Progress in the Synthesis of Hydrobenzofurans from O-Cyclohexadienone-tethered 1,6-Enynes

Abstract

Hydrobenzofurans are abundant in bioactive molecules, natural products and drug molecules. Transition-metalcatalyzed intramolecular or intermolecular C-H bond functionalization/cyclization cascade of O-linkered cyclohexadienone-tethered 1,6-enynes is an economic and efficient way to construct this skeleton. The progress in the synthesis of hydrobenzofurans from cyclohexadienone-tethered 1,6-enynes via C-H bond functionalization/cyclization cascade catalyzed by different transition-metals is discussed. The relevant reaction modes, mechanisms and the selection of ligands for chiral control are mainly introduced. Finally, the challenges and development prospects in this field are also prospected and discussed.

Design and Synthesis of Planar-Chiral Oxazole–Pyridine N,N-Ligands: Application in Palladium-Catalyzed Asymmetric Acetoxylative Cyclization

“…Optically active cis -hydrobenzofurans are ubiquitous structural motifs in natural products and bioactive molecules . Transition-metal-catalyzed enantioselective cascade reactions of alkyne-tethered cyclohexadienones have been useful and provided access to the rapid construction of structurally diverse chiral cis -hydrobenzofurans and considerable attention has been paid to them . In 2013, Harned’s group identified an elegant palladium-catalyzed asymmetric acetoxylative cyclization of alkyne-tethered cyclohexadienones, providing the chiral cis -hydrobenzofuran products, which exhibit the activity against the NF-κB signaling pathway .…”

Cp*Co(III)-Catalyzed C(8)-Nucleophilic Cascade Cyclization of Quinoline N-Oxide with 1,6-Enyne

“…On the basis of this background, considering the versatile reactivity of cyclohexadiene-tethered 1,6-enyne in transition metal catalysis, and inspired by the work of Li et al using cobalt, we hypothesized that the regioselective insertion of Ar–[Co] to alkyne via C–H bond activation could result in the alkenyl–[Co] intermediate. Following that, it is expected that a highly nucleophilic alkenyl–[Co] intermediate will undergo Michael addition to tethered cyclohexadienone, yielding bicyclic skeletons (Scheme b).…”

“…On the basis of the control experiments and literature precedents, ,, a plausible mechanism for this cascade cyclization is proposed (Scheme ). At first, ionization of pre-catalyst Cp*Co­(CO)­I 2 in the presence of silver salt and carboxylic acid additive generates the cationic active catalyst A .…”