Comparison of the Efficiency of B–O and B–C Bond Formation Pathways in Borane-Catalyzed Carbene Transfer Reactions Using α-Diazocarbonyl Precursors: A Combined Density Functional Theory and Machine Learning Study

Lewis acidic boranes, especially tris(pentafluorophenyl)borane [B(C₆F₅)₃], have emerged as metal-free catalysts for carbene transfer reactions of α-diazocarbonyl compounds in a variety of functionalization reactions. The established mechanism for how borane facilitates carbene generation for these compounds in the scientific community is based on the formation of a B-O (C=O) intermediate (<i>path O</i>). Herein, we report an extensive DFT study that challenges the notion of a ubiquitous <i>path O</i>, revealing that B-C(=N=N) bond formation (<i>path C</i>) for certain diazocarbonyl substrates proves to be the preferred pathway. This study elucidates, through the introduction of 22 various substituents on each side of the α-diazocarbonyl backbone, how the electron-donating and -withdrawing properties of substituents influence the competition between these B-O and B-C pathways. To elucidate the impact of the electronic features of diazo substrates on the competition between the O and C pathways in the studied dataset, we employed a machine learning approach based on the Random Forest model. This analysis revealed that substrates with higher electron density on the diazo-attached carbon, lower electron density on the carbonyl carbon, and more stable HOMO orbitals tend to proceed via <i>path</i> <i>C</i>. Furthermore, this study not only demonstrates that borane efficiency in facilitating N₂ release is greatly affected by the nature of substituents on both sides of the α-diazocarbonyl functionality but also shows that for some substrates, borane is incapable of catalyzing the release of molecular nitrogen.