(Diisopropoxymethylsilyl)methylmagnesium Chloride

[85719-58-0]  · C8H19ClMgO2Si  · (Diisopropoxymethylsilyl)methylmagnesium Chloride  · (MW 235.08)

(a nucleophilic hydroxymethylating agent for organic halides, in combination with metal-catalyzed coupling reaction followed by oxidative cleavage of the silicon-carbon bonds)

Solubility: sol THF.

Preparative Method: prepared under nitrogen by reaction of commercially available chloromethyl(diisopropoxy)methylsilane [2212-08-0] with Magnesium in THF, using essentially the same method as that described for the preparation of the monoisopropoxy analog (see (Chloromethyl)isopropoxydimethylsilane).

Analysis of Reagent Purity: the yield of the reagent is usually >90%, but may be titrated before use by one of the standard methods.

Handling, Storage, and Precautions: can be stored under nitrogen at rt for at least two days without loss of activity.

Nucleophilic Hydroxymethylating Agent.

The Grignard reagent serves as a versatile nucleophilic hydroxymethyl anion equivalent in combination with the Hydrogen Peroxide oxidation of the silicon-carbon bond (eq 1).1,2 The primary products, (i-PrO)2MeSiCH2E, are stable to weakly basic and acidic aqueous workup and silica gel chromatography. The method is suitable for the nucleophilic hydroxymethylation of halides via a transition metal-catalyzed cross-coupling reaction, but works poorly with carbonyl groups because of the formation of complex mixtures in the first step. When transition metal catalysts such as copper, nickel, or palladium are used, care should be taken to remove them before the oxidation, otherwise vigorous decomposition of hydrogen peroxide may occur.

Allylic halides, such as geranyl and neryl chlorides (eq 2), are hydroxymethylated without loss of regio- and stereochemistry.2 This method, among others, has been reported to be successfully used for the nucleophilic hydroxymethylation of a 2,3-epoxyalkyl bromide (eq 3).3 The hydroxymethylation of alkenyl and aryl halides can be attained via a nickel- or palladium-catalyzed cross-coupling reaction with the Grignard or zinc reagent, followed by hydrogen peroxide oxidation (eqs 4 and 5).2 An enol phosphate can also be hydroxymethylated via the nickel-catalyzed cross-coupling (eq 6).2 Since the enol phosphate is readily available from ketone, this transformation provides a novel method for the regioselective dehydration-hydroxymethylation of ketones.

Related Reagents.

The transformations described here may also be carried out with the monoisopropoxy analog of this reagent (see (Chloromethyl)isopropoxydimethylsilane). See also t-Butoxymethyllithium; 3-(1-Ethoxyethoxy)propyllithium; Trimethylsilylmethyllithium; Trimethylsilylmethylmagnesium Chloride; and (Triphenylstannylmethyl)lithium.

1. Tamao, K.; Ishida, N.; Ito, Y.; Kumada, M. OS 1990, 69, 96.
2. Tamao, K.; Ishida, N.; Kumada, M. JOC 1983, 48, 2120.
3. Tius, M. A.; Fauq, A. JACS 1986, 108, 6389.

Kohei Tamao

Kyoto University, Japan

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