Theoretical Study on the Origin of Abnormal Regioselectivity in Ring-Opening Reaction of Hexafluoropropylene Oxide

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 CF3 substituted beta-C rather than the fluorine substituted alpha-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 beta-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 alpha-C results from a significant strengthening of the C(alpha)-O bond by the negative hyperconjugation between the lone pair of epoxide O atom and the antibonding C-F orbital.

Automated summary

It has been widely accepted that nucleophiles prefer to attack the less sterically hindered carbon of epoxides under neutral and basic conditions. However, this rule does not apply to perfluorinated epoxides like HFPO, where nucleophiles attack the more hindered CF3 substituted beta-C instead of the fluorine substituted alpha-C. In this study, density functional theory calculations were used to explain this abnormal regioselectivity. The calculations reproduced the observed regioselectivities and attributed the preference for the sterically hindered beta-C of HFPO to the lower destabilizing distortion energy needed for the corresponding ring-opening transition state.