The Key Role of the Latent N-H Group in Milstein's Catalyst for Ester Hydrogenation

Abstract

<p>We previously demonstrated that Milstein’s seminal diethylamino-substituted PNN-pincer-ruthenium catalyst for ester hydrogenation is activated by dehydroalkylation of the pincer ligand, releasing ethane and eventually forming an NHEt-substituted derivative that we proposed is the active catalyst. In this paper, we present a computational and experimental mechanistic study supporting this hypothesis. Our DFT analysis shows that the minimum-energy pathways for hydrogen activation, ester hydrogenolysis, and aldehyde hydrogenation rely on the key involvement of the nascent N-H group. We have isolated and crystallographically characterized two catalytic intermediates, a ruthenium dihydride and a ruthenium hydridoalkoxide, the latter of which is the catalyst resting state. A detailed kinetic study shows that catalytic ester hydrogenation is first-order in ruthenium and hydrogen, shows saturation behavior in ester, and is inhibited by the product alcohol. A global fit of the kinetic data to a simplified model incorporating the hydridoalkoxide and dihydride intermediates and three kinetically relevant transition states showed excellent agreement with the results from DFT. <b></b></p><br>

Bulky PNP Ligands Blocking Metal-Ligand Cooperation Allow for Isolation of Ru(0), and Lead to Catalytically Active Ru Complexes in Acceptorless Alcohol Dehydrogenation

“…The results from the current study and our earlier two papers, as well as those by others, 21,33 show that ADC is a versatile reaction that may proceed by several different pathways depending on the complex, or can be completely shut down by a rather trivial ligand modification. In this regard, the presence of acetate complexes formed in super dry ethanol (Supelco, max 1 ppm H2O), where the maximum water amount present would have been several times less than the amount of excess base, shows that a Guerbet reaction is an important consideration for catalyst deactivation.…”

Near-Ambient-Temperature Dehydrogenative Synthesis of the Amide Bond: Mechanistic Insight and Applications

“…Several ruthenium and manganese pincer complexes were screened for the amide synthesis under Et 2 O reflux (boiling point 34.6 °C) in the presence of catalytic amounts of t -BuOK. Interestingly, among these complexes, Ru–PNNH complexes 11 1 and 2 , featuring a terminal N–H moiety, displayed catalytic activities toward amide formation even at this low temperature (entries 1–2). Ru–PNNH complexes 1–3 are capable of two distinct modes of metal–ligand cooperation (MLC), amido–amine and aromatization–dearomatization, 11 unlike complexes 4–6 , where only aromatization–dearomatization is possible.…”

“…Interestingly, among these complexes, Ru–PNNH complexes 11 1 and 2 , featuring a terminal N–H moiety, displayed catalytic activities toward amide formation even at this low temperature (entries 1–2). Ru–PNNH complexes 1–3 are capable of two distinct modes of metal–ligand cooperation (MLC), amido–amine and aromatization–dearomatization, 11 unlike complexes 4–6 , where only aromatization–dearomatization is possible. Ru–P Ph NNH complex 3 , with electron-withdrawing Ph substituents on the P donor atom, did not show catalytic activity at this temperature (entry 3).…”

“…Complex 1 , upon addition of 2 eq of t -BuOK, forms the anionic complex 1a which is intensely violet in diethyl ether solution ( Scheme 3 a). 11 Addition of 1-hexanol (4 equiv) to this complex results in the formation of the aromatic alkoxy complex 1b (see Figure S20 for reaction progress). Noteworthily, the alkoxy ligand of 1b exchanges quickly with the free alcohol in solution, and as the excess alcohol is removed from the solution, peak broadening in 31 P{ 1 H} and 1 H NMR is observed.…”

Epoxide Hydrogenation Catalyzed by Ruthenium PNN and PNP Pincer Complexes

“…In a comprehensive experimental and computational study, we demonstrated that RuPNN HEt is a key on-cycle catalytic intermediate, and that the nascent N-H group is intimately involved in both hydrogen activation and the transfer of hydrogen to the substrate. 12 Scheme 1. Conversion of Milstein's Catalyst RuPNN dearom to the form active for ester hydrogenation.…”