1-Ethoxy-1-(trimethylsilyloxy)cyclopropane

[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


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Eiichi Nakamura

Tokyo Institute of Technology, Japan



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