Indole-indolenine tautomerism

The substitution reaction may occur on a prototropic nonaromatic form. Both types of tautomerism, i.e., that prevailing in the parent heterocycles (pyrrole-pyrrolenine, indole-indolenine) and that typical of the hydroxy and amino derivatives, must be considered. 

Like Walker, Snyder and colleagues found that catalytic hydrogen conditions with paUadium-on-carbon improves the yield of indoles and are superior to the tin reduction of Stephen (Scheme 3) [5]. Snyder suggests that the mechanism of this indole synthesis involves initial reduction of the o-nitrobenzylcyanide to the imine 1 followed by cycli-zation and loss of ammonia and tautomerization of indolenine 2 to indole (equation 3), rather than Walker s mechanism via 2-aminoindole. 

The enamine-imine tautomerism of the indolenine system gives rise to rearrangement reactions of interest in indole alkaloid chemistry. Thus the synthesis of dihydroburnamicine (625) utilized the rearrangement of an acetoxyindolenine to an a-hydroxyalkyl indole, presumably through an intermediate enamine. Similarly 2,3-dialkyl indoles undergo oxidations to 2-acyl indoles (626-631). 

The next step is tautomerization of indole to the reactive indolenine (Fig. 9.13,... 

The mechanism of the p-elimination reaction catalyzed by tryptophanase is thought to require tautomerization of the indole ring to an activated indolenine intermediate with tetrahedral geometry at the C-3 carbon of the indole ring. Therefore, interactions between active-site residues and the ring nitrogen are likely to be very important for binding and catalysis. 

The secondary amino group of the indole ring in tryptophan has a low field shift (293 ppm), probably because of rapid tautomerism with the C = N indolenine form, in which the nitrogen has a 7i-bonded structure. However, the equilibrium favours the indole form, the deshielding contribution from the ru-electrons in the indolenine form is, therefore, small, moving the chemical shift of the indole nitrogen atom in tryptophan to much higher field than in imidazole, but to lower field than in the saturated counterpart, proline. 

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