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Microwave‐Assisted, Asymmetric Synthesis of 3‐Amino‐2,3‐Dihydrobenzofuran Flavonoid Derivatives from Chalcones
Author(s) -
Helgren Travis R.,
Xu Lianyan L.,
Sotelo Daniel,
Mehta Yash R.,
Korkmaz Melissa A.,
Pavlinov Ivan,
Aldrich Leslie N.
Publication year - 2018
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201705984
Subject(s) - intramolecular force , regioselectivity , chalcone , chemistry , combinatorial chemistry , aldol condensation , stereochemistry , nucleophile , catalysis , organic chemistry
A route to access 3‐amino‐2,3‐dihydrobenzofurans that utilizes microwave‐assisted organic synthesis to rapidly generate analogues has been developed. The route begins with an acid‐catalyzed, microwave‐assisted aldol condensation to generate chalcone intermediates, followed by a Corey–Bakshi–Shibata reduction and subsequent Sharpless asymmetric epoxidation to access stereoisomeric epoxyalcohols. The final step is a one‐pot, microwave‐assisted, regioselective, acid‐catalyzed epoxide opening with various amines followed by an intramolecular nucleophilic aromatic substitution reaction to generate the 3‐amino‐2,3‐dihydrobenzofurans. This route provides ready access to stereochemically and structurally diverse analogues of these flavonoid scaffolds. Additionally, a pilot library was synthesized, and the biological activity diversity of the chalcones and dihydrobenzofurans was explored in human carcinoma cell lines.