Alkoxymethyl ethers

A study of the reductive cleavage of a series of alkoxymethyl ethers using the glucose backbone shows that, depending on the reagent, excellent selectivity can be obtained for deprotection vs. methyl ether formation for most of the common protective groups. ... 

An extensive survey has been carried out by McKervey and coworkers [7], who prepared the carbo-alkoxymethyl ethers of p-tert-h x y calix[4]arene, p-/< r/-butyl calix[6]arene, p-tert-bu y calix[8]arene, ca-lix[4]arene, calix[6Jarene, and calix[8]arene, and measured their abilities to extract cations from the aqueous phase into the nonaqueous phase. They concluded the following general aspects for the phase-transfer experiments (1) the calix[4]arene compounds show the greatest selectivity for Na (2) phase-transfer of Li is inefficient with all of the compounds (3) the calix[6]arene compounds show less affinity for Na than for K, with plateau selectivity for Rb" and Cs (4) the calix[8]ar-ene compounds are the least efficient of the cyclic oligomers, showing low levels of transport and low discrimination for all five cations (5) the calix[6]arene... 

MOM ethers are the first and simplest of the acetal-type protecting groups whose prime virtues are ease of introduction, MOM ethers are the most robust of the alkoxymethyl ethers. In some cases, the conditions required to liberate a... 

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... 

To date, the last total synthesis of a sesquiterpene picrotoxane (132) is a variant of the above-described picrotoxinin/corianin synthesis by Trost et al. Again, the synthesis started with (—)-carvone and the introduction of the C-1 unit corresponds with the earlier syntheses. The choice of the protective group was governed by the discovery that the oxygen(s) of alkoxymethyl ethers had a directing effect in the following addition of (cyanomethyl)lithium. 

Alkoxymethyl Ethers The principal members of this set of protecting groups are methoxy-methyl ether (MOM) [188], methoxyethoxymethyl ether (MEM) [189], benzyloxymethyl ether (BOM) [190], /7-methoxybenzyloxymethyl ether (PMBM) [191], and trimethylsi-lylethoxymethyl ether (SEM) [192] (O Fig. 4). Since these protecting units are devoid of chirality, their use introduces no stereochemical complications. 

Appropriate alkyl iodides or bromides were reacted with 57 and 2-epi-Sl in the presence of Ag20 in CH3CN with yields ranging from 36 to 77% (74, Scheme 10) [34, 51]. However, with these conditions preparation of branched alkyl ethers was unsuccessful [51]. Reacting 57 with chloromethyl methyl ether, diisopropylethy-lamine, and catalytic DMAP in CH2CI2 afforded 75 in a 72% yield and was the first 1 derivative reported to have increased affinity at the KOP receptor relative to 1. [41, 52]. Based on the successful increase in affinity of derivative 75, additional simple alkoxymethyl ethers were obtained using appropriate alkyoxymethyl chloride with diisopropylethylamine in DMF (76-78). However, more complex alkoxymethyl derivatives were synthesized from the common methylthiomethyl ether intermediate (79), which was obtained from reaction of 57 with acetic acid, acetic anhydride, and dimethylsulfoxide (DMSO) [52]. Compound 79 was then... 

Munro TA, Duncan KK, Xu W et al (2008) Standard protecting groups create potent and selective k opioids salvinorin B alkoxymethyl ethers. Bioorg Med Chem 16 1279-1286... 

On treatment with PtCl2 under CO in toluene o-alkynylaryl alkoxymethyl ethers cyclize to afford benzofurans, by transfer of the alkocymethyl group to C-3 ... 

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