[27374-25-0]  · C8H18O2Si  · 1-Ethoxy-1-(trimethylsilyloxy)cyclopropane  · (MW 174.32)

(preparation of 3-metallopropionates;1 metal homoenolate precursor2)

Physical Data: bp 50-53 °C/22 mmHg.

Solubility: insol H2O.

Form Supplied in: colorless liquid.

Analysis of Reagent Purity: GLC, NMR.

Preparative Methods: for the synthesis of the parent and the 2-monoalkyl-substituted compounds, reduction of ethyl 3-chloropropionate with Sodium-Potassium Alloy alloy in the presence of Chlorotrimethylsilane in ether.3 A recent modification using ultrasound irradiation is much more convenient and more widely applicable.4 Other substituted derivatives are prepared by cyclopropanation of alkyl silyl ketene acetals with the Furukawa reagent (Diiodomethane/Diethylzinc).5

Purification: distillation under reduced pressure.

Handling, Storage, and Precautions: moisture sensitive, yet, once purified by distillation, is stable for a long period of time in a tightly capped bottle at room temperature.

Stoichiometric Precursor of Metal Homoenolates.

The reaction of 1-alkoxy-1-trimethylsilyloxycyclopropane with a variety of Lewis acidic metal chlorides affords the 3-metallated propionate esters in good to excellent yield (see below).1,6,7 For instance, the reaction of 1-ethoxy-1-trimethylsilyloxycyclopropane with one equivalent of Tin(IV) Chloride gives a 3-stannylpropionate, which further reacts with another equivalent of the cyclopropane to give a dialkylated tin compound (eq 1).

The reaction of the siloxycyclopropane with Titanium(IV) Chloride produces the titanium homoenolate (3-titaniopropionate) in good yield; this, however, is relatively unreactive (eq 2).8 Addition of one equivalent of Ti(ORŽ)4 generates a more reactive RTiCl2ORŽ species, which smoothly reacts with carbonyl compounds below room temperature.9 The g-hydroxy ester adducts are useful synthetic intermediates and serve as precursors to g-lactones and cyclopropanecarboxylates.10 A useful variation involves the use of the cyclopropanecarboxylate ester as a functionalized homoenolate precursor to obtain levulinic acid derivatives (eq 3).11

The zinc homoenolate prepared by the treatment of the siloxycyclopropane with Zinc Chloride is a versatile synthetic reagent (eq 4).12 Reduction of 3-iodopropionate with activated Zinc also produces a zinc homoenolate species.13

Treatment of the silyloxycyclopropane with ZnCl2 followed by addition of an enone, HMPA, THF, and a catalytic amount of a CuI salt results in quantitative formation of a conjugate adduct as an enol silyl ether (eq 4). The chlorosilane, a byproduct, is essential for the conjugate addition of the copper homoenolate.14,15 Boron Trifluoride Etherate promotes the copper-catalyzed conjugate addition reaction with a different stereochemical outcome.16 A useful application of the conjugate addition reaction is a [3 + 2] synthesis of cyclopentenones, wherein the homoenolate acts as a 1,3-dipole equivalent (eq 5).17

The zinc homoenolate undergoes copper-catalyzed allylation with allylic chlorides. The reaction is not only extremely SN2Ž regioselective but stereoselective for d-chiral allylic chlorides.18 Arylation and vinylation of the zinc homoenolates proceed in the presence of a palladium-phosphine complex.19 Similarly, palladium-catalyzed acylation reaction gives g-keto esters (eq 6).

Catalytic Generation of Homoenolate Reactive Species.

Homoaldol reaction between the siloxycyclopropane and an aldehyde with a catalytic amount of Zinc Iodide in methylene chloride affords a g silyloxy ester (eq 7).18,20 Arylation21 and acylation22,23 of the silyloxycyclopropanes in the presence of a palladium catalyst take place via direct attack of an aryl- or acylpalladium intermediate on the C-C bond of the cyclopropane (eqs 8 and 9). The reaction is applicable not only to ester synthesis but also to ketone and aldehyde synthesis. Heating a chloroform solution of the silyloxycyclopropane in the presence of a palladium-phosphine catalyst under 1 atm Carbon Monoxide produces a g-keto pimelate (eq 10).24

Precursor of Lithiocyclopropane.

Bromination of the silyloxycyclopropane with Phosphorus(III) Bromide produces 1-bromo-1-ethoxycyclopropane. Successive treatment of the bromide with t-Butyllithium and an enal affords a cyclopropylcarbinol, which undergoes acid-catalyzed ring enlargement to give 2-vinylcyclobutanone (eq 11).25

Reactions with Azidoformates.

Photolysis of an acetonitrile solution of the cyclopropane and Ethyl Azidoformate at rt gives a C-H insertion product (eq 12).26 However, thermolysis of the same mixture in DMSO gives a 3-aminopropionate by insertion of nitrene into the cyclopropane ring (eq 13).27

Cyclopropanone Hemiacetals and Their Use.

Mild alcoholysis of the silyloxycyclopropane gives a cyclopropanone hemiacetal. This compound serves as a stable equivalent of unstable cyclopropanones.3 Treatment with two equivalents of alkynylmagnesium bromide gives a 1-ethynyl-1-hydroxycyclopropane (eq 14).28

The cyclopropanol also serves as a source of homoenolate radical species. Treatment of a mixture of the cyclopropanol and an enol silyl ether with manganese(III) 2-pyridinecarboxylate in DMF gives a 1,5-dicarbonyl compound (eq 15).29

Strecker amino acid synthesis starting with the cyclopropanone hemiacetal provides a enantioselective route to a cyclopropane amino acid (eq 16).30

1. Nakamura, E.;. Shimada, J.; Kuwajima, I. OM 1985, 4, 641.
2. Kuwajima, I.; Nakamura, E. COS 1991, 2, Chapter 1.14.
3. Salaün, J.; Marguerite, J. OS 1985, 63, 147.
4. Fadel, A.; Canet, J.-L.; Salaün, J. SL 1990, 89.
5. Rousseau, G.; Slonghi, N. TL 1983, 24, 1251.
6. Murakami, M.; Inouye, M.; Suginome, M.; Ito, Y. BCJ 1988, 51, 3649.
7. Ryu, I.; Murai, S.; Sonoda, N. JOC 1986, 51, 2389.
8. Nakamura, E.; Kuwajima, I. JACS 1983, 105, 651.
9. Nakamura, E.; Oshino, H.; Kuwajima, I. JACS 1986, 108, 3745.
10. Nakamura, E.; Kuwajima, I. JACS 1985, 107, 2138.
11. Reissig, H.-U. Top. Curr. Chem. 1988, 144, 73.
12. Nakamura, E.; Aoki, S.; Sekiya, K.; Oshino, H.; Kuwajima, I. JACS 1987, 109, 8056.
13. Tamaru, Y.; Ochiai, H.; Nakamura, T.; Tsubaki, K.; Yoshida, Z.-i. TL 1985, 26, 5559. Tamaru, Y.; Ochiai, H.; Nakamura, T.; Yoshida, Z.-i. TL 1986, 27, 955. Yeh, M. C. P.; Knochel, P. TL 1988, 29, 2395. Tamaru, Y.; Ochiai, H.; Nakamura, T.; Yoshida, Z.-i. AG(E) 1987, 26, 1157.
14. Nakamura, E.; Kuwajima, I. JACS 1984, 106, 3368. Nakamura, E.; Kuwajima, I. OS 1987, 66, 43.
15. (a) Corey, E. J.; Boaz, N. W. TL 1985, 26, 6015, 6019-6021. (b) Alexakis, A.; Berlan, J.; Besace, Y. TL 1986, 27, 1047. (c) Horiguchi, Y.; Matsuzawa, S.; Nakamura, E.; Kuwajima, I. TL 1986, 27, 4025. (d) Nakamura, E.; Matsuzawa, S.; Horiguchi, Y.; Kuwajima, I. TL 1986, 27, 4029. (e) Matsuzawa, S.; Horiguchi, Y.; Nakamura, E.; Kuwajima, I. T 1989, 45, 349. (f) Nakamura, E. In Organocopper Reagents; Taylor, R. J. K., Ed.; Oxford: Oxford University Press, 1994; Chapter 6.
16. Horiguchi, Y.; Nakamura, E.; Kuwajiama, I. JACS 1989, 111, 6257.
17. Crimmins, M. T.; Nantermet, P. G.; Wesley, B.; Vallin, I. M.; Watson, P. S.; AcKerlie, L. A.; Reinhold, T. L.; Cheung, A. W.-H.; Stetson, K. A.; Dedopoulou, D.; Gray, J. L. JOC 1993, 58, 1038.
18. Nakamura, E.; Sekiya, K.; Arai, M.; Aoki, S. JACS 1989, 111, 3091.
19. Aoki, S.; Fujimura, T.; Nakamura, E.; Kuwajima, I. TL 1989, 30, 6541.
20. Gore, V. G.; Mahendra, D.; Chordia, D.; Narasimhan, S. T 1990, 46, 2483.
21. Aoki, S.; Fujimura, T.; Nakamura, E.; Kuwajima, I. JACS 1988, 110, 3296.
22. Fujimura, T.; Aoki, S.; Nakamura, E. JOC 1991, 56, 2810.
23. Aoki, S.; Nakamura, E. T 1991, 47, 3935.
24. Aoki, S.; Nakamura, E.; Kuwajima, I. TL 1988, 29, 1541.
25. Gadwood, R. C.; Rubino, M. R.; Nagarajan, S. C.; Michel, S. T. JOC 1985, 50, 3255.
26. Mitani, M.; Tachizawa, O.; Takeuchi, H.; Koyama, K. CL 1987, 1029.
27. Mitani, M.; Tachizawa, O.; Takeuchi, H.; Koyama, K. JOC 1989, 54, 5397.
28. Salaün, J. JOC 1976, 41, 1237.
29. Iwasawa, N.; Hayakawa, S.; Isobe, K.; Narasaka, K. CL 1991, 1193.
30. Fadel, A. T 1991, 47, 6265. Fadel, A. SL 1993, 503.

Eiichi Nakamura

Tokyo Institute of Technology, Japan

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