Nitrogen Heterocycle Synthesis through Hydride Abstraction of Acyclic Carbamates and Related Species: Scope, Mechanism, Stereoselectivity, and Product Conformation Studies

Acyliminium ions and related species are potent electrophiles that can be quite valuable in the synthesis of nitrogen-containing molecules. This manuscript describes a protocol to form these intermediates through hydride abstractions of easily accessible allylic carbamates, amides, and sulfonamides that avoids the reversibility that is possible in classical condensation-based routes. These intermediates are used in the preparation of a range of nitrogen-containing heterocycles, and in many cases high levels of stereocontrol are observed. Specifically areas of investigation include the impact of chemical structure on oxidation efficiency, the geometry of the intermediate iminium ions, the impact of a substrate stereocenter on stereocontrol, and an examination of transition state geometry. Acyliminium ions and related species can be formed through hydride abstraction reactions that obviate the need for leaving group installation and avoid issues of unfavorable equilibria. This allows for the study of several previously unappreciated reactivity properties of these species in the context of cyclization reactions, including intermediate geometry, transition state conformation, stereoselectivity and product geometry.image

Automated summary

This manuscript describes a protocol to form acyliminium ions and related species through hydride abstractions of easily accessible allylic carbamates, amides, and sulfonamides. These intermediates are used in the synthesis of nitrogen-containing heterocycles, demonstrating high levels of stereocontrol. Areas of investigation include oxidation efficiency, geometry of intermediate iminium ions, substrate stereocenter impact on stereocontrol, and transition state geometry.