In this article we review some fundamental engineering concepts and evaluate components and materials required to assemble and operate safe and effective FlowNMR setups that reliably generate meaningful results.

Operando spectroscopy shows a transition from dehydrogenation to hydrogen transfer during the reaction, and allows measuring optimal conditions for maximum rate and efficiency.

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.

Chemical solution-phase equilibria such as acid/base reactions and complex formation are typically investigated by titration studies that either use in situ analysis of a continuously changing sample with techniques that...