Thiol-Regulated Rhodium Nanocatalyst for Electrochemical Reductive Perdeuteration of Alkenes

Perdeuterated compounds are essential in various fields, including the development of deuterated pharmaceuticals and stable isotope-labeled internal standards (SIL-IS). The reductive perdeuteration of alkenes offers an economical and efficient method to obtain alkanes with multiple deuterium atoms. Despite progress in heterogeneous catalytic reductive deuteration of alkenes, the perdeuteration analogue remains elusive, mainly due to difficulties in generating controllable surface-active deuterium species, which are necessary for efficient and selective labeling. Herein, we present an electrochemical strategy for the reductive perdeuteration of alkenes using Rh nanoparticles and D₂O as the deuterium source. Thioalcohol serves as a crucial additive that modifies Rh nanoparticles, enhancing deuterium incorporation from 2 to 5 D atoms per molecule. Mechanistic studies reveal that thioalcohol functions as a sulfur anion coordinating with the nanoparticles during the reaction, suppressing reductive deuteration while significantly improving both the H-D exchange between Rh-D and alkenes, and the regeneration of Rh-D from Rh-H and D₂O. This method demonstrates high site-selectivity for both aryl and alkyl alkenes, and is broadly effective with alkenes of varying electronic character. The strategy can be readily applied to the synthesis of deuterated pharmaceuticals, typically yielding products with over 4.0 deuterium atoms per molecule, thus providing a rapid and cost-effective pathway for practical SIL-IS applications.