Organocatalytic Asymmetric Formal [2 + 1] Cycloaddition Reactions for the Synthesis of Spiro-cyclopropane-pyrazolones

Herein, we have developed an efficient and highly enantioselective approach for the synthesis of spiro-cyclopropane-pyrazolones via a proline-based secondary amine-catalyzed formal [2 + 1] cycloaddition reaction. The protocol provides access to structurally diverse spiro-cyclopropane-pyrazolone derivatives bearing three contiguous stereogenic centers in good to excellent diastereoselectivities and excellent enantioselectivities. Mechanistic studies support the proposed reaction pathway, while the scalability of the reaction further demonstrates its practical utility.