Sustainable and Scalable Electrochemical Decarboxylative Cyanation of an Amino Acid Using KCN as Both Cyanide Source and Base

Organic nitriles are an important class of compounds found in pharmaceuticals and agrochemicals, as well as useful intermediates in synthesis. Decarboxylative cyanation as a method to generate nitriles enables the use of widely available carboxylic acids as starting materials. Although this method has been well-explored synthetically, current methodologies often feature poor atom economy or require harsh reaction conditions. Herein, an electrochemical method for the decarboxylative cyanation of Cbz-protected alanine that uses inexpensive KCN as the cyanide source has been developed. The operationally simple procedure only requires electrolyzing a mixture of the amino acid with the cyanide in DMSO/EtOH as the solvent, without any additional chemicals such as base or supporting electrolyte, resulting in excellent green chemistry metrics. Using inexpensive graphite and stainless-steel as electrodes, excellent conversion and selectivity towards the desired nitrile product were obtained. Translation of the process to a flow electrolysis cell confirmed that the electrochemical protocol is scalable. Thus, gram amounts of material were obtained in a parallel plate reactor, with a space-time yield of 1026 g L-1 h-1. The space-time yield in the flow system was ca. 70 times larger than its batch counterpart, confirming the suitability of flow electrolysis cells for scale-up purposes.