Functionalized Polyhydroquinolines from Amino Acids Using a Key One-Pot Cyclization Cascade and Application to the Synthesis of (±)-Δ-Mesembrenone.

Substituted polyhydroquinolines are ubiquitous skeletal cores found in drugs and bioactive natural products. As a new route to access this motif, we successfully developed a one-pot cyclization cascade with high chemocontrol and diastereoselectivity. The sequence generates two cycles, three carbon-carbon bonds, and an all-carbon quaternary center in a highly convergent process. Functionalized polyhydroquinolines and congeners can be accessed from commercially available amino acids. This versatile and robust strategy was applied to the synthesis of (±)-Δ-mesembrenone.