Controlled Synthesis of CD2H-ketones

Selective deuteration is an important chemical challenge. In particular, the synthesis of compounds containing partially deuterated groups such as CD2H is very difficult and lacks general methods. These compounds could be very important for fine control of metabolic processes in drug discovery, or in the development of multifunctional probes containing both H and D for analysis by complementary spectroscopic techniques. Here, a convenient route to CD2H-methyl ketones is reported through coupling of esters with bis[(pinacolato)boryl]methane. The approach demonstrates efficient capture of the α,α-bis(enolate) intermediate with inexpensive D2O as the deuterium source. This allowed high and controlled levels of deuterium-incorporation to give CD2H ketones that is scalable and retained throughout further transformations of the molecule. No exchange of deuterium was observed under the reaction conditions or on storage.