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On the Regioselective Intramolecular Nucleophilic Addition of Thiols to C 60
Author(s) -
Izquierdo Marta,
Osuna Sílvia,
Filippone Salvatore,
MartínDomenech Angel,
Solà Miquel,
Martín Nazario
Publication year - 2009
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200900835
Subject(s) - chemistry , intramolecular force , regioselectivity , nucleophile , double bond , fullerene , nucleophilic addition , stereochemistry , medicinal chemistry , photochemistry , organic chemistry , catalysis
The 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 C 60 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)