Palladium on Carbon‐Catalyzed One‐Pot N‐Arylindole Synthesis: Intramolecular Aromatic Amination, Aromatization, and Intermolecular Aromatic Amination

Abstract

Indole and indoline derivatives were selectively and temperature dependently synthesized via the intramolecular cross‐coupling reaction between the amino and aromatic bromine functionalities of 2‐bromophenethylamine derivatives in the presence of 10% palladium on carbon (Pd/C), 1,1′‐bis(diphenylphosphino)ferrocene (DPPF), and sodium tert‐butoxide (NaO‐t‐Bu) in mesitylene at 140 and 200 °C, respectively. The neutralization using acetic acid after formation of the indoline derivatives effectively promoted their aromatization, and the corresponding indole derivatives were obtained at 140 °C. Furthermore, various aryl groups were also introduced to the N‐1 position of the indole, pyrrole, and carbazole rings by their direct intramolecular arylation with aryl halides and a one‐pot protocol for N‐arylindole synthesis from 2‐bromophenethylamine was developed.magnified image

Base-Assisted Intramolecular C–N Coupling Reaction from NH2-Bound Cyclopalladated l-Phenylalanine to Indoline-2-carboxylic Acid

“…This strategy is often hampered by the strong complexation ability of RNH 2 precursors to Pd II complexes, preventing further C­(sp 2 )–H activation events . Nevertheless, the ortho palladation of arylalkyl­(primary)­amines by a stoichiometric amount of Pd II species (R 1 = H) has been known for decades, even for the more challenging six-membered-ring NH 2 -bound palladacycle B . , As a matter of fact, the so-called Buchwald–Hartwig Pd 0 -catalyzed intramolecular amination of ortho-halogenated phenethylamines was also applied to NH 2 derivatives (R 1 = H, Y = halide or (pseudo)­halide). , The sequence was described through the proposed NH 2 -palladacycle intermediates B (ligated by Y after the oxidative addition event) before the final base-promoted amination process. Importantly, these types of palladacycles were isolated and employed as a source of active Pd 0 catalysts under basic conditions (Scheme b), as demonstrated by Buchwald .…”

Synthesis of 1,2-Disubstituted Indoles from α-Aminonitriles and 2-Halobenzyl Halides

“…The Buchwald group obtained indoles 9 by dehydrogenation of indolines 11 prepared by Pd-catalyzed aryl amination reaction from dibromides 12 . Following the same strategy, Monguchi et al obtained indoles 9 from phenethylamines 10 . The Willis group synthesized benzofurans and benzothiphenes from benzyl ketones .…”

“…14 Following the same strategy, Monguchi et al obtained indoles 9 from phenethylamines 10. 15 The Willis group synthesized benzofurans and benzothiphenes from benzyl ketones. 16 The same authors also employed 2-(2-haloalkenyl) halides 2 and amines as substrates for the synthesis of indoles 9.…”

Recent Advances of Pd/C-Catalyzed Reactions

“…In 2013, Sajiki's group disclosed the synthesis of indoles 204 via an intramolecula amination by applying the Buchwald-Hartwig amination strategy (Scheme 44) [94]. Th reaction employed 2-bromophenethylamines 202 treated with a 10% Pd/C-dppf-t BuONa catalytic system.…”