Mesylate, as a leaving group

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)... 

Fig. 8.12 Nickel-catalyzed couplings, (a) Kaeriyama s PPP synthesis (b) Naarmann s PPP derivative 27 (c) Percec s PPP route using mesylate as the leaving group.

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. 

X is a leaving group such as halide, mesylate or tosylat... 

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... 

Both enantiomers of a member of the new chiral pool, propylene oxide 44, can be made from lactic acid 33. The idea is to reduce the acid and cyclise in two different ways. One is simple enough. Ethyl lactate 41 is mesylated, to turn the secondary alcohol into a leaving group 42, and then the ester is reduced. Cyclisation uses the primary alcohol of 43 as the nucleophile in an internal SN2 reaction so that inversion gives (R) -propylene oxide15 44. 

An acetonide is used as a protecting group in the synthesis of a corticoid that incorporates no fewer than four halogen atoms. The sequence starts with the conversion of the terminal hydroxyl on the side chain at C21 to a better leaving group, a mesylate, by means of methylsulfonyl chloride (30-2) (Scheme 7.30). Treatment of that intermediate with lithium chloride displaces the mesylate to afford the 21-chloro analogue (30-3). Addition of chlorine then leads to the 9a,l l)8-dichloro derivative (30-4). 

The first step is the attack of a nucleophile on an epoxide. It s an Sn2 reaction, because it goes with inversion of configuration, and we need a phenol as the nucleophile. To make the phenol more reactive, we probably want to deprotonate it to make the phenoxide, and NaOH will do this. Why does this end of the epoxide react Well, it is next to a phenyl ring, and benzylic Sn2 reactions are faster than reactions at normal secondary carbons. Next the end hydroxyl group is made into a leaving group (a mesylate ), for which we need methanesulfonyl chloride (mesyl chloride) and triethylamine. The primary hydroxyl group must react faster than the secondary one because it is less hindered. 

A leaving group such as mesylate can exercise the pull and in the next example a carbonyl group provides the push after it has been attacked by a nucleophile. This five-membered cyclic ketone fragments on treatment with base—can you detect hints of the benzylic acid rearrangement ... 

One-bond disconnection via Path B leads a symmetrical species of type 4. The strategy introduced in Chapter 6 suggests that making one of the carbons in the disconnected bond an electrophile (place a leaving group on the carbon), and the other a nucleophile (place a carbonyl adjacent to the carbon). After stereochemical considerations (stereoelectronic requirements of an 8 2 reaction), keto mesylate 5 can be proposed as a 1,5-difunctional intermediate that might undergo the required bond construction. 

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