The Electrogenerated Cyanomethyl Anion: An Old Base Still Smart

The cathodic reduction of acetonitrile solutions containing a tetraalkylammonium salt leads to the formation of the cyanomethyl anion (-CH2CN, cyanomethanide). This electrolysis can be carried out under very simple experimental conditions (constant-current electrolyses), using various cathodic materials, controlling the amount of base by simply controlling the amount of charge. Despite the fact that the mechanism for this electrochemical reaction is still debated (and it depends on the cathodic material), the outcome of the electrolysis is the formation of a strong base, -CH2CN (pKa 31.3 for acetonitrile in DMSO). The chemical behavior of this electrogenerated base (EGB) strongly depends on its counterion, which in this case is a tetraalkylammonium cation, with a low charge density and thus not coordinated. The very weak interaction between R4N+ and -CH2CN renders the cyanomethyl anion a "naked" ion, and thus highly reactive. In particular, the cyanomethyl anion can react as a base and as a nucleophile. In the first case, it behaves as a strong base and, after deprotonation of a weak acidic substrate, transforms itself into a solvent molecule, acetonitrile, thus generating no byproducts. In the second case, the reactivity as a nucleophile of the cyanomethyl anion obviously depends on the reaction partner. When an electrophile is present in the reaction mixture, a cyanomethylation is obtained (e.g., with aromatic aldehydes, possessing no acidic hydrogen atoms, which undergo nucleophilic attack on the carbonyl carbon atom by -CH2CN); on the contrary, when no reagent is present other than acetonitrile and tetraalkylammonium salt, an attack on the parent molecule leads to the acetonitrile dimer, 3-aminocrotononitrile, which in turn can behave as a base and/or as a nucleophile. In this regard, some authors report that it is preferable to carry out the electrogeneration of the cyanomethyl anion under different experimental conditions, i.e., using an undivided cell and a sacrificial magnesium anode. In this way, a Grignard-type reagent is formed (Mg(CH2CN)2) which highly stabilizes the cyanomethyl anion, preventing its dimerization. It should be noted that in our laboratory the electrogenerated tetraalkylammonium cyanomethanide was extensively used in various reactions (both acid-base and nucleophile-electrophile, vide infra), and in almost no case, the amount of acetonitrile dimer formed exceeded 5%, confirming the validity of this electrochemical methodology to generate a very efficient base. Moreover, when in the reaction mixture both a weak acid and an electrophile are present, the prevalent reactivity of the cyanomethyl anion is as a base, leaving the possibility of a cyanomethylation reaction to those cases in which no acidic substrate is present. We have successfully used the electrogenerated cyanomethyl anion in many base-induced reactions, as the synthesis of the β-lactam ring (chiral or not), the insertion of carbon dioxide into amines and amino alcohols, the activation of elemental sulfur and insertion into carbonyl compounds, the selective alkylation of difunctional compounds, etc.