Aiming the development of stable and controlled way of the chemical functionalization of fullerenes, there have been many reactions so far reported. The Prato reaction¹ (1,3-dipolar cycloaddition reaction) has been used by many groups as one of the efficient chemical conversion methods in the preparation of functional fullerene derivatives. This method usually provides sufficiently stable fullerene derivatives in reasonable synthetic yields. Addressing the preparation of biocompatible fullerene derivatives, we are using this Prato reaction for the controlled functionalization of C₆₀, C₇₀ and TNT-EMF² (M₃N@I_h-C₈₀ or M₃N@C₈₀).

C₆₀ usually produces the mono-Prato adduct selectively on the [6,6]-junction. However, as reported by the groups of Dorn³ and Echegoyen,⁴ M₃N@C₈₀ provides the mono-Prato adduct on both [6,6]- and [5,6]-junctions as a results of [6,6]-to-[5,6] isomerization via a [1,5]-sigmatropic rearrangement. The ratio of the thermodynamic regioisomers ([6,6]-mono and [5,6]-mono) was dependent on the size of metal cluster (M₃N) inside C₈₀⁵ and was not affected by the exohedral functional groups outside C₈₀ cage. ⁶

Although the bis-Prato addition of C₆₀ proceeded uncontrolled manner, interestingly, bis-Prato addition of M₃N@C₈₀ proceeded in a regioselective manner especially in the presence of larger size of endohedoral metal clusters such as Y₃N and Gd₃N.⁷ Thermal treatment of bis-Prato adduct of Y₃N@C₈₀ caused random isomerization, but the bis-Prato adduct of Gd₃N@C₈₀ stayed rather stable presumably by the effect of larger endohedral metal cluster.

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