Selective Catalytic Deuterium Labeling of Alcohols during a Transfer Hydrogenation Process of Ketones Using D2O as the Only Deuterium Source. Theoretical and Experimental Demonstration of a Ru–H/D+ Exchange as the Key Step

• Published in: ACS catalysis Vol. 4; no. 4; pp. 1040 - 1053
• Main Authors: Carrión, M. Carmen, Ruiz-Castañeda, Margarita, Espino, Gustavo, Aliende, Cristina, Santos, Lucía, Rodríguez, Ana M, Manzano, Blanca R, Jalón, Félix A, Lledós, Agustí
• Format: Journal Article
• Language: English
• Published: American Chemical Society 04.04.2014
• Subjects: catalysis in water; ruthenium; density functional calculations; deuterium labeling; hydrogen transfer; umpolung
• ISSN: 2155-5435; 2155-5435
• DOI: 10.1021/cs401224g

The new complex [(η6-p-cym)RuCl(κ2-N,N-dmbpy)](BF4) (p-cym = p-cymene; dmbpy = 4,4′-dimethyl-2,2′-bipyridine) is water-soluble and active in the catalytic transfer hydrogenation (TH) of different ketones (cyclohexanone, 2-cyclohexenone, and 3-pentanone) to the corresponding alcohols using aqueous HCOONa/HCOOH as the hydrogen source at pH 4.4. A higher activity was found for the TH of the imine N-benzyl­ideneaniline under the same conditions. Excellent results have been obtained for catalyst recycling. Aqua, formato, and hydrido species were detected by 1H NMR experiments in D2O. Importantly, when the catalytic reaction was carried out in D2O, selective deuteration at the Cα of the alcohols was observed due to a rapid Ru–H/D+ exchange, which was also deduced theoretically. This process involves a reversal of polarity of the D+ ion, which is transformed into a Ru–D function (“umpolung”). Negligible deuterium labeling was observed for the imine, possibly due to the high activity in the TH process and also to the decrease in the hydrido complex concentration due to the stability of a hydrido-imine intermediate. Both facts should ensure that the TH reaction will compete favorably with the Ru–H/D+ exchange. The basic nature of the imine hydrogenation product can also hinder the stated Ru–H/D+ exchange. On the basis of DFT calculations, all these hypotheses are discussed. In addition, calculations at this level also support the participation of the stated aqua, formato, and hydrido intermediates in the catalytic reaction and provide a detailed microscopic description of the full catalytic cycle. In the case of the imine TH process, the formation of the hydrido complex (decarboxylation step) is clearly the limiting step of the cycle. On the contrary, in the hydrogenation of cyclohexanone, both decarboxylation and reduction steps exhibit similar barriers, and due to the limitations of the solvent model employed, a definitive conclusion on the rate-determining step cannot be inferred.