Mechanism and Origin of CuH‐Catalyzed Regio‐ and Enantioselective Hydrocarboxylation of Allenes

Abstract The CuH‐catalyzed hydrocarboxylation of allenes is an enantio‐ and regioselective approach for the synthesis of (S)‐carboxyl‐containing compounds. With density functional theory (DFT) calculations, we elucidate the reaction mechanism and the origins of the enantioselectivity and regioselectivity. The hydrocarboxylation proceeds through the migratory insertion of allenes on CuH complex, the enantioselective addition of fluoroformate, and the β‐fluoride elimination gives the branched carboxylation products. The electron‐donating alkyl and phenyl groups in the allene polarize the C=C bond and thus lead to the anti‐Markovnikov‐selective migratory insertion. In addition, the enantioselective addition of fluoroformate by either (R)‐ or (S)‐addition determines the enantioselectivity. The (S)‐addition is more favorable due to the bulky −tBu group of (R)‐DTBM‐SEGPHOS ligand, which prefers keeping the C=C bond of allene away from the reaction center in six‐membered transition state and thus results in (S)‐carboxyl‐containing products.