[55249-20-2]  · C5H8Br2O  · 1,1-Dibromo-2-ethoxycyclopropane  · (MW 243.93)

(cyclopropyllithium reagent; cyclopropene precursor)

Alternate Name: 2,2-dibromocyclopropyl ethyl ether.

Physical Data: bp 45-48 °C/4 mmHg.

Analysis of Reagent Purity: 1H NMR (CCl4-Me4Si, 60 MHz) d 1.27 (t, J = 7.0 Hz, 3H), 1.55-1.95 (m, 2H), 3.35-4.05 (m, 3H).

Preparative Method: 1 to a mixture of ethoxyethylene (1 equiv), n-Bu3N (0.024 equiv), and CHBr3 (1.5 equiv), is added aq. NaOH solution (50%, 6.25 equiv of NaOH) at rt. The reaction mixture is stirred for 48 h and poured into water and extracted with Et2O. The organic phase is washed with water, dried over anhydrous Na2SO4, filtered and concentrated using a rotary evaporator at 25 °C/60 mmHg. The residue is distilled at 25 °C/0.2 mmHg and further purified by silica gel column chromatography (petroleum ether/CH2Cl2 = 4:1) to give pure 1,1-dibromo-2-ethoxycyclopropane (1) (eq 1).

Purification: distillation followed by silica gel column chromatography.

Cyclopropylidenating Reagent.

A carbenoid reagent, 1-bromo-2-ethoxycyclopropyllithium (2), is generated from (1) upon treatment with 1 mol equiv of n-Butyllithium in THF at -95 °C. The lithium reagent reacts with various electrophiles to give 1-substituted cyclopropane derivatives. The electrophile is introduced preferentially cis to the ethoxyl group.

The cyclopropyllithium (2) reacts with 2-cyclopentenone in a 1,2-addition manner to give the corresponding alcohol, which is converted into an ethanol adduct of chalicene (eq 2).2

Cyclopropene Precursor.

Reduction of (1) with Zinc in methanol gives a mixture of cis- and trans-1-bromo-2-ethoxycyclopropane (5). The cyclopropane (5) is dehaloalkoxylated with Magnesium in THF at reflux to afford cyclopropene (6) (eq 3),3 which is trapped with cyclopentadiene or bromine to give tricyclo[,4]-6-octene (7) (eq 4) or trans-1,2-dibromocyclopropane (8) (eq 5), respectively.

Solvolytic Ring Opening.4

Treatment of (1) with Sodium Ethoxide/EtOH gives 3,3-diethoxy-1-propyne (9) (eq 6). When Potassium Fluoride is used as a base, 1,1,3-triethoxy-2-bromopropane (10) is the product (eq 7).

The 1-substituted cyclopropanes (11) undergo solvolysis in ethanol/Potassium Carbonate to give 2-substituted 3,3-diethoxy-1-propene derivatives (12), which upon hydrolysis afford a-substituted acroleins (13) (eq 8). Thus the carbenoid reagent (2) is a synthetic equivalent of acrolein a-anion. This method is applied to the synthesis of b-sinensal (eq 9) and juvenile hormone JH-II.5

In ethanol containing Boron Trifluoride Etherate, (11) are converted into 3-substituted 3-bromo-1,1-diethoxypropanes (14), which are used in the synthesis of jasmones (eq 10).5

1. Weber, A.; Sabbioni, G.; Galli, R.; Neuenschwander, M. C 1981, 35, 57.
2. Sabbioni, G.; Weber, A.; Galli, R.; Neuenschwander, M. C 1981, 35, 95.
3. D'yachenko, A. I.; Abramova, N. M.; Rudashevskaya, T. Yu.; Nesmeyanova, O. A.; Nefedov, O. M. Izv. Akad. Nauk SSSR., Ser. Khim. 1982, 1193 (CA 1982, 97, 109 579z).
4. Aksenov, V. S.; Filimoshkina, V. A. Izv. Sib. Otd. Akad. Nauk SSSR., Ser Khim. Nauk. 1975, 147 (CA 1975, 83, 147 154a).
5. Morizawa, Y.; Kanakura, A.; Yamamoto, H.; Hiyama, T.; Nozaki, H. BCJ 1984, 57, 1935. Hiyama, T.; Kanakura, A.; Yamamoto, H.; Nozaki, H. TL 1978, 3047 and 3051. Corey, E. J.; Ulrich, P. TL 1975, 3685.

Tamejiro Hiyama & Manabu Kuroboshi

Tokyo Institute of Technology, Yokohama, Japan

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