Complex Polycyclic Lactams from Pericyclic Cascade Reactions of Zincke Aldehydes

In the course of a simple mechanistic study on the rearrangement of Zincke aldehydes to Z-alpha,beta,gamma,delta-unsaturated amides, a thermally induced pericyclic cascade rearrangement that converts Zincke aldehydes derived from allylic and homoallylic amines into polycyclic lactams was discovered. The key reaction involves an E-Z alkene isomerization, a 6pi electrocyclic ring closure, a [1,5]-sigmatropic shift of hydrogen, a 6pi electrocyclic ring-opening, and a Diels-Alder cycloaddition, and proceeds with excellent stereoselectivity. The unusual observation that furans and an indole serve as dienophiles in this cascade reaction permitted the synthesis of complex, functional group-rich tri- and tetracyclic lactams. In all cases, the rigid polycyclic products are available in only two steps from pyridinium salts and the allylic or homoallylic secondary amines.