Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, China.
School of Chemistry and Materials Science, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, 1 Sub-lane Xiangshan, Hangzhou 310024, China.
Molecules. 2023 Feb 9;28(4):1669. doi: 10.3390/molecules28041669.
That nucleophiles preferentially attack at the less sterically hindered carbon of epoxides under neutral and basic conditions has been generally accepted as a fundamental rule for predicting the regioselectivity of this type of reaction. However, this rule does not hold for perfluorinated epoxides, such as hexafluoropropylene oxide (HFPO), in which nucleophiles were found to attack at the more hindered CF substituted β-C rather than the fluorine substituted α-C. In this contribution, we aim to shed light on the nature of this intriguing regioselectivity by density functional theory methods. Our calculations well reproduced the observed abnormal regioselectivities and revealed that the unusual regiochemical preference for the sterically hindered β-C of HFPO mainly arises from the lower destabilizing distortion energy needed to reach the corresponding ring-opening transition state. The higher distortion energy required for the attack of the less sterically hindered α-C results from a significant strengthening of the C(α)-O bond by the negative hyperconjugation between the lone pair of epoxide O atom and the antibonding C-F orbital.
亲核试剂在中性和碱性条件下优先进攻环氧化物位阻较小的碳，这已被普遍认为是预测此类反应区域选择性的基本规则。然而，对于全氟环氧化物（如六氟丙烯氧化物（HFPO）），该规则并不适用，因为亲核试剂进攻的是位阻较大的 CF 取代的 β-C，而不是氟取代的 α-C。在本研究中，我们旨在通过密度泛函理论方法揭示这种有趣的区域选择性的本质。我们的计算很好地再现了观察到的异常区域选择性，并表明 HFPO 中空间位阻较大的 β-C 的异常区域化学偏好主要源于达到相应的开环过渡态所需的较低的去稳定化扭曲能。进攻位阻较小的 α-C 需要更高的扭曲能，这是由于环氧氧原子的孤对电子和反键 C-F 轨道之间的负超共轭作用显著增强了 C(α)-O 键。
