Mesylates Metalation

The metal salts of MSA are highly soluble in water as well as in some organic solvents, making MSA usefijl in electroplating operations. For example, lead sulfate is insoluble in water, whereas lead methanesulfonate (lead mesylate) is water soluble. 

The mesylate group, introduced with methanesulfonyl chloride, can be cleaved with lithium aluminum hydride and dissolving metal reduction (Na, /-BuOH, HMPT, NH3, 64% yield). ... 

Ester eliminations are normally one of two types, base catalyzed or pyrolytic. The usual choice for base catalyzed j5-elimination is a sulfonate ester, generally the tosylate or mesylate. The traditional conditions for elimination are treatment with refluxing collidine or other pyridine base, and rearrangement may occur. Alternative conditions include treatment with variously prepared aluminas, amide-metal halide-carbonate combinations, and recently, the use of DMSO either alone or in the presence of potassium -butoxide. 

Allenyl iodides can be prepared from propargylic mesylates by Sn2 displacement with LiCuI2 (Eq. 9.143) [118]. The reaction proceeds primarily by an anti pathway with slight racemization. Metallation of these iodides with powdered indium in various donating solvents leads to transient allenylindium intermediates which react in situ with aldehydes to afford anti homopropargylic alcohols (Table 9.52). Additions... 

Alkyl azides are conveniently prepared from the reaction of alkali metal azides with an alkyl halide, tosylate, mesylate, nitrate ester or any other alkyl derivative containing a good leaving group. Reactions usually work well for primary and secondary alkyl substrates and are best conducted in polar aprotic solvents like DMF and DMSO. The synthesis and chemistry of azido compounds is the subject of a functional group series. ... 

Metallation of 3,4-dimethyl-l,2,5-thiadiazole (55) to the anion (56) was accomplished with the use of a nonnucleophilic base, lithium diisopropylamide <82JHC1247>. Nucleophilic attack at sulfur resulted in an alkyllithium reagent <70CJC2006>. The lithiomethyl derivative (56) was carboxylated to (57) with carbon dioxide and converted to the vinyl derivative (58) via an esterification, reduction, mesylation, and base elimination sequence (Scheme 12). 

The synthesis of organozinc compounds by electrochemical processes from either low reactive halogenated substrates (alkyl chlorides) or pseudo-halogenated substrates (phenol derivatives, mesylates, triflates etc.) remains an important challenge. Indeed, as mentioned above, the use of electrolytic zinc prepared from the reduction of a metal halide or from zinc(II) ions does not appear to be a convenient method. However, recent work reported by Tokuda and coworkers would suggest that the electroreduction of a zinc(II) species in the presence of naphthalene leads to the formation of a very active zinc capable of reacting even with low reactive substrates (equation 23)11. 

The demonstration that 3-alkoxypyridines are metalated in the 2-position (Scheme 91) (82S235) allowed the preparation of a series of ribo-furanosyl pyridines 565 as potential deazapyrimidine nucleosides for evaluation as thymidylate synthetase inhibitors (Scheme 170) (86MI2). Thus, metalation of the 3-alkoxypyridines 291 followed by condesation at lower temperatures with a protected D-ribose aldehyde afforded diaster-eoisomeric mixtures of compounds 564 which, upon mesylation and acid-catalyzed cyclization, delivered the ribofuranosyl pyridines 565 in high yields. Purification by affinity chromatography afforded the a- and /3-anomers, which showed insignificant antileukemic activity. 

Sulfonates such as mesylates or tosylates are readily prepared from alcohols under mild conditions, and are therefore attractive alternatives to halides as electrophiles. Although sulfonates often undergo clean displacement by nucleophiles, alternative reaction pathways are accessible to these intermediates, which can lead to unexpected results. If the nucleophile used is strongly basic, metalation instead of displacement of the sulfonate can occur. Some potential reactions of such metalated sulfonates include fragmentation into sulfenes and alcoholates, or into sulfmates and carbonyl compounds, or self-alkylation (Scheme4.15). 

Several mechanisms for the catalytic action of Cu(I) and Ag(I) have been considered6. Among these, the metal-assisted addition-elimination sequence shown in equation 85 and illustrated with cuprous triflate was deemed most consistent with various control studies. A mechanism not discussed but equally plausible is the metal-assisted MC sequence depicted in equation 86. The greater separation of iodonium-sulfonate ion pairs in acetonitrile versus benzene should provide the tosylate (or mesylate) ions with sufficient mobility to add to the /7-carbon atom of the alkynyliodonium ion. 

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