Unraveling Polymorphic Control in the Solid-State [2 + 2] Cycloaddition of Vitamin K: Insights from Single-Crystal Irradiation.

The solid-state [2 + 2] cycloaddition of vitamin K (VK3) polymorphs has been systematically reexamined, overcoming the limitations of powder-based studies by focusing on single-crystal behavior. Using THz micro-Raman and FTIR-ATR vibrational spectroscopies combined with X-ray diffraction and solid-state density functional theory (DFT) calculations, we unveil distinct photoreactivity and stereoselectivity in both polymorphs. Monochromatic irradiation at the absorption tail preserved the crystal integrity, enabling a detailed investigation of the reaction outcomes. While both polymorphs undergo photoreaction, their transformations proceed via distinct crystal-to-crystal processes, yielding and dimers selectively. The photochemical pathway to the formation of the -isomers is analyzed by quantum mechanical calculations. These findings highlight the critical role of polymorphism in solid-state photochemistry while questioning the conventional dichotomy between defect-driven and purely topochemical mechanisms.