Stereoselective construction of multi-substituted tetrahydrofurans via three components-condensation reaction

Stereoselective construction of multi-substituted tetrahydrofurans is described. The procedure is consisted in three steps: stereoselective Michael/aldol tandem reaction, alkenylation, and radical cyclization. A chiral or racemic adduct of the tandem Michael/aldol reaction, β-hydroxyl-α-(phenylseleno)alkyl carbonyl compound, was alkenylated by treatment with propiolic ester to give a precursor of radical cyclization in good yields. Exposure of the precursor to Bu3SnH in hot toluene gave tri- or tetrasubstituted tetrahydrofurans in a good yield. The good control of relative configuration between C2 and C3 during the tandem reaction stage and the excellent 2,5-cis-induction in the radical cyclization brought the stereoselective formation of trisubstituted tetrahydrofurans. A prochiral radical carbon generated from a secondary selenide attacked the double bond in a stereoselective manner and one of four possible diastereomers of tetrahydrofuran was formed stereoselectively.