Protection methylthiomethyl ethers

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... 

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). 

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. 

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. 

Another new reagent for the protection of alcohols and phenols is 2-trimethyl-silylethoxymethyl chloride (67), said to be readily available. The derived SEM ethers (Scheme 30) are stable to acidic conditions that remove 2-tetrahy-dropyranyl, 2-tetrahydrofurfuryl, and trialkylsilyl groups, but can be cleaved by fluoride ion. Phenylthiomethyl ethers may be used in the protection of phenols. They have been reported as more resistant to hydrolysis than aliphatic or aromatic methylthiomethyl ethers, and are removed with mercuric chloride. 

Methyl iodide/sodium hydrogen carbonate Protection of alcohol groups as methylthiomethyl ethers Selective removal of the protective group... 

Treatment with the system DMSO-TFAA (trifluoroacetic anhydride) followed by treatment with base provides an effective procedure for oxidation of alcohols to carbonyl compounds, and is particularly useful for oxidation of hindered alcohols. On the other hand, tertiary alcohols react with DMSO-AC2O to give methylthiomethyl ethers, which can be used as protecting groups since they are hydrolytically cleaved under HgCl2 catalysis. ... 

The methylthiomethyl group is a related alcohol-protecting group. There are two alternative methods for introduction of the thiomethylmethyl group. Alkylation of an alcoholate by thiomethylmethyl chloride is efficient if catalyzed by iodide ion. Alcohols also react with dimethyl sulfoxide in the presence of acetic acid and acetic anhydride to give methylthiomethyl ethers... 

Further study has been made of the use of the methylthiomethyl group for protection of alcohols in synthesis. Primary and secondary alcohols and tertiary alcohols are converted into methylthiomethyl ethers using dimethyl sulphoxide and AcgO, and de-protection is brought about under neutral conditions with a mercury(n) salt. Under these conditions, a 1,3-dithian moiety or a silyl ether grouping in the same molecule are unaffected. Protection of alcohols as 2-phenylselenoethyl ethers and their de-protection by oxidation has been proposed. ... 

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... 

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). 

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] ... 

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... 

The methylthiomethyl group has been used for the protection of phenols since it is stable under conditions in which primary alcohol ethers are hydrolysed, allowing selective removal of the phenolic protecting group. 

---