Alkene oxyamination using malonoyl peroxides : preparation of pyrrolidines and isoxazolidines

Alamillo-Ferrer, Carla and Curle, Jonathan M and Davidson, Stuart C and Lucas, Simon C C and Atkinson, Stephen J and Campbell, Matthew and Kennedy, Alan R and Tomkinson, Nicholas C O (2018) Alkene oxyamination using malonoyl peroxides : preparation of pyrrolidines and isoxazolidines. Journal of Organic Chemistry, 83 (12). pp. 6728-6740. ISSN 0022-3263 (https://doi.org/10.1021/acs.joc.8b00392)

[thumbnail of Alamillo-Ferrer-etal-JOC-2018-Alkene-oxyamination-using-malonoyl-peroxides-preparation-of-pyrrolidines]
Preview
Text. Filename: Alamillo_Ferrer_etal_JOC_2018_Alkene_oxyamination_using_malonoyl_peroxides_preparation_of_pyrrolidines.pdf
Accepted Author Manuscript

Download (1MB)| Preview

Abstract

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.