NMR Structure Elucidation of Small Organic Molecules and Natural Products: Choosing ADEQUATE vs HMBC

Abstract

Long-range heteronuclear shift correlation methods have served as the cornerstone of modern structure elucidation protocols for several decades. The (1)H-(13)C HMBC experiment provides a versatile and relatively sensitive means of establishing predominantly (3)J(CH) connectivity with the occasional (2)J(CH) or (4)J(CH) correlation being observed. The two-bond and four-bond outliers must be identified specifically to avoid spectral and/or structural misassignment. Despite the versatility and extensive applications of the HMBC experiment, it can still fail to elucidate structures of molecules that are highly proton-deficient, e.g., those that fall under the so-called "Crews rule". In such cases, recourse to the ADEQUATE experiments should be considered. Thus, a study was undertaken to facilitate better investigator understanding of situations where it might be beneficial to apply 1,1- or 1,n-ADEQUATE to proton-rich or proton-deficient molecules. Equipped with a better understanding of when a given experiment might be more likely to provide the necessary correlation data, investigators can make better decisions on when it might be advisible to employ one experiment over the other. Strychnine (1) and cervinomycin A2 (2) were employed as model compounds to represent proton-rich and proton-deficient classes of molecules, respectively. DFT methods were employed to calculate the relevant (n)J(CH) heteronuclear proton-carbon and (n)J(CC) homonuclear carbon-carbon coupling constants for this study.