Flow chemistry approach for partial deuteration of alkynes: synthesis of deuterated taxol side chain

Organocatalytic Imidazolium Ionic Liquids H/D Exchange Catalysts

“…Deuterium-labeled compounds have a broad range of applications in pharmaceutical, environmental, material, and chemical science, although they have not been found in nature. − Pharmaceutical companies and researchers in medicinal chemistry came up with the idea that exchanging the C–H bond with a C–D bond can create drugs with altered physiological profiles. Significant pharmacological effects on the metabolic profile, toxicity, and efficacy of pharmaceutical compounds have been discovered due to these deuterium substitutions. , Deuterated compounds are additionally required as internal standards for GC and LC-MS analysis of pesticides and environmental pollutant studies. , Moreover, they have a particular use for the development of efficient optical devices, such as optical polymer fibers and materials for organic light-emitting diodes .…”

“…Numerous methods for H/D exchange based on homogeneous or heterogeneous catalysis have already been described . The most common involve the metal catalysts with Ir, , Pd, Pt, Rh, Re, and Cr with or without carbon, including the oxidized form of metals like PtO 2 . ,, In addition, D 2 gas can be used to deuterate organic molecule analogues to hydrogenation of olefins, acetylenes, and cyanides. For these types of reactions, D 2 O has been studied extensively as a precursor for D 2 gas, because it is the least expensive and most readily available source of deuterium.…”

“…a Reaction conditions: r.t., 20 mol% BMMI•X, without stirring in a concentration of 2 mol•L −1 (0.5 mL of solvent). b Determined by1 H NMR spectroscopy (see Figures S6−S27…”

Current electrochemical approaches to selective deuteration

“…A case study of this simple methodology of D 2 O electrolysis to form D 2 can be seen a decade ago in the synthesis of a deuterated Taxol side chain through the in situ consumption of D 2 in a flow system, which had been generated from D 2 O (Scheme 2a). 16 Here, Lindlar conditions allowed partial deuteration of an alkyne as the preliminary step, with subsequent derivatisation achieved without loss of isotopic purity. However, this process does not eliminate the need for D 2 in terms of chemical reactivity; rather it is an operational refinement which removes any requirement for external handling of D 2 .…”

Deuterium labelling by electrochemical splitting of heavy water

“…Deuterium is installed by deuterohydrogenation of the unsaturated bonds or deuterodehalogenation of carbon-halogen bonds, offering excellent site selectivity, as shown in Figure 1B [23,24] . In general, deuterium gas (D 2 ) as the deuterium source is activated in the initial step for reductive addition across the unsaturated bonds [25][26][27] , where complete deuteration can be achieved with stoichiometric amounts of the deuterium transfer reagents. The major challenge lies in the use of inconvenient and expensive D 2 gas, where on-site generation from D 2 O or other sources is highly preferred.…”