Determining Interproton Distances from Severely Overlapped NMR Spectra Using Ultraselective Experiments

Abstract

Stereoselectivity is a desirable property of many chemical reactions, with much effort geared toward devising synthetic pathways with high selectivity. In the early stages of designing such pathways, mixtures of diastereomeric products are typically formed. Characterization of these products provides valuable insight into reaction mechanisms, enabling chemists to adjust reaction conditions to maximize selectivity. NMR enables the study of such mixtures intact, with relative configurations determined by measuring scalar couplings or probing through-space 1H–1H interactions. However, for crowded 1H NMR spectra, critical information required to determine configuration is often inaccessible. Here, we use the ultraselective GEMSTONE method to measure diagnostic interproton distances even where overlap in 1H NMR spectra prevents selective excitation by conventional methods. The methodology is validated using strychnine, a well-studied rigid alkaloid, and used to characterize diastereomeric compounds formed in a synthetic reaction.