Computational study of polyhomologation: understanding reactivity with B, Al, and Ga

Abstract

In the polyhomologation (PH) reaction, boron reagents (BR₃, where R = alkyl) react with Corey's ylide (H₂C⁻S⁺(O)(CH₃)₂) to achieve methylene insertions into carbon–boron bonds. The reaction mechanism begins with the formation of an ate complex, driven by the interaction between the electron pair of the methylide and the vacant p orbital of the initiator (BR₃). Subsequently, a 1,2-migration occurs, yielding a new carbon–carbon bond with an energy barrier of 21.1 kcal mol⁻¹, determined by density functional theory (DFT) calculations. Given the crucial role of the empty p orbital in the initiation step, theoretically, aluminum and gallium may serve as promising candidates as initiators in PH with Corey's ylide. However, there are no laboratory reports of PH reactions utilizing these elements. To address this gap, we performed mechanistic calculations using DFT. Our results demonstrate that AlR₃ and GaR₃ present higher energy barriers, with 36.9 and 38.3 kcal mol⁻¹, respectively, compared to BR₃, thereby limiting their practical applicability. Additionally, activation strain model (ASM) calculations indicate that both strain energy and interaction energy are significant factors in the reaction. Strain energy is primarily influenced by the initiator fragment, while interaction energy is predominantly governed by orbital interactions, electrostatic contribution, and exchange repulsion, as evidenced by energy decomposition analysis.