Treatment of homoallylic N-tosyl amines or allylic N-tosyl hydroxylamines with 1.5 equiv of a malonoyl peroxide provides a stereoselective method to access functionalized pyrrolidines and isoxazolidines. This metal free alkene oxyamination proceeds in 50-85% yield and up to 13:1 trans-selectivity. In addition, the relative stereochemistry of the oxygen and nitrogen substituents can be inverted through an oxidation/reduction sequence or inverting the stereochemistry of the starting alkene. Mechanistic investigations show a higher reactivity for hydroxyl nucleophiles over sulfonamide nucleophiles revealing a preference for dioxygenation over oxyamination.
- organic synthesis
Alamillo-Ferrer, C., Curle, J. M., Davidson, S. C., Lucas, S. C. C., Atkinson, S. J., Campbell, M., ... Tomkinson, N. C. O. (2018). Alkene oxyamination using malonoyl peroxides: preparation of pyrrolidines and isoxazolidines. Journal of Organic Chemistry, 83(12), 6728-6740. https://doi.org/10.1021/acs.joc.8b00392