Machine-Learning Photodynamics Simulations Uncover the Role of Substituent Effects on the Photochemical Formation of Cubanes.

Photochemical [2 + 2]-cycloadditions store solar energy in chemical bonds and efficiently access strained organic molecular architectures. Functionalized [3]-ladderdienes undergo [2 + 2]-photocycloadditions to afford cubanes, a class of strained organic molecules. The substituents (e.g., methyl, trifluoromethyl, and cyclopropyl) affect the overall reactivities of these cubane precursors; the yields range from 1 to 48%. However, the origin of these substituent effects on the reactivities and chemoselectivities is not understood. We now integrate single and multireference calculations and machine-learning-accelerated nonadiabatic molecular dynamics (ML-NAMD) to understand how substituents affect the ultrafast dynamics and mechanism of [2 + 2]-photocycloadditions. Steric clashes between substituent groups destabilize the 4π-electrocyclic ring-opening pathway and minimum energy conical intersections by 0.72-1.15 eV and reaction energies by 0.68-2.34 eV. Noncovalent dispersive interactions stabilize the [2 + 2]-photocycloaddition pathway; the conical intersection energies are lower by 0.31-0.85 eV, and the reaction energies are lower by 0.03-0.82 eV. The 2 ps ML-NAMD trajectories reveal that closed-shell repulsions block a 6π-conrotatory electrocyclic ring-opening pathway with increasing steric bulk. Thirty-eight percent of the methyl-substituted [3]-ladderdiene trajectories proceed through the 6π-conrotatory electrocyclic ring-opening, whereas the trifluoromethyl- and cyclopropyl-substituted [3]-ladderdienes prefer the [2 + 2]-photocycloaddition pathways. The predicted cubane yields (H: 0.4% < CH: 1% < CF: 14% < cPr: 15%) match the experimental trend; these substituents predistort the reactants to resemble the conical intersection geometries leading to cubanes.