Palladium‐Catalyzed Remote C−H Phosphonylation of Indoles at the C4 and C6 Positions by a Radical Approach.

Palladium‐catalyzed direct C−H activation of indole benzenoid moiety has been achieved in the past decade. However, palladium‐catalyzed remote C−H activation of indoles is rare. Herein, we report a challenging palladium‐catalyzed remote C4‐H phosphonylation of indoles by a radical approach. The method provides access to a series of C4‐phosphonylated indoles, including tryptophan and tryptophan‐containing dipeptides, which are typically inaccessible by direct C4‐H activation due to its heavy reliance on C3 directing groups. Notably, unexpected C6‐phosphonylated indoles were obtained through blocking of the C4 position. The preliminary mechanistic studies indicated that the reactions may proceed via a C7‐palladacycle/remote‐activation process. Based on the strategy, examples of remote C4‐H difluoromethylation with BrCF2COOEt are also presented, suggesting that the strategy may offer a general blueprint for other cross‐couplings. [ABSTRACT FROM AUTHOR]