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

Polyoxometalates (POMs) are known for their well-established catalytic properties, particularly in photocatalysis, and have made significant strides in achieving selective C(sp3)−H functionalization. However, due to the complexity of the 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 via 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 does α-regioselective activation; this is due to the reduction in activity of the 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. The outstanding reactivity of [W10O32]4− is attributable to its rigid structure and exposed active surface sites. We demonstrate 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 Cβ–H bond activation product. We hope that this theoretical analysis will provide valuable guidance for obtaining high selectivity target products in experimental setups.