FlowNMR spectroscopy is an excellent technique for non-invasive real-time reaction monitoring under relevant conditions that avoids many of the limitations that bedevil other reaction monitoring techniques.

No 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.

We demonstrate how FlowNMR spectroscopy can readily be applied to investigate photochemical reactions that require sustained input of light and air to yield mechanistic insight under realistic conditions. The Eosin Y mediated photo-oxidation of N-allylbenzylamine is shown to produce imines as primary reaction products from which undesired aldehydes form after longer reaction times. Facile variation of reaction conditions during the reaction in flow allows for probe experiments that give information about the mode of action of the photocatalyst.

Noyori–Ikariya type [(arene)RuCl(TsDPEN)] (TsDPEN, sulfonated diphenyl ethylenediamine) complexes are widely used C=O and C=N reduction catalysts that produce chiral alcohols and amines via a key ruthenium–hydride intermediate that determines the stereochemistry of the product. Whereas many details about the interactions of the pro-chiral substrate with the hydride complex and the nature of the hydrogen transfer from the latter to the former have been investigated over the past 25 years, the role of the stereochemical configuration at the stereogenic ruthenium center in the catalysis has not been elucidated so far. Using operando FlowNMR spectroscopy and nuclear Overhauser effect spectroscopy, we show the existence of two diastereomeric hydride complexes under reaction conditions, assign their absolute configurations in solution, and monitor their interconversion during transfer hydrogenation catalysis. Configurational analysis and multifunctional density functional theory (DFT) calculations show the λ-( R , R ) S Ru configured [(mesitylene)RuH(TsDPEN)] complex to be both thermodynamically and kinetically favored over its λ-( R , R ) R Ru isomer with the opposite configuration at the metal. Computational analysis of both diastereomeric catalytic manifolds show the major λ-( R , R ) S Ru configured [(mesitylene)RuH(TsDPEN)] complex to dominate asymmetric ketone reduction catalysis with the minor λ-( R , R ) R Ru [(mesitylene)RuH(TsDPEN)] stereoisomer being both less active and less enantioselective. These findings also hold true for a tethered catalyst derivative with a propyl linker between the arene and TsDPEN ligands and thus show enantioselective transfer hydrogenation catalysis with Noyori–Ikariya complexes to proceed via a lock-and-key mechanism.