Catalytic Asymmetric Reductive Amination for Planar Chiral [2,2]Paracyclophanes via Desymmetrization and/or Kinetic Resolution ^†

Comprehensive Summary Despite the significant potential of planar chiral [2.2]paracyclophane (PCP) derivatives in medicinal chemistry, asymmetric catalysis, and material science, their efficient synthesis remains a great challenge. The organocatalytic asymmetric reductive amination (ARA) represents a cornerstone methodology in the production of optically active amines. However, the application of ARA for the control of planar chirality in [2.2]PCPs has yet to be explored. To fill this gap, we describe herein an unprecedented chiral phosphoric acid (CPA)‐promoted ARA of center‐symmetrical pseudo ‐ para ‐diformyl [2.2]PCP with aromatic amines in the presence of Hantzsch ester, which involves a desymmetrization/kinetic resolution (KR) sequence. The CPA serves as a competent bifunctional catalyst to facilitate differentiation of enantiotopic faces, allowing for access to a wealth of benzylamine‐containing 4,16‐disubstituted planar chiral [2.2]PCPs with good yields and high to perfect enantioselectivities (up to 89% yield, >99% ee). The ARA‐KR of racemic formyl [2.2]PCPs also proceeds smoothly with moderate to good selectivity factors. The diverse late‐stage functionalization further highlights the value of current chemistry.