Highly Enantio‐ and Diastereoselective Synthesis of Tetrahydrofuran Frameworks via Chiral Lewis Acid‐Catalyzed Formal [3+2] Cycloaddition of Allylsilanes

Description

Lee and colleagues report in 2026 a reaction that builds tetrahydrofuran rings, five-membered oxygen rings common in natural products and drug candidates. The reaction controls the rings' three-dimensional shape precisely. Shaping four stereocenters, the atoms whose arrangement defines handedness, in one step is a prized result.

The reaction joins allylsilanes with glyoxal partners through a formal cycloaddition followed by a hydrogen shift, steered by a chiral catalyst that acts as a Lewis acid, an electron-pair acceptor. Yields reached the high eighty percent range at their best. The desired handedness was produced almost exclusively, and one ring shape was favored more than twenty to one over its rival in the best cases. Earlier versions of this reaction relied on chirality already built into the starting materials; this one creates the asymmetry from scratch.

Catalog record

Source: https://europepmc.org/article/MED/PMC13592307