ABSTRACT Structural elucidation of reaction intermediates and side products is often key to mechanistic understanding. However, individual isolation of these species is time‐consuming, labor‐intensive, and often technically challenging, if not impossible. Here, we present an NMR experimental workflow involving the time‐resolved acquisition and processing of multiple types of two‐dimensional NMR spectra acquired in tandem using NOAH supersequences on an active reaction. This time‐resolved NOAH nonuniform sampling method (TR‐NOAH‐NUS) enables the generation of robust concentration–time plots for kinetic analysis in parallel to structural characterization of reaction components. Here, we demonstrate the application of TR‐NOAH‐NUS on an organo‐catalyzed acylation of alcohols. Despite the short (30 min) timespan of the reaction, we are able to obtain high‐quality HSQC, HMBC, and COSY spectra with excellent (less than 15 s) temporal resolution. From these data, we can observe both an on‐cycle catalytic intermediate and an off‐cycle catalyst degradation product and can directly assign the structures of both without need for further isolation.
Guzman et al. (Sun,) studied this question.