Synthesis of Pyrazolines via Enantioselective 1,3-Dipolar Cycloadditions

Significance

Cycloadditions are among the best ways to rapidly create complexity in heterocycle synthesis. Readily available diazoesters 2 can now be used in enantioselective dipolar cycloadditions with activated alkenes 1. Previous methods were limited either to diazomethane derivatives, or did not tolerate β-substitution on the alkene (R² in 1). The method was applied to a rapid total synthesis of (-)-manzacidin A (6), where the stereochemistry of the quaternary tert-alkyl amino stereocenter was fully controlled in the key step.