Molecular structures of Ugi’s amine ferrocene-conjugates with R,R-tartaric acid and DFT calculations versus experimental resolution of their diastereomers

Classical synthetic approach to highly enantiomeric-enriched ferrocenes relies on the formation of their conjugates with (R,R)-tartaric acid. Herein, the quantum chemical calculations based on X-ray data as an initial approximation, were carried out for both (R)- and (S)-diastereomers of N,N-(dimethyl-1-ferrocenyl)ethylamine (Ugi’s amine) with (R,R)-tartaric acid. A high correlation between the experimental data and the calculated Gibbs free energies values of solvation was obtained. Based on the advanced DFT calculations, the chemical aspects of the separation of the diastereomeric complexes of (R)- and (S)-FcCH(CH3)N(CH3)2 with (R,R)-tartaric acid were clarified. Quantum chemical calculations made it possible to justify the use of methanol as a solvent in the successful separation of the diastereomeric complexes of the Ugi’s amine. This mathematical approach can be used in practice to separate racemates of other bioactive ferrocene compounds, for example, ferrocenyl alkyl azoles.