Modular Access to P(V)-Stereogenic Compounds via Cu-Catalyzed Desymmetrization of (Thio)Phosphonic Dichlorides.

Chiral phosphorus(V) centers-particularly those bearing fully heteroatom-substituted frameworks-are key stereochemical motifs in pharmaceuticals, nucleic acid therapeutics, and functional materials. However, their stereoselective construction remains a long-standing challenge in synthetic chemistry. Here, we report a copper-catalyzed desymmetrization strategy enabled by rationally engineered PIM ligands that affords broad and modular access to structurally diverse P(V)-stereogenic compounds.

Modular access to saturated bioisosteres of anilines via photoelectrochemical decarboxylative C(sp)-N coupling.

In drug development, the substitution of benzene rings in aniline-based drug candidates with saturated bridged bicyclic ring systems often enhances pharmacokinetic properties while preserving biological activity. However, current efforts predominantly focuses on bicyclo[1.1.

Ligand-Enabled Cu-Catalyzed Stereoselective Synthesis of P-Stereogenic ProTides.

Nucleoside analogues have seen significant advancements in treating viral infections and cancer through ProTide technology, leading to a series of FDA-approved drugs such as sofosbuvir, tenofovir alafenamide, and remdesivir. The stereochemical configuration at the phosphorus center of ProTides significantly influences their pharmacological properties, necessitating efficient stereoselective synthesis. Traditional methods using chiral auxiliaries or nonracemic phosphorylating agents are labor-intensive and inefficient, while recent organocatalytic approaches, despite their promise, still face limitations.

Enantioselective Deaminative Alkylation of Amino Acid Derivatives with Unactivated Olefins.

Herein, we report the first Ni-catalyzed enantioselective deaminative alkylation of amino acid and peptide derivatives with unactivated olefins. Key for success was the discovery of a new sterically encumbered bis(oxazoline) ligand backbone, thus offering a de novo technology for accessing enantioenriched - linkages via C-N functionalization. Our protocol is distinguished by its broad scope and generality across a wide number of counterparts, even in the context of late-stage functionalization.