A Theoretical Stereoselectivity Model of Photochemical Denitrogenations of Diazoalkanes Towards Strained 1,3-Dihalogenated Bicyclobutanes

Photochemical reactions exemplify ‘green’ chemistry and are essential for synthesizing highly strained molecules with mild conditions with light. The light-promoted denitrogenation of bicyclic azoalkanes affords functionalized, stereoenriched bicyclo[1.1.0]butanes. We revisited these reactions with multireference calculations and non-adiabatic molecular dynamics (NAMD) simulations for a series of diazabicyclo[2.1.1]hexenes to predict the photophysics, reactivities, and stereoselectivities. We used complete active space self-consistent field (CASSCF) calculations with an (8,8) active space and ANO-S-VDZP basis set; the CASSCF energies were corrected with CASPT2(8,8)/ANO-S-VDZP. The excitation is consistently n→π* and ranges from 3.77–3.91 eV for the diazabicyclo[2.1.1]hexenes. Minimum energy path calculations showed stepwise C–N bond breaking and led to a minimum energy crossing point, which favors the stereochemical ‘double inversion’ bicyclobutane product. Wigner sampling of 1 provided Franck-Condon points for 692 NAMD trajectories. We identified competing complete stereoselective and stereochemical scrambling pathways. The stereoselective pathways feature concerted bicyclobutane inversion and N 2 extrusion. The stereochemical scrambling pathways involve N 2 extrusion followed by bicyclobutane planarization, leading to non-stereoselective outcomes. The predicted diastereomeric excess almost exactly match experiment (calc .d.e. =46% vs. exp .d.e. =47%). Our NAMD simulations with 672, 568, and 596 trajectories for 1-F , 1-Cl , and 1-Br predicted diastereomeric excess ( d.e. ) of 94–97% for the double inversion products. Halogenation significantly perturbs the potential energy surface (PES) towards the retention products because of powerful hyperconjugative interactions. The n C →σ * C–X , X = F, Cl, Br hyperconjugative interaction leads to a broadened shoulder region on the PES for double inversion.