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 -> pi* 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 diazabicyclo[2.1.1]hexene 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-2 extrusion. The stereochemical scrambling pathways involve N-2 extrusion followed by bicyclobutane planarization, leading to stereochemical scrambling. The predicted diastereomeric excess (d.e.) almost exactly matches the 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 a d.e. 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(C) -> sigma*(C-X= F, Cl, Br) hyperconjugative effect leads to a broader shoulder region on the PES for double inversion.