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

Overview

Journal J Org Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2024 Feb 29

PMID 38422508

Authors

Athenea N Aloiau

Briana M Bobek

Kersti Caddell Haatveit

Kelly E Pearson

Ashlee H Watkins

Benjamin Jones

Christopher R Smith

John M Ketcham

Matthew A Marx

Stephen J Harwood

Affiliations

Soon will be listed here.

Abstract

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- and stereoselective reductions of sulfinyl ketimines. The development of this zirconocene-mediated reduction helped to accelerate our drug discovery efforts and is applicable to several motifs commonly used in medicinal chemistry. Computational investigation supported a cyclic half-chair transition state to rationalize the high selectivity in benzyl systems.

Citing Articles

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PMID: 39843889 PMC: 11754598. DOI: 10.1038/s41467-025-56234-w.

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