One-pot H/D exchange and low-coordinated iron electrocatalyzed deuteration of nitriles in D2O to α,β-deuterio aryl ethylamines

Developing a step-economical approach for efficient synthesis of alpha,beta-deuterio aryl ethylamines (alpha,beta-DAEAs) with high deuterium ratios using an easy-to-handle deuterated source under ambient conditions is highly desirable. Here we report a room-temperature one-pot two-step transformation of aryl acetonitriles to alpha,beta-DAEAs with up to 92% isolated yield and 99% alpha,beta-deuterium ratios using D2O as a deuterium source. The process involves a fast alpha-C - H/C - D exchange and tandem electroreductive deuteration of C equivalent to N over an in situ formed low-coordinated Fe nanoparticle cathode. The moderate adsorptions of nitriles/imine intermediates and the promoted formation of active hydrogen (H*) on unsaturated Fe sites facilitate the electroreduction process. In situ Raman confirms co-adsorption of aryl rings and the C equivalent to N group on the Fe surface. A proposed H*-addition pathway is confirmed by the detected hydrogen and carbon radicals. Wide substrate scope, parallel synthesis of multiple alpha,beta-DAEAs, and successful preparation of alpha,beta-deuterated Melatonin and Komavine highlight the potential.

Automated summary

This study reports a room-temperature one-pot two-step transformation of aryl acetonitriles to alpha,beta-deuterio aryl ethylamines (alpha,beta-DAEAs) using D2O as a deuterium source. The process includes fast alpha-C - H/C - D exchange and tandem electroreductive deuteration over an in situ formed low-coordinated Fe nanoparticle cathode. The method demonstrates wide substrate scope, parallel synthesis of multiple alpha,beta-DAEAs, and potential for the preparation of alpha,beta-deuterated Melatonin and Komavine.