DMAP-Promoted Cascade Synthesis of Bispirooxindole-Cyclopentene-Isoxazolones
Wei Zhang1, Rong-Rong Zhu1, Da-Ming Du1
1School of Chemistry and Chemical Engineering, Beijing Institute of Technology, Beijing 100081, China.
Abstract:
A DMAP-catalyzed Michael addition/cyclization cascade reaction has been developed for the efficient construction of a bispirooxindole-cyclopentene-isoxazolone framework. Under the optimized conditions (10 mol% DMAP, CH2Cl2, room temperature), the desired product was obtained in 92% yield with >20:1 diastereoselectivity. The reaction exhibited broad substrate scope, tolerating various substituents on both the isoxazolone and oxindole rings, and affording the corresponding products in 72-96% yields. The relative configuration of a representative product was determined as rel-(2'S,3R,3'R) by X-ray single-crystal diffraction. The utility of this method was further demonstrated by a gram-scale experiment (82% yield). This cascade reaction provides a concise and efficient route to structurally novel spiroisoxazolone derivatives bearing a cyano group and multiple spiro chiral centers.
Related Concept Videos
Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
Cycloaddition Reactions: Overview
Diels–Alder Reaction Forming Cyclic Products: Stereochemistry
Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
Preparation of Diols and Pinacol Rearrangement
The reaction begins with transferring a proton from the acid catalyst to one of the hydroxyl groups, producing an oxonium ion.


![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)