Chiral　heterocycles　with　two　or　more　carbon　stereocenters　are　quite　important　skeletons　in　many　fields.　However,　powerful　strategies　for　the　construction　of　such　synthetically　valuable　heterocycles,　especially　with　two　or　more　remote　carbon　stereocenters,　have　largely　lagged　behind.　We　report　here　a　powerful　method　for　the　synthesis　of　chiral　γ-butyrolactones　with　two　non-vicinal　carbon　stereocenters　from　readily　available　chemical　feedstocks　under　mild　conditions.　Both　of　the　two　diastereoisomers　can　be　obtained　with　good　to　excellent　enantioselectivities.　The　well-designed　copper/PyBox　catalytic　system　overrides　the　intrinsic　stereoinduction　of　the　close　chirality　center　generated　by　the　previous　innocent　radical　addition　step.　Nevertheless,　this　work　has　the　power　to　selectively　provide　one　single　diastereoisomer　by　taking　advantage　of　the　epimerization　effect　but　also　to　synthesize　all　four　diastereoisomers　with　the　pair　of　chiral　ligands　L2　and　L2′　having　opposite　chirality.　The　obtained　useful　chiral　γ-butyrolactones　can　be　synthetically　transformed　into　acyclic　or　cyclic　molecules　with　two　non-vicinal　carbon　stereocenters.　Mechanistic　studies　reveal　that　this　radical　reaction　follows　a　linear　relationship　and　can　be　well　performed　with　a　less　loading　amount　of　ligand　compared　to　that　of　the　copper　catalyst.　©　2023　Wiley-VCH　GmbH.