Catalysis, intramolecular

Of the many reagents, both heterogeneous and homogeneous, that can facilitate chemical reactions, the cycloamyloses stand out. Reactions can be catalyzed with many species such as hydronium ions, hydroxide ions, general acids, general bases, nucleophiles, and electrophiles. More effective catalysis can sometimes be achieved by combinations of catalytic species as in multiple catalysis, intramolecular catalysis, and catalysis by com-plexation. Only the latter catalysis can show the real attributes of an efficient catalytic system, namely speed and selectivity. In analogy to molecular sieves, selectivity can be attained by stereospecific complexation and speed can be likewise attained if the stereochemistry within the complex is correct. The cycloamyloses, of any simple chemical compound, come the closest to these goals. 

These findings are compatible with a mechanism of intramolecular catalysis for both acyl migration and hydrolysis, as proposed in Fig. 8.5. Also, the possibility that both reactions share a common intermediate is emphasized. Reactions a and b in Fig. 8.5 involve a first step of deprotonation, in agreement with the observed specific base catalysis. Intramolecular nucleophilic attack (Reactions c and d) generates a tetrahedral intermediate that can result in acyl migration or hydrolysis (Reaction e). 

Tucker JW, Narayanam JMR, Krabbe SW, Stephenson CRJ (2010) Electron transfer photoredox catalysis Intramolecular radical addition to indoles and pyrroles. Org Lett 12 368-371... 

Covalent strategy enamine catalysis Intramolecular process Hajos-Parrish-Eder-Sauer-Wiechert reaction... 

Lewis acid catalysis intramolecular Diels-Alder 30,56,57... 

To better understand the mode of action of pyridoxal-P, let us examine in detail equation 7-3 the conversion of homosereine phosphate to threonine. It is an elimination-hydration transformation. The first process (Fig. 7.10) involves an aldimine ketimime tautomerization which is subjected to general-acid catalysis intramolecularly by the hydroxyl group, followed by the slow breaking of a C—H bond. The latter is the rate-determining step. 

Ill. Barber, S.E., Dean, K.E.S., Kirby, A.J. A mechanism for efficient proton-transfer catalysis. Intramolecular general acid catalysis of the hydrolysis of 1-arylethyl ethers of salicylic acid. Can. J. Chem. 1999, 77(5/6), 792-801. 

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