Institute of Organic Chemistry, Justus Liebig University, Heinrich-Buff-Ring 17, 35392, Giessen, Germany.
Institute of Inorganic and Analytical Chemistry, Justus Liebig University, Heinrich-Buff-Ring 17, 35392, Giessen, Germany.
Angew Chem Int Ed Engl. 2022 Jul 18;61(29):e202204393. doi: 10.1002/anie.202204393. Epub 2022 Jun 14.
We present an experimental and computational study on the conformers of N,N'-diphenylthiourea substituted with different dispersion energy donor (DED) groups. While the unfolded anti-anti conformer is the most relevant for thiourea catalysis, intramolecular noncovalent interactions counterintuitively favor the folded syn-syn conformer, as evident from a combination of low-temperature nuclear magnetic resonance measurements and computations. In order to quantify the noncovalent interactions, we utilized local energy decomposition analysis and symmetry-adapted perturbation theory at the DLPNO-CCSD(T)/def2-TZVPP and sSAPT0/6-311G(d,p) levels of theory. Additionally, we applied a double-mutant cycle to experimentally study the effects of bulky substituents on the equilibria. We determined London dispersion as the key interaction that shifts the equilibria towards the syn-syn conformers. This preference is likely a factor why such thiourea derivatives can be poor catalysts.
我们进行了一项实验和计算研究，探讨了取代不同色散能给体（DED）基团的 N,N'-二苯基硫脲的构象。虽然展开的反反构象最有利于硫脲催化，但从低温核磁共振测量和计算的结合来看，分子内非共价相互作用反直觉地有利于折叠的顺顺构象。为了量化非共价相互作用，我们在 DLPNO-CCSD(T)/def2-TZVPP 和 sSAPT0/6-311G(d,p)理论水平上使用了局部能量分解分析和对称自适应微扰理论。此外，我们应用双突变循环实验研究了大取代基对平衡的影响。我们确定伦敦色散是将平衡转向顺顺构象的关键相互作用。这种偏好可能是这些硫脲衍生物为何可能成为不良催化剂的一个因素。
