Diastereo- and enantioselective [3 + 3] cycloaddition of spirocyclopropyl oxindoles using both aldonitrones and
Peng-Wei Xu1, Jia-Kuan Liu2, Lan Shen2
1Shanghai Key Laboratory of Green Chemistry and Chemical Processes, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, China.
Abstract:
Optically active spirocyclic compounds play an important role in drug discovery, and new synthetic strategies for the efficient generation of spiro stereocenters are in much demand. Here we report a catalytic enantioselective cycloaddition using spirocyclic donor-acceptor cyclopropanes as a promising approach for the generation of spiro stereocenters. A diastereo- and enantioselective [3 + 3] cycloaddition of spirocyclopropyl oxindoles with both aldonitrones and ketonitrones is developed. The key to reaction development is the activation of spirocyclopropyl oxindoles by a suitable electron-withdrawing N-protecting group. This activation approach offers the promise of a general solution to enable spirocyclopropyl oxindoles as synthons for catalytic enantioselective synthesis of spirocyclic oxindoles featuring a C3 spiro stereocenter, a prominent structural motif in drugs and pharmaceutically active compounds. This protocol also constitutes the catalytic enantioselective reaction using unactivated achiral ketonitrones to construct tetrasubstituted carbon stereocenters.
Related Concept Videos
Cycloaddition Reactions: Overview
Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
Aldol Condensation with β-Diesters: Knoevenagel Condensation
Acid-Catalyzed Aldol Addition Reaction
Oxidation of Alkenes: Syn Dihydroxylation with Osmium Tetraoxide

![Solid-phase Synthesis of [4.4] Spirocyclic Oximes](/_next/image?url=https%3A%2F%2Fcloudfront.jove.com%2FCDNSource%2Fteasers%2F58508.jpg&w=3840&q=50)
