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

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.

Automated summary

In this paper, a novel strategy for the stereocontrolled synthesis of versatile chiral P-stereogenic alkenylphosphonamidates is reported. This strategy involves a one-pot Ni-catalyzed C-P coupling/diastereoselective hydrolysis of readily available phosphoramidites and alkenyl halides. The reaction conditions were found to exhibit chemo- and diastereodivergent behavior, and the chiral alkenylphosphonamidates obtained can be selectively derivatized for the synthesis of structurally diverse P-stereogenic compounds.