A short and elegant synthetic approach for 9-substituted tetrahydro coumestan derivatives and synthesis of some naturally occurring coumestan derivatives

Abstract

The biomimetic synthesis of substituted tetrahydro coumestan (3–8) derivatives is accomplished from 4-hydroxycoumarins (1a–f) and cyclohexanone derivatives (2a–n) using a 20 mol% FeCl₃·6H₂O catalyst in DMSO solvent upon heating at 110 °C. The significant features of the present strategy are mild reaction conditions, easy handling, readily available starting materials, no need for dry solvents, additives, and inert atmospheric reaction conditions, broad substrate scope, good to excellent yields, and high atom economy. In addition, coumestan derivatives (9) were obtained from the corresponding tetrahydro coumestan derivatives by dehydrogenation with DDQ. Moreover, synthesizing naturally occurring coumestan, coumestrol dimethyl ether, and 4-O-methyl coumestrol validated the two-step synthetic route.