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

Abstract A method for the selective deuteration of polyfunctional organic molecules using catalytic amounts of [RuCl2(PPh3)3] and D2O as a deuterium source is presented. Through variation of additives like CuI, KOH, and various amounts of zinc powder, orthogonal chemoselectivities in the deuteration process are observed. Mechanistic investigation indicates the presence of different, defined Ru‐complexes under the given specific conditions.

reported in ppm down field using tetramethylsilane or the signal of the deuterated solvent as an internal standard. Coupling constants J are given in Hz. The following abbreviations are used in the analysis of NMR spectra: s=singlet, d=doublet, t=triplet, q=quartet, hept=heptet, sept=septet. Combination of these abbreviations is applied whenever more than one coupling is observed. IR spectra were measured on a FT-IR spectrometer in an ATR mode. The intensity of the observed peaks is given in parenthesis: s=strong, m=medium,w=weak. Mass spectra were measured using electrospray ionization on a Bruker micrOTOF-Q. High performance liquid chromatography (HPLC) was performed using a Knauer K-501 pump, Knauer RI-detector K 2400 and a Macherey-Nagel VP250/21 Nucleodur 100-5 column.
E/Z-ratios and yields were determined by crude-NMR with internal standard. Degree of deuteration was determined by comparing the 1 H NMR integral of non-reactive protons with the deuterated proton signals. In order to identify the signals the pure compounds were measured and displayed unless the compounds were not stable which was the case for some of the (Z)-isomers of the obtained alkenes. In that case signals were compared with literature.
Signals of non-reactive protons are marked in blue whereas reactive positions are marked in red. Deuteration is given in percent next to the corresponding position. If the deuteration degree is lower than 10% the numbers were not added to the position in the molecule as we consider the measurement error in the NMR to be too significant for that value.
For volatile and very polar substrates the solvent 1,4-dioxane was replaced by THF-d 8 in order to measure NMRs without prior work-up.
Physical State: yellow solid.

3.1
General procedure for the deuteration following the CuI procedure (condition A)

General remarks on overview tables
All experiments performed on each substrate are condensed into a    3 3 and RuHI(PPh 3 ) 3 2 were in accordance with those given in the literature. [11][12][13][14] Characteristic hydride-signals, as well as 31 P-signals for the given complexes in THF-d 8 or CD 2 Cl 2 were recorded as reference and are listed in table 1.

Mechanistic studies
In order to investigate the additive-dependent chemoselectivity we focused on isolating the hypothetically catalytic active species and subsequent evaluation of their activity in deuteration reactions.
The following scheme shows the additive-dependent pathways that lead to each species.

Scheme 1:
Overview of hypothetical catalytic species.

KOH-protocol
We started our studies by subjecting complex 1 to exemplary basic conditions and observed the formation of the dimeric (µ-OH) complex 48 (Figure 1).

S199
When the equivalents of water were raised to a level similar to the reaction conditions ( Figure   2) we observed an increase in the monomeric ruthenium hydroxy species 4. Wilkinson reported the formation of both complexes depending on reaction time and equivalents of water and base. [11] In our case we observed that the ratio of monomeric to dimeric species is highly dependent on the amount of water used.

S201
indication that a mixture of both the monomeric complex 4 as well as the dimeric complex 4 are present in our catalysis. Ultimately we assume the monomeric species to be the major component and thus the catalytic active species.

KOH/Zn-protocol
Under reductive basic conditions the formation of the tetrahydrido ruthenium complex 3 and its closely related dimeric complex 49 is observed.

S202
We assigned the signals of the hydride complexes by previously reported literature. [12,14] By recording the 1 H NMR at low temperature (-50 °C) we obtained a better resolution for the  We increased the equivalents of the reagents to match the conditions in our catalytic protocol ( Figure 5) but saw no significant change in complex ratio. We assume that the tetrahydrido ruthenium complex 3 is the active species in our catalysis as there are many reported applications in which complex 3 acts as a powerful reduction catalyst. [15]

Deuteration with RuH 2 (H 2 )(PPh 3 ) 3
Furthermore, we synthesized the complex 3 following a slightly modified procedure from Grushin [12] and employed the complex in an exemplary catalysis ( Figure 6). To our delight, we saw the same degree of deuteration compared to our result when using RuCl 2 (PPh 3 ) 3 as precatalyst. This is a strong indication that under these conditions the reactive species of our deuteration is indeed the tetrahydrido species 3.

CuI-protocol
For the CuI protocol, we were able to observe the iodide complex 2 that was smoothly formed under the reaction conditions ( Figure 7).

Deuteration with RuHI(PPh 3 ) 3 2
When the iodide catalyst 2 was used in an exemplary deuteration reaction, we were able to surpass the degree of deuteration that we observed when we used the precatalyst 1 ( Figure 8).
Additionally, we observed the same selectivity and thus conclude that the iodide ruthenium complex 2 is the catalytic active species under conditions A.

Reduction with RuHI(PPh 3 ) 3 2
Regarding the chemoselectivity we studied the behaviour of complex 2 in the reduction of 4-(phenylethinyl)acetophenone 38. To our delight we were able to demonstrate the high S207 selectivity of 2 towards the reduction of alkynes while no reduction of the carbonyl was observed. This further strengthens our hypothesis that 2 is the catalytic active species.