Catalysis and Neighbouring-group Participation

Neighbouring-group participation in the hydrolysis of esters and amides has been reviewed. The effects of urea, Na+ and Li+ on the intramolecular general-base-catalysed glycolysis of phenyl salicylate (217) in glycol-acetonitrile solvent at constant water concentration have been reported.  

The stereoisomeric bicyclic amino alcohols (218) and (219) each undergo in tetrahy-drofuran solvent ready acetylation with acetyl chloride and ready mesyiation with methanesulfonyl chloride. Reaction of the endo isomer (219) very probabiy proceeds via the intramolecular 5-exo-Trig pathway, similar intermediates being formed in 

The o-carboxyl group in the acetal (177) enhances the rate of acetal ring opening by a factor of 220 compared with the analogous -isomer.142 Compounds with other o- and -derivatives (e.g. C02Me) have straightforward pH-log (rate constant) profiles with slopes of ca —1.0. 

Intramolecular catalysis of amide bond isomerization is believed to play a key role in the folding of several proteins and this process has now been demonstrated experimentally including evidence for an H-bond between the side-chain and the prolyl Na in a c/. v-prolinc peptidomimetic.143 The amide (178) and the ester (179) have been used as substrates for these studies. Support for intramolecular nucleophilic attack 

Reference 306 also deals with a neighbouring-group effect. 

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Figure 8.46 Schematic illustration to show the principle of intramolecular catalysis. Rate of reaction between the two substrates is enabled by binding and close proximity in the active site region (a). Neighbouring group participation involving neighbouring functional group assistance provides additional rate enhancement (anchimeric assistance) (b) for bond construction (c).

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