Exploitation of Nitrone and Hydroxylamine N–O Bonds for the Construction of Functionalized Heterocycles

In the Anderson group at UIC, we aim to develop new transformations involving N-vinylnitrone and N,O-divinylhydroxylamine intermediates to access functionalized molecules and novel heterocyclic scaffolds by harnessing the reactivity of N–O bonds. Recently, we have expanded the scope of these methods to include the synthesis of azetidine nitrones through the 4π-electrocyclization of N-vinylnitrones, and we have also laid the foundation for asymmetric catalysis of this transformation to access stereodefined azetidine precursors. These azetidine nitrones have proven to be excellent tools for accessing functionalized azetidine scaffolds. We have also discovered the preparation of 2-aminotetrahydrofurans via the addition of N-vinylhydroxylamine derivatives to electron-deficient allenoates. These nucleoside analogue products can be used in Aza-Petasis-Ferrier rearrangements for the diastereoselective generation of a variety of cyclopentanone products. Finally, a novel [3+2]-cycloaddition/[3,3’]-rearrangement cascade has been discovered, generating densely substituted spirocyclic 1-pyrrolines from N-vinylnitrones and strained cyclic alkyne intermediates. The optimization, scope, and limitations of these transformations will be discussed to highlight the fundamental reactivity of the intermediates involved. A detailed description of their utility in heterocycle synthesis will be presented to illustrate their versatility in the rapid preparation of sophisticated structures.