Leaving group mesylate

Direct nucleophilic SN2 exchanges F/leaving group (mesylate, tosylate, nosy-late, triflate, iodide or bromide) in a complex structure using [ Fj fluoride anion are more frequent in aliphatic than in aromatic series. The choice of the leaving group is strongly dependent on the substrate to label [206] and it is often neces-... 

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)... 

Condensation of sodium phenoxide witli 2,2,2-trifluoroethyl iodide gives a product of direct substitution in a low yield, several other ethers are formed by eliminatton-addition reactions [7] Use of mesylate as a leaving group and hex amethyl phosphoramide (HMPA) as a solvent increases the yield of the substitution [S] Even chlorine can be replaced when the condensation is performed with potassium fluoride and acetic acid at a high temperature [9] (equations 6-8)... 

The oxygen atom at 21 is similarly an expendable group. Reaction of 241 (obtained from 185 by the usual procedure for introduction of the 9a-fluoro group) with methanesulfonyl chloride affords the 21 mesylate (242a). Replacement of the leaving group at 21 with iodine by means of potassium iodide in acetone followed by reduction of the halogen with zinc in acetic acid leads to fluorometholone (243). ... 

Although halides are common leaving groups in nucleophilic substitution for synthetic purposes, it is often more convenient to use alcohols. Since OH does not leave from ordinary alcohols, it must be converted to a group that does leave. One way is protonation, mentioned above. Another is conversion to a reactive ester, most commonly a sulfonic ester. The sulfonic ester groups tosylate, brosylate, nosylate, and mesylate are better leaving groups than... 

The cyclic kotal (19) was again used as protection and the methane sulphonyl (MeSOg or Ms, mesylate) group was used as the leaving group X (p T2S) (20). The protecting group was left in until the end to avoid any side reactions. 

The objective in selecting the reaction conditions for a preparative nucleophilic substitution is to enhance the mutual reactivity of the leaving group and nucleophile so that the desired substitution occurs at a convenient rate and with minimal competition from other possible reactions. The generalized order of leaving-group reactivity RSOj" I- > BF > CF pertains for most Sw2 processes. (See Section 4.2.3 of Part A for more complete data.) Mesylates, tosylates, iodides, and bromides are all widely used in synthesis. Chlorides usually react rather slowly, except in especially reactive systems, such as allyl and benzyl. 

Our investigations began by examining the direct displacement of 64 bearing various leaving groups with alcohol 10 under strictly SN2 reaction conditions (Scheme 7.19). Treatment of a mixture of 10 with lOequiv of mesylate 65 in the... 

This clearly need not necessarily occur under nucleophilic conditions. But we note that in the above case, mesylate, a better leaving group is involved whilst in the present case bromide ion is the leaving group. Does one always get a propellane with the worse... 

Here, in contrast with the above examples, the retrosynthetic process is purely "mental", since the mesylate, as a good leaving group, is a poor nucleophile and the "reaction" will never take place whatever the reaction conditions. 

Scheme 6.32. Different stereochemical results with mesylate (156) and carbamate (158) leaving groups upon allylic substitution with organocuprates.

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. ... 

The purpose of the first reaction with methanesulfonyl chloride (mesyl chloride) is to form a mesylate ester, a derivative with a better leaving group than hydroxide. Then, the Sn2 reaction can proceed more favourably. Esterification with mesyl chloride is mechanistically analogous to esterification with acetyl chloride. 

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