deviated from the indole molecular plane with an angle d as shown in Sect. 4. As a result, the bromonium ion is attracted close to the 7-position and forms a a-complex (D) at the 7-position. In the latter mechanism, a nucleophilic substitution reaction takes place through transition state (B), where the bromide ion attacks the nearby 7-position with the concomitant liberation of the oxonium group from the 1-position [25].

Iodination of methyl indole-3-carboxylate (77a) with KI/NaIO4 afforded 5-iodo- (78, 58%), 6-iodo- (79, 25%)-, and 7-iodoindole-3-carboxylates (80, 2%) as reported previously [27], while the same reaction of methyl 1-methoxyindole-3-carboxylate (77b) provided methyl 5-iodo-1-methoxy-indole-3-carboxylate (81, 72%) as a sole product (Scheme 10).

Additional halogenation of 78 and 81 exhibits interesting results [28]. Bromination (1.3-mol eq.) of the former in AcOH provides methyl 6-bromo-5-iodoindole-3-carboxylate (82, 56%) and the corresponding carboxylic acid (83, 18%). On the other hand, bromination of the latter gives complex mixtures of products under various reaction conditions. Relatively clean reaction takes place with Br2 (1.3-mol eq.) in AcOH at 100 °C providing methyl 6-bromo- (84, 17%), methyl 2-bromo-5-iodo-1-methoxyindole-3-carboxylates (85, 33%), 5-iodo-1-methoxyindole-3-carboxylic acid (86, 7%),

Br2, AcOH

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