Alcohols 2- methoxyethoxymethyl

The methoxymethyl (MOM) and (3-methoxyethoxymethyl (MEM) groups are used to protect alcohols and phenols as formaldehyde acetals. These groups are normally introduced by reaction of an alkali metal salt of the alcohol with methoxymethyl chloride or (3-methoxyethoxymethyl chloride.157... 

The availability of oxepins that bear a side chain containing a Lewis basic oxygen atom (entry 2, Table 6.4) has further important implications in enantioselective synthesis. The derived alcohol, benzyl ether, or methoxyethoxymethyl (MEM) ethers, in which resident Lewis basic heteroatoms are less sterically hindered, readily undergo diastereoselective uncatalyzed alkylation reactions when treated with a variety of Grignard reagents [17]. The examples shown below (Scheme 6.7) demonstrate the excellent synthetic potential of these stereoselective alkylations. 

Methoxyethoxymethyl ethers, MEM-ethers, are formed by reaction of an alcohol (1 mol) with 2-methoxyethoxymethyl chloride (1.5 mol, MEM-chloride) in dichloromethane solution (10 ml/g of MEM-chloride) at room temperature in the presence of ethyldiisopropylamine (1.5 mol)80 this literature report also notes other preparative procedures. 

Methoxyethoxymethyl (MEM)-protected arylquinolizidines 25 and 27 were prepared from MEM-protected isovanillin (29) through the same sequence as shown in Scheme 2. Treatment of the alcohol 28, obtained by basic hydrolysis of 27, with the anhydride 30 gave 31 in 73% yield. Removal of the MEM groups with trifluoroacetic acid in methylene chloride afforded 10-epidemethoxyabreso-line (3) in 12% overall yield from 29. 

The norephedrine-derived Masamune asymmetric aldol reaction was utilized in the total synthesis of (+)-testudinariol A (12), a triterpene marine natural product that possesses a highly functionalized cyclopentanol framework with four contiguous stereocenters appended to a central 3-alkylidene tetrahydropyran6 (Scheme 2.2f). The norephedrine-derived ester 13 was enolized with dicyclo-hexylboron triflate and triethylamine in dichloromethane and then treated with 3-benzyloxypropanal to afford the aldol adduct (14) as a 97 3 mixture of anti/syn diastereomers in 72% yield. Diastereoselectivity within the anti -manifold was 90 10. Protection of alcohol as the methoxyethoxymethyl (MEM) ether followed by conversion of the ester to an aldehyde by LiAlELt reduction and subsequent Swem oxidation gave the aldehyde 16 in 64% yield over three steps. 

Alkylation of alcohols with 2-(methoxyethoxy)methyl chloride (MEMC1, bp 50-52 C/1.7 kPa) (HAZARD carcinogenic) under an assortment of conditions pioneered by Corey still retain favour. These include reaction of the lithium or sodium alkoxide (generated from sodium or potassium hydride) with ME MCI in THF or DME at 0 °C (10-60 min) and reaction of the alcohol with MEMCI in dichloromethane in the presence of /-Pr NEt at room temperature for 3 h. For hindered alcohols, sodium iodide can be added to generate the more reactive 2-methoxyethoxymethyl iodide in situ. Alternatively, reaction of the alcohol with [(2-methoxyethoxy)methyl]triethylammonium chloride (prepared from MEMO and trie thy lamine) in refluxing acetonitrile is recommended for acid-sensitive substrates such as tertiary alcohols [Scheme 4,271],500... 

Isopropyhhiomethyl ethers, ROCH2SCH(CHj)2. Methoxyethoxymethyl (MEM) ethers on reaction with 1 and 4-dimethylaminopyridine in CH2CI2 are converted into isopropylthiomethyl ethers. In the absence of DMAP, the MEM ether is cleaved to the free alcohol. Isopropylthiomethyl ethers can be cleaved to the alcohol under nonacidic conditions by silver nitrate and 2,6-lutidine. 

Deprotection of MEM and MOM ethers. Methoxyethoxymethyl and methoxy-methyl ethers are cleaved to the alcohol by this reagent in high yields. Either 2-butanone or 2-methyl-2-propanol is recommended as solvent. The procedure is particularly useful for cleavage of ethers of allylic alcohols, for which ZnBr, and TiCh are not useful. 

Protection of tertiary alcohols,2 Methylthiomethyl (MTM) ethers have the advantage that they can be prepared from tertiary alcohols (7,135), but the disadvantage that they are prone to oxidation. They can be converted into 2-methoxyethoxymethyl (MEM) ethers, methoxy methyl (MOM) ethers, or ethoxy methyl (EOM) ethers by reaction with... 

Acyclic 0,0-acetals are used for the temporary protection of mono-alcohols. Most commonly used are the tetrahydropyranyl (THP), the methoxymethyl (MOM), the benzyloxymethyl (BOM), or the methoxyethoxymethyl (MEM) protecting groups. 

Protection of hydroxy groups. Alcohols (primary, secondary, tertiary) can be protected as j3-methoxyethoxymethyl (MEM) ethers. These ethers can be prepared by reaction of (1), slight excess, with either the sodio or lithio derivative of the alcohol in THF or DME at 0° (argon). Alternatively, the ethers can be prepared by the reaction of (1) with alcohols in the presence of ethyldiisopro-pylamine. A third method for etherification is reaction of alcohols with the triethylammonium salt of (1), CH30CH2CH20CH2N (C2H5)3C1, in CH3CN at reflux. Yields by the three methods are >90%. 

Phosphonium-based IL-coated lipase (ILl-PS)-catalyzed reaction has been reported. ILl-PS was used as a catalyst in 2-methoxyethoxymethyl-(tri-n-butyl)-phosphonium bis(trifluoromethanesulfonyl)-amide for the transesterification of secondary alcohols [128]. McNulty et al. studied the anionic effect of Pd-catalyzed Buchwald-Hartwig amination reaction in phosphonium-based ILs [129]. Phosphonium-based ILs are also used in ... 

Carboxylic acids, their esters, and amides are usually resistant to sodium borohydride reduction, whereas carboxylic acid chlorides may be reduced in inert solvents to give alcohols. Where this proves unsatisfactory a new alternative procedure for acid chloride reduction in ether solution involves sodium borohydride adsorbed on alumina. Other recently published borohydride reductions of acid derivatives to primary alcohols include those of the 1-succinimidyl esters (8)" and the N-nitroso-amides (9). 2-Methoxyethoxymethyl (MEM) esters have the possibility of co-ordinating the metal cation of complex hydrides at the MEM group, and hence of activating the carbonyl group towards reduction by intramolecular hydride delivery. The selective reduction of the less hindered ester group in the bis-MEM ester (10) to give (11) illustrates this idea. 

Protection of Phenols. Methoxyethoxymethyl chloride can also be used to protect phenols. The conditions for its introduction are similar to those used for alcohols (NaH, THE, 0°C MeOCH2CH20CH2Cl, 0°C 25°C, 2 h, 75% yield). In contrast to the alcohol derivatives, phenolic MEM ethers can be cleaved with Trifluoroacetic Acid (CH2CI2, 23 °C, 1 h, 74% yield). 1 M HCl (THE, 5 h, 60 °C) and HBr/EtOH will also effect cleavage. In general, the cleavage conditions used for alcohols are also effective with the phenolic derivatives. During an examination of the asymmetric reduction of an acetophenone derivative with (+)-B-Chlorodiisopinocampheylborane, it was found that a phenolic MEM ether was slowly cleaved (eq 4). ... 

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