Site-selective deuteration of C–H bonds increases the lifetime and efficacy of drug molecules. Although effective methods to form C(sp²)–D bonds are known, processes for making C(sp³)–D bonds often have low site selectivity, require expensive and unrecoverable D₂ gas, or use stoichiometric reagents. Here we report cost-efficient and site-selective reductive deuteration using a tandem electrochemical chemical palladium membrane reactor. This architecture mediates the chemical reaction of deuterium atoms (derived from reusable D₂O in an electrochemical compartment) with alkynes, aldehydes and imines. The formation of C(sp³)–D and C(sp²)–D bonds in the isolated chemical compartment is made possible by the deuterium-selective permeability of the membrane that partitions the electrochemical compartment from the chemical compartment. We have utilized the reactor for the deuteration step in the construction of a common drug, cinacalcet, to demonstrate that this method can be used to incorporate deuterium atoms in a pharmaceutical.

C–H键的位点选择性氘化可延长药物分子的寿命和功效。尽管已知形成C（sp ³）-D键的有效方法，但制备C（sp ³）-D键的过程通常具有较低的位点选择性，需要昂贵且不可回收的D ₂气体或使用化学计量试剂。在这里，我们报告了使用串联电化学化学钯膜反应器的低成本高效率和现场选择性还原氘。该体系结构介导氘原子（源自电化学隔室中可重复使用的D ₂ O）与炔烃，醛和亚胺的化学反应。C（sp ³）–D和C（sp ^2的形成）–通过将电化学隔室与化学隔室分隔开的膜的氘选择性渗透性，可以在隔离的化学隔室中实现D键。我们已经在构建普通药物西那卡塞特中将反应器用于氘化步骤，以证明该方法可用于将氘原子掺入药物中。