Inhibiting Isomerization via Confinement in Ice-Water Interfaces Enhances Stereoselectivity in [2 + 2] Cycloaddition

Cyclobutanes serve as fundamental motifs in natural products, bioactive substrates, and pharmaceuticals. Despite numerous efforts to synthesize cyclobutane products, particularly through light-driven [2 + 2] cycloaddition, significant challenges persist, such as the rapid cis/trans isomerization of olefin substrates and the thermodynamic difficulty in synthesizing syn-cyclobutane derivatives, which limit their widespread application across various fields. Here, by introducing a confined ice-water interface to mediate the [2 + 2] photocycloadditions, we not only efficiently inhibit reactant isomerization but also achieve the syn-cyclobutane products (syn-dimer > 95%) without the need for additional chemical auxiliary reagents. The specific proportional relationship of reaction kinetics and the active ice surface area reveals the unique catalytic role of the ice surface in [2 + 2] cycloaddition reactions. Theoretical simulations and experimental studies demonstrate that at the ice-water interface, solute molecules tend to adsorb on the ice surface and form molecular pairs in a prereactive arrangement. Compared to molecular monomers, these molecular pairs exhibit a higher energy barrier for photoisomerization and tend to align in a syn-configuration, thereby inhibiting isomerization and facilitating stereoselective [2 + 2] cycloaddition. This work highlights the potential of ice-assisted photochemical methods in advancing sustainable and environmentally friendly chemical synthesis.