Precise Deuteration at the Tailored Surface of Nickel Phosphide Nanocatalysts

Objective

The efficient production of deuterated organic molecules is critical for many technological applications: pharmaceuticals, metabolic tracers, organic LEDs... The global market is €190-430 million in 2024 and expected to reach €1 billion by 2033. The main challenges are the cost and efficiency of production, hence the ability to introduce the deuterium at a late stage with high yield and regioselectivity. Today’s best strategy relies on transition metal catalysts. Supported nanoparticles of ruthenium and iridium have recently emerged as the benchmark for technological development because of their strong tolerance to functional groups, high yields of selective deuteration and the possibility to use them in a flow process with recirculation of D2O as a cheap deuterium source. However, they come with two major limitations: the cost of the raw materials (Ru: 20 000 €/kg, Ir: 120 000 €/kg), and their limited regioselectivity. In ERC NanoFLP, we developed low-temperature hydrogenation nanocatalysts using nickel (15 €/kg). Their surface reactivity was boosted by the addition of phosphines (PR3, with R alkyl or aryl) as Lewis bases, forming a reactive pocket where both the steric and electronic parameters were tailored. The hydrogenation of alkynes was achieved at low temperatures. Excellent hydrogenation catalysts are generally effective for hydrogen/deuterium exchange because they achieve C–H activation. In PRELUDE, we optimize the NanoFLP catalyst as a supported nanocatalyst modified with organic ligands to achieve the precise deuteration of benchmark compounds. This catalyst may outperform Ru/Ir nanoparticles while being fully compatible with the flow recirculation process. Here, the deuteration site will be dictated by the fine variation of steric and electronic parameters, adjusted on demand upon selection of commercial ligands.