A Green Chemistry Approach for the Synthesis of Indanones as Fixed Ring Chalcone Analogues

When using chalcones as therapeutic agents, a potential drawback is their susceptibil-ity in solution to light-induced isomerisation around the double bond of their α,β-unsaturated carbonyl moiety giving rise to a mixture of cis- and trans-isomers. This photoisomerisation can be circumvented by transforming chalcones into indanones thus creating a conformationally constrained frame incorporating a five membered ring whilst retaining the structural key features of the parent compound. Herein, we have synthesised indanone DMU5401, i.e. 3-(benzo[d][1,3]dioxol-5-yl)-4,5,6-trimethoxy-2,3-dihydro-1H-inden-1-one, starting from chalcone DMU135, i.e. (E)-3-(benzo[d][1,3]dioxol-5-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one, via Nazarov cyclisation reaction using a green solvent, i.e. 4-methyltetrahydropyran (4-MeTHP). Although the yield was lower compared to that of previously reported methods, the green solvent procedure we adopted here did not include harmful sol-vents or hazardous chemicals, and significantly shortened the work-up stage of the Nazarov cyclisation reaction making this process more sustainable.