“Anion pool” synthesis is a technique that incorporates both electrochemistry and organic synthesis for the derivatization of pharmaceutically important molecules. This is a base and metal free procedure carried out in common organic solvents. The anion pool procedure generates reactive nucleophiles in situ via reduction of heteroaromatic substrates. The adoption of such a methodology prevents generation of waste from bases. Hydrogen is the main by-product of anion pool synthesis, which, if produced at a large enough scale could be used as a renewable fuel. These attributes comply with the principles of green chemistry, allowing synthetic chemists to carry out reactions in an atom-economic and environmentally friendly manner. We established the “anion pool” method with the derivatization of benzimidazoles. We were able to achieve selective substitution at the 1H position in high yields with a variety of benzimidazoles and electrophiles bearing a variety of functional groups. We have continued to apply “anion pool” method to a wider variety of substrates. The second study was aimed at selective acylation of indazoles at the N1 position. Indazoles bear two nitrogen atoms on the pyrazole ring that tend to undergo non-selective reactions with electrophiles. By adopting the anion pool approach, we were able to achieve great selectivity to N1-position while also improving the yields, decreasing chemical additives, and utilizing safe solvents. We have also shown that this procedure can be carried out in an inexpensive set-up connected to a 9 V battery, indicating that this reaction could easily be adapted to being driven by the power of a basic solar cell. This procedure is currently applied toward amidation reactions. Amide formation avoiding poor atom economy reagents has been identified as a priority for the ACS GCI Pharmaceutical roundtable. This procedure produces two pharmaceutically important compounds in a single cell with very good atom economy.

“Anion pool”-driven organic transformations

2019 Spring National Meeting

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