Atomically Dispersed Rhodium on TiO2 for Tandem Hydrogenation–H/D Exchange of Cinnamic Acid

An atomically dispersed rhodium on TiO2 catalyst enables a tandem process, combining hydrogenative reduction with α,β-hydrogen–deuterium exchange of cinnamic acid, in which D2O serves as the deuterium source. In contrast with previous reductive deuteration methods that yield only partially labeled 3-phenylpropanoic acids (Dα-inc.: ≤50%, Dβ-inc.: ≤50%), this heterogeneous system delivers near-quantitative deuterium incorporation (Dα-inc.: 94%, Dβ-inc.: 99%) under mild conditions, outperforming Rh nanoparticles and homogeneous Rh catalysts. Mechanistic studies indicate that α-C–H activation is the slowest transformation step within the overall process, owing to the exceptional C–H bond activation capability of the atomically dispersed catalyst; efficient α-C–H hydrogen–deuterium exchange is readily achieved. In addition, although catalyst recyclability is constrained by Rh aggregation, no Rh leaching is detected. This work provides a concise, operationally simple route to alkyl fully deuterated 3-phenylpropanoic acids (d4-PA) and showcases the application of an atomically dispersed catalyst in tackling challenging deuterium-labeling transformations.