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.