Bisindolines from the reaction of 3,5-dimethoxyaniline with vicinal diones

Abstract

Substituted bisindolines were synthesized from the reaction of 3,5-dimethoxyaniline and vicinal diones (2,3butanedione, benzil, and 4-methylbenzil). The reaction of 3,5-dimethoxyaniline with 2,3-butanedione under polar acidic conditions proceeded with an unanticipated double cyclization reaction forming 2,2 0dimethyl-5,5 0 ,7,7 0 -tetramethoxybisindole, (+/À)-1. The reaction of 3,5-dimethoxyaniline with benzil under similar conditions did not form a bisindoline, but instead formed cis-1,2-diphenyl-2-[(3,5dimethoxyphenyl)imino]ethanone, 2. When the solvent, acid, and reaction temperature were changed for the reaction of 3,5-dimethoxyaniline with benzil, 3,3-diphenyl-4,6-dimethoxyindolin-2-one, 3 (an isomer of 2), and 2,2 0 -diphenyl-5,5 0 ,7,7 0 -tetramethoxybisindole, (+/À)-4, were isolated as major and minor products, respectively. Similarly, the reaction of 3,5-dimethoxyaniline with 4-methylbenzil produced a 1 : 1 mixture of cis-1-(4-methylphenyl)-2-phenyl-2-[(3,5-dimethoxyphenyl)-imino]ethanone, 6a, and cis-1- (3,5-dimethoxyphenyl)imino]ethanone, 6b, under polar acidic conditions and 3-(4-methylphenyl)-3-phenyl-4,6-dimethoxyindolin-2-one, (+/À)-7 and 2-(4-methylphenyl)-2 0phenyl-5,5 0 ,7,7 0 -tetramethoxybisindole, (+/À)-8, under apolar acidic conditions at elevated temperature. We propose the mechanism of bisindoline and indolinone formation to include a Friedel-Crafts type electrophilic attack on the electron rich aryl ring at the ring closing C-C bond forming steps, and further propose a common carbocationic monocyclized intermediate.

Synthetic Studies toward 1,2,3,3a,4,8b-Hexahydropyrrolo[3,2-b]indole Core. Unusual Fragmentation with 1,2-Aryl Shift

“…To the best of our knowledge, no total synthesis of aristone has been reported. Synthetic efforts leading to assembly of non-natural compounds possessing this core have been reported regularly in the past few decades; however, most of these activities revolved around assembly of C2-symmetric bis-indoline structures B . − To access a nonsymmetric tricyclic core A , several synthetic approaches were developed, which include Lewis acid mediated cyclization of α,β-unsaturated N , N -dimethylhydrazones with imines, TFA-assisted intramolecular double cyclization of 3,5-diaminopentan-2-ones, cascade [1 + 4]/[2 + 3]-annulation of prop-2-ynylsulfonium salts, and gold-catalyzed cascade cyclizations of 2-alkynyl- N -propargylanilines to name a few. Herein, we wish to report a new approach to manufacture 1,2,3,3a,4,8b-hexahydro­pyrrolo­[3,2- b ]­indoles 5 via base-assisted intramolecular cyclization of 2-(3-oxoindolin-2-yl)­acetonitriles 4 (Scheme ).…”

Crystal structure of 3-[(2-acetamidophenyl)imino]butan-2-one

“…-(Arylimino)ketone compounds, resulting from condensation between -diketones and anilines in a 1:1 fashion, are useful bidentate ligands in transition metal coordination chemistry (Binotti et al, 2004) and important synthetic intermediates toward -diimines (Schmid et al, 2002) and iminebased multidentate ligands (Schmiege et al, 2007). X-ray structural studies of -(arylimino)ketones have primarily focused on those derived from aromatic diketones such as acenaphthenequinone (Kovach et al, 2011), benzil (Kovach et al, 2014;Gü ner et al, 2000), and phenanthrenequinone (Farrell et al, 2017). In contrast, structural reports on -(arylimino)ketone compounds derived from aliphatic -diketones are rare (Azoulay et al, 2009).…”

Construction of Bisindolines via Oxidative Coupling Cyclization

“…8 Therefore, it is very necessary to development of new methodologies to synthesized bisindolines via intermolecular reaction. 7,9 Recently, we reported a general strategy that could effectively stabilize transient 3-chloroindolenines derived from tetrahydro-γ-carbolines (THγCs) and tetrahydrocarbazoles (THCs) 10 for further functionalization. 11 Based on the basic skeleton of bisindolines, we envisioned that 3chloroindolenines 12 as versatile intermediates might react with anilines to construct complex bisindolines via oxidative coupling cyclization (Figure 1B).…”

“…However, only a few approaches have been developed to synthesize bisindolines in an intramolecular manner . These methods are needed to prepare precursors such as cyclic bisimines, trans -2,2′-diaminostilbenes, or vicinal diamines for further intramolecular reactions, indicating that each final product requires at least two steps (Figure A) . Therefore, it is very necessary to development of new methodologies to synthesized bisindolines via intermolecular reaction. , …”