Copper‐Catalyzed Amino Radical Transfer‐Mediated Deborylation for Chiral Ester Synthesis

ABSTRACT 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(sp 3 )–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.