Base‐Catalyzed One‐Pot Elimination and <i>N</i> ‐Alkylation of 3‐Alkyl‐3‐hydroxyisoindolin‐1‐ones

Abstract The base‐mediated elimination of 3‐alkyl‐3‐hydroxyisoindolin‐1‐ones containing either an acidic proton or a hydroxymethyl substituent on the nitrogen atom was investigated. Upon deprotonation, these substrates were found to undergo elimination via an E1cb mechanism, forming an imine intermediate that subsequently tautomerized to yield ( Z )‐3‐alkyleneisoindolin‐1‐ones. Furthermore, by employing haloalkanes as N‐alkylation agents, a one‐pot elimination‐alkylation process was achieved under basic conditions, providing access to ( Z )‐ N ‐alkyl‐3‐alkyleneisoindolin‐1‐ones. This approach offers a complementary route to existing acidic methods, in which ( E )‐ N ‐alkyl‐3‐alkyleneisoindolin‐1‐ones are obtained from N ‐alkyl‐3‐hydroxyisoindolin‐1‐one precursors.