Enantioselective Synthesis of 2,3,3a,8a-Tetrahydrofuro[2,3-b]benzofuran Scaffolds Enabled by Cu(II)/SPDO-Catalyzed [3+2] Cycloaddition of 2,3-Dihydrofuran and Quinone Esters

Abstract

An asymmetric [3+2] cycloaddition of quinone esters with 2,3-dihydrofuran has been realized via a newly developed Cu­(II)/SPDO complex. It provides straightforward access to 2,3,3a,8a-tetrahydrofuro­[2,3-b]­benzofurans (TFB) with high enantioselectivity (up to 97.5:2.5 er) and diastereoselectivity (all >20:1 dr). The resulting adducts contain two adjacent stereocenters and a continuously functionalized benzene ring. Additionally, this transformation could be easily performed on a gram scale, allowing for expedient synthesis of natural dihydroaflatoxin D2 and aflatoxin B2.

Development of novel transition metal-catalyzed synthetic approaches for the synthesis of a dihydrobenzofuran nucleus: a review

“…An enantioselective and diastereoselective pathway towards the synthesis of dihydrobenzofurans 163 was given by Zhu 96 et al in 2023. They exploited copper( ii )/SPDO complex (chiral spirocyclic pyrrolidine (oxazoline)) catalyst for carrying out asymmetric [3 + 2] cycloaddition reaction between 2,3-dihydrofuran 173 and quinone esters 168 utilizing copper triflate Cu(OTf) 2 and ligand L in toluene, wet tetrahydrofuran or mestylene solvent, to enable the asymmetric synthesis of benzofuran derivatives 175 .…”

Annulations involving p-benzoquinones: stereoselective synthesis of fused, spiro and bridged molecules

“…The chiral phosphoric acid may serve as a Brønsted acid/Lewis base bifunctional catalyst to activate simultaneously (E)-1-styrylnaphthol and benzoquinone to form To obtain the furobenzofuran skeleton, Wang, Tu and coworkers used 2,3-dihydrofurans 24 and quinone esters 23 to carry out a [3+2] cycloaddition reaction. 66 Under Cu(II)/SPDO catalysis, a library of tetrahydrofuro[2,3-b]benzofuran derivatives 25 was produced with high stereoselectivity (up to 97 : 3 er, 420 : 1 dr). The synthesized heterocycles were comprised of two adjacent stereocenters and a richly decorated benzene ring.…”

Asymmetric Synthesis of Hydrodibenzofurans from Norcaradienes: Kinetic Resolution via [3 + 2] Cycloaddition with Quinones

“…Hydrodibenzofuran frameworks are widely found in many bioactive natural products and pharmaceuticals (Scheme a) . The preparation of these scaffolds in a diastereo- and enantioselective manner has attracted continued interest. , [3 + 2] cycloaddition reactions of 1,4-benzoquinones are among the most powerful tools for accessing hydrobenzofuran and fused polycyclic scaffolds (Scheme b, path a) . In 2005, Zhou and Corey used chiral oxazoborolidinium triflimidate to catalyze the reaction with vinyl ether, rending a short synthesis of the pentacyclic natural product aflatoxin B2 .…”