A molecular electron density theory study on the [3+2] cycloaddition reaction of thiocarbonyl ylides with hetaryl thioketones

Abstract

Utilizing the newly proposed molecular electron density theory (MEDT), a detailed study was performed on the [3+2] cycloaddition (32CA) reaction of thiocarbonyl ylide TCY 2 with thioketone THK 3 at the B3LYP/6-31G(d) computational level. In the gas phase, this reaction displays a very low total electronic activation energy of 1.6 kcal mol⁻¹ arising from the pseudo(di)radical (pdr) character of TCY 2, which was distinguished by electron localization function (ELF) analysis over the ground-state electronic structure (GES) of this species. Further exploration of the relative Gibbs free energies in the presence of THF at −40 °C indicates that, in excellent agreement with the experimental findings, the C1–C4 regioisomeric channel is kinetically preferred over the C1–S5 channel, leading to the formation of cycloadduct CA 4 as the sole product. Meanwhile, due to the high global nucleophilicity index of TCY 2 and the high global electrophilicity index of THK 3, a highly polar 32CA reaction between the reagents is expected; however, this pdr-type 32CA reaction displays non-polar character. The exclusive C1–C4 regioselectivity can be explained via probing molecular electrostatic potential (MEP) maps, which portray enormous electrostatic repulsion between two interacting fragments of the transition state (TS) involved in the unfavorable C1–S5 regioisomeric channel. An ELF analysis of the most relevant points located along the intrinsic reaction coordinate (IRC) profile of the TS connecting the separate reagents to CA 4 establishes a non-concerted two-stage one-step molecular mechanism for the non-polar pdr-type 32CA reaction of TCY 2 with THK 3.