C(sp 3)–H trifluoromethylation of pyrrolidine by [W 10O 32] 4−/copper synergetic photocatalysis: Theoretical investigation on reactivity and regioselectivity

Polyoxometalates (POMs), known for their well-established catalytic properties, particularly in photocatalysis, have made significant strides in achieving selective C(sp³)−H functionalization. However, due to the complexity of POM structures, the reactivity and regioselectivity of POMs in organic conversions remain unclear. Here, the reactivity and regioselectivity of the C(sp³)–H trifluoromethylation of pyrrolidine by decatungstate anion/copper ([W₁₀O₃₂]⁴⁻/Cu) dual catalysis were theoretically investigated. Density functional theory (DFT) computations revealed that the β-regioselective activation of pyrrolidine occurs more readily than α-regioselective one due to the reduction in activity of ortho α-C–H bond by protonation. Furthermore, the reactivity of hydrogen atom transfer (HAT) catalysts for C(sp³)–H bond activation follows the order: [W₁₀O₃₂]⁴⁻ > amine radical cation > fluorescein. This outstanding reactivity of [W₁₀O₃₂]⁴⁻ stems from its rigid structure and exposed active surface sites. We demonstrated a linear relationship between the steric volume of the protective group on pyrrolidine and the C–H bond selectivity catalyzed by [W₁₀O₃₂]⁴⁻. In other words, a larger steric volume of the protective group on pyrrolidine leads to easier attainment of a single C_β–H bond activation product. We hope that this theoretical analysis will provide valuable guidance for achieving high-selectivity target products in experimental setups.