Ethers, 2- ethoxymethyl

Trimethylsilyl)ethoxymethyl Ether (SEMOR) Me3SiCH2CH20CH20R Formation... 

Ethoxymethyl ethers, ROCH2OC2H5.1 These ethers are readily prepared by reaction of an alcohol or phenol with excess ethylal and an acid catalyst (H, S04, HC1, TsOH, ion exchange resin), equation (I). The excess reagent and its azeotrope with... 

The toxicity of HMPA can be avoided by using N.N -dimethylpropylene urea (DMPU)543 or DMF as the solvent.511 The beneficial hardiness of SEM groups was the cause of problems attending deprotection of the intermediate 297.1 [Scheme 4.297] during studies aimed at the structural elucidation of the macro-tide Amphidinolide L.544 Treatment of 297.1 with TBAF in HMPA returned the desired did 297<2 (35%) along with triethylsilyl-deprotected compound 2973 (33%) and the ethoxymethyl ether 297,4 (11%). However, when DMPU was used as solvent, the desired dial 297-2 was obtained in 82% yield. 

Since its introduction in 1986315, the 2-(trimethylsilyl)ethylsuifonyl group has been widely adopted in alkaloid, carbohydrate and amino acid chemistry, it is every bit as stable as the arylsulfonyl groups discussed above it is impervious to the ravages of trifluoroacetic add, hot 6 M HC1, trifluoroborane etherate, or 40% HF in ethanol. Nevertheless, under very specific non-reductive conditions, it can be cleaved. The link with 2-(trimethylsilyl)ethyl esters, 2-(trimethylsilyl)ethoxycarbon-y t derivatives, and 2-(thmethylsilyl)ethoxymethyl ethers hardly needs comment. 

Primary, secondary and tertiary alcohols can be protected in good yield as their 2-(trimethylsil-yl)ethoxymethyl ethers (abbreviated SEM ethers) by reaction with 2-(trimethylsilyl)ethoxymethyl chloride (SEM-Cl) in dichloromethane in the presence of Pr 2NEt. The resultant ethers are stable to the conditions used to remove THP and TMS ethers (3 1 1 THF HOAc H20). Deprotection takes place on treatment with TBAF in THF at 45 °C. 

MgBr2, Et20, CH2CI2, 70% yield." In this case previous attempts to cleave the phenolic EOM groups (ethoxymethyl ether) with acid all failed because of epoxide opening. 

Figure 5.5 Ammonium--Lariat ether complexes top view (left) shows complementary tetrahedral symmetry with an ethoxymethyl ether derivative, side view (right) shows the slight destabilizing effect of a longer pendent ether...

Lithiation in the 2-position of 4-methylphenyl 2-(trimethylsilyl)ethoxymethyl ether in diethyl ether solution by treatment with n-butyllithium at ambient temperature and reaction over 2.5 hours followed by the addition of benzaldehyde led upon work-up to a-[5-methyl-2-(2-trimethylsilyl)ethoxymethylphenyl]benzyl alcohol in an overall yield of 80% (ref.128). 

A variation of the OMEM group is the 2-(trimethylsilyl)ethoxymethyl ether (0-CH20CH2CH2-SiMc3,... 

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