(Phenyldimethylsilyl)methoxymethyl Chloride

[128784-94-1]  · C10H15ClOSi  · (Phenyldimethylsilyl)methoxymethyl Chloride  · (MW 214.79)

(reagent for the protection of hydroxyl groups1)

Alternate Name: SMOM-Cl.

Solubility: sol most organic solvents.

Preparative Method: prepared by a three-step sequence starting from (chloromethyl)dimethylphenylsilane. Displacement with NaOAc followed by reduction with Lithium Aluminum Hydride furnishes PhMe2SiCH2OH. Subsequent reaction with Formaldehyde-Hydrogen Chloride provides the crude chloride (>90% pure) which can be used without further purification.

Handling, Storage, and Precautions: although stability and toxicological data for this compound are not available, it is expected to be readily hydrolyzed, toxic, and carcinogenic.

Protection of Hydroxyl Groups.

Hydroxyl groups on sugars may be protected as (phenyldimethylsilyl)methoxymethyl (SMOM) ethers using PhMe2SiCH2OCH2Cl and Diisopropylethylamine in MeCN (76-91%). Removal of the SMOM group is effected by treatment with Peracetic Acid/KBr in AcOH/NaOAc (82-92%) (eq 1); this presumably proceeds through a Si -> OH conversion2 and decomposition of the resultant hemiacetal. The SMOM group is stable to hydrogenolysis conditions (H2, Pd/C), benzylation conditions (NaH, BnBr), fluoride (excess n-Bu4NF in dioxane, 20 °C, 15 h), and base (4 N NaOH, dioxane, MeOH, 20 °C, 8 h). It also survives conditions required to remove an isopropylidene or a trityl group (HOAc, H2O) (eq 2).

The SMOM group was developed for use in sugar chemistry. It has the advantage of being stable under many reaction conditions including halophilic promoter mediated glycosidation conditions [e.g. Hg(CN)2, HgBr2, MeCN] and being readily removed under mild conditions. It differs from the trimethylsilylethoxymethoxy (SEM) group3 in its resistance to fluoride cleavage. A closely related function is the phenyldimethylsilyl unit which may be used to protect anomeric hydroxyl groups.1 It is attached by treatment of a glycosyl halide with phenyldimethylsilylmethanol under glycosidation conditions. It has comparable stability to the SMOM group and is also removed by oxidative cleavage (AcOOH, KBr). 2-(Trimethylsilyl)ethanol has been used in a similar capacity.4

Related Reagents.

2-Methoxyethoxymethyl Chloride; 2-(Trimethylsilyl)ethanol; 2-(Trimethylsilyl)ethoxymethyl Chloride.

1. Boons, G. J. P. H.; Elie, C. J. J.; van der Marel, G. A.; van Boom, J. H. TL 1990, 31, 2197.
2. Fleming, I.; Sanderson, P. E. J. TL 1987, 28, 4229.
3. (a) Lipshutz, B. H.; Pegram, J. J. TL 1980, 21, 3343. (b) Lipshutz, B. H.; Miller, T. A. TL 1989, 30, 7149.
4. Lipshutz, B. H.; Pegram, J. J.; Morey, M. C. TL 1981, 22, 4603.

J. Michael Chong

University of Waterloo, Ontario, Canada

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