Methylthiomethyl group

A methylthiomethyl group can be inserted into the ortho position of phenols by... 

The action of the amine over the alkoxysulfonium intermediate— ROS(+)Me2—can produce either the desired oxidation, or the generation of H2C=S(+)-Me. This compound can react with alcohols, resulting in the formation of methylthiomethyl ethers, R-0-CH2-S-Me. It can also react with other nucleophilic sites, resulting in the introduction of a methylthiomethyl group. Unhindered alcohols are particularly prone to the generation of methylthiomethyl ethers, whose formation can be difficult to avoid by adjusting reaction conditions. Nevertheless, like other Molfatt oxidations, it... 

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-workers586 and its virtues exploited by them in a synthesis of the antibiotics Erythronolide587 588 and Brefeldin.589... 

The methylthiomethyl group is removed in nearly quantitative yield by reaction with methyl iodide in moist acetone. 

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] ... 

Methylthiomethylation. The Corey-Kim reagent (NCS-dimethyl sulfide) induces cyclization of tryptamine derivatives while introducing a methylthiomethyl group at C-3. An efficient route to physostigmine is based on this process. 

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... 

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. 

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. ... 

Methylthiomethyl ethers are quite stable to acidic conditions. Most ethers and 1,3-dithianes are stable to the neutral mercuric chloride used to remove the MTM group. One problem with the MTM group is that it is sometimes difficult to introduce. 

CH3CN H20 (4 1), HgCl2, 24 h, 90-94% yield. The methylthiomethyl ether group can be removed in the presence of the phenylthiomethyl ether. ... 

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 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. 

The synthesis of 3-benzylcyclobutanone (3) is an illustration of an overall intramolecular alkylation of an acyl anion equivalent (Section 5.9). The a,a>-dihalide is 2-benzyl-l,3-dibromopropane, and the acyl anion equivalent is methyl methylthiomethyl sulphoxide2 the product is 1-methylsulphinyl-l-methylthio-3-benzylcyclobutane which is obtained as a mixture of cis/trans isomers [(9) and (10)] (Expt 7.3). Aqueous acid hydrolysis in ethereal solution unmasks the carbonyl group. The possible mechanism of the reaction is via a Stevens-type rearrangement of the intermediate sulphur ylide, which may proceed in a pericylic, radical or ion pair fashion. 

For the C, 5 Nuphar alkaloids containing quinolizidine rings, deoxynupharidine (14), 7-epideoxynupharidine (15), nupharolutine (50), and 7-epinupharolutine (60), and also for the synthetic model compounds 3(e)-methyl-3(a)-methylthio-methylquinolizidine (68) and 3(a)-methyl-3(e)-methylthiomethylquinolizidine (69), the diagnostic carbon atoms that determine the conformation of the methyl and methylthiomethyl substituents are the carbon atoms of those groups as well as the carbon atoms of the quinolizidine ring at which the substituents are situated (67). For substituents in an axial conformation, the above-mentioned carbon... 

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... 

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