Synthesis of Benzofuran Derivates via a Gold-Catalyzed Claisen Rearrangement Cascade

Abstract

A novel method toward a facile synthesis of diverse benzofuran derivates from easily obtained quinols and alkynyl esters has been reported. A gold-catalyzed intermolecular alkoxylation/Claisen rearrangement/condensation cascade was involved. The introduction of difluorodiphenylsilane as a water-trapping reagent in the reaction leads to a higher yield.B enzofurans are significant and widespread structures found in many natural products, bioactive molecules, and functional materials. 1 Specifically, compounds bearing various substitutions at the C-2 and C-3 positions are widely distributed in nature as well as medicinally functional molecules. 2a As shown in Figure 1, for example, benzbromarone (I), reported as an antigout agent, 2b and ailanthoidol (II), an antiviral drug used in Chinese traditional herbal medicine, were isolated from the chloroform-soluble fraction of stem woods of Zanthoxylum ailanthoidos. 2c Diverse synthetic methods have been developed to synthesize the key backbone. 3 Traditional synthetic methods include the transitionmetal-catalyzed intramolecular cyclization of o-alkynyl phenols. New efficient modular syntheses of benzofurans from readily available starting materials are still highly desirable.Simple phenols are widely present and easily available synthetic materials; however, to the best of our knowledge, phenols are rarely used as substrates to build benzofuran directly. Recently, Shi's group developed a novel rhodium-catalyzed copper-mediated oxidative cyclization of phenol with unreactive alkynes (Scheme 1a). 4 This method has the advantage of step economy and high bonding formation efficiency; however, this reaction is limited to diaryl alkynes,

A Comprehensive Review on Benzofuran Synthesis Featuring Innovative and Catalytic Strategies

“…Benzofuran Synthesis via Gold-and Silver-Based Catalysts. In 2022, Li et al 84 described a novel approach toward the formation of a benzofuran nucleus by treating alkynyl esters 51 and quinols 52 via gold-promoted catalysis. The use of a JohnPhosAuCl/AgNTf 2 catalyst and Ph 2 SiF 2 additive in the presence of dichloroethane gave moderate to good yields.…”

Advancements in Gold‐Catalyzed Cascade Reactions to Access Carbocycles and Heterocycles: An Overview

“…Xu group described a gold‐catalyzed synthetic methodology of benzofuran derivative 146 from quinol 144 and alknyl ester 145 (Scheme 57). [101] The reactions proceed via three sequential steps such as intermolecular alkoxylation, and Claisen rearrangement followed by a condensation cascade reaction. Quinol derivative treated with alkynyl ester in presence of 5 mol% JohnPhosAuCl, 5 mol% AgNTf 2 , 3 equiv.…”

Gold-catalyzed tandem reaction of o-alkynylphenols with diazo compounds: access to 2,3-disubstituted benzofurans

“…Among various methods, gold-catalyzed tandem reaction from o -alkynylphenols, via the formation a vinyl gold intermediate, 3 has become an important tool in benzofuran synthesis. In 2015, Hashmi and co-workers reported a gold( i )-catalyzed tandem 5- endo-dig -cyclization/rearrangement of an alkyloxonium intermediate, in which the formation of a vinyl gold species had been considered as the key step for this transformation (Scheme 1a).…”