On the Regioselective Intramolecular Nucleophilic Addition of Thiols to C60

Abstract

AbstractThe first intramolecular nucleophilic addition of a thiol to a fullerene double bond is reported. Whereas the reaction of cysteine (4) or cystine (11) with formaldehyde and [60]fullerene in chlorobenzene at reflux afforded the new compound 10 bearing a thiazolidine moiety fused to the fullerene sphere, the reaction of commercially available N‐methylglycine (12; sarcosine) with 1,4‐dithiane‐2,5‐diol (13) and C60 in chlorobenzene at reflux led to the desired cyclized compound 3 in poor yield. The favorable geometrical approach of the reactive thiol group towards the fullerene double bond is followed by a 5‐exo‐trig intramolecular nucleophilic addition of the S–H group to the adjacent double bond of the fullerene to form compound 3 in which a tetrahydrothiophene ring is simultaneously fused to the pyrrolidine and the fullerene moieties. Compound 3 was spectroscopically and electrochemically characterized and CV revealed that saturation of a second double bond of the fullerene sphere (cis‐1 regioisomer) is compensated by the electronegative character of the sulfur atom, resulting in reduction potentials similar to those observed for fullerene monoadducts. The two‐fold cyclization reaction occurs in a totally regioselective stepwise process leading exclusively to the cis‐1 isomer. Theoretical calculations (DFT and the ONIOM approach) predict that the formation of the sulfur pentagonal ring is highly favored and does not present structural constraints. Furthermore, the activation barrier for the nucleophilic attack of the thiol group on the fullerene surface was found to be substantially higher in comparison with the analogous previously reportedhydroxy group (activation barrier about 8 kcal mol–1 larger for SH than for OH), thus accounting for the poor yields of tetrahydrothiophene 3. The formation of 3 competes with the formation of 1,2‐dimethylpyrrolidino[3,4:1,2][60]fullerene (15), which is formed as the main reaction product by loss of the SH group. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)