Catalytic Asymmetric Hydrogen Atom Transfer: Enantioselective Hydroamination of Alkenes

• Published in: Journal of the American Chemical Society 2023-07, Vol.145 (29), p.16118-16129
• Main Authors: Hejna, Benjamin G., Ganley, Jacob M., Shao, Huiling, Tian, Haowen, Ellefsen, Jonathan D., Fastuca, Nicholas J., Houk, Kendall N., Miller, Scott J., Knowles, Robert R.
• Format: Article
• Language: English
• ISSN: 0002-7863; 1520-5126; 1520-5126
• DOI: 10.1021/jacs.3c04591

We report a highly enantioselective radical-based hydroamination of enol esters with sulfonamides jointly catalyzed by an Ir photocatalyst, Brønsted base, and tetrapeptide thiol. This method is demonstrated for the formation of 23 protected β-amino-alcohol products, achieving selectivities up to 97:3 er. The stereochemistry of the product is set through selective hydrogen atom transfer from the chiral thiol catalyst to a prochiral C-centered radical. Structure–selectivity relationships derived from structural variation of both the peptide catalyst and olefin substrate provide key insights into the development of an optimal catalyst. Experimental and computational mechanistic studies indicate that hydrogen-bonding, π–π stacking, and London dispersion interactions are contributing factors for substrate recognition and enantioinduction. These findings further the development of radical-based asymmetric catalysis and contribute to the understanding of the noncovalent interactions relevant to such transformations.