The Hull Group have been investigating novel methodologies to access nitrogen-containing compounds due to their ubiquity in the field of organic chemistry, pharmaceuticals, and beyond. Three-component carboamination of unsaturated substrates is an emerging class of transformations that allow for a rapid and modular assembly of complex nitrogen-containing scaffolds. In 2018, we reported methodologies on three-component Cu-catalyzed difunctionalizations of vinyl- and heterovinylarenes, electron deficient olefins and vinylboronates.

To improve the synthetic applicability of this previously developed method, it was of interest to explore underrepresented substrates. Vinylcyclopropanes were selected due to their ability to undergo a rapid ring opening with relocation of the radical density, also known as radical clocks. This could be leveraged to capture the resulting radical adduct with the catalyst to yield a densely functionalized homoallylic amine motif.

To this end, the reaction generally occurs with outstanding regio- and good diastereoselectivity. The scope of the reaction was explored with respect to all three components: alkyl halide, vinylcyclopropane, and amine nucleophiles. A total of 39 examples were produced, with yields up to 95%. Lastly, the catalytic cycle and stereochemical model were discerned. This 1,5-carboamination provides a consistent method to access homoallylic amine derivatives with moderate to good yields, and a reaction scope that is relatively diverse.

Summary and potential application of the recently developed 1,5-carboamination of vinylcyclopropanes by the Hull group.

Kami Hull

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