Electrochemical C-H phosphorylation of arenes in continuous flow suitable for late-stage functionalization

The development of efficient and sustainable methods for carbon-phosphorus bond formation is of great importance due to the wide application of organophosphorus compounds in chemistry, material sciences and biology. Previous C-H phosphorylation reactions under nonelectrochemical or electrochemical conditions require directing groups, transition metal catalysts, or chemical oxidants and suffer from limited scope. Herein we disclose a catalyst- and external oxidant-free, electrochemical C-H phosphorylation reaction of arenes in continuous flow for the synthesis of aryl phosphorus compounds. The C-P bond is formed through the reaction of arenes with anodically generated P-radical cations, a class of reactive intermediates remained unexplored for synthesis despite intensive studies of P-radicals. The high reactivity of the P-radical cations coupled with the mild conditions of the electrosynthesis ensures not only efficient reactions of arenes of diverse electronic properties but also selective late-stage functionalization of complex natural products and bioactive compounds. The synthetic utility of the electrochemical method is further demonstrated by the continuous production of 55.0 grams of one of the phosphonate products. Synthesis of aryl phosphorus compounds with electron-withdrawing substituents on the arene is difficult to do simply. Here the authors show a method to form aryl carbon-phosphorus bonds through electrochemistry, without requiring any catalyst or external oxidant.

Automated summary

The study presents a catalyst- and external oxidant-free continuous flow electrochemical C-H phosphorylation reaction for synthesizing aryl phosphorus compounds. The reaction involves arenes reacting with anodically generated P-radical cations, allowing for efficient reactions of arenes with diverse electronic properties and selective late-stage functionalization of complex natural products and bioactive compounds. The method demonstrates the synthetic utility by producing 55.0 grams of phosphonate product in a continuous manner.