Synthesis of Polysubstituted Furans: An Update Since 2019

Abstract

Polysubstituted furans are widespread structural motifs, extensively dispersed in natural products, in numerous bioactive compounds, pharmaceuticals, agrochemicals and organic functional materials. Hence, the development of rapid and competent methodologies for the synthesis of multisubstituted furans has drawn much attention over the years. This review summarizes the synthesis of polysubstituted furans using transition‐metal catalyzed, transition metal‐free, photochemical and electrochemical approaches with plausible mechanistic insights. In each reaction, the highest yields of di‐, tri‐ or tetrasubstituted furans are highlighted and some applications of the methodology towards the synthesis of natural products and biologically active compounds are mentioned. The present review highlights the recent progresses in the synthesis of polysubstituted furans reported from 2019 to 2023.

Palladium-Catalyzed Domino Heck/Cross-Coupling Cyclization Reaction: Diastereoselective Synthesis of Furan-Containing Indolines

“…On the other hand, highly substituted furans as the most important classes of aromatic heterocycles are broadly distributed in many natural products, agrochemicals, and synthetic pharmaceuticals . Among the various synthetic approaches to polysubstituted furan derivatives, the palladium-catalyzed coupling cyclization reaction involving 1,2-allenyl ketones has been well documented . For example, Ma and co-workers reported the synthesis of polysubstituted furans through the Pd(0)-promoted coupling cyclization of organohalides with 1,2-allenyl ketones, which involves an intramolecular nucleophilic attack to the resulting π-allyl-Pd­(II) species (Scheme d) .…”

Substrate-controlled [4+1] and [3+2] annulations of ninhydrin-derived Morita–Baylis–Hillman carbonates to access polysubstituted furans and cyclopentenes

“…Polysubstituted furans as important privileged heterocyclic scaffolds extensively distribute in numerous important natural products, 1 biologically active compounds and pharmaceutical molecules, and as key building blocks that can also be applied in total syntheses for the construction of highly complex target structures. 2 Because of their significant importance in fields like chemistry, biology, and medicine, the preparation of polysubstituted furans has increasingly gained particular and extensive attention over the years and numerous effective and advanced methodologies have been well established, 3 such as traditional Paal–Knorr reaction, the transition metal-catalyzed synthesis of polysubstituted furans from pre-functionalization of the substrates or cycloaddition reactions from acyclic substrates. Despite these impressive advances, more diverse, mild and environmentally friendly synthetic methods without noble metal catalysts to access diverse polysubstituted furans are still strongly desired in this organic synthesis field.…”

Iron-Catalyzed Photoredox Alcohol α-C–H Alkylation and Tandem Intramolecular Cyclization: Facile Access to Multisubstituted 2,3-Dihydrofurans and γ-Butyrolactones

“…Multisubstituted furans are extensively integrated as structural motifs within natural products and pharmaceutical compounds, and versatile precursors in organic synthesis . They exhibit profound biological and pharmacological activities that are crucial for the prevention and treatment of cardiovascular diseases, food safety, advancements in the wine industry, antiviral therapies, animal disease management, and antineoplastic interventions . 2,3-Dihydrofurans and γ-butyrolactones, as two distinctive frameworks among this family, are not only integral to a multitude of bioactive natural and pharmaceutical entities but also critical in the synthesis of bioactive tetrahydrofurans with notable stereoselectivity .…”