The Elements of Chiral Brønsted Acids for Stereoselective Transformations

ABSTRACT

Chiral Brønsted acids (CBAs) are powerful organocatalysts for asymmetric synthesis, with their performance governed by three modular elements: the acidic core, the chiral scaffold, and peripheral substituents . This review systematically examines each component. The acidic core (O─H, N─H, S─H, or C─H) dictates proton donor strength and conjugate base stability, ranging from classical phosphoric acids to superacidic imidodiphosphorimidates (IDPis) and disulfonimides. The chiral scaffold establishes the asymmetric environment; axial (BINOL, SPINOL), central (TADDOL, BPOL), planar (paracyclophane, ferrocene), and helical architectures each offer distinct steric and electronic profiles. Peripheral substituents fine‑tune the chiral pocket via steric shielding (e.g., 2,4,6‑triisopropylphenyl, triphenylsilyl), electronic modulation (π‑interactions, pKa control), and additional functionalities (Brønsted acid‐assisted systems, photoactive groups). Recent advances highlight synergistic effects where noncovalent interactions complement or override pure steric control, enabling enantio‑ and diastereodivergent pathways. This review combines three design elements to frame rational catalyst development, guide optimal CBA architectures for challenging reactions, and outline future directions.