Theoretical study on DABCO-catalyzed ring expansion of cyclopropyl ketone: Mechanism, chemoselectivity, and role of catalyst

Abstract

The possible mechanisms of 1,4-diazabicyclo[2.2.2]octane (DABCO)-catalyzed ring expansion of cyclopropyl ketone for forming dihydrofurans have been studied using density functional theory (DFT). According to the calculated results, the reaction occurs via two competing paths including paths A and B, which lead to two different products (i.e. 2-methyl-4,5-dihydrofuran and 2-phenyl-4,5-dihydrofuran), respectively. Path A is revealed to be more energetically favorable than path B, which is consistent with the experimental observation. Two reaction steps are contained in the favorable path: (1) nucleophilic addition of DABCO to cyclopropyl ketone coupled with three-membered ring opening; (2) five-membered ring closure process accompanied with dissociation of DABCO and product via the SN2-type transition state. Moreover, global reactivity index (GRI) and non-covalent interaction (NCI) analyses were performed to disclose the role of catalyst and explain the chemoselectivity. By analysing of the efficiency of different catalysts (i.e. tricyclohexylphosphine (PCy3), triphenylphosphine (PPh3), tributylphosphine (PBu3), 4-dimethylaminopyridine (DMAP), and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)), it was found that the stronger nucleophilicity of amine catalyst would be corresponding to the lower energy barrier of the ring expansion reaction.