The mechanism and diastereoselectivity in the formation of trifluoromethyl-containing spiro[pyrrolidin-3,2′-oxindole] by a catalyst-free and mutually activated [3+2]-cycloaddition reaction: a theoretical study

Abstract

The mechanism and diastereoselectivity of the [3+2] cycloaddition reaction between (Z)-1-methyl-3-[(2,2,2-trifluoroethyl)imino]indolin-2-one and 5-nitro-2-vinylpyridine with no catalyst in acetonitrile to produce spiro[pyrrolidin-oxindoles] have been investigated by DFT at the M06-2X/6-311+G(d,p)//M06-2X/6-31G(d,p) level combined with the solvation SMD model. A new mechanism has been reported. Our computed results revealed that the most favoured reaction pathway has three steps: the first and second steps are the proton transfer reactions, and the third step is the [3+2] cycloaddition reaction. The reliability of this mechanism is demonstrated by the natural bond orbital (NBO) and reduced density gradient (RDG) analysis. The calculations of atomic charges, second-order perturbation stabilization energies E(2), and atomic dipole corrected Hirshfeld (ADCH) atomic charge showed that the –CF₃ group facilitates the proton transfer step. The origin of the diastereoselectivity of the catalyst-free reaction was investigated by distortion/interaction analysis. It is the lower distortion energy and the stronger interaction energy in E-TS3-a that control the diastereoselectivity to generate R-configuration product 3aa. And the higher polarity of acetonitrile makes the reaction easier.