Enantioselective synthesis of highly functionalized dihydrofurans through copper-catalyzed asymmetric formal [3+2] cycloaddition of β-ketoesters with propargylic esters

Abstract

An enantioselective synthesis of highly functionalized dihydrofurans through a copper-catalyzed asymmetric [3+2] cycloaddition of β-ketoesters with propargylic esters has been developed. With a combination of Cu(OTf)2 and a chiral tridentate P,N,N ligand as the catalyst, a variety of 2,3-dihydrofurans bearing an exocyclic double bond at the 2 position were obtained in good chemical yields and with good to high enantioselectivities. The exocyclic double bond can be hydrogenated in a highly diastereoselective fashion to give unusual cis-2,3-dihydrofuran derivatives, thus further enhancing the scope of this transformation.

Keywords: 2,3-dihydrofurans; asymmetric catalysis; copper; cycloadditions; synthetic methods.