Application of Electrophilic Substitution in Synthesis

Another important aspect of indole chemistry is the ability to achieve regioselectivity for the N-1 position. The formation of the anion usually results in this position being the most nucleophilic site. For example, deprotonation and subsequent reaction with an aUcyl halide or sulfonate is a standard method for introduction of a nitrogen substituent. However, this reactivity can also be exploited in catalytic systems. We will encounter several cases where N-1 or C-3 selectivity can be achieved by the choice and strength of a base. 

These various synthetic methods have been applied to many syntheses of potential dmgs, alkaloids and other natural products. Ring-forming reactions are particularly valuable and the high reactivity of the indole 3-position can be used to induce nucleophilic addition at C-2. Depending on the electrophile, it may subsequently be eliminated, reestablishing aromaticity. 

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