Mesylate, as leaving group

There are very many enantiomerically pure starting materials available cheaply from nature. The amino acids are varied in structure and the hydroxy acids such as malic acid 11 and lactic acid 13 provide another resource. We shall give just one example of this kind of synthesis. Ethyl lactate 14 can be converted into the mesylate (a leaving group like tosylate) 15 and then reduced to the... 

Figure 14.11 Nucleophilic aliphatic substitution of a mesylate ester leaving group using fluoride ion as cesium salt in protic and aprotic organic solvents.

To reduce the number of steps involved in the synthesis of 242, an alternative route where a mesyl equivalent leaving group is placed in the beginning of the synthesis (i.e., by replacing bromoethanol with dibromoethane) was explored. As shown in Scheme 30.45, 5-iodovaniUin (230) was heated with 1,2-dibromoethane and K2CO3 in DMF to afford the... 

Friedel-Crafts chemistry at an as3mimetric center generally proceeds with racemization, but the use of mesylates or chlorosul-fonates as leaving groups has resulted in alkylations with excellent... 

Friedel-Crafts chemistry at an asymmetric center generally proceeds with racemization, but the use of mesylates or chlorosul-fonates as leaving groups has resulted in alkylations with excellent control of stereochemistry. The reactions proceed with inversion of configuration (eq 3). Cyclopropane derivatives have been used as three-carbon units in acylation reactions (eq 4). In conjunction with triethy Isilane, a net alkylation is possible under acylation conditions (eq 5). These conditions are compatible with halogen atoms present elsewhere in the molecule. Acylation reactions of phenolic compounds with heteroaromatic systems have also been accomplished (eq 6). ... 

Where possible, the leaving group (Y ) should be as hydrophilic as possible good candidates are Cl and mesylate. Anionic leaving groups that are particularly hydrophobic such as iodide and p-toluenesulfonate, tend to form tighter ion pairs with the quat cation and slow down or stop the PTC process. 

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 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. 

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. 

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