(1; R = Me)

[32583-40-7]  · C9H22O2Si2  · 1-Methoxy-2-trimethylsilyl-1-(trimethylsilyloxy)ethylene  · (MW 218.49) (E)-(1)

[35003-73-7] (Z)-(1)

[35003-74-8] (2; R = Et)

[65946-56-7]  · C10H24O2Si2  · 1-Ethoxy-2-trimethylsilyl-1-(trimethylsilyloxy)ethylene  · (MW 232.52)

(two-carbon nucleophile toward aldehydes2 and a,b-unsaturated ketones3 with the assistance of Lewis acids; in combination with TiCl4, a reagent for (Z)-selective alkenation of aldehydes2)

Alternate Name: O-methyl-C,O-bis(trimethylsilyl)ketene acetal.

Physical Data: (1) bp 40-41 °C/0.5 mmHg; d 0.852 g cm-3. (E)-(1) bp 86-87 °C/45 mmHg. (Z)-(1) bp 80-81 °C/25 mmHg. (2) bp 55-60 °C/0.3 mmHg.

Solubility: sol most aprotic solvents; reacts readily with H2O and protic solvents.

Form Supplied in: colorless liquid.

Analysis of Reagent Purity: measurement of the 1H NMR spectrum is the most reliable way to evaluate the purity and isomer ratio; 1H NMR, d (CCl4, 60 MHz), (E): 0.00 (CSiMe3), 0.27 (OSiMe3), 3.00 (CH), 3.54 (OMe); (Z): 0.00 (CSiMe3), 0.18 (OSiMe3), 2.87 (CH), 3.55 (OMe). 13C NMR, d (CDCl3, 25 MHz), (E): -0.30 (=CSiMe3), 0.04 (OSiMe3), 53.79 (OMe), 72.61 (=CH), 161.45 (=C); (Z): 0.04 (=CSiMe3), 0.38 (OSiMe3), 54.96 (OMe), 63.78 (=CH), 164.57 (=C).

Preparative Methods: to a THF solution (260 mL) of Lithium Diisopropylamide (LDA), generated from n-Butyllithium (0.218 mol) and Diisopropylamine (22.4 g, 0.222 mol), is added methyl (trimethylsilyl)acetate (23.0 g, 0.517 mol) at -78 °C. After being stirred for 3.5 h at -78 °C, the reaction mixture is quenched with an excess of Chlorotrimethylsilane (28.3 g, 0.260 mol) at the same temperature. The mixture is stirred for 1.5 h at rt and concentrated under reduced pressure. Distillation of the residual liquid yields 27.8 g (81% E:Z &AApprox; 3:1) of the title reagent as a colorless liquid. The pure (E)-form is prepared by distillation of the mixture obtained immediately after quenching of the ester enolate anion formed by the use of Lithium Hexamethyldisilazide instead of LDA.4 The pure (Z)-form is prepared by isomerization of the (E)-form in a CH2Cl2 solution containing an equimolar amount of Bromotrimethylsilane and a catalytic amount of HgBr2.5

Handling, Storage, and Precautions: the pure liquid and solutions must be stored in the absence of moisture. The sample sealed in an ampule under Ar can be stored for more than a year without decomposition; however, gradual isomerization from the (E)-form to the (Z)-form is observed on the storage.

Two-Carbon Homologation.

This reagent, like most O-silyl-ketene acetals,6-8 becomes a powerful nucleophile in the presence of Titanium(IV) Chloride2,3 or other types of accelerators. The trimethylsilyl group on the a-carbon atom plays an important role as a control factor in stereodifferentiation in aldol reactions. Essentially, syn selectivity is observed in the reaction with aldehydes (eq 1) despite small variations in the geometry of the starting ketene acetal. The nucelophilic species generated by the addition of TiCl4 is also highly reactive as a Michael donor toward a,b-unsaturated ketones. The C-trimethylsilyl group remaining in the products is readily replaced by H after protodesilylation under mild conditions.3,9 As a consequence, this reagent has remarkable advantages as an equivalent of the methyl trimethylsilylacetate anion or the dimethyl malonate anion in the reactions with aldehydes, ketones, and a,b-unsaturated ketones. It has been utilized for introducing the b-side chain in the synthesis of (±)-methyl jasmonate3,10 (eq 2) and (±)-methyl dihydrojasmonate.3

The resulting C-trimethylsilyl group in the Michael-type adducts is capable of participating in the Peterson-type alkenation.11 For example, the O-ethyl analog of the title reagent has been used for the synthesis of a-methylene d-lactones from a,b-unsaturated ketones (eq 3).12 Intermolecular coupling has also been accomplished by the reaction of silyl ketene acetals with 1-adamantyl bromide,13 GeCl4,14 PCl3,15 or AsCl3.16

Carbonyl Alkenations.

The title ketene acetal is an efficient C2 condensation unit toward aldehydes and gives methyl 2-alkenoates in a one-pot operation with the assistance of Lewis acids.2 The high (Z) selectivity of the TiCl4-induced reactions contrasts with the results of analogous condensations using the ethyl trimethylsilylacetate anion11 or Wittig-Horner-type reagents.17 That this transformation is the overall result of two steps, aldol-type addition and Peterson-type b-elimination, has been confirmed by the isolation of aldol adducts under kinetic conditions. Reaction of the isolated syn isomer with TiCl4 or BF3.Et2O leads specifically to (Z)-methyl 2-alkenoates (eq 4). On the other hand, the anti-isomers give (E)-alkenes (eq 5). The predominant formation of (Z)-methyl 2-alkenoate is attained by the syn-selective aldol-type coupling under acidic conditions. High (Z) selectivity has been realized by use of (Z)-ketene acetals or modified Lewis acids (eq 6 and Table 1).2,18

Related Reagents.

1,2-Diethoxy-1,2-bis(trimethylsilyloxy)ethylene; Ethyl Lithio(trimethylsilyl)acetate; Ethyl Trimethylsilylacetate; Ketene Bis(trimethylsilyl) Acetal; Ketene t-Butyldimethylsilyl Methyl Acetal; 1-Methoxy-1-(trimethylsilyloxy)propene; Methylketene Bis(trimethylsilyl) Acetal; Methylketene Dimethyl Acetal; Tetramethoxyethylene; Tris(trimethylsilyloxy)ethylene.

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2. Matsuda, I.; Izumi, Y. TL 1981, 22, 1805.
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18. Matsuda, I., unpublished results.

Isamu Matsuda

Nagoya University, Japan

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