Synthesis of indoles: Efficient functionalisation of the 7-position

Traditional strategies in indole chemistry do not allow high-yielding access to some substitution patterns such as 3,5,7-trisubstituted indoles. We report in this article the efficient synthesis of this type of indole. The Heck cyclisation strategy we used allows the synthesis of 7-iodo-, 7-alkoxy-, 7-amino-, and 7-nitroindoles bearing other functionalities at the 3- and 5-positions. We believe that the mild conditions used should allow the preparation of indoles with a wide range of substituents in these two positions as shown by the synthesis of a 5-bromo-7-iodoindole. However, this strategy has some limitations in the case of very electron-deficient indoles such as a 7-nitroindole where the aromatisation of the 7-nitrodihydroindole intermediate is not complete. In this case, Larock's indole synthesis from disubstituted acetylenes proved to be more appropriate.