Comparison of the\nEfficiency of B–O and B–C\nBond Formation Pathways in Borane-Catalyzed Carbene Transfer Reactions\nUsing α‑Diazocarbonyl Precursors: A Combined Density\nFunctional Theory and Machine Learning Study

Lewis acidic boranes, especially tris(pentafluorophenyl)borane\n[B(C<sub>6</sub>F<sub>5</sub>)<sub>3</sub>], have emerged as metal-free\ncatalysts for carbene transfer reactions of α-diazocarbonyl\ncompounds in a variety of functionalization reactions. The established\nmechanism for how borane facilitates carbene generation for these\ncompounds in the scientific community is based on the formation of\na B–O (CO) intermediate (<i>path O</i>).\nHerein, we report an extensive DFT study that challenges the notion\nof a ubiquitous <i>path O</i>, revealing that B–C(NN)\nbond formation (<i>path C</i>) for certain diazocarbonyl\nsubstrates proves to be the preferred pathway. This study elucidates,\nthrough the introduction of 22 various substituents on each side of\nthe α-diazocarbonyl backbone, how the electron-donating and\n-withdrawing properties of substituents influence the competition\nbetween these B–O and B–C pathways. To elucidate the\nimpact of the electronic features of diazo substrates on the competition\nbetween the O and C pathways in the studied dataset, we employed a\nmachine learning approach based on the Random Forest model. This analysis\nrevealed that substrates with higher electron density on the diazo-attached\ncarbon, lower electron density on the carbonyl carbon, and more stable\nHOMO orbitals tend to proceed via <i>path</i> <i>C</i>. Furthermore, this study not only demonstrates that borane efficiency\nin facilitating N<sub>2</sub> release is greatly affected by the nature\nof substituents on both sides of the α-diazocarbonyl functionality\nbut also shows that for some substrates, borane is incapable of catalyzing\nthe release of molecular nitrogen.