Nucleophilic Influences and Origin of the S_N2 Allylic Effect

Abstract

The potential energy surfaces for the S 2 reactions of allyl and propyl chlorides with 21 anionic and neutral nucleophiles was studied by using ωB97X-D/6-311++G(3df,2pd) computations. The "allylic effect" on S 2 barriers was observed for all reactions, and compared with propyl substrates, the energy barriers differed by -0.2 to -4.5 kcal mol in the gas phase. Strong correlations of the S 2 net activation barriers with cation affinities, proton affinities, and electrostatic potentials at nuclei demonstrated the powerful influence of electrostatic interactions on these reactions. For the reactions of anionic (but not neutral) nucleophiles with allyl chloride, some of the incoming negative charge (0.2-18 %) migrated into the carbon chains, which would provide secondary stabilization of the S 2 transition states. Activation strain analysis provided additional insight into the allylic effect by showing that the energy of geometric distortion for the reactants to reach the S 2 transition state was smaller for each allylic reaction than for its propyl analogue. In many cases, the interaction energies between the substrate and nucleophile in this analysis were more favorable for propyl chloride reactions, but this compensation did not overcome the predominant strain energy effect.

Suppressing carboxylate nucleophilicity with inorganic salts enables selective electrocarboxylation without sacrificial anodes

“…was used in experiments with benzylic bromides due to their high susceptibility to S N 2 reactions. [71][72][73] For primary alkyl bromides and iodides, moderate to good yields (34-66%) were obtained; the primary alkyl chloride tested had a low yield of 2a. GC-FID analysis found a large amount of unreacted substrate ($70% conversion), which is in agreement with the more reductive potentials needed to cleave alkyl-chloride bonds.…”

Understanding chemical reactivity using the activation strain model

“…The ASM can be applied to all unimolecular and bimolecular reactions in both homogeneous and heterogeneous systems and has been used routinely by theoretical and experimental chemists [28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] . We provide specific examples of the ASM being applied to understand inorganic, organic, and supramolecular chemistries, namely, the transition metal-mediated oxidative addition of C-X bonds in cross-coupling reactions, the reactivity of cycloalkynes in 1,3-dipolar cycloadditions, the reactivity of dihalogen-catalyzed Michael addition reactions, and the bonding mechanism in hydrogen-bonded systems.…”

SN2 versus E2 Competition of F–and PH2–Revisited

“…The activation strain model (ASM) in combination with Kohn–Sham molecular orbital (KS-MO) theory and the matching energy decomposition analysis (EDA) , were employed to provide quantitative insight into the factor controlling the S N 2/E2 preference of the aforementioned reactions. This methodological approach facilitates the analysis of the potential energy surface and, more importantly, the activation barrier, by decomposing the total energy of the system into physically meaningful and easily interpretable terms, proving to be valuable for understanding the reactivity of, amongst others, nucleophilic substitution and elimination reactions …”