engleski

Pyrrolidine vs. piperidine in Hofmann-Löffler-Freytag reaction. A thermodynamic perspective on rearrangement reactions

Hofmann-Löffler-Freytag (HLF) reaction has seen a resurgence in interest due to shift from metal-based catalysis to organo- catalysis. Recent one-pot approach requires hypervalent iodine compound with source of iodine (I2 or NaI) for generating radical precursor, that can under UV irradiation form N-centered radical. Rearrangement to a more stable C-centered radical via 6- membered ring transition state is well described and produces predominately pyrrolidine, while trace amounts of piperidine is formed via 7-membered ring transition state. Regioselective synthesis of piperidine is usually done when C5 position is blocked, or when C6 position provides greater thermodynamic driving force. Our work has concluded that: pyrrolidine (1, 5-HAT) and piperidine (1, 6-HAT) pathways are kinetically and thermodyanamically indistinguishable. In order to find the location of the most stable radical in the molecule, molecular fragments can be used for the prediction. C6 radical may rearrange to more stable C2 radical via 1, 5-HAT, which is the probable reason for pyrrolidine regioselectivity. Thus, radical stabilities play crucial role in determination of products in the reaction sequence.

hydrogen atom transfer ; radicals ; Hofmann-Löffler-Freytag (HLF) reaction

nije evidentirano