Stereoselective Amine Synthesis Mediated by a Zirconocene Hydride to Accelerate a Drug Discovery Program

• DOI: 10.1021/acs.joc.3c02723
• Publication Date: 2024-02-29T22:09:42Z
• Authors: Athenea N. Aloiau; Briana M. Bobek; Kersti Caddell Ha...; Kelly E. Pearson; Ashlee H. Watkins; Benjamin Jones; Christopher R. Smith; John M. Ketcham; Matthew A. Marx; Stephen J. Harwood
• Keywords: Reactivity; Formal synthesis

Chiral amine synthesis remains a significant challenge in accelerating the design cycle of drug discovery programs. A zirconium hydride, due to its high oxophilicity and lower reactivity, gave highly chemo- stereoselective reductions sulfinyl ketimines. The development this zirconocene-mediated reduction helped accelerate our efforts is applicable several motifs commonly used medicinal chemistry. Computational investigation supported cyclic half-chair transition state rationalize selectivity benzyl systems.