Zirconium Hydride Catalysis Initiated by Tetrabutylammonium Fluoride

• DOI: 10.1021/acs.joc.4c01227
• Publication Date: 2024-07-29T16:10:42Z
• Authors: Athenea N. Aloiau; Briana M. Bobek; Kelly E. Pearson; Kendall E. Cherry; Christopher R. Smith; John M. Ketcham; Matthew A. Marx; Stephen J. Harwood
• Keywords: Chemoselectivity; Organic Synthesis; Tetrabutylammonium fluoride

In our drug discovery campaigns to target the oncogenic drivers of cancers, demand for a chemoselective, stereoselective and economical synthesis chiral benzylamines drove development catalytic zirconium hydride reduction. This methodology uses inexpensive, bench stable zirconocene dichloride, novel tetrabutylammonium fluoride activation tactic catalytically generate metal under ambient conditions. The diastereo- chemoselectivity this reaction was tested with preparation key intermediates from programs in scope sulfinyl ketimines carbonyls relevant medicinal chemistry natural product synthesis. A preliminary mechanistic investigation conducted into role indicates that formation occurs initiate catalysis. implications convenient approach may provide expanded roles hydrides transformations.