Organoboron compounds are indispensable in modern organic synthesis and biomedical research. This study describes the first synthesis of bench-stable boryl dicationic compound via chemical or electrochemical thianthrenation of vinyl MIDA boronate. Notably, the MIDA boryl group plays a crucial role in thianthrenation, suppressing undesired deborylation and promoting exclusive mono-adduct formation via a formal [4+2] cycloaddition pathway. This unique boryl dication enables a transition-metal-free, chemo- and diastereoselective synthesis of aziridinyl boronates, utilizing a broad range of nitrogen nucleophiles. The method demonstrates remarkable generality, practicality, and functional group tolerance, as evidenced by its application to diverse substrates, including the late-stage modification of several drug molecules. The strategic significance of this approach is further highlighted through electrochemical one-pot protocol and multiple downstream transformations of aziridinyl boronates, offering new opportunities for synthetically challenging boron-containing drug-like scaffolds.

The development of efficient synthetic methods for α-boryl ureas and carbamates is of significant interest due to their potential as drug-like scaffolds in medicinal chemistry. This study presents a novel one-pot synthesis of α-boryl ureas and carbamates via α-boryl isocyanates, generated in situ from widely available α-haloboronates. The method leverages an in situ activation of trimethylsilyl isocyanate by sodium iodide to generate a more nucleophilic isocyanate species, facilitating the formation of α-boryl isocyanates under mild conditions. The broad substrate scope and functional group tolerance of this protocol enable the synthesis of diverse α-boryl ureas and carbamates, including biologically relevant molecules and late-stage pharmaceutical derivatives. To showcase the potential of this methodology in drug discovery, an α-boryl urea analog of nirmatrelvir, a SARS-CoV-2 main protease inhibitor, was synthesized, demonstrating enhanced potency (IC50 = 12 nM) compared to nirmatrelvir. This work not only offers a streamlined, direct approach for the preparation of synthetically challenging α-boryl ureas and carbamates with broad structural diversity, but also underscores the importance of α-boryl ureas as valuable scaffolds for the development of new therapeutics.