Copper-Catalyzed Amino Radical Transfer-Mediated Deborylation for Chiral Ester Synthesis.

The asymmetric functionalization of nonactivated alkylboronic pinacol esters (APEs) represents a longstanding challenge, owing to their intrinsic inertness toward conventional two-electron transmetalation pathways and the difficulty in achieving precise stereochemical control over carbon-centered radicals. Herein, we report a copper-catalyzed asymmetric deborylative radical coupling enabled by amino radical transfer (ART). By employing aminobenzoates as dual-function reagents, acting both as aminyl radical precursors to trigger ART-mediated homolytic C(sp3)-B bond cleavage and as oxygen nucleophiles, this three-component transformation enables enantioselective coupling of APEs with conjugated dienes. The method delivers structurally diverse chiral allylic esters with excellent enantioselectivities (up to 99% ee). Furthermore, this protocol enables the concise formal synthesis of natural products and the modular construction of chiral ionizable lipids with precise three-dimensional architectures. These lipids achieve enhanced organ-selective mRNA delivery, exhibiting extrahepatic targeting with an improved preference for the spleen. Notably, this work establishes a versatile catalytic platform for transforming bench-stable APEs feedstocks into oxygen-containing chiral molecules, facilitating the development of tissue-specific genetic medicines.