Elaboration of Furopyridine Scaffolds

Abstract

Over the past few decades, furopyridines have emerged as key structural subunits prevalent in a number of natural products and structural analogues associated with interesting biological activities. Consequently, considerable efforts have been devoted to the synthesis of these fused heterocyclic scaffolds. This review covers the main methodologies reported in the literature for the preparation of furopyridines.

Furo[3,2‐b]pyridine: A Privileged Scaffold for Highly Selective Kinase Inhibitors and Effective Modulators of the Hedgehog Pathway

“…Assembly of the furo[3,2-b]pyridine core by precedented intramolecular Heck [9] and Sonogashira [10] reactions proceeded uneventfully and provided the intermediates 2 and 4.The compound 2 was converted into 3 (Scheme 1). Of note, chlorination of the N-oxide intermediate provided as ignificant part of the 2-chloro regioisomer.F or compounds lacking substituents at position 3( e.g.,t he desilylated N-oxide of 5; see compound S6 in the Supporting Information), the chlorination was even more problematic and it exclusively yielded the undesired 2-chloro isomer.I nc ontrast, chlorination of the TMS-containing N-oxide of 5 (see compound S7) proceeded well and ultimately provided the desired 6 in good yield.…”

Construction of Enantioenriched 4,5,6,7‐Tetrahydrofuro[2,3‐b]pyridines through a Multicatalytic Sequence Merging Gold and Amine Catalysis

“…Moving from a silicon-based reducing agent to trimethylallylsilane allowed the formation of more substituted piperidine ring 5 bearing three continuous stereocentres. Finally, the construction of biologically valuable furo[3,2b]pyridines [18] from 3a was considered. A racemic mixture of 3a was engaged in an oxidative transformation in the presence of trimethylsilyl trifluoromethanesulfonate (1 equiv) to afford furo[3,2b]pyridine 6 in 61% yield.…”

Charting the Chemical Reactivity Space of 2,3-Substituted Furo[2,3-b]pyridines Synthesized via the Heterocyclization of Pyridine-N-oxide Derivatives

“…Despite their importance, synthetic methodologies for furopyridines remain limited . There are two main strategies for the synthesis of this heterocyclic fragment, differing by the heterocyclic starting material, whether furan or pyridine . To the best of our knowledge, when pyridine substrates are used, only three methods to obtain furo­[2,3- b ]­pyridine 2,3-substituted compounds (Scheme ) have been described in the literature.…”

“…5 There are two main strategies for the synthesis of this heterocyclic fragment, differing by the heterocyclic starting material, whether furan or pyridine. 6 To the best of our knowledge, when pyridine substrates are used, only three methods to obtain furo [2,3-b]pyridine 2,3substituted compounds (Scheme 1) have been described in the literature. Eastman et al 4 explored the Sonogashira coupling, producing 2-hydroxy-3-alkyne-substituted pyridines that underwent palladium-catalyzed cyclization to afford the furan ring (eq 1).…”