Absolute Asymmetric Synthesis for a Homologous Series of Five Isomorphic Oxoamide Derivatives

High Resolution Image Download MS PowerPoint Slide The development of absolute asymmetric synthesis in the solid state, without chiral auxiliaries or external templates, remains a significant challenge in chemistry. A few examples of absolute asymmetric synthesis using conglomerate chiral crystals of achiral molecules via photoreaction have been reported. However, these examples remain isolated, and systematic investigations across molecular series are lacking. Here, we report the first enantioselective solid-state photoconversion study across a complete isomorphic series of achiral m -Y-phenyl- N,N -diisopropylglyoxylamide (abbreviated as Y-oxo, Y = H, F, Cl, Br, or I) into optically active 3-hydroxy-1-isopropyl-4,4-dimethyl-3-( m -Y-phenyl)-azetidin-2-one (abbreviated as Y-β) lactams via Norrish-Yang photocyclization. We confirmed that the photoconversion of R a - and S a -Y-oxo crystals selectively afforded R -(+)- and S -(−)-Y-β, respectively, with enantiomeric excess ≥98%. This transformation establishes a direct correlation between conformational chirality in the solid state and the absolute configuration of the molecular product. The solid-state photoreaction is irreversible under the studied photochemical and thermal conditions. The supramolecular to molecular chirality transfer is enabled by rigid crystal packing and modulated by substituent-dependent spin–orbit coupling, providing a robust and tunable platform for enantioselective photochemistry. The findings advance our understanding of the intricate relationship between chiral crystals, solid-state reactivity, and the rational design of novel materials.