Differentiation and identification of enantiomers by nuclear magnetic resonance spectroscopy with support of quantum mechanical computations

• Published in: Chirality (New York, N.Y.) N.Y.), 2024-01, Vol.36 (1), p.e23623-n/a
• Main Authors: Brzezicki, Artur, Garbacz, Piotr
• Format: Article
• Language: English
• Subjects: chiral solvating agents; nuclear magnetic resonance; phenyltetrahydroisoquinoline; quantum chemical computations; quinuclidinol; solifenacin
• ISSN: 0899-0042; 1520-636X
• DOI: 10.1002/chir.23623

We report nuclear magnetic resonance studies of two chiral building blocks of solifenacin, phenyltetrahydroisoquinoline and quinuclidinol, in which chiral solvating agents, Mosher's acid, and Pirkle's alcohol were used for spectral discrimination between enantiomers of solifenacin constituents. Based on the constraints following from measurements of the nuclear Overhauser effect, structures of phenyltetrahydroisoquinoline and Pirkle's alcohol solvates were found. Next, shifts of nuclear magnetic resonance signals of phenyltetrahydroisoquinoline due to the application of Pirkle's alcohol were computed using density functional theory methods. The computed carbon‐13 shifts reproduce those determined experimentally, allowing us to attribute the absolute configuration to phenyltetrahydroisoquinoline enantiomers without the need for the use of empirical rules. Shifts of carbon‐13 nuclear magnetic resonance signals of enantiomers due to the application of chiral solvating agents are correctly reproduced by quantum chemistry computations based on the structure of the solvates they form.