Ruthenium-Catalyzed Deuteration of Alcohols with Deuterium Oxide

Abstract

The catalytic properties of a series of ruthenium complexes for H/D exchange between D 2 O and alcohols were studied. The catalytic activity of the ruthenium complexes and the regioselectivity of the H/D exchange reactions were found to be dependent on the auxiliary ligands. While ruthenium η 6 -cymene complexes such as [(η 6 -c ym e ne) Ru C l (NH 2 CH 2 CH 2 NTs)]Cl, (η 6 -cymene)RuCl 2 / NH 2 CH 2 CH 2 OH, and (η 6 -cymene)Ru{(S,S)-NHCHPhCHPhNTs} catalyzed regioselective deuteration of alcohols with D 2 O at the β-carbon positions only, octahedral ruthenium complexes such as RuCl 2 (2-NH 2 CH 2 Py)(PPh 3 ) 2 (2-NH 2 CH 2 Py = 2-aminomethylpyridine) and RuCl 2 (NH 2 CH 2 CH 2 NH 2 )(PPh 3 ) 2 catalyzed regioselective H/D exchange reactions of D 2 O with alcohols at both the α-and β-carbon positions of alcohols. The H/D exchange reactions proceed through reversible dehydrogenation of alcohols and hydrogenation of carbonyl compounds involving hydride species and H/D exchange among D 2 O and carbonyl and hydride species. The different regioselectivities of the H/D exchange reactions can be related to the relative ease of H/D exchange of ruthenium hydride intermediates with D 2 O.

Highly Selective Directed Iridium‐Catalyzed Hydrogen Isotope Exchange Reactions of Aliphatic Amides

“…Recent examples based on homogeneous Ru catalysis include the Beller group's a,b-deuteration of biologically relevant amine, [16] as elective and stereoretentive deuteration of achiral amines reported by Szymczak and co-workers, [17] and ar egioselective labelling of aliphatic alcohols from Linand and co-workers. [18] Additionally,P ieters and co-workers developed ap rocess for the selective and enantiospecific C(sp 3 )ÀHactivation/ deuteration of a-amino groups in amino acids using heterogeneous Ru nanoparticles, [19] and Chirik and co-workers reported ac obalt-catalyzed stereoretentive HIE of arylarenes. [20] However,a ll of these methods either require harsh reaction conditions,a ir-sensitive,non-commercial catalysts,orprocedures that are not compatible with the requirements of tritium chemistry.…”

σ-H–H, σ-C–H, and σ-Si–H Bond Activation Catalyzed by Metal Nanoparticles

“…223 The reaction proceeded through a migration/cyclization/dealkylation pathway, in which the fate of the N-methyl group is not known. 224 The reactions were carried out in DMF at 120…”

“…al. that catalyzes the regioselective deuteration of alcohols with D2O [120][121]. Additionally, rhodium, 122 palladium 123 and platinum124 complexes have also been described in literature to catalyze H/D exchange in homogeneous phase.…”

Highlights of aliphatic C(sp3)‐H hydrogen isotope exchange reactions

“…In addition to amines, ruthenium catalysts have been explored by Bai et al for the regioselective labeling of aliphatic alcohols. They reported the β‐ and α,β‐labeling of alcohols with D 2 O applying two complementary pre‐catalysts 51 and 53 (Scheme ) . With the help of calculations, it was postulated that pre‐catalyst 53 produced hydride intermediates that exchange with D 2 O more readily than with 51 .…”