[147-14-4] · C5H14OSi · (Methoxymethyl)trimethylsilane · (MW 118.28)
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.
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.
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.
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.
William R. Roush
Indiana University, Bloomington, IN, USA