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.
Steinhardt
Sarah E
SE
Department of Chemistry, University of California, Irvine, California 92697-2025, USA.
Vanderwal
Christopher D
CD
D000447:Aldehydes / Q000737:chemistry*; D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry; D003500:Cyclization; D005663:Furans / Q000737:chemistry*; D007769:Lactams / Q000138:chemical synthesis*; D011090:Polyenes / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D011728:Pyridones / Q000138:chemical synthesis
D000447:Aldehydes; D000577:Amides; D005663:Furans; D007769:Lactams; D011090:Polyenes; D011725:Pyridines; D011728:Pyridones