Sunlight Induced and Alternative Sc(OTf)₃ Catalyzed Remote C−H Halogenation of Indoles

Abstract

A mild and catalyst‐free sunlight induced protocol for the remote meta bromination of electron‐deficient indoles is described for the first time. Herein, N‐bromosaccharin is activated by sunlight irradiation. Alternately, a synergistic activation model (Sc(OTf)3/HFIP) has also been developed for the activation of haloniums, complementary to the light induced strategy. In addition, the cascade C6‐H bromination and benzylic C−H oxidation under photocatalytic conditions was also discussed. High regio‐and chem‐selectivity, mild reaction conditions, and scalability demonstrate great potential of the developed methods in practical applications and further functionalization.

TBA−Br and Selectfluor Mediated Bromination of Glycals and Heterocyclic Compounds: Substrate Scope and Synthetic Utility

“…[31] There are numerous methods to compose halogenated scaffolds from heterocyclic compounds. [32][33][34] Brominated indoles are utilized to prepare CÀ C linkage between indoles and substituted aryl and alkyl groups. [35] Selectfluor and Oxone were used as a green, efficient oxidant in numerous coupling reactions, Diels-Alder reactions, ring-opening metathesis, and many organic reactions.…”

Site-Selective Synthesis of Antitumor C5-Aminated Indoles via Neighboring Aldehyde Group Assisted Catellani Reaction

“…For instance, the Li group demonstrated a C5 regioselective benzylation of L -tryptophan via enzyme catalysis . Very recently, Wang and Liu’s group respectively reported C5–H direct iodination and bromination of indole-3-aldehydes and indole-3-ketones through a radical process . Shi and Song elegantly rendered a regiocontrolled C–H arylation and selenylation on the C5 position of indoles enabled by copper and silver catalysis, respectively .…”

“…Due to its innate electron-rich property, the C3 position itself exhibits much higher reactivity and becomes relatively easier to be decorated compared with other places . In sharp contrast, the C5 and C6 positions on the indole benzenoid core remained a much less explored challenge, and there are only a few examples concerning site-selective C5-functionalization − (Scheme a). For instance, the Li group demonstrated a C5 regioselective benzylation of L -tryptophan via enzyme catalysis .…”