Asymmetric Redox-Annulation of Cyclic Amines

Cyclic amines such as 1,2,3,4-tetrahydroisoquinoline
undergo regiodivergent
annulation reactions with 4-nitrobutyraldehydes. These redox-neutral
transformations enable the asymmetric synthesis of highly substituted
polycyclic ring systems in just two steps from commercial materials.
The utility of this process is illustrated in a rapid synthesis of
(−)-protoemetinol. Computational studies provide mechanistic
insights and implicate the elimination of acetic acid from an ammonium
nitronate intermediate as the rate-determining step.