Stereoselective synthesis of (Z)-1,3-bis(α,β-unsaturated carbonyl)-isoindolines from aldehydes and phenacyl azides under metal free conditions

Here in the present manuscript, we report our observation of an unprecedented stereoselective synthesis of 2H-isoindolin-1,3-ylidenes from 2-(formylphenyl)acrylates and phenacylazide in the presence of piperidine. Unlike in our previous findings, in which we accessed 3-keto-isoquinolines from the same starting materials under slightly modified reaction conditions, this unexpected one-pot tandem reaction allows an efficient and simple method to access a variety of highly functionalized ethyl (Z)-2-((Z)-3-(2-oxo-2-arylethylidene)-2,3-dihydro-1H-benzo[e]isoindol-1-ylidene)-acetates in very good to excellent yields (up to 91%). The present methodology is compatible with a wide variety of functional groups.

Automated summary

In this study, a novel stereoselective synthesis of 2H-isoindolin-1,3-ylidenes from 2-(formylphenyl)acrylates and phenacylazide in the presence of piperidine was successfully demonstrated. The one-pot tandem reaction provides a simple and efficient method to access highly functionalized ethyl (Z)-2-((Z)-3-(2-oxo-2-arylethylidene)-2,3-dihydro-1H-benzo[e]isoindol-1-ylidene)-acetates in good to excellent yields (up to 91%), and is compatible with a wide variety of functional groups.