Mechanisms and stereoselectivities of the DABCO-catalyzed Rauhut–Currier reaction of α,β-unsaturated ketones and aryl acrylates: a computational investigation

Abstract

It has been experimentally reported that a great acceleration of the Rauhut–Currier reaction of aryl acrylates with α,β-unsaturated ketones is achieved in the presence of phenol (PhOH) [W. Liu, G. Zhao, Org. Biomol. Chem., 12 (2014) 832–835]. A theoretical investigation on the mechanisms as well as stereoselectivities of the 1,4-diazabicyclo[2.2.2]octane (DABCO)-catalyzed RC reaction of phenyl acrylate R₁ with (E)-2-benzoyl-3-phenyl-acrylonitrile R₂ in the absence and in the presence of PhOH has been performed using density functional theory (DFT). Multiple possible reaction pathways (associated with RRS, RSR, SRS and SSR configurations) have been explored. The whole reaction process can be characterized by four steps: (1) the conjugate addition of DABCO to R₁, (2) the nucleophilic attack at R₂, (3) the 1,3-H-shift process (direct H-shift in the absence of PhOH and stepwise H-shift in the presence of PhOH) and (4) the catalyst release affording the final product. The calculated results show a relatively high energy barrier (42.2–46.0 kcal mol⁻¹, corresponds to the direct 1,3-H-shift step) for the reaction in the absence of PhOH. For the reaction in the presence of PhOH, the pathway leading to the (SSR)-product is the most favorable pathway. The first step of the hydrogen-shift process is found to be the rate-determining step, whereas the second step is the stereoselectivity determining step. The role of PhOH on the title reaction is discussed.