Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

chemistry Medicinal and pharmaceutical chemistry Nano- and molecular-scale electronics Nano-biomaterials and bioscience Nanomagnetics Nanomaterials, thin films and nanointerfaces Nanomedicine Nanometrology and nanomechanics Nano-optics Nanopatterning, self-assembly and nanofabrication Nanostructures for energy and sensing applications Natural products chemistry Organo main group chemistry Other nanotechnology (unclassified) Other organic chemistry (unclassified) Photochemistry and photovoltaics Physical organic chemistry Supramolecular chemistry Photochemical denitrogenation reactions of bicyclic azoalkanes produce strained bicyclic compounds of interest to synthetic organic chemists. We report a computational study on the mechanism of diazabicyclo[2.2.1]heptenes to address long standing mechanistic questions. Indeed, the mechanism of these reactions have been disputed for over six decades. We employed non-adiabatic molecular dynamics (NAMD) simulations combined with state-of-the-art multireference quantum mechanical calculations to understand the photophysical properties and mechanisms of these diazabicyclo[2.2.1]heptenes. The energetically accessible lowest excitations are nNN(σCN) → π* and range from 3.94 – 3.97 eV. From the >292 trajectories, the reaction proceeds through a dynamically concerted but asynchronous denitrogenation reactions. One σCN bond breaks along the S1-surface; the other σCN breaks after hopping to the S0. We identified two clusters of S₁/S₀ surface hopping points from these trajectories. In the first cluster, the methylene bridge is fully inverted relative to the reactant geometry. In the second cluster, the inversion is only partial, with one of the carbon atoms in the methylene bridge inverted relative to the reactant. We identified each cluster's corresponding minimum energy conical intersection (MECI), indicating at least two possible S1/S0-MECIs. Our dynamics simulations illustrate that inversion begins in the excited state immediately after the first σCN bond breaks. This inversion is driven by the atomic momenta acquired after the bond breaks. These dynamical effects promote the formation of the inverted housane, thereby explaining the observed selectivities. A minority of trajectories undergo thermal conversion in the ground state, producing the minor retained housane product from inverted housane.

Photochemistry; non-adiabatic molecular dynamics; quantum mechanical calculations; stereoselectivity | Format: DOCX | Size: 1.1 MB | Download | When a peer-reviewed version of this preprint is available, this information will be updated in the information box above. If no peer-reviewed version is available, please cite this preprint using the following information: Adao Gomes, L.; Lopez, S. A. Beilstein Arch. 2025, 202531. doi:10.3762/bxiv.2025.31.v1 Citation data can be downloaded as file using the "Download" button or used for copy/paste from the text window below. Citation data in RIS format can be imported by all major citation management software, including EndNote, ProCite, RefWorks, and Zotero. © 2025 Adao Gomes and Lopez; licensee Beilstein-Institut. This is an open access work licensed under the terms of the Beilstein-Institut Open Access License Agreement (https://www.beilstein-archives.org/xiv/terms), which is identical to the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0). The reuse of material under this license requires that the author(s), source and license are credited. Third-party material in this work could be subject to other licenses (typically indicated in the credit line), and in this case, users are required to obtain permission from the license holder to reuse the material.