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% < CH3: 1% < CF3: 14% <
cPr: 15%) match the experimental trend; these substituents predistort
the reactants to resemble the conical intersection geometries leading
to cubanes.