Kinetics of Asymmetric Transfer Hydrogenation, Catalyst Deactivation, and Inhibition with Noyori Complexes As Revealed by Real-Time High-Resolution FlowNMR Spectroscopy

Abstract

Catalytic hydrogen transfer from basic isopropyl alcohol to aryl ketones mediated by [(arene)­(TsDPEN)­RuCl] complexes has been investigated by operando 1H NMR spectroscopy using a recirculating flow setup. Selective excitation pulse sequences allowed fast and quantitative monitoring of the key [(mesitylene)­(TsDPEN)­RuH] intermediate during catalysis, which is shown to interact with both substrates by polarization transfer experiments. Comparison of reaction profiles with catalyst speciation traces in conjunction with reaction progress kinetic analysis using variable time normalization and kinetic modeling showed the existence of two independent catalyst deactivation/inhibition pathways: whereas excess base exerted a competitive inhibition effect on the unsaturated catalyst intermediate, the active hydride suffered from an inherent first-order decay that is not evident in early stages of the reaction where turnover is fast. Isotopic labeling revealed arene loss to be the entry point into deactivation pathways to Ru nanoparticles via hydride-bridged intermediates.

Insight into catalyst speciation and hydrogen co-evolution during enantioselective formic acid-driven transfer hydrogenation with bifunctional ruthenium complexes from multi-technique operando reaction monitoring

“…19 The maximum rate observed aer 2 h at 40 C of k obs ¼ 1.1 mM min À1 was signicantly lower than that found for the same reaction in propan-2-ol (k obs ¼ 9.2 mM min À1 at 20 C), but conversions of >95% were reached aer 10 h with FA/TEA, whereas a maximum of 82% equilibrium conversion could be obtained in propan-2-ol under otherwise identical conditions. 6 Enantioselectivity to (R)-1-phenylethanol was constant at 97 AE 1% over more than 18 h in FA/NEt 3 , whereas a gradual erosion of $2% ee per hour from the initial level of 98% has been observed in propan-2-ol. 6 Closer inspection of the reaction prole revealed an induction period of about 2 h during which product formation gradually sped up until it reached its maximum rate.…”

“…6 Enantioselectivity to (R)-1-phenylethanol was constant at 97 AE 1% over more than 18 h in FA/NEt 3 , whereas a gradual erosion of $2% ee per hour from the initial level of 98% has been observed in propan-2-ol. 6 Closer inspection of the reaction prole revealed an induction period of about 2 h during which product formation gradually sped up until it reached its maximum rate. When formic acid consumption was analysed using the integration of its formyl proton at 8.3 ppm in the 1 H NMR spectra, it became apparent that a large amount of reductant had been consumed during the 2 hour induction period (Fig.…”

“…The fact that most of the catalyst resides in the relatively stable formate complex 3 during the reaction may also explain the lower levels of catalyst deactivation seen in FA/NEt 3 mixtures (no signs of Ru black formation were observed, see ESI †) as opposed to using basic propan-2-ol. 6 As a demonstration of the utility of our ndings for applied catalysis, a reaction started at the optimum FA concentration of 1.5 M under the conditions applied showed an immediate onset of transfer hydrogenation without any lag phase, and a steady 20-22% catalyst distribution of hydride complex 4 throughout the reaction (Fig. 13).…”

“…5 We have recently revisited the kinetics of hydrogen transfer catalysis of aryl ketones from propan-2-ol using [(mesitylene)RuCl(R,R)-(TsDPEN)] using real-time high resolution 1 H FlowNMR, where selective excitation pulse sequences allowed tracking of the key [Ru-H] intermediate during the reaction. 6 Correlation of catalyst speciation with product formation kinetics thus showed catalyst deactivation caused by arene decoordination to be independent of competitive base inhibition. 6 Here we investigate the same reaction using formic acid/ triethylamine mixtures as the reductant, conditions which are sometimes preferred for application due to their tolerating higher substrate loadings and giving higher conversions.…”

“…6 Correlation of catalyst speciation with product formation kinetics thus showed catalyst deactivation caused by arene decoordination to be independent of competitive base inhibition. 6 Here we investigate the same reaction using formic acid/ triethylamine mixtures as the reductant, conditions which are sometimes preferred for application due to their tolerating higher substrate loadings and giving higher conversions. 7 To gain insight into the multiple interactions occurring in this system we have complemented the solution phase analysis via 1 H and 13 C FlowNMR and UV-vis with on-line HPLC and head-space MS.…”