Synthesis of oxindoles via reductive CO₂ fixation

Abstract

The synthesis of 3-aryl-3-hydroxy-2-oxindoles, which are a structural motif found in various natural products and pharmaceutically active compounds, was conducted via reductive coupling of (2-aminophenyl) (aryl)methanone derivatives and CO 2 as a key step. The conditions employing Mg with chlorotrimethylsilane in DMA are the best for the reductive coupling, where the aryl halide moiety is intact. This reaction proceeds well without the protection of the amino group. The reductive coupling and acid-catalyzed lactam formation can be performed in a one-pot reaction to give the oxindoles. Results and discussionOur investigation commences with the screening of the combination of an early-transition metal catalyst and Zn or Mg as a Scheme 1 (a) Representative examples of the previously reported retrosynthesis for 3-aryl-3-hydroxy-2-oxindoles 1. (b) Our retrosynthesis for 1. † This paper is dedicated to Professor Barry M. Trost on the occasion of his 75thbirthday. ‡ Electronic supplementary information (ESI) available: 1 H NMR spectrum for 1a, and 1 H and 13 C NMR spectra for 1d, 1e, 1f, 1h, 1i and 2h. See

Challenges and recent advancements in the transformation of CO2into carboxylic acids: straightforward assembly with homogeneous 3d metals

“…Apart from the synthesis of commodity chemicals such as formic acid and propiolic acids, the direct fixation of CO 2 to generate carbonyl compounds has also been reported. 294–297 This coupling reaction provides easier synthesis of α-hydroxycarboxylic acids, which are widely used as intermediates for fine chemicals. 298 However, this transformation using a transition metal catalyst was not reported until Nozaki et al published a copper-catalyzed reductive coupling of CO 2 and an aldehyde in 2020.…”

Magnesium-Promoted Reductive Carboxylation of Aryl Vinyl Ketones: Synthesis of γ-Keto Carboxylic Acids

“…Magnesium is a promising reducing agent, which is abundant in the earth, eco-friendly, and less harmful, and we have reported many types of reductive coupling reactions by magnesium metal . Carboxylation of aromatic conjugated compounds using carbon dioxide through magnesium-promoted reduction was studied by other groups and us . In this study, magnesium-promoted reductive carboxylation of easily available aryl vinyl ketones in the presence of carbon dioxide under mild reaction conditions was carried out to give a variety of γ-keto carboxylic acids with a wide substrate scope in one step (Scheme d).…”

Reductive Coupling of Carbon Dioxide and an Aldehyde Mediated by a Copper(I) Complex toward the Synthesis of α-Hydroxycarboxylic Acids

“…Along with the established processes to produce commodity chemicals such as formic acid, methanol, − methane, , polycarbonates, urea, or salicylic acid, CO 2 has also been applied to carbon–carbon bond-forming reactions through the carboxylation of various carbon nucleophiles or electrophiles such as unsaturated compounds, organometallic compounds, organic (pseudo)­halides, and arenes. , Among these carboxylation reactions using CO 2 , reductive coupling between CO 2 and carbonyl compounds (Scheme a) is a powerful tool to produce α-hydroxycarboxylic acids that are widely used as building blocks for fine chemicals (e.g., mandelic acid) . To date, several methods were reported using low-valent metals such as metallic ytterbium and magnesium as stoichiometric reductants. , However, to the best of our knowledge, there is no example of transition-metal-catalyzed carbon–carbon bond-forming carboxylation of carbonyl compounds.…”