Mild, Selective Ru‐Catalyzed Deuteration Using D₂O as a Deuterium Source

Abstract

Am ethodf or the selective deuteration of polyfunctional organic molecules using catalytic amounts of [RuCl 2 (PPh 3 ) 3 ]a nd D 2 Oa sadeuterium source is presented. Throughv ariation of additives like CuI, KOH, and various amounts of zinc powder,o rthogonal chemoselectivities in the deuteration process are observed.M echanistic investigation indicates the presence of different, defined Rucomplexes under the given specific conditions. Scheme1.Activation of the precatalyst [RuCl 2 (PPh 3 ) 3 ]( 1)t hrough additives. Scheme2.Additive-directed chemoselective reductive deuteration of carbonylc ompounds and alkynes.[ a] 16 hreactiont ime.

Recent Developments for the Deuterium and Tritium Labeling of Organic Molecules

“…Reported directing groups for transition-metal-catalyzed aromatic HIE. 56,62,63,[67][68][69][70][71][72][73][75][76][77][79][80][81]83,[85][86][87][88][89]91,[96][97][98][99][100][101][102][103][104][105][106]109,110,112,113,118 Finally, it should be noted that, depending on the substrate, more expensive calculations which include solvation models as well as thermal corrections to the electronic energies can be needed to accurately reproduce experimental results. Building on these computational results, Kerr, Reid, and co-workers were able to successfully predict catalysts with higher or inverse selectivity by changing the steric properties of the NHC ligand.…”

“…While homogeneous methods usually aim for selective HIE transformations that leave reducible functional groups untouched, a recent study shows that by choosing appropriate cocatalysts, ruthenium-catalyzed ortho-directed HIE with or without concomitant reductive labeling of alkynes or ketones can be chosen deliberately. 110 Thus, in the presence of catalytic deuterated potassium hydroxide and a slight excess of deuterium oxide, the catalyst [RuCl 2 (PPh 3 ) 3 ] forms a hydroxo species (4) which selectively labels the ortho positions of a number of nitrogen-containing directing groups while leaving internal alkynes untouched (Scheme 14a). On the other hand, adding catalytic copper iodide along with an excess of zinc to the precatalyst furnishes a ruthenium hydride species (5).…”

Synthesis of Deuterated (E)-Alkene through Xanthate-Mediated Hydrogen–Deuterium Exchange Reactions

“…Functionalized olefins are found in some natural products and synthetic drugs . At present, the synthesis of deuterated olefins is mainly achieved through the semideuteration of alkynes and H/D exchange reactions of alkenes catalyzed by transition metals . Xanthate is currently the most widely used ore beneficiation agent of heavy metal sulfide ore, which also has important applications in organic synthesis .…”

C–H deuteration of organic compounds and potential drug candidates

“…This was a fine example of Ru-catalysed deuteration of functional organic molecules using D 2 O as a deuterium source under mild reaction conditions. 41 The role of additives was to convert the precatalyst [RuCl 2 (PPh 3 ) 3 ] into different Ru complexes which in turn act as active catalysts and perform chemoselective deuteration (Scheme 28). When CuI was used along with Zn as additives, alkyne reduction took place while carbonyl reduction was performed when KOD was used with Zn.…”