As recognized by the 2021 Nobel Prize in Chemistry, urea and thiourea cores are commonly used to construct dual-hydrogen-bond-donor (DHBD) organocatalysts for important asymmetric organic reactions. Yet, experimental microwave studies and quantum mechanical computations are in disagreement over the gas-phase structures, vibrations, and energies of unsubstituted ureas and thioureas. Previous computations predict an intuitive nonplanar geometry known as anti- (C2) and an unusual syn-conformation (CS), which microwave studies could not identify. This disagreement has resulted in a perennially unresolved conundrum that is preventing a fundamental understanding of DHBDs in asymmetric organocatalysis. Our work, therefore, defines the structures, vibrations, and energies of urea and thiourea in the gas-phase using state-of-the-art quantum chemistry. Through our systematic and complete approach, we find that in order to understand how to treat pure urea and thiourea systems appropriately and accurately, the complete basis set limit, anharmonic vibrations, and zero-point energy corrections are critical. Typically, quantum predictions do not require these formally correct approximations to yield experimental agreement. However, for urea and thiourea, we find that the inclusion of the complete basis set limit, anharmonic vibrations, and zero-point energy eliminates the syn-conformer as a possible ground state. Thus, we conclude that only the anti-conformation exists with a large-amplitude motion, which explains the experimental observations. These findings will give the organocatalysis community a more fundamental understanding of important urea and thiourea DHBD cores and can be applied to other substituted DHBD compounds to design more efficient catalysts for asymmetric organic reactions.

Implications of the complete basis set limit, anharmonic frequencies, and zero-point energy corrections on the structures of dual-hydrogen-bond-donor cores

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