Formation and trapping of azafulvene intermediates derived from manganese-mediated oxidative malonate coupling

• Published in: Tetrahedron Vol. 72; no. 26; pp. 3775 - 3780
• Main Authors: Lofstrand, Verner A., Matsuura, Bryan S., Furst, Laura, Narayanam, Jagan M.R., Stephenson, Corey R.J.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 30.06.2016; Elsevier
• Subjects: Acetic acid; Carbon; Carboxylic acids; Chemical reactions; Chemistry; Chemistry, Organic; Coupling; C–H functionalization; Dimethyl; Heterocycle functionalization; Oxidation; Oxidative coupling; Physical Sciences; Radical reaction; Science & Technology; Tetrahedrons; Heterocycle functionalization; Radical reaction; Oxidative coupling; C–H functionalization; FREE-RADICAL REACTION; NATURAL-PRODUCTS; (+/-)-ACTINOPHYLLIC ACID; VINBLASTINE; INDOLE-DERIVATIVES; C-H functionalization; STEREOCONTROLLED TOTAL-SYNTHESIS; DIMETHYL MALONATE; ELECTRON-RICH HETEROCYCLES; ALKALOIDS
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2016.03.012

The one-pot, three-component, coupling reaction of indoles/pyrroles, dimethyl malonate, and acetic acid was performed using Mn(III) acetate as an oxidant. In the presence of Mn(OAc)3, indole-2, and indole-3-carbonyl compounds were alkylated at the 3- and 2- positions, respectively, with subsequent oxidation and nucleophilic capture occurring at the newly formed benzylic carbon. In contrast, oxidation of 2- and 3-indole carboxylic acids afforded the corresponding 2-oxindol-3-ylidenes and 3-oxindol-2-ylidenes. The reaction conditions, scope, and mechanism are discussed herein. [Display omitted]