Stereoselective construction of 2,3,4-trisubstituted tetrahydrofuran core using NBS mediated cyclization

Abstract

An efficient asymmetric construction of chiral trisubstituted tetrahydrofuan core 1 achieved using D-mannitol as chiral starting material. The chiral glyceraldehyde, derived from D-mannitol, converted into alkene which on Clainsen rearrangement converted into chiral 2-substitutedpent-4-enal. The chiral aldehyde on reduction followed by protection subjected for allylic oxidation and afforded diastereomeric inseparable mixture of alcohols 3 and 3′. The mixture of 3 and 3′ was converted into separable mixture of benzyl ethers 2 and 2′. To confirm the stereochemistry of 2 and 2′, they were converted into acetonides 12 and 12′, respectively. Rychnovsky’s method was employed to confirm the absolute stereochemistry of 12 and 12′. Compound 2′ was converted into its diastereomer 2 by using Mitsunobu protocol. The compound 2 was converted into target compound 1 through NBS mediated cyclization. The stereochemistry of chiral trisubstituted tetrahydrofuran core 1 was resembling to THF core present in natural products Aureonitol and Musanahol.