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

An efficient asymmetric construction of chiral trisubstituted tetrahydrofuan core <b>1</b> 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 <b>3</b> and <b>3′</b>. The mixture of <b>3</b> and <b>3′</b> was converted into separable mixture of benzyl ethers <b>2</b> and <b>2′</b>. To confirm the stereochemistry of <b>2</b> and <b>2′</b>, they were converted into acetonides <b>12</b> and <b>12′</b>, respectively. Rychnovsky’s method was employed to confirm the absolute stereochemistry of <b>12</b> and <b>12′</b>. Compound <b>2′</b> was converted into its diastereomer <b>2</b> by using Mitsunobu protocol. The compound <b>2</b> was converted into target compound <b>1</b> through NBS mediated cyclization. The stereochemistry of chiral trisubstituted tetrahydrofuran core <b>1</b> was resembling to THF core present in natural products Aureonitol and Musanahol.