Mechanochemical Solvent-Free Synthesis of Indenones from Aromatic Carboxylic Acids and Alkynes

Abstract

The mechanochemical solvent-free synthesis of indenones from aromatic carboxylic acids and alkynes was achieved through triflic anhydride (Tf2O)-induced cyclization reaction. A variety of indenones including a bioactive PPARγ agonist were obtained in up to 90% yield at room temperature. The present protocol has the advantages of mild reaction conditions, high reaction efficiency, and feasibility of scalable synthesis, providing a facile and sustainable route to diverse indenones.

Sustainable Mechanosynthesis of Biologically Active Molecules

“…[67] Inspired by the work of Khodaei et al, [68] a mechanochemical method was developed to obtain these compounds through a direct annulation of an aromatic carboxylic acid with an alkyne and Tf 2 O as activating agent, while trying to avoid solvents, major pollutants in industrial solution synthesis (Scheme 26). [69] Using this method, the PPARγ agonist 13 was synthesized in less than 2 hours, resulting in a 67 % yield after a purification by flash chromatography on silica gel. This compound was previously obtained through a four- step synthesis and in 20 % overall yield, thus demonstrating the benefits of the milling approach.…”

Solvent-Free Mechanosynthesis of Polysubstituted 1,2-Dihydroquinolines from Anilines and Alkyne Esters

“…Among the current solvent-free techniques, ball-milling technique has proved to be an attractive and powerful tool for performing solvent-free reactions. − Compared with the liquid-phase reactions, reactions conducted under solvent-free ball-milling conditions generally result in higher product yields within shorter time. Therefore, the ball-milling technique has been widely utilized in organic synthesis. − In view of our successful studies in mechanochemical organic synthesis − and the aforementioned importance of 1,2-dihydroquinolines, herein we present a one-pot synthesis of polysubstituted 1,2-dihydroquinolines from readily available anilines and acetylenedicarboxylate diesters under solvent-free ball-milling conditions (Scheme ). It should be pointed out that this is the first mechanosynthesis of 1,2-dihydroquinolines from anilines and alkyne esters, and the four ester moieties and the CC double bond in the formed products can be exploited for further functionalizations.…”

Mechanochemical Dimerization of Aldoximes to Furoxans

“…In addition, mechanochemical protocols have the advantages of shortening the reaction time, reducing the reaction temperature, improving reaction selectivity, and can even provide products that are difficult or impossible to access in liquid-phase reactions [27][28][29][30][31]. Therefore, solvent-free mechanochemical reactions have been effectively used in organic synthesis [32][33][34][35][36][37][38].…”