Design, Validation, and Implementation of a Rapid-Injection NMR System

Abstract

A Rapid Injection NMR (RINMR) apparatus has been designed and constructed to allow the observation of fast chemical reactions in real time by NMR spectroscopy. The instrument was designed to allow the rapid (<2 s) injection and mixing of a metered volume of a reagent into a spinning NMR tube followed by rapid acquisition of the data resulting from the evolution of the chemical process. The various design criteria for this universal system included the ability to deliver any chemical reagent at any temperature and allow for the observation of any nucleus. The various challenges associated with the construction and implementation of this instrument are documented along with the validation of the accuracy of the apparatus with respect to volume and temperature. Finally, the ultimate validation and reproducibility of the technique is presented in the form of three case studies that used the instrument to elucidate various aspects of organic reaction mechanisms. The authors urge interested parties to not embark on the construction of their own instrument and invite those whose research problems might be amenable to this kind of analysis to contact the corresponding author for access to the apparatus described herein.

Practical aspects of real-time reaction monitoring using multi-nuclear high resolution FlowNMR spectroscopy

“…Fast-injection methods, including stopped-flow NMR techniques, have been developed to overcome this, although these typically use a static sample that is discarded after measurement. [33][34][35][36][37][38][39][40] Capturing fast events that are naturally occurring in a flowing sample during the reaction, however, is not limited by the pump delay but the NMR acquisition parameters.…”

Lewis Base Catalysis of the Mukaiyama Directed Aldol Reaction: 40 Years of Inspiration and Advances

“…[32] and a,bunsaturated carbonyl compounds [33] with aldehydes which uniformly gave high levels of site, diastereo-, and enantioselectivity (Scheme 8). By considering the selectivity trends observed within this diverse class of p nucleophiles, combined with mechanistic studies, [34] a unified mechanism emerged and helped rationalize the large body of data. In addition, this mechanistic understanding also provided confidence to extend this novel mode of catalysis to reactions outside of the typical scope of Lewis acid catalyzed processes, as is nicely illustrated in the case of the Lewis base catalyzed Passerini reaction of isonitriles.…”

Lewis‐Base‐Katalyse der gerichteten Mukaiyama‐Aldolreaktion: 40 Jahre Inspiration und Fortschritt

“…Die Reaktionen ergaben durchweg hohe Regio-, Diastereo-und Enantioselektivitäten (Schema 8). Aus der Betrachtung von Selektivitätstrends unter Einbeziehung mechanistischer Studien [34] ergab sich ein einheitlicher Mechanismus, auf dessen Basis die große Menge an Daten rationalisiert werden konnte, und der außerdem half, diese neuartige Katalyse auf Reaktionen über den typischen Bereich Lewis-Säure-katalysierter Prozesse hinaus auszudehnen. Ein schçnes Beispiel hist die Lewis-Base-katalysierte Passerini-Reaktion von Isonitrilen.…”