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

Photochemical reactions exemplify "green" chemistry and are an essential tool for synthesizing highly strained molecules under mild conditions with light. The light-promoted denitrogenation of bicyclic azoalkanes affords functionalized, stereoenriched bicyclo[1.1.0]butanes. These reactions were revisited with multireference calculations and non-adiabatic molecular dynamics (NAMD) simulations to provide a detailed analysis of the photophysics, reactivities, and unexplained stereoselectivity of a series of diazabicyclo[2.1.1]hexenes. 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 nature of the electronic excitation is n → π* and ranges from 3.77 to 3.91 eV for the diazabicyclo[2.1.1]hexenes reported here. Minimum energy path calculations showed stepwise C-N bond breaking and led directly to a minimum energy crossing point, corresponding to a stereochemical "double inversion" product. Wigner sampling of provided initial conditions for 692 NAMD trajectories. We identified competing complete stereoselective and stereochemical scrambling pathways. The stereoselective pathways feature concerted bicyclobutane inversion and N extrusion. The stereochemical scrambling pathways involve N extrusion followed by bicyclobutane planarization, leading to stereochemical scrambling. The predicted diastereomeric excess () almost exactly matches the experiment (calc = 46% vs exp = 47%). Our NAMD simulations with 672, 568, and 596 trajectories for , , and predicted a of 94-97% for the double inversion products. Halogenation significantly perturbs the potential energy surface (PES) toward the retention products due to hyperconjugative interactions. The n → σ* hyperconjugative effect leads to a broader shoulder region on the PES for double inversion.