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De Novo and Divergent Synthesis of Highly Functionalized Furans by Cascade Reactions of 2‐Hydroxy‐1,4‐diones with Nucleophiles
Author(s) -
Liu Haixuan,
Ji Fei,
Chen Yu,
Gao Ya,
Wang Junke,
Zhang Mingzhi,
Liu Fang,
Sha Qiang
Publication year - 2021
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.202005098
Subject(s) - furan , chemistry , nucleophile , indole test , pyrrole , friedel–crafts reaction , divergent synthesis , nucleophilic substitution , cascade reaction , reagent , thiophene , combinatorial chemistry , catalysis , conjugate , organic chemistry , medicinal chemistry , mathematical analysis , mathematics
Herein, a divergent synthesis of a variety of 2α‐ and 5α‐substituted furan derivatives from 2‐hydroxy‐1,4‐diones is reported. By using appropriate substrates and an acid catalyst, the reactions occurred selectively through cyclization/1,6‐conjugate addition or cyclization/Friedel–Crafts‐type cascade reactions. A broad range of nucleophilic reagents (>10 types for the 1,6‐conjugate addition for 5α substitution and >20 types for the Friedel–Crafts‐type cascade reaction for 2α substitution), including alcohols, amides, furan, thiophene, pyrrole, indole, phenols, and many others, can successfully participate in the reactions, providing a universal strategy for a diversity‐oriented synthesis of α‐substituted furan derivatives. Deuteriation experiments and DFT calculations were carried out to support the proposed reaction mechanisms. Antifungal activity experiments revealed that products with an indole or 4‐hydroxycoumarin core substituted at the 2α position showed moderate activities against Rhizoctorzia solani and Botrytis cinerea , respectively.