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

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.

SUBMITTER: Aloiau AN

PROVIDER: S-EPMC10949245 | biostudies-literature | 2024 Mar

REPOSITORIES: biostudies-literature

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

Aloiau Athenea N AN Bobek Briana M BM Caddell Haatveit Kersti K Pearson Kelly E KE Watkins Ashlee H AH Jones Benjamin B Smith Christopher R CR Ketcham John M JM Marx Matthew A MA Harwood Stephen J SJ

The Journal of organic chemistry 20240229 6

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 tran ...[more]

PMID: 38422508

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