“Thermal” S_RN1 Reactions:  How Do They Work? Novel Evidence that the Driving Force Controls the Transition between Stepwise and Concerted Mechanisms in Dissociative Electron Transfers

Abstract

In SRN1 reactions, unlike in conventional nucleophilic substitutions, the nucleophile does not react directly with the electrophile but with a radical resulting from its reductive cleavage. Many SRN1 substitutions require an external stimulation involving the injection of a catalytic amount of electrons. In “thermal” SRN1 reactions, there is no other source of initiating electrons than the nucleophile which is usually a poor electron donor. Such reactions are unlikely to be initiated by a simple outersphere electron transfer from the nucleophile followed by the cleavage of the substrate anion radical. Rather, initiation follows a mechanism in which electron transfer and bond cleavage are concerted. These conclusions are based on a full analysis of a model system involving 4-nitrocumyl chloride as the substrate and the 2-nitropropanate ion as the nucleophile where all the pertinent thermodynamic and kinetic parameters were determined by direct or indirect electrochemical methods. They extend to other examples of thermal SRN1 reactions reported earlier. These results provide new and unambiguous evidence that a decrease in driving force is able to change the mechanism of homogeneous reductive cleavage reactions from stepwise to concerted. The observation of this mechanism change was made possible by the kinetic amplification offered by the chain character of the SRN1 process, which allows the investigation of very slow electron transfers resulting from very low driving forces, that would have otherwise escaped characterization.

Ionic Liquids as Solvents for SN2 Processes. Demonstration of the Complex Interplay of Interactions Resulting in the Observed Solvent Effects

“…This is exemplified in Figure 4, noting the large uncertainties as a result of compounding errors and the logarithmic scale. It was considered that alternative mechanisms may also be contributing, likely a radical mechanism based on literature precedent [35] as well as EPR studies ( Figure S34). It was considered that alternative mechanisms may also be contributing, likely a radical mechanism based on literature precedent [35] as well as EPR studies ( Figure S34).…”

“…[34] It should be noted that during this analysis, the nitro case 2 g was a particular outlier, being faster than might be expected at low proportions of the salt 4 in the reaction mixture. It was considered that alternative mechanisms may also be contributing, likely a radical mechanism based on literature precedent [35] as well as EPR studies ( Figure S34). [36] As such, it was not considered during subsequent analysis.…”

An expedient route to heterocycles through α-arylation of ketones and arylamides by microwave induced thermal SRN1 reactions

“…In this reaction, the source of initiating electrons could be the nucleophile itself, which transfers an electron to the PhI to generate Ph radical and I À by a dissociative ET. 17,18 In this case, the increase in temperature or the direct microwave energy applied to the substrate could provide the necessary energy to the initial ET from the nucleophile to the ArX. Alternatively, the slightly excess of tBuO À anion could also act as the electron donor in an entrainment reaction.…”

About the Inhibition of Grignard Reagent Formation by p‐Dinitrobenzene: Comparing the Mechanism of Grignard Reagent Formation and the SRN1 Mechanism

“…[49,50] 8) The possible coexistence of radical and non-radical pathways starting from a unique electrophilic substrate-nucleophilic reagent couple. [2,5,43,51] This coexistence was also reported for the oxidative addition of alkyl or aryl halides to Ir I , Pt 0 and Pd 0 complexes. [21,52,53] For both types of reactions, structural effects in the organic halide may lead to mechanisms no longer displaying the characteristics of radical intermediate involvement.…”

“…[39] 5) In the electrochemical version of the reaction (the substitution is triggered by a cathode), catalytic quantities of electrons are sufficient to initiate the reaction. [40][41][42][43] 6) In the electrochemical version, some reactions demand the presence of mediators to provide good yields of the desired product. [44][45][46][47] This concept of electrochemical mediator was extended to thermal reactions by Rossi and coworkers.…”