Direct and Selective 3-Amidation of Indoles Using Electrophilic N-[(Benzenesulfonyl)oxy]amides

Abstract

Selective C–H amidation of 1H-indoles at the C3 position is reported as a direct entry to biologically important 3-aminoindoles. This transformation is achieved using novel N-benzenesulfonyloxyamides as electrophilic nitrogen agent in the presence of ZnCl2. Interestingly, analogous reactions in the absence of ZnCl2 resulted in the formation of indole aminal products.

The hydrogen atom transfer reactivity of sulfinic acids

“…TrptSO 2 H, PhSO 2 H and dicumylketone were synthesized as described in the ESI. † TrptSOH, 28 PBD-BODIPY, 31 STY-BODIPY, 44 NMBHA, 67 tosyl iodide, 68 as well as the GC standards for the alkyl radical clock kinetics 69 were synthesized following previously reported procedures. Chlorobenzene was dried over 3 Å molecular sieves before use.…”

A Simple and Broadly Applicable C−N Bond Forming Dearomatization Protocol Enabled by Bifunctional Amino Reagents

“…Nucleophilic substitution at N(sp 2 )−OR and N(sp 3 )−OR centers is unusual but has been invoked in other contexts . Of particular relevance is the recent work of Wang and co‐workers, who disclosed intermolecular C3 aminations of indole anions using O‐sulfonyl activated N ‐hydroxy amides and carbamates . In the current processes, the mild base (K 2 CO 3 or K 2 HPO 4 ) presumably enhances the nucleophilicity of the aromatic unit by deprotonating it before or during the C−N bond forming dearomatization step.…”

Keteniminium Salts as Key Intermediates for the Efficient Synthesis of 3‐Amino‐Indoles and ‐Benzofurans

“…In the literature, the synthesis of 3‐amino‐indoles and ‐benzofurans is achieved following three main strategies. The first one is the functionalization of the naked benzoheterole through either direct amination or a nitr(os)ation/reduction sequence . The second is the generation of the heterocyclic core followed by in‐situ amination of the latter and the third is the one‐step formation of the 3‐aminobenzoheterole moiety.…”