Iron‐Catalyzed Crossed‐Aldol Condensation for the Synthesis of 3‐Benzylidene‐4‐chromanones: An Efficient Synthesis of Homoisoflavanoids^†

Abstract

A new, convenient and sustainable protocol for the aldol condensation of chroman‐4‐one derivatives with aldehydes using iron as a catalyst under microwave irradiation in the presence of green solvent (2‐methyl‐THF) is presented. The protocol offers a very simple, cost efficient and environmentally benign procedure with good to excellent yields of 3‐benzylidene‐4‐chromanone derivatives. The methodology is demonstrated to be useful for the synthesis of homoisoflavanoids Boundecullin, Sappanone A and their derivatives. The present method offers a potential to generate a quick library of homoisoflavanoids and their synthetic derivatives of medicinal importance.

3‐Arylidene‐4‐Chromanones and 3‐Arylidene‐4‐Thiochromanones: Versatile Synthons towards the Synthesis of Complex Heterocycles

“…or using bases such as KOH, NaOH, NaOCH 3 , CH 3 COOK, piperidine, pyrrolidine, amberlyst‐15, Ba(OH) 2 , etc ( Path‐A ) as catalysts [13] . Lewis acid catalysts like TiCl 4 , Fe(OTf) 3 , etc are also widely employed for their synthesis ( Path‐A ) [14] . Acid promoted intramolecular Friedel‐Crafts acylation of (2 E )‐2‐phenoxymethyl‐3‐phenylprop‐2‐enoic acid derivatives are known to afford 3‐arylidene‐chromanones ( Path‐B ) [15] .…”

“…[13] Lewis acid catalysts like TiCl 4 , Fe(OTf) 3 , etc are also widely employed for their synthesis (Path-A). [14] Acid promoted intramolecular Friedel-Crafts acylation of (2E)-2-phenoxymethyl-3-phenylprop-2-enoic acid derivatives are known to afford 3arylidene-chromanones (Path-B). [15] A few other alternative approaches, although quite tedious, are known such as Nheterocyclic carbenes based cascade reactions (Path-C) [16] and palladium catalysed carbonylation using benzene-1,3,5-triyl triformate as a solid CO source [17] have been developed towards the synthesis of 3-arylidene-4-chromanones 1 (Path-D) (Scheme 1).…”