Catalytic Ring Strain Release for the Synthesis of Heterocycles and Natural Products

Cycloaddition reactions have been recognized as a robust method to construct carbocyclic or heterocyclic systems in a highly convergent manner through a concerted or stepwise mechanism since the original discovery of the Diels-Alder reaction. N-Heterocyclic compounds are considered “privileged structures” in pharmaceutical and medicinal chemistry for their core structure being present in many biologically active molecules and building blocks. Hence, the development of efficient methods to achieve such heterocycles from low-cost starting materials has attracted considerable attention over the past decades. Our group is involved in exploring strain ring systems, pyridine, quinoline, isoquinoline, and other azine derivatives as potent precursors for the synthesis of such molecular frameworks because of their easy access. We have discovered dearomatization/rearomatization strategy as a new methodology for cycloaddition reactions of reactive azinium ylides with dipolarophiles for the construction of new heterocyclic systems. New metal catalyzed transformations of various dipolarophiles with donor-acceptor oxiranes recently discovered in our group will also be discussed.