Microwave induced formal [2 + 1] Michael-cyclization cascade sequence of 3-ylidene oxindoles and pyridinium phenacyl salts

Abstract

A simple and efficient strategy has been developed for the construction of Spirocyclopropyl oxindoles. This process has several advantages like usage of mild base, microwave assisted, and green synthesis i.e., aqueous medium. The reaction proceeds in a cascade manner i.e., Michael-cyclization via [2 + 1] annulation between trans-methyl-2-(2-oxoindolin-3-ylidene)acetate and pyridinium salts of phenacyl bromides. This protocol leads to the generation two chiral centers along with an all carbon quaternary carbon center. A wide range of substrates with electron rich and electron deficient substituents on aryl rings were accepted well and yielded related spirocyclopropyl oxindoles in reasonable to good yields up to 80% for a total of 28 examples. A series of controlled experiments has been performed to illustrate the reaction pathway and reactivity of phenacyl bromide and its corresponding pyridinium salt toward methyl 2-oxoindolin-3-ylidene acetate.

Graphical Abstract

Keywords:

• Cyclopropanation
• green solvent
• microwave
• oxindoles
• pyridinium salts
• spirocyclo propane

Acknowledgments

The authors grateful to acknowledge Aragen Life Sciences for providing research and high-resolution analytical facilities. We specially thank to Dr. Sudhir Kumar Singh and Dr. Somesh Sharma for their valuable suggestions.