Friedel–Crafts Coupling of Electron-Deficient Benzoylacetones Tuned by Remote Electronic Effects

Abstract

Acid-catalyzed electrophilic aromatic substitution for C-C bond formation, commonly referred to as the Friedel-Crafts reaction in recognition of its discoverers, has been one of the most useful reactions in organic chemistry for over a century. However, the Friedel-Crafts reaction cannot occur on a benzene ring having a strongly electron withdrawing group, such as an acyl group, which deactivates the aromatic ring toward electrophilic substitutions and remains a major challenge. Herein, the synthesis of naphthoquinones and 1,3-indandiones, bearing two acyl groups at positions ortho to each other on a benzene ring, are demonstrated by means of copper-catalyzed intramolecular aerobic oxidative acylation of benzoylacetone derivative precursors. This unusual Friedel-Crafts reaction reveals a new activation mode for the in situ polarity reverse of an electron-deficient aromatic ring to a reactive, electron-rich ring tuned by remote electronic effects.

Chemistry of Ketene N,S-Acetals: An Overview

“… − Recently, Li and co-workers described a method for synthesis of 124 bearing an N -Ts group at the acetal carbon. Compounds 124 can be applied to the synthesis of 2-(methylthio)- N -tosylpyrroles through intramolecular cyclization of 127 , formed probably by isomerization of 124 under heating conditions in the absence of catalysts (Scheme ) involving a geometrically favorable 5-exo-trig process …”

“…Compounds 124 can be applied to the synthesis of 2-(methylthio)-N-tosylpyrroles through intramolecular cyclization of 127, formed probably by isomerization of 124 under heating conditions in the absence of catalysts (Scheme 29) involving a geometrically favorable 5-exo-trig process. 155 Treatment of 36, having the pyridin-2-ylamino group (see Scheme 10), with cupric chloride as oxidant in THF at reflux gave the products, 2-(methylthio)-3-aroylimidazo[1,2-a]-pyridines, in high to excellent yields (Scheme 30) 156 100 The aziridine ring is very reactive toward nucleophilic attack. Treatment of 22 with potassium iodide in acetone at room temperature under nitrogen atmosphere enabled the synthesis of spiro compounds 138 (Scheme 32).…”

An efficient and green method for regio- and chemo-selective Friedel–Crafts acylations using a deep eutectic solvent ([CholineCl][ZnCl2]3)

“…[8][9][10][11][12][13][14][15] Over the past decade there has been an explosion in the development of green catalysts for Friedel-Cras acylation, and a large number of papers have been published. 7,[16][17][18][19][20] Among these catalysts, ionic liquids have attracted increasing interest as solvents because of their unique chemical and physical properties, such as low or non-volatility, thermal stability and large liquid range. [21][22][23] Consequently, ionic liquids gain a special attraction as green solvents to replace volatile organic solvents.…”