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

Abstract

Developing a step-economical approach for efficient synthesis of α,β-deuterio aryl ethylamines (α,β-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 α,β-DAEAs with up to 92% isolated yield and 99% α,β-deuterium ratios using D2O as a deuterium source. The process involves a fast α-C − H/C − D exchange and tandem electroreductive deuteration of C ≡ 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 ≡ 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 α,β-DAEAs, and successful preparation of α,β-deuterated Melatonin and Komavine highlight the potential.

­Field-induced concentration and low coordination-enhanced adsorption boost electroreductive deuteration of nitriles over copper nanotips

“…In addition, introducing low-coordination sites into electrode materials is an e cient way to greatly increase the intrinsic activity of active sites by optimizing the local electronic properties. 31,[41][42] As Fig. 2d shows, the d band center of LC-Cu upshifts toward the Fermi level compared with coordination-saturated Cu (CS-Cu), which is conducive to enhancing the adsorption of AN and the related imine intermediate, thus observing greater adsorption energy (E ads ) of AN and imine on LC-Cu than those on CS-Cu (Fig.…”

“…Because the base-assisted H/D exchange of AANs with D 2 O is irrelevant to electrocatalysis, 19,20,31 the rate and FE of the whole reaction are highly dependent on the C≡N reductive deuteration step. Cu-based materials are widely studied as electrode candidates in electrocatalytic CO 2 and acetylene hydrogenation reactions.…”

“…Commonly, the hydrogenation of nitriles to primary amines proceeds via a two-step procedure involving an imine intermediate (C≡N→CH=NH→CH 2 NH 2 ). 26,31,36,40 Enhancing the adsorption of substrates and H 2 O on the electrode surface is usually favorable to accelerate their activation and the formation of active hydrogen (H*) from water electrolysis, thus boosting the electrocatalytic hydrogenation reactions.…”

“…4d), 5.8 times faster than the reaction rate (0.019 mmol h -1 cm -2 ) of our previous work. 31 Additionally, a 67 h continuous electrolysis of 2a over LC-Cu NTs is realized by using a ow reactor at -1.3 V (Fig. 4e and Supplementary Note 3).…”

“…Recently, our group reported a low-coordination iron-promoted electroreductive deuteration of C≡N combined with K 2 CO 3 -assisted quick α-H/D exchange of AANs with D 2 O for the onepot synthesis of α,β-DAEPAs. 31 However, the Faradic e ciency (FE) of α,β-DAEPAs was only 20% owing to the competitive deuterium evolution reaction (DER). Additionally, gram-scale synthesis of α,β-DAEPAs was unsuccessful, which was due to the long reaction time causing enhanced hydrolysis side reaction of C≡N under basic conditions.…”