Methylthiomethyl MTM Ethers

Methylthiomethyl ethers are comparable in stability to alkoxymethyl ethers towards strongly basic conditions or mild acid. For example, methylthiomethyl ethers survive aqueous acetic acid under conditions that hydrolyse TBS ethers, dioxolanes or tetrahydropyranyl protectors. They can be removed under rather specific and mild conditions that do not affect most acetal-type protectors such as MEM, MOM, etc. (see above). The presence of the sulfur makes this group liable to oxidation by strong oxidants such as peracids. Cr(VI), and N-bromo-succinimide, and it will poison Pd catalysts. The methylthiomethyl group was first introduced by Corey and co-workers and its virtues exploited by them in a synthesis of the antibiotics Erythronolide and Brefeldin.  

Methylthiomethyl ethers, like most 0,5-acetals, are stable to aqueous acid, but they can be removed under essentially neutral conditions in the presence of heavy metal catalysts with a high affinity for sulfur such as mercury(II) or sil-ver(I). Typically, the substrate is treated with mercury(II) chloride in acetoni-trile-H20 (4 1) at room temperature or slightly above. With acid-sensitive 

There are a very large number of different ester protecting groups available and we have selected only five of the more common representatives which exemplify the breadth of graduated hydrolytic lability that is available by simple steric or electronic tuning. Thus pivalate esters, with their greater steric hin- 

Commercially available scandium triflate is a remarkably active acid catalyst for acylation of alcohols with acid anhydrides. Its catalytic activity is even higher than DMAP. However, in the case of allylic and some tertiary alcohols, migration or elimination products are observed. Moreover, scandium is expensive. 

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Some of the methods used to cleave methylthiomethyl (MTM) ethers should also be applicable to the cleavage of tetrahydrothiofuranyl ethers. 

A 1,3-dithiane is stable to the conditions (HgCl2, CaC03, CH3CN-H2O, 25°, 1-2 h) used to cleave a methylthiomethyl (MTM) ether (i.e., a mono-thio acetal). ... 

N -Fmoc serine benzyl ester 2, which could be prepared as shown or purchased commercially, was smoothly converted to the crystalHne O-methylthiomethyl (MTM) ether 3 in high yield via a Pummerer-Hke reaction using benzoyl peroxide and dimethyl sulfide in acetonitrile [39]. This common intermediate was used to synthesize both 5 and 8 [40]. Both Ogilvie [41] and Tsantrizos [42] had reported that I2 was an effective activator with similar MTM ether substrates. The H promoted nucleosidation reaction between O-MTM ether 3 and bis-silylated thymine 4 produced the nucleoamino acid 5 in 60% isolated yield (100% based on recovered 3). Hydrogenolytic deprotection of the benzyl ester with H2, Pd/C in MeOH gave the thymine-containing nucleoamino acid 6 in quantitative yield. 

Methylthiomethyl (MTM) ethers. These ethers (h, 109-lltY) ear he prepared by reaction of alcohols with dimethyl sulfide (8 equiv.) and dibenzoyl peroxide (4 equiv.) in CH3CN at 0° (75-90% yield). Excess dimethyl sulfide is required since some of the sulfide is oxidized to dimethyl sulfoxide. 

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... 

The effects of changes in the nature of the aikoxy group (equation 3) are evident in Table 2. High levels of asymmetric induction are achieved by the use of a-substituents such as methoxymethyl ether, benzyl ether, and methylthiomethyl (MTM) ether. The sterically demanding tetrahydropyranyl ether substituent, however, interferes with chelate formation, and its use generates poor selectivities. 

The methylthiomethyl (MTM) ethers (32), mainly applied in natural product synthesis, represent thioacetals of formaldehyde. These ethers again are formed by Williamson-type reactions however, the... 

A report has appeared on the protection of phenols as their methylthiomethyl (MTM) ethers, which can be formed from sodium phenoxides and chloromethyl... 

The usefulness of the methylthiomethyl (MTM) ether function (48), which has been recommended previously for temporary protection of primary alcohol groups, has been extended to secondary and tertiary alcohols, MTM ethers of tertiary alcohols are formed from the alcohols and DMSO-acetic anhydride, whereas those of the secondary alcohols require, in addition, the presence of acetic acid to suppress the competing oxidation process. The latter authors also propose an alternative removal procedure to the known and Ag -mediated routes, - involving methyl iodide in moist acetone. Corey has continued his... 

Full details have now appeared of the general method for formation of methylthiomethyl (MTM) ethers from alcohols by treatment with DMSO in acetic anhydride containing acetic acid. These authors also report their mild cleavage method of methyl iodide in moist acetone the use of volatile reagents is advantageous as it allows easier product isolation than the previous Ag and Hg procedures. 

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