Exposed and Isolated Ru in RuP Nanoparticles Enhance C(sp ³ )–H Deuteration Performance of Piperazine

Deuterated nitrogen-containing saturated heterocycles are indispensable motifs in pharmaceuticals, yet activation of inert C(sp 3 )–H bonds in heterogeneous catalysis remains challenging because of the intrinsic chemical inertness and restricted geometric accessibility. This study demonstrates that efficient C(sp 3 )–H activation arises from a phosphorus-modulated Ru-site environment, rather than from simply favoring planar metal configurations or electronic perturbation. Phase-selective synthesis of Ru–P nanoparticles on N-doped carbon identifies RuP as a distinct phase that enables near-quantitative (99%) deuteration of piperazine C(sp 3 )–H bonds under mild conditions using D 2 as the sole deuterium source, even at a low H/D molar ratio of 1:5. KIE measurements uncover distinct kinetic signatures across the Ru–P phases, suggesting that the relative kinetic relevance of D 2 activation and C(sp 3 )–H cleavage depends strongly on the Ru-site environment. Theoretical calculations indicate that RuP nanoparticles favor exposed and isolated Ru sites, which give rise to the lowest C(sp 3 )–H activation barrier (0.47 eV), while accompanying charge density analyses further reveal an optimal-rather than maximal-degree of charge transfer that promotes N–Ru anchoring and C–H bond polarization. Collectively, these findings provide a nanoscale structure-guided framework for heterogeneous C(sp 3 )–H deuteration, enabling an efficient and practical route to deuterated saturated heterocycles through hydrogen isotope exchange.