Although best known for their [3+2]-dipolar cycloaddition reactivity and use in the preparation of isoxazolines and isoxazolidines, nitrones are versatile reagents that undergo a variety of transformations for the synthesis of a diverse array of heterocyclic compounds. The breadth of heterocycle synthesis using nitrone reagents includes: 1) stepwise [3+3]-cycloaddition reactions of nitrones with vinyl diazoacetates, transition-metal-coordinated cycloisomerization intermediates, trimethylene methanes, and cyclopropane diesters to form dihydro- and tetrahydro-1,2-oxazines; 2) internal redox cyclization reactions of alkyne-tethered nitrones to provide access to azabicyclooctanes, isoindoles, aminoindanones, and isoquinolones; 3) electrocyclizations of in situ generated N-allenylnitrones to form pyridines and azetidine-N-oxides, as well as metal-catalyzed cyclizations and rearrangements of nitrones to form azepine-N-oxides, spirocyclic isoxazolines, and α,β-epoxyimines; and 4) the use of [3+2]-cycloaddition reactions of nitrones to trigger cascade reactions for the formation of tetrahydrooxazepines, dihydrocarbazoles, and benzoindolizines. This Focus Review aims to highlight these diverse applications of nitrones for the synthesis of heterocycles to emphasize the broad utility of these reactive intermediates and to inspire their further development as important synthons beyond the scope of traditional [3+2]-dipolar cycloaddition reactions.

An asymmetric method for the synthesis of dihydropyrido[1,2-a]indoles from mixtures of nitrones and allenoates has been developed. This transformation showcases the use of squaramide catalysis in a complicated cascade system that has been shown to be highly sensitive to reaction conditions and substituent effects. The new method provides access to enantiomerically enriched dihydropyridoindoles from modular, non-indole reagents. The optimization and scope of the new transformation is discussed in addition to initial mechanistic experiments that indicate the role of the catalyst.

An asymmetric method for the synthesis of dihydropyrido[1,2-a]indoles from mixtures of nitrones and allenoates has been developed. This transformation showcases the use of squaramide catalysis in a complicated cascade system that has been shown to be highly sensitive to reaction conditions and substituent effects. The new method provides access to enantiomerically enriched dihydropyridoindoles from modular, non-indole reagents. The optimization and scope of the new transformation is discussed in addition to initial mechanistic experiments that indicate the role of the catalyst.

A solvent-controlled cascade process has been identified for the dual purpose of the preparation of either dihydrocarbazoles or dihydropyridoindoles from identical N-aryl-α,β-unsaturated nitrones and electron-deficient allene starting materials. These reactions proceed smoothly under mild metal-free conditions affording a range of two types of skeletally distinct indole-based heterocycles in high yield and diastereoselectivity. These transformations demonstrate the use of a bifurcated cascade process that hinges on the ring-opening event of a benzazepine intermediate for the synthesis of skeletally diverse heterocyclic products and rapid access to biologically-significant, indole-based structures.