Influence of N ‐Substitution in 3‐Alkyl‐3‐hydroxyisoindolin‐1‐ones on the Stereoselectivity of Brønsted Acid‐Catalyzed Synthesis of 3‐Methyleneisoindolin‐1‐ones

A comprehensive study on the influence of N ‐substitution on the stereoselective outcome of the synthesis of 3‐methyleneisoindolin‐1‐ones from 3‐alkyl‐3‐hydroxyisoindolin‐1‐ones is reported. The study was performed on an array of structurally diverse 3‐alkyl‐3‐hydroxyisoindolin‐1‐ones with tunable sizes of N ‐substituents. In a methanesulfonic acid‐catalyzed reaction, substrates without N ‐substituent (N−H) afforded exclusively the Z ‐isomer, while an increase in their size was followed by the formation of a stereoisomeric mixture with the E ‐isomer as the major component.