[13837-45-1]  · C5H10O2  · 1-Ethoxycyclopropanol  · (MW 102.07)

(homoenolate formation, ring expansion to b-lactams and pyrrolines via 1-aminocyclopropanols, to cyclobutanones via 1-vinylcyclopropanols, and to cyclopentanones via 1-trimethylsiloxy-1-vinylcyclopropanes1)

Physical Data: bp 60 °C/20 mmHg.

Solubility: sol usual organic solvents (ether, THF, CH2Cl2).

Preparative Methods: acyloin-type reaction of ethyl 3-halopropionates with highly dispersed Sodium (or Lithium) in refluxing Et2O in the presence of Chlorotrimethylsilane provides 1-ethoxy-1-trimethylsiloxycyclopropane in high yields.2,3 Use of sonochemical activation simplifies the procedure.4 Then, simple methanolysis (MeOH, ClSiMe3) leads to the hemiacetal (eq 1).

Cyclization of optically pure b-halo esters gives enantiomerically pure cyclopropanes at C-2 and a 1:1 diastereomeric mixture at C-1.5

Handling, Storage, and Precautions: can be kept unaltered for several months at 0 °C. On heating at 100 °C, or on standing in acidic solvents, it undergoes ring opening to ethyl propionate.

Preparation and Reactions of Isolable Metal Homoenolates.

With metals (Ti, Hg, Zn, Sn, Bi, Sb, Te, Nb, etc.), siloxycyclopropanes afford reactive homoenolate species which are stable enough for isolation and characterization.1b For instance, an exothermic reaction occurred with Titanium(IV) Chloride to provide fine violet needles of a titanium species in 89% yield (eq 2).1b

Many examples of carbon-carbon bond formation from metal homoenolates with various electrophiles have been reported. Thus reaction of zinc homoenolates with acid chlorides in ethereal solvents containing 2 equiv of HMPA produces g-keto esters in high yield (eq 3).6 Palladium catalysis accelerates the reaction.7

In a polar solvent, treatment of zinc homoenolates with Me3SiCl results in cyclopropane formation.1b Palladium homoenolates, from siloxycyclopropanes and Palladium(II) Chloride or its phosphine complex, can also serve as useful reaction intermediates.8

Reactivity and Synthetic Applications.

Ring expansion of properly activated cyclopropanes is now one of the major methods of forming cyclobutane derivatives.1 Thus, addition of vinylmagnesium halides to the cyclopropanone hemiacetal provides 1-vinylcyclopropanols,9 which on simple heating at 100 °C in liquid phase or by reaction with a variety of electrophilic reagents (HBr, PhCO3H, t-BuOCl, etc.), undergo quantitative C3 -> C4 ring expansion to substituted cyclobutanones, thus providing convenient intermediates for the creation of a wide range of structural building blocks (eq 4).1a,c For instance, Baeyer-Villiger oxidation leads to g-butyrolactones,10 and reaction with sodium azide in buffered acetone provides g-lactams.9

Conversely, O-silylation (ClSiMe3, NEt3, 5% DMSO)11 affords 1-siloxy-1-vinylcyclopropanes, which undergo thermal vinylcyclopropane-cyclopentene rearrangement to 1-silyloxycyclopentenes exclusively (eq 5).1

Acid or basic hydrolysis gives 2-substituted cyclopentanones. Alternatively, the generation of corresponding lithium enolates (Methyllithium in Et2O) followed by a-alkylation produces a,b-disubstituted cyclopentanone derivatives, which constitute the basic framework of several natural products of biological importance.12 For instance, the total synthesis of (±)-11-deoxyprostaglandin E2 has been performed from the cyclopropanone hemiacetal, via the thermal C3 -> C5 ring expansion of a suitable 1-butadienyl-1-trimethylsiloxycyclopropane (eq 6).13

Reaction of enolates with the cyclopropanone hemiacetal magnesium salt led to substituted hydrazulenones.14 b-Amino esters are formed on photolysis of Ethyl Azidoformate and 1-ethoxy-1-trimethylsiloxycyclopropane in MeCN.15 Treatment of 1-alkoxy-1-siloxycyclopropane with a catalytic amount of palladium-phosphine complex in CHCl3 under carbon monoxide atmosphere gives 4-ketopimelate.8a Arylation of siloxycyclopropanes by aryl triflates is effected by palladium catalysis.8b Inactivation of cytochrome P-450 by heteroatom-substituted cyclopropanes has been interpreted by the ring opening of a cyclopropanone hemiacetal to ethyl 3-hydroxypropionate.16

1-Vinylcyclopropyl sulfonates and allylically isomeric 2-cyclopropylidenethyl carbonate and acetate, which are readily available from the cyclopropanone hemiacetal, undergo regioselective palladium(0)-catalyzed nucleophilic substitutions. With stabilized anions Nu1 (e.g. enolates of malonic esters or b-dicarbonyl compounds), the substitution occurs exclusively at the terminal vinylic position providing cyclopropylidene derivatives; on the other hand, use of organometallic or hydride reagents Nu2 (e.g. Phenylzinc Chloride) entails tertiary substitution on the cyclopropane ring exclusively (eq 7).17

Related Reagents.

Cyclopropanone; Cyclopropenone 1,3-Propanediyl Acetal; 1-Ethoxy-1-(trimethylsilyloxy)cyclopropane; 1-(Tetrahydropyranyloxy)cyclopropanecarbaldehyde.

1. (a) Salaün, J. CRV 1983, 83, 619. (b) Kuwajima, I.; Nakamura, E. Top. Curr. Chem. 1990, 155, 1. (c) Salaün, J. Top. Curr. Chem. 1988, 144, 1. (d) Salaün, J. In The Chemistry of the Cyclopropyl Group; Rappoport, Z., Ed.; Wiley: New York, 1987; Part 2, Chapter 13, p 809.
2. Rühlmann, K. S 1971, 236.
3. Salaün, J.; Marguerite, J. OS 1985, 63, 147.
4.Fadel, A.; Canet, J. L.; Salaün, J. SL 1990, 89.
5. Nakamura, E.; Sekiya, K.; Kuwajima, I. TL 1987, 28, 337.
6. Oshino, H.; Nakamura, E.; Kuwajima, I. JOC 1985, 50, 2802.
7. (a) Nakamura, E.; Kuwajima, I. TL 1986, 27, 83 (b) Aoki, S.; Nakamura, E. SL 1990, 741. (c) Fujimara, T.; Aoki, S.; Nakamura, E. JOC 1991, 56, 2809.
8. (a) Aoki, S.; Fujimura, T.; Nakamura, E.; Kuwajima, I. JACS 1988, 110, 3296. (b) Aoki, S.; Nakamura, E.; Kuwajima, I. TL 1988, 29, 1541.
9. Wasserman, H. H.; Cochoy, R. E.; Baird, M. S. JACS 1969, 91, 2375.
10. Trost, B. M. Top. Curr. Chem. 1973, 41, 1; ACR 1974, 7, 85; PAC 1975, 43, 565.
11. Visser, R. G.; Bos, H. J. T.; Brandsma, L. RTC 1980, 99, 70.
12. Mikolajczyla, M.; Grsejszczak, S.; Lyzwa, P. TL 1982, 23, 2237.
13. Salaün, J.; Ollivier, J. NJC 1981, 5, 587.
14. Helquist, P.; Reydellet, V. TL 1989, 30, 6837.
15. Mitani, M.; Tachizawa, O.; Takeuchi, H.; Koyama, K. JOC 1989, 54, 5397.
16. Guengerich, F. P.; Willard, R. J.; Shea, J. P.; Richards, L. E.; Macdonald, T. L. JACS 1984, 106, 6446. For a review, see: Salaün, J.; Baird, M. S. Curr. Med. Chem 1995, 2, 545.
17. Stolle A.; Ollivier, J.; Piras, P. P.; Salaün, J.; de Meijere, A. JACS 1992, 114, 4051.

Jacques Salaün

Université de Paris-Sud, Orsay, France

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