Relativity as a Synthesis Design Principle: A Comparative Study of [3 + 2] Cycloaddition of Technetium(VII) and Rhenium(VII) Trioxo Complexes with Olefins

Abstract

The difference in [3 + 2] cycloaddition reactivity between <i>fac</i>-[MO₃(tacn)]⁺ (M = Re, ⁹⁹Tc; tacn = 1,4,7-triazacyclononane) complexes has been reexamined with a selection of unsaturated substrates including sodium 4-vinylbenzenesulfonate, norbornene, 2-butyne, and 2-methyl-3-butyn-2-ol (2MByOH). None of the substrates was found to react with the Re cation in water at room temperature, whereas the ⁹⁹Tc reagent cleanly yielded the [3 + 2] cycloadducts. Interestingly, a bis-adduct was obtained as the sole product for 2MByOH, reflecting the high reactivity of a ⁹⁹TcO-enediolato monoadduct. On the basis of scalar relativistic and nonrelativistic density functional theory calculations of the reaction pathways, the dramatic difference in reactivity between the two metals has now been <i>substantially</i> attributed to differences in relativistic effects, which are much larger for the 5d metal. Furthermore, scalar-relativistic Δ<i>G</i> values were found to decrease along the series propene > norbornene > 2-butyne > dimethylketene, indicating major variations in the thermodynamic driving force as a function of the unsaturated substrate. The suggestion is made that scalar-relativistic effects, consisting of greater destabilization of the valence electrons of the 5d elements compared with those of the 4d elements, be viewed as a new design principle for novel ^99mTc/Re radiopharmaceuticals, as well as more generally in heavy-element coordination chemistry.