Organocatalytic desymmetrization provides access to planar chiral [2.2]paracyclophanes

• Published in: Nature communications 2024-04, Vol.15 (1), p.3090-3090, Article 3090
• Main Authors: Dočekal, Vojtěch, Koucký, Filip, Císařová, Ivana, Veselý, Jan
• Format: Article
• Language: English
• Subjects: 140/131; 140/58; 639/638/403/933; 639/638/77/883; 639/638/77/889; Asymmetric synthesis; Asymmetry; Benzene; Carbonyl compounds; Carbonyl groups; Carbonyls; Catalysts; Chemical synthesis; Enantiomers; Humanities and Social Sciences; Materials science; multidisciplinary; Organic compounds; Polymers; Science; Science (multidisciplinary); Substrates
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-024-47407-0

Planar chiral [2.2]paracyclophanes consist of two functionalized benzene rings connected by two ethylene bridges. These organic compounds have a wide range of applications in asymmetric synthesis, as both ligands and catalysts, and in materials science, as polymers, energy materials and dyes. However, these molecules can only be accessed by enantiomer separation via (a) time-consuming chiral separations and (b) kinetic resolution approaches, often with a limited substrate scope, yielding both enantiomers. Here, we report a simple, efficient, metal-free protocol for organocatalytic desymmetrization of prochiral diformyl[2.2]paracyclophanes. Our detailed experimental mechanistic study highlights differences in the origin of enantiocontrol of pseudo - para and pseudo-gem diformyl derivatives in NHC catalyzed desymmetrizations based on whether a key Breslow intermediate is irreversibly or reversibly formed in this process. This gram-scale reaction enables a wide range of follow-up derivatizations of carbonyl groups, producing various enantiomerically pure planar chiral [2.2]paracyclophane derivatives, thereby underscoring the potential of this method. Planar chiral [2.2]paracyclophanes have a wide range of applications in asymmetric synthesis and materials science. However, they are accessed via time-consuming chiral separations or kinetic resolution approaches. Here, the authors report a simple, metal-free protocol for organocatalytic desymmetrization of prochiral diformyl[2.2]paracyclophanes.