Simple aza-conjugate addition methodology for the synthesis of isoindole nitrones and 3,4-dihydroisoquinoline nitrones

Org Lett. 2015 Feb 20;17(4):994-7. doi: 10.1021/acs.orglett.5b00103. Epub 2015 Feb 11.

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.

Publication types

  • Research Support, Non-U.S. Gov't