Methanesulfonate, leaving group

Oseltamivir is an ethyl ester, and esterification comes first, followed by selective protection of the cis diol (the cis-6,5-ring system is more stabie than the alternative trans) and conversion of the remaining hydroxyl group to a methanesulfonate leaving group. 

The phase transfer cyanide reaction appears to be superior even to the reaction conducted in dipolar aprotic media. 5-Chlorooctane, for example, yields 85—90% substitution products and only 10—15% elimination products under phase transfer conditions [1], whereas the homogeneous reaction in dimethyl sulfoxide resulted in only 70% of s-cyanooctane [8]. The phase transfer reaction is applicable for chloride, bromide, or methanesulfonate leaving groups but is less satisfactory when the nucleo-fuge is either iodide or p-toluenesulfonate (tosylate). This is due to the fact that the large, lipophilic and polarizable quaternary cations tend to ion pair irreversibly with iodide and tosylate. This difficulty can often be overcome by renewing the aqueous reservoir of nucleophile. 

The ability of nucleophilic substitution to provide either 2,6-cis or 2,6-trans THP has been exploited in the synthesis of several natural products. Williams and coworkers reported the formation of both the A and B ring of leucascandrolide A by nucleophilic substitution (Scheme 14) [35]. Both examples relied oti a methanesulfonate leaving group and secondary alcohol nucleophile. Subjecting mesylate 44 (or 46) to sodium hydride deprotonation followed by heating resulted in THP product 45 (or 47) in 75 % yield as a single diastereomer. 

In contrast to phosphorus esters, sulfur esters are usually cleaved at the carbon-oxygen bond with carbon-fluorine bond formation Cleavage of esteri nf methanesulfonic acid, p-toluenesidfonic acid, and especially trifluoromethane-sulfonic acid (tnflic acid) by fluoride ion is the most widely used method for the conversion of hydroxy compounds to fluoro derivatives Potassium fluoride, triethylamine trihydrofluoride, and tetrabutylammonium fluoride are common sources of the fluoride ion For the cleavage of a variety of alkyl mesylates and tosylates with potassium fluoride, polyethylene glycol 400 is a solvent of choice, the yields are limited by solvolysis of the leaving group by the solvent, but this phenomenon is controlled by bulky substituents, either in the sulfonic acid part or in the alcohol part of the ester [42] (equation 29)... 

Cleavage of C—O bonds by direct electron transfer from a cathode is usually difficult because of the negative reduction potential of the bond. Therefore, the reduction of aliphatic alcohols (R-OH) to the corresponding hydrocarbons (R-H) is often carried out by the transformation of hydroxyl groups to good leaving groups such as halides (X = Br, I), methanesulfonates (OMs), and... 

The CH3S02-0- group in methanesulfonate esters is a good leaving group, facilitating nucleophilic displacements. The utility of MSC for methanesulfonylation is well known in the agricultural, pharmaceutical, and specialty chemical industries. Methanesulfonyl chloride is a product of Elf Atochem North America (386—388). 

A better leaving group to exchange with halide anions is a methanesulfonate orp-toluene-sulfonate (tosylate). Thus, potassium salts in aqueous solutions of all the halides react with methyl octanesulfonate under mild conditions in presence of either tributylhexadecylphosphonium bromide200,201 or dicyclohexano-18-crown-6202 catalysts (equation 17) ... 

Primary and secondary alcohols are readily converted to mesylate or tosylate esters by reaction with the corresponding sulfonyl chloride. The mesylate and tosylate esters derived from tertiary alcohols are too reactive and cannot be isolated. (Although we will not go into the mechanism of these reactions in detail at this point, the reactions involve the attack of the oxygen [the nucleophile] of the alcohol at the sulfur [the electrophile], ultimately displacing chloride [the leaving group].) Pyridine is often used as a solvent for these preparations in order to react with the HC1 that is produced as a by-product. An example of the preparation of a methanesulfonate (mesylate) ester is shown in the following equation ... 

Two other commonly used sulfonic acids are methanesulfonic acid (CH3SO3H) and tiifluoromethanesulfonic acid (CF3SO3H). Which has the weaker conjugate base Which conjugate base is the better leaving group Which of these acids has the higher pKg ... 

In the majority of substitution and elimination reactions, the sulfonate moiety functions as the leaving group, and certain sulfonates, e.g. methanesulfonate (mesylate), p-toluenesulfonate (tosylate) and trifluoromethanesulfonate (triflate), are exceptionally good leaving groups. The introduction of these sulfonate groups therefore greatly facilitate... 

The first cinchona rearrangement is also feasible without Ag +, provided stringent stereochemical and experimental conditions are fulfilled. In the preferred conformation of epi-la-OMs, the C9-OMs leaving group and migrating C7-C8 0-bond are antiperiplanar (Scheme 12.41). Under optimized conditions with NaOBz as a buffer (for the liberated methanesulfonic acid), a-amino ether 107-OMe was formed in 81%... 

Conversion of alcohols to sulfonate esters is a way of labilising them to nucleophilic substitution and elimination. The common leaving groups are arenesulfonates, particularly p-toluenesulfonate (tosylate), methanesulfonates (mesylate) and trifluromethanesulfonate (triflate) they are introduced by reaction of the acid chlorides (or, in the case of the trifluoromethanesulfonates, acid anhydrides) in a basic solvent such as pyridine. Traditionally, the reactions are carried out in pyridine as solvent, but both this solvent and the liberated... 

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