Highly Enantioselective Synthesis of Functionalized Glutarimide Using Oxidative N‑Heterocyclic Carbene Catalysis: A Formal Synthesis of (−)-Paroxetine

A simple yet highly effective approach toward enantioselective synthesis of trans-3,4-disubstituted glutarimides from readily available starting materials is developed using oxidative N-heterocyclic carbene catalysis. The catalytic reaction involves a formal [3 + 3] annulation between enals and substituted malonamides enabling the production of glutarimide derivatives in a single chemical operation via concomitant formation of C–C and C–N bonds. The reaction offers easy access to a broad range of functionalized glutarimides with excellent enantioselectivity and good yield. Synthetic application of the method is demonstrated via formal synthesis of (−)-paroxetine and other bioactive molecules.