Petasis Sequence Reactions for the Scaffold-Diverse Synthesis of Bioactive Polycyclic Small Molecules

The multicomponent Petasis reaction is a versatile method
to access
functionalized amines. The combination of Petasis reaction with subsequent
ring-closing reactions is a powerful strategy to build novel polycyclic
scaffolds. In this study, we report the generation of a diverse set
of small molecules with polycyclic scaffolds featuring a high content
of sp3-hybridized carbon atoms and multiple stereogenic
centers by employing three-component Petasis reaction (3C-PR)Intramolecular
Diels–Alder (IMDA) and 3C-PRring-closing metathesis
(RCM)IMDA sequence reactions. This work demonstrates the wide
substrate tolerance and broad applicability to access unexplored polycyclic
scaffolds of biological interest using Petasis sequence reactions.