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Asymmetric Synthesis of Chiral‐at‐P Alkenylphosphonamidates through Nickel‐Catalyzed C−P Coupling of Phosphoramidites and Alkenyl Halides

Xiaobing Chen, Damián Padín, Charlotte N. Stindt, Ben L. Feringa

2023Angewandte Chemie International Edition29 citationsDOIOpen Access PDF

Abstract

P-stereogenic compounds are widely used as ligands in asymmetric catalysis and are present in a myriad of bioactive compounds and pharmaceuticals. Yet, their stereocontrolled preparation remains challenging. Herein, we report a novel strategy towards versatile chiral-at-P alkenylphosphonamidates through a one-pot Ni-catalyzed C-P coupling/diastereoselective hydrolysis of readily available phosphoramidites and alkenyl halides. Remarkably, a chemo- and diastereodivergent behavior was observed upon subtle changes in the reaction conditions. Additionally, selective derivatizations of chiral alkenylphosphonamidates demonstrate their versatility as building blocks for the synthesis of structurally diverse P-stereogenic compounds.

Topics & Concepts

StereocenterHalideChemistryCatalysisEnantioselective synthesisCombinatorial chemistryNickelStereochemistryOrganic chemistryAsymmetric Hydrogenation and CatalysisSynthetic Organic Chemistry MethodsOrganophosphorus compounds synthesis