[147-14-4]  · C5H14OSi  · (Methoxymethyl)trimethylsilane  · (MW 118.28)

(Peterson alkenation reagent;1 synthesis of enol ethers;2 one-carbon homologation of ketones to aldehydes;2 synthetic equivalent of lithiomethyl methyl ether2)

Physical Data: bp 83 °C/760 mmHg;2b d 0.758 g cm-3.3

Solubility: sol common solvents (THF, Et2O, CH2Cl2, etc.).

Form Supplied in: colorless liquid, 98% purity.

Analysis of Reagent Purity: 1H NMR: (CCl4) d 3.4 (s, 3 H), 3.1 (s, 2 H), 0.2 (s, 9 H).2b

Preparative Methods: prepared in 75% yield by the reaction of (Chloromethyl)trimethylsilane and Sodium Methoxide in dry methanol at reflux.3

Handling, Storage, and Precautions: the reagent is flammable and an irritant. It should be used in a well ventilated fume hood. Contact with the eyes and skin should be avoided.

Carbonyl Addition Reactions.2

Treatment of the title reagent with s-Butyllithium (1.4 M in cyclohexane) in THF at -78 °C to -25 °C provides a solution of methoxy(trimethylsilyl)methyllithium (1) that reacts with aldehydes and ketones to give the carbonyl adducts that are isolated in 55-89% yield (eq 1). Elimination of lithium trimethylsilanolate (Me3SiOLi) does not occur under these conditions.

Peterson Alkenation.2

Treatment of the (b-hydroxy-a-methoxyalkyl)trimethylsilane adducts with Potassium Hydride in THF at 60 °C results in elimination of potassium trimethylsilanolate to give enol ethers in 70-87% yield (eq 2). Alternatively, when the 1:1 carbonyl adducts are treated with 90% Formic Acid at ambient temperature, they undergo elimination and hydrolysis to give the one-carbon homologated aldehydes (eq 3). This procedure fails with acid-sensitive aldehydes, such as 1-prenylacetaldehyde.2b

Kende utilized this methodology for the conversion of (2) to (3) during the total synthesis of (±)-warburganal and (±)-isotadeonal (eq 4).4 The ketone function of (2) is quite hindered and failed to give satisfactory results in reactions with methylenetriphenylphosphorane, a-methoxymethylphosphonate, and tosylmethyl isocyanide.

Other Conversions.

Treatment of the carbonyl adducts of (1) with dry Cesium Fluoride in DMSO at 80 °C results in protodesilylation without elimination of the b-hydroxy group (eq 5). Alternatively, oxidation of the carbonyl adducts with Pyridinium Chlorochromate provides a-methoxy-a-trimethylsilyl ketones, which desilylate when chromatographed on silica gel to give a-methoxy ketones (eq 6). Carbanion (1) thus functions as a synthetic equivalent of MeOCH2Li for carbonyl addition reactions.

Related Reagents.

Methoxymethyl(diphenyl)phosphine Oxide; Methoxymethylenetriphenylphosphorane; p-Tolylsulfonylmethyl Isocyanide.

1. (a) Ager, D. J. OR 1990, 38, 1. (b) Kelly, S. E. COS 1991, 1, 729. (c) Chan, T.-H. COS 1991, 2, 595. (d) Colvin, E. W. Silicon Reagents in Organic Synthesis; Academic: New York, 1988; p 63.
2. (a) Magnus, P.; Roy, G. CC 1979, 822. (b) Magnus, P.; Roy, G. OM 1982, 1, 553.
3. Speier, J. L. JACS 1948, 70, 4142.
4. Kende, A. S.; Blacklock, T. J. TL 1980, 21, 3119.

William R. Roush

Indiana University, Bloomington, IN, USA

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