Methylthiomethyl protection

The methylthiomethyl (MTM) group is a related alcohol-protecting group. There are several methods for introducing the MTM group. Alkylation of an alcoholate by... 

The methylthiomethyl (MTM) group is a related alcohol-protecting group. There are several methods for introducing the MTM group. Alkylation of an alcoholate by methylthiomethyl chloride is efficient if catalyzed by iodide ion.9 Alcohols are also converted to MTM ethers by reaction with dimethyl sulfoxide in the presence of acetic acid and acetic anhydride10 or with benzoyl peroxide and dimethyl sulfide.11 The latter two methods involve the generation of the methylthiomethylium ion by ionization of an acyloxysulfonium ion (Pummerer reaction). 

Methylthiomethyl has been used as the protecting group in the total synthesis of neoechinulin A (80TL2817). Cyclo(L-Ala-Gly) was treated with sodium hydride in DMF and N-alkylated with chloromethyl methyl thioether at room temperature, to give the bis(methylthiomethyl) derivative. After further chemical transformations, deprotection was achieved by treatment with methyl iodide in the presence of NaHC03 at 40°C for 3 days, followed by heating in dioxane at 100°C for 1 h. 

In a synthesis of the pyrrolizidine alkaloid Integerrimine, a methylthiomethyl ether protecting group was removed in the final step by hydride abstraction using triphenylcarbenium tetrafiuoroborate [Scheme 4321J.593... 

In 1968 Miller and Stirling showed that the 2-tosylethyl ester function (abbreviated TSE) underwent easy base-catalysed elimination in the presence of 1 M sodium hydroxide or sodium carbonate (but not sodium hydrogen carbonate) in aqueous dioxane at room temperature to give p-toluenesulfinate anion, ethylene. and a carboxylate 215 Thus, this ester function complements the methylsul-fonylmethyl function (see section 6.4) derived from methylthiomethyl esters in its base-sensitivity. Electron withdrawing groups (e.g., p-nitro) on the aryl ring increase base lability — a feature that has been exploited for the protection of the 2f hydroxyl function in oligoribonucleotide synthesis.216... 

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 methylthiomethyl ether (MTMOR) Tertiary hydroxyl groups, which are susceptible to acid-catalyzed dehydration, can be easily protected as MTM ethers and recovered in good yield. The MTM ether of a hydroxyl group can be formed either by a typical Williamson ether synthesis or on reaction with dimethylsulfoxide (DMSO) and acetic anhydride (AC2O). In the latter case, the reaction proceeds with the Pummerer rearrangement " (Scheme 1.25). 

Methylthiomethyl esters. Carboxylic acids are converted into their methylthiomethyl esters by reaction with t-butyl bromide-dimethyl sulfoxide in the presence of sodium bicarbonate. Methylthiomethyl esters of N-protected amino acids can be obtained in high yield without racemization by this method. ... 

Protection of alcohols. Primary and secondary alcohols are converted into the 2-tetrahydrothienyl (THT) ethers by acid-catalyzed exchange with 1. The ethers can be cleaved quantitatively by HgCU in aqueous acetonitrile in fact the THT group is cleaved faster than the methylthiomethyl group (6, 302). 

Protection of carboxyl groups (8, 94). Two new methods for deprotection of methylthiomethyl esters have been reported one involves oxidation to the sulfone followed by alkaline hydrolysis, and the other involves methylation to a sulfonium iodide and hydrolysis. ... 

Melhybkiomethylesters. Methylthiomethyl esters are useful as protective groups for carboxylic acids. They are prepared by treatment of the acid with the reagent and... 

The methylthiomethyl group is used as a protecting group of hydroxy functions. A deprotection can be carried out by electrolysis in an undivided cell with Pt electrodes in AcOH containing NaOAc. The resulting acetoxymethyl ether can be hydrolyzed in weakly alkaline medium [Eq. (43)] to the hydroxy function [132] ... 

Further extensions of the use of the methylthiomethyl (MTM) protecting group for alcohols have been reported.88-9... 

Protection of hydroxyl groups. Hydroxyl groups can be protected as the methylthiomethyl ether, prepared by reaction of a sodium alkoxide with chloromethyl methyl sulfide and sodium iodide (1 eq. of each) at 0° for 1 hr. and... 

For protection of primary alcohols as the methylthiomethyl ether, see Chloro-methyl methyl sulfide, this volume. 

Ribonucleoside 2 - and 4 -0-methylthiomethyl derivatives have been synthesized directly from selectively protected nucleosides by reaction with DMSO-AC2O-ACOH mixtures. ... 

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

Miscellaneous. Protection of phenols as methylthiomethyl ethers and of amines as dithiasuccinoyl or -nitrophenylsulphenyl derivatives has been recom-... 

Sodium hydride sodium iodide Protection of hydroxyl groups as methylthiomethyl ethers... 

Startg. m. treated with 1.1 equivalents NaH in dimethoxyethane, and the resulting Na-alkoxide allowed to react with 1 equivalent each of chloromethyl methyl sulfide and dry Nal in the same solvent at 0° for 1 hr. and at 25° for 1.5 hrs. -> methylthiomethyl ether. Y 82%. - The protective group can be selectively removed under neutral conditions in the presence of mercuric ion. E. J. Corey and M. G. Bode, Tetrah. Let. 7975, 2643, 3269. 

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