Reactivity of Divinylhydroxylamine Intermediates Generated in Cascade Reactions of Nitrones and Alkynes

N,O-Divinylhydroxylamines are unusual [3,3]-sigmatropic rearrangement precursors that have been reported to form transiently under conditions that facilitate conversion of the resulting 1,4-iminoketone to the corresponding pyrrole or indole. Our group is interested in developing mild conditions to access N,O-divinylhydroxylamine intermediates, control the facial selectivity of their sigmatropic rearrangements, and use these transformations to install stereochemical information into saturated heterocyclic motifs and synthons. This thesis describes two new cascade reactions that use dipolar and nucleophilic additions of N-vinylnitrones and alkynes to generate N,O-divinylhydroxylamines and control their subsequent rearrangement under mild conditions. The project described in Chapters 1 and 2 demonstrates the regio- and diastereselective synthesis of 1-pyrrolines through dearomative and non-dearomative [3,3]-sigmatropic rearrangement of N-vinylisooxazolines prepared via the dipolar cycloaddition of an N-vinylnitrone and an aryne or alkyne. This transformation can be considered a formal [4+1]-cycloaddition and represents a new retrosynthetic alternative for 1-pyrroline synthesis. The project described in Chapter 3 involves the copper-catalyzed activation of ynamides towards nucleophilic attack by N-vinylnitrones for the generation of metallo-N,O-divinylhydroxylamines and synthesis of γ-ketoamides via rearrangement. This transformation illustrates the unusual reactivity of N-vinylnitrones that can be tuned to favor C–C bond formation over ynamide oxidation.