2- Methylindole side-chain reactions

In the absence of efficient Nps-Q (92) capture, this intermediate reacts with the indole side chain of tryptophan residues to produce the related 2-Nps derivatives 96 (Scheme 48). Although reaction of sulfenyl hahdes with indoles was exploited by Wieland et al.t for the synthesis of phaUoidin, this side reaction leads to irreversible modification of Trp-containing peptides.This side reaction does not occur via an intramolecular electrophilic substitution as postulated previously,but by a direct attack of the Nps-Cl (92) in fact, it is efficiently suppressed by the addition of a large excess of an indole derivative as a scavenger.These scavengers serve also to decrease the proton activity of the acids vide supra). Due to the unpleasant odor of 2-methylindole the less volatile 1-acetyltryptophan butyl ester has been proposed as scavenger.f ... 

A large number of nitrogen heterocycles can be synthesized by Pd -catalyzed cyclization of aminoalkenes. The first reported intramolecular aminopalladation of olefins mediated by Pd consisted of the cyclization of o-allylic anilines to 2-methylindoles. Both catalytic and stoichiometric procedures were developed using PdCl2(CH3CN)2 as catalyst (eq 14). This reaction features high yields, and tolerance toward functional groups and substitution on the allyl side chain. When the aniline substrate bears a methallyl side chain, palladium 8-hydride elimination is prevented and the cyclized alkylpalladium intermediate can be trapped by olefins in a Heck-type process (eq 15). Similar conditions have been used to convert o-amino styrenes into indoles. ... 

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