Addressing the stereochemistry of complex organic molecules by density functional theory-NMR

Determining the stereochemistry of organic molecules is a long-standing problem, with implications for stereoselective reactions, catalysis, and the structure of natural products. NMR spectroscopy is widely employed to this purpose; however, the interpretation of results is often entrusted to empirical methods or expert systems. Quantum chemical calculations, generally based on density functional theory, provide a reliable framework to predict the relevant parameters (chemical shifts and coupling constants, generally involving 1H and 13C) of diastereoisomers with useful accuracy. While the approach virtually spans all molecules of interest in organic chemistry, including those that contain heavy atoms, the analysis of results still poses significant challenges.