De Novo and Divergent Synthesis of Highly Functionalized Furans by Cascade Reactions of 2‐Hydroxy‐1,4‐diones with Nucleophiles

Abstract

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.

Phosphoric Acid Catalyzed N-Addition/ C-Addition Reaction of 3-Vinyl Indoles with Pyrazole/Pyrazolone to Construct Pyrazole-Substituted 3-(1-Heteroarylethyl)-indole Scaffolds

“…Compound [B] is useful for preventing, treating, or ameliorating human cytomegalovirus infection . Compound [C] is effective against Rhizoctonia solani . Thus, the development of efficient methods for the construction of 3-(1-heteroarylethyl)-indole scaffolds is important for the discovery of new drugs and other utilities.…”

Permanganate oxidation of α,β-unsaturated carbonyls to vicinal tricarbonyls

“…As a result, VTCs are highly reactive and can be used as useful synthons. 1,2 A series of carbo- and heterocyclic compounds can be obtained from VTCs, such as cyclopentane, 3 furan, 4 benzofuran, 5 pyrrole, 6 indole, 7 imidazole, 8 isoquinoline, 9 and quinoxaline. 10 VTCs have also been reported in the total synthesis of natural products.…”

Transformation of 3-(Furan-2-yl)-1,3-di(het)arylpropan-1-ones to Prop-2-en-1-ones via Oxidative Furan Dearomatization/2-Ene-1,4,7-triones Cyclization

“…The development of methodologies for the synthesis of substituted furans is the focus of many research groups [ 21 , 22 , 23 , 24 ]. In 2013, Yin et al described an original approach for the synthesis of substituted 4-(furan-2-yl)but-3-en-2-ones C based on the oxidative rearrangement of 4-(furan-2-yl)butan-2-ones A ( Scheme 1 ) [ 25 ].…”