This study examines how substitution degrees in SN2 reactions using CN– and alkyl halides (RI/RF) are determined through detailed electronic structure calculations. The results reveal that for ambident nucleophile CN–, sp3 hybridized C dominates SN2 pathways at low substitution degrees (α = 1–2), while sp hybridized N demonstrates superior reactivity at high substitution degrees (α = 3). However, E2 pathways consistently favor C as the reactive center, regardless of the substitution degree. For CN– + RI systems, SN2 barriers increase significantly with α-methyl substitution, with activation strain model (ASM) analysis identifying strain energy as the primary influence of barrier heights, showing strong correlation with geometric distortion parameters (%D‡, R2 = 0.81–0.99). Conversely, E2 pathways maintain relatively stable geometric distortion through the concerted cleavage of Cα–I and Hβ–Cβ bonds, resulting in gradually decreasing barriers. Notably, the superior leaving group I leads to lower SN2 transition state barriers than E2 at α = 1–2, attributable to the weak C–I bond and minimal steric hindrance. At α = 3, increased steric bulk stabilizes the E2 pathway, providing an explanation for the experimentally observed significant rate enhancement at α = 3. In contrast, for CN– + RF systems, the barrier difference between E2 and SN2 pathways becomes smaller with increasing substitution degrees. This suggests distinct substitution degree-dependent trends in rate constants between systems containing leaving groups F and I.
Liu et al. (Thu,) studied this question.
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