Simple aza-conjugate addition methodology for the synthesis of isoindole nitrones and 3,4-dihydroisoquinoline
Lucy R Peacock1, Robert S L Chapman, Adam C Sedgwick
1Department of Chemistry, University of Bath , Bath, BA2 7AY, U.K.
Abstract:
Aryl-aldehydes containing ortho-substituted α,β-unsaturated carboxylic acid derivatives react with hydroxylamine to afford reactive N-hydroxy-carbinolamine intermediates that undergo intramolecular aza-conjugate addition reactions to afford isoindole nitrones and 3,4-dihydroisoquinoline nitrones in good yield. Conditions have been developed to reduce these isoindole nitrones to their corresponding hydroxylamine, enamine, and amine derivatives. Isoindole nitrones react with dimethyl acetylenedicarboxylate (DMAD) via a [4 + 2]-cycloaddition/deamination pathway to afford substituted naphthalene derivatives, while 3,4-dihydroisoquinoline nitrones react with DMAD via a [1,3]-dipolar cycloaddition pathway to afford tricyclic heteroarenes.
Related Concept Videos
Preparation of Nitriles
Conjugate Addition (1,4-Addition) vs Direct Addition (1,2-Addition)
Conjugate addition results in a thermodynamically stable product. The reaction retains the stronger C=O bond at the expense of the weaker C=C π bond. The process is slow as the β carbon is less electrophilic than the carbonyl carbon.
Direct addition products are...
Conjugate Addition to α,β-Unsaturated Carbonyl Compounds
Nitrosation of Enols
Aldehydes and Ketones with Amines: Imine and Enamine Formation Overview
1° Amines to Diazonium or Aryldiazonium Salts: Diazotization with NaNO2 Mechanism


