Lithium Diisopropylamide‐Mediated Ring‐Opening of Tetrahydrofuran in the Synthesis of Polyhydroxylated Indolizidines

A synthesis of novel hydroxyethyl‐substituted tri‐ and penta‐hydroxylated spiro[cyclopentane‐indolizidines] has been reported, featuring an interesting lithium diisopropylamide “LDA”‐mediated α‐diallylation and tetrahydrofuran “THF” ring opening in one‐pot procedure as the key transformation. The synthetic sequence explored herein uses an enantiopure tricyclic lactam as a common chiral precursor, prepared on a gram scale from cost‐effective basic reagents. The key steps in this synthetic way included diastereoselective dihydroxylation reaction, ring‐closing ene–ene metathesis, enamine reduction, and finally lactam reduction. These transformations enabled the efficient and stereoselective construction of the ultimate polyhydroxy‐indolizidine scaffolds. As an application, the biological activity of the synthesized spiro‐indolizidines was evaluated against a panel of α‐glucosidases.