MEM ethers

Pyridinium p-toluenesulfonate, r-BuOH or 2-butanone, reflux, 80-99% yield.This method is recommended for allylic alcohols. MEM ethers are also cleaved under these conditions. 

HgCl2, CH3CN, H2O, 25°, 1-2 h, 88-95% yield. If 2-methoxyethanol is substituted for water, the MTM ether is converted to a MEM ether. Similarly, substitution with methanol affords a MOM ether. If the MTM ether has an adjacent hydroxyl, it is possible to form the formylidene acetal as a byproduct of cleavage. 

It is possible to introduce this group selectively onto a primary alcohol in the presence of a secondary alcohol. The derivative is stable to KMn04, w-chloro-peroxybenzoic acid, LiAlH4, and Cr03 Pyr. Since this derivative is similar to the p-methoxyphenyl ether it should also be possible to remove it oxidatively. The GUM ethers are less stable than the MEM ethers in acid but have stability comparable to that of tlie SEM ethers. It is possible to remove the GUM ether in the presence of a MEM ether. 

MgBr2, Et20, rt, 66-95% yield.l-Butyldimethylsilyl and MEM ethers are not affected by these conditions, but the MOM ether is slowly cleaved. The THP derivatives of benzylic and tertiaiy alcohols give bromides. 

Me2Sn(SMe)2, BF3-Et20, PhCH3, 0°, 3-24 Ji AcOH, 75-100% yield." An ethyl ester can be hydrolyzed in the presence of an MEC ester with 1 N aqueous NaOH-DMSO (1 1), and MEC esters can be cleaved in the presence of ethyl, benzyl, cinnamyl, and t-butyl esters as well as the acetate, TBDMS and MEM ethers. 

MgBr2, ether, BuSH, rt, 40-97% yield. Tertiary and allylic MOM derivatives give low yields. MTM and SEM ethers are also cleaved, but MEM ethers axG stable." ... 

In a study of the deprotection of the MEM ethers of hydroxyproline and serine derivatives, it was found that the MEM group was stable to conditions that normally cleave the t-butyl and BOC groups [CF3COOH, CH2CI2, 1 1 (v v)]. The MEM group was also stable to 0.2 N HCl, but not stable to 2.0 N HCl or HBr-AcOH. ... 

Bu3SnSMe, BF3-Et20, toluene, -20° 0°, 1.5 h H30, 70-97% yield. When treated with various electrophiles, the intermediate stannanes from this reaction form benzyl and MEM ethers, benzoates, and tosylates, and when treated with PCC, they form aldehydes." " ... 

Yb(OTf)3, MeOH, 0-25°, 92-99% yield. Acetates, benzoates, THP, TBDMS, TBDPS, and MEM ethers are not affected by this reagent. ... 

Schemes 16-19 present the details of the enantioselective synthesis of key intermediate 9. The retrosynthetic analysis outlined in Scheme 5 identified aldoxime 32 as a potential synthetic intermediate the construction of this compound would mark the achievement of the first synthetic objective, for it would permit an evaluation of the crucial 1,3-dipolar cycloaddition reaction. As it turns out, an enantioselective synthesis of aldoxime 32 can be achieved in a straightforward manner by a route employing commercially available tetronic acid (36) and the MEM ether of allyl alcohol (74) as starting materials (see Scheme 16).

An intramolecular palladium(o)-catalyzed cross-coupling of an aryl iodide with a trans vinylstannane is the penultimate maneuver in the Stille-Hegedus total synthesis of (S)-zearalenone (142) (see Scheme 38).59 In the event, exposure of compound 140 to Pd(PPh3)4 catalyst on a 20% cross-linked polystyrene support in refluxing toluene brings about the desired macrocyclization, affording the 14-membered macrolide 141 in 54% yield. Acid-induced hydrolysis of the two methoxyethoxymethyl (MEM) ethers completes the total synthesis of 142. 

The availability of non-racemic oxepins through tandem catalytic RCM and Zr-catalyzed kinetic resolution has additional important implications. Optically pure heterocycles that carry a heteroatom within their side chain (cf. (S)-14 in Scheme 3) can be used in stereoselective uncatalyzed alkylations. The alcohol, benzyl ether or MEM-ethers derived from (S)-14 readily undergo directed [10] and diastereoselective alkylations when treated with a variety of Grignard reagents [11]. 

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. 

Conversion of MEM ethers to esters. 2-Methoxyethoxymethyl (MEM) ethers are converted into carboxylic esters by reaction with an anhydride in the presence of FeCl3 (0.4 equiv.) (equation I). Selective cleavage is possible in the presence of a benzyl ether but not in the presence of a f-butyl ether. Aromatic rings, if present, can undergo acylation. 

Chiu found that the diastereoselectivity had eroded slightly from an earlier synthetic study that included a methyl group in place of the MEM ether side chain of the A ring. Since it had been demonstrated that many of these catalytic systems are metal associated, Chiu attempted to change rhodium ligands from acetate to the... 

Addition to a-aikoxy carbonyl compounds. n-Butylmagncsium bromide reacts stercosclcctivcly with protected, chiral a-hydroxy ketones. For example, reaction of the Grignard reagent with the MEM ether of 3-hydroxy-2-decanone in THF leads to the f/ireo-product [>95% isolated yield (equation I)]. The stereoselectivity is much lower when n-butyllilhium is used in addition the solvent plays an important role. Stereoselectivity is lower in C5H, 2, CH2CI2, and ether. A number of protective... 

Detritylation. 1 Zinc bromide.is effective for removal of 5 -trityl ethers of deoxynuclcosides with only a slight effect on 3 -trityl ethers (cf. cleavage of MEM ethers, 7, 228). The reaction may involve chelation of ZnBr2 with the ether oxygen and the dcoxyribose ring oxygen. 

Methylthio)methyl ethers (MTM ethers, ROCH2SCH3).1 Methoxymethyl (MOM) and (2-methoxyethoxy)methyl (MEM) ethers are converted to MTM ethers by reaction with (CH3)2BBr in CH2C12 at -78° for 1 hour followed by reaction with... 

ArOCH(Rl)OR2 —> ArOH.1 Alkoxymethyl aryl ethers are cleaved by P2I4 in CH2C12 at 25° to phenols in 55-90% yield. This reagent is more useful for cleavage of SEM, MOM, and MEM ethers than Bu4NF, BBr3, or tris(diethylamino)sulfonium difluorotrimethylsilicate (TASF). 

The MEM ethers of 3 are cleaved by lithium triethylborohydride to the MEM ethers of 1,3-diols. 

Hydroxybenzyl alcohols have been converted to dioxepins, as the major product, by forming methoxyethoxy-methyl (MEM) ethers either on the phenolic -OH or on the benzylic -OH and reacting the other -OH group with bromoacetaldehyde dimethyl acetal, followed by treatment with BF3-OEt2 (Scheme 9) <2004T11453>. 

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. 

Benzylic ethers (Ph CH2 OR), allylic ethers (R-CH=CH-CH2 OR) and vinylic ethers [R CH=CH(OR)] together with the most commonly encountered tetrahydropyranyl ethers [THP-ethers, (5)] and /J-methoxyethoxymethyl ethers [MEM-ethers, R0CH2 0(CH2)2 0CH3] play an important role in the protection of a hydroxyl group (p. 550). Macrocyclic ethers (the crown ethers) are important phase transfer catalysts [e.g. 18-Crown-6 (6)]. 

---