Access to 2‐Arylindoles via Decarboxylative C−C Coupling in Aqueous Medium and to Heteroaryl Carboxylates under Base‐Free Conditions using Diaryliodonium Salts

Abstract

Easily accessible heteroaromatic carboxylic acids and diaryliodonium salts were successfully employed to construct valuable 2-arylindoles and heteroaryl carboxylates in a regioselective fashion. C2-arylated indoles were produced using a Pd-catalyzed decarboxylative strategy in water without any base, oxidant, or ligand. Heteroaryl carboxylates were prepared under metal and base-free conditions. This protocol was successfully utilized to synthesize Paullone, a cyclin-dependent kinase (CDK) inhibitor.

Synthesis of Indoles via Domino Reactions of 2-Methoxytoluene and Nitriles

“… , Consequently, numerous synthetic methods have been developed to access the 2-arylindole substructure. Classic routes include the Fischer indole synthesis while contemporary approaches employ transition-metal catalysts, including direct C-2 arylation of pre-existing indoles, − and intramolecular cyclization of functionalized anilines, − and many others. − Some of these approaches employ harsh reagents, highly functionalized precursors, or cryogenic temperatures that are challenging to access on scale. Therefore, more straightforward, efficient, and practical synthetic methods without addition of transition metals for the assembly of 2-arylindoles remain in demand.…”

Diaryliodoniums Salts as Coupling Partners for Transition-Metal Catalyzed C- and N-Arylation of Heteroarenes

“…After the oxidation by the aryliodane of the Pd(II) intermediate to the Pd(IV) species, the reductive elimination provided the desired products and the Pd(II) catalyst was regenerated. Although decarboxylative cross-coupling reactions are not covered in this review, it is worth mentioning a recent report from the group of Kumar who described the synthesis of 2-arylindoles from indole-3-carboxylic acid and diaryliodoniums under base-and ligand-free conditions [70].…”

Polarclean/Water as a Safe and Recoverable Medium for Selective C2-Arylation of Indoles Catalyzed by Pd/C

“…Direct C–H functionalization of indoles is potentially of great synthetic utility, providing access to an important class of heterocyclic systems. − In fact, an indole scaffold is considered as a privileged structure in medicinal chemistry, and it is present in a large number of natural products endowed with biological activity. − …”

“…While catalytic methods for direct C2–H arylation of indoles have been widely explored, − to our knowledge, only a few reports have been disclosed on the use of heterogeneous Pd/C as a catalyst. − Among them, two papers are based on the use of diphenyliodonium tetrafluoroborate in EtOH or water, which allowed the arylation of indole or N -methylindole, respectively. High C2 selectivity has been achieved although the yields of isolated products are moderate. , …”