraniol, and the C(2)–C(3) olefinic bond is left intact.
2The present cyclopropanation using trialkylaluminum-methylene iodide may proceed via dialkyl(iodomethyl)aluminum as an active intermediate,
4 which also can be generated by the reaction of dialkylaluminum iodide with
diazomethane.
5 In addition, reaction of
diiodomethane with
triisobutylaluminum (each 1 equiv) afforded nearly 1 equiv of
isobutyl iodide as a product, suggesting the formation of
diisobutyl(iodomethyl)aluminum in the solution.
2The combined use of a wide variety of trialkylaluminum compounds and alkylidene iodide serves as a highly convenient and versatile method for cyclopropanation of simple olefins under mild conditions.
2 For example, treatment of
1-dodecene with CH
2I
2/R
3Al (R = Me, Et,
i-Bu) in
dichloromethane at room temperature for 3–8 hr gave
decylcyclopropane in
96–98% yields.
Appendix
Chemical Abstracts Nomenclature (Collective Index Number);
(Registry Number)
(S)-(−)-PERILLYL ALCOHOL
sodium hydroxide (1310-73-2)
sodium sulfate (7757-82-6)
oxygen (7782-44-7)
diiodomethane (75-11-6)
dichloromethane (75-09-2)
Diazomethane (334-88-3)
hexane (110-54-3)
geraniol (106-24-1)
argon (7440-37-1)
triisobutylaluminum (100-99-2)
trimethylsilyl ether (107-46-0)
1-Hydroxymethyl-4-(1-methylcyclopropyl)-1-cyclohexene,
1-Cyclohexene-1-methanol, 4-(1-methylcyclopropyl)- (98678-72-9)
perillyl alcohol
1-hydroxymethyl-4-isopropenylbicyclo[4.1.0]-heptane,
1-hydroxymethyl-4-isopropenylbicyclo[4.1.0]heptane
Isobutyl iodide (513-38-2)
diisobutyl(iodomethyl)aluminum
1-dodecene (112-41-4)
decylcyclopropane
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