Electrolytic deuteration of unsaturated bonds without using D 2

Site-selective deuteration of C–H bonds increases the lifetime and efficacy of drug molecules. Although effective methods to form C( sp 2 )–D bonds are known, processes for making C( sp 3 )–D bonds often have low site selectivity, require expensive and unrecoverable D 2 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 D 2 O in an electrochemical compartment) with alkynes, aldehydes and imines. The formation of C( sp 3 )–D and C( sp 2 )–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.