Regioselective electrosynthesis of tetra- and hexa-functionalized [60]fullerene derivatives with unprecedented addition patterns

The regioselective electrosynthesis of tetra- and hexa-functionalized [60]fullerene derivatives with unprecedented 1,2,4,17-(cis-3′) and 1,2,3,4,9,10-(“S”-shaped) addition patterns is achieved.


Results and discussion
A heterolytic cleavage of the C 60 -N bond would occur aer [60] fulleroindoline 1 accepts two electrons, and the dianionic 1 2À has its most electronegative carbon atom at the para position of the carbon linked with the aryl group, which is more prone to react with an electrophile. 7b,e,f We surmise that when 1 2À is allowed to react with a bis-electrophile such as 1,2-bis(bromomethyl) benzene, the most electronegative para carbon on the fullerene skeleton is expected to attack one of the two -CH 2 Br groups of 1,2-bis(bromomethyl)benzene, followed by a ring-closure process via the C 60 -N bond formation to afford the fullerenyl monoanion INT-1 bearing a heterocycle fused with a [5,6]-junction, and nal intramolecular cyclization of the nearby anionic fullerenyl carbon with another -CH 2 Br group to provide product 2 with an unprecedented 1,2,4,17-addition pattern. Product 2 has a carbocycle fused to a [6,6]-junction and a heterocycle xed to a [5,6]junction at the cis-3 0 site (Fig. 1c). Density functional theory (DFT) calculations at the B3LYP/6-31G(d) level 15 indicate that INT-1 is preferably formed and that the desired product 2 is most likely generated because it is more stable than other two possible isomers 2 0 and 2 00 by at least 18.9 kcal mol À1 (Fig. 2) (see ESI † for details).
[60]Fulleroindoline 1 was synthesized according to our previous procedure. 16 To testify our assumption, we performed the reaction of 1 2À , which was generated from neutral 1 in orthodichlorobenzene (o-DCB) solution containing 0.1 M tetra-nbutylammonium perchlorate (TBAP) by controlled potential electrolysis (CPE) at À1.1 V, 7b with 10 equiv. of 1,2-bis(bromomethyl)benzene and 10 equiv. of NaH solution under an argon atmosphere. NaH was added to the reaction system in order to remove the trace amount of residual water and further reduce byproduct formation. 17 We found that when the reaction was allowed to proceed at 25 C for 3 min and then immediately quenched with 2 equiv. of triuoroacetic acid (TFA), 1,2,3,16adduct 3 was obtained in 48% yield. The yield of 3 could be further increased to 58% if the reaction was conducted at 0 C for 10 min under otherwise same conditions (Scheme 1).
The isolation of 3 indicated that the proposed intermediate INT-1 was indeed formed. Surprisingly, it was found that further reaction at 25 C and 0 C for 5 h afforded totally different products, exhibiting temperature-controlled regioselectivity (Scheme 2). When the reaction was performed at 0 C, the desired product 2 could be generated in 49% yield. Product 2 has an unprecedented 1,2,4,17-addition pattern, which can also be named as cis-3 0 isomer and possesses a carbocycle fused to a [6,6]-junction and a heterocycle connected to a [5,6]-junction (see Fig. 1c). For a bis-cycloadduct, the two cycles are usually attached to two [6,6]-junctions of C 60 . 2,3 To the best of our knowledge, there has been no precedent with the two cycles bonded to a [6,6]-junction and a [5,6]-junction, respectively, for a non-tethered bis-cycloadduct. 18 In sharp contrast, another regioisomer 4 with the 1,2,3,4-addition pattern, also named as cis-1 isomer where both the carbocycle and heterocycle are fused to two neighboring [6,6]-junctions of C 60 (see Fig. 1b), could be generated in 33% yield at 25 C. It should be mentioned that part of 2 decomposed when it was puried on a silica gel column at 25 C, and the isomerized product 4 could be isolated. This phenomenon was not observed when the purication process was performed at 0 C.
Theoretical calculations showed that cis-3 0 isomer 2 was less stable than cis-1 isomer 4 by 14.2 kcal mol À1 at the B3LYP/6-31G(d) level (see ESI † for details). Although 2 was not very stable, it remained nearly unchanged aer being stirred in pure o-DCB at ambient temperature for 5 h. However, 2 tended to decompose to generate isomeric 4 in a low yield of 13% and some unidentied residue along with 21% of recovered 2 when stirred in o-DCB containing NaH and 0.1 M TBAP at room temperature for 5 h.
Monitoring of the reaction of 1 2À with 1,2-bis(bromomethyl) benzene at 25 C showed that cis-3 0 isomer 2 was initially formed and then gradually converted to cis-1 isomer 4, indicating that 2 was the precursor of 4 under our electrochemical conditions at 25 C. Control experiments precluded the thermal rearrangement of 2 to 4 at 25 C as the predominant process due to the low efficiency and poor yield (vide supra). The cyclic voltammogram (CV) of 2 exhibited irreversible rst redox process of 2 (Fig. S3 †) and more positively shied than that of 1 (Table S1 †). 7b This CV result suggested that the formed 2 could be reduced in situ by the unreacted 1 2À to produce radical anions 1c À and 2c À during the reaction. On the other hand, aer completion of the reaction, 2 could also be reduced to 2c À by the negatively charged system generated by CPE. Radical anion 2c À might undergo rearrangement to provide 4c À , which was subsequently oxidized to neutral 4 by an oxidizing species such as oxygen during the workup process. This assumption was supported by a control experiment, which showed that the electrochemically generated radical monoanion 2c À by CPE from 2 indeed underwent rearrangement within 1 h to afford 4 in 78% yield at 25 C (Scheme 3).
As seen in the CV of 2 (Fig. S3 †), the rst redox process of 2 was irreversible and its second one was quasi-reversible. This result indicated that the dianionic species 2 2À should also have a ring-opened structure and could be employed for further functionalization. Pleasingly, it was found that the protonation of the dianionic 2 2À with 2 equiv. of TFA at 0 C for 5 min afforded 1,2,3,4,9,10-adduct 5 in 59% yield (Scheme 4). The preferred formation of 5 from the protonation of 2 2À was also supported by theoretical calculations (see ESI † for details).
Products 2, 3, 4 and 5 were characterized by HRMS, 1 H NMR, 13 C NMR, FT-IR, UV-vis and uorescence spectra as well as CV and DPV. Particularly, the UV-vis spectra exhibit characteristic absorption peaks and features for each type of fullerene derivatives. 2 Products 2 and 5 are new types of fullerene derivatives with unprecedented addition patterns, thus displaying new absorption features. However, the UV-vis absorption feature of 3 was very similar to those of other 1,2,3,16-adducts, 7 while that of 4 showed a diagnostic spike at 431 nm, pretty close to those of other 1,2,3,4-adducts. 4 The observed similar absorption features of 3 and 4 to those reported in the literature conrmed their structural assignments. The uorescence spectra of biscycloadducts 2 and 4 in chloroform solution with an excitation wavelength of 550 nm resembled each other and exhibited two peaks at $720 and $800 nm, while those of 3 and 5 showed two peaks at 711 and 790 nm for the former and 696 and 766 nm for the latter, respectively. Two similar uorescence peaks have also been observed for bis-cycloadducts of C 60 in the literature. 19 The CVs and DPVs of tetra-functionalized products 2-4 in the range of 0 to À2.0 V showed predominantly four redox processes, whereas Scheme 2 Reaction of 1 2À with 1,2-bis(bromomethyl)benzene at 0 C and 25 C to afford 2 and 4, respectively.
Scheme 3 Electrochemical rearrangement of 2 to 4 at 25 C.
those of hexa-functionalized product 5 exhibited only three redoxes in the same range probably due to its decreased electronaccepting ability. The rst and second redox waves of 4 were reversible, while the rst redox of 3 was quasi-reversible. In contrast, both 2 and 5 showed an irreversible wave for the rst redox process. These results hint that compounds 2, 3 and 5 may be further functionalized by the electrochemical reduction to their monoanionic and/or dianionic stages. In addition, the assigned structure of 5 was unequivocally conrmed by its single-crystal X-ray crystallography (Fig. 3). 20 As a consequence of the inherent chirality possessed by 5, the crystal structure contains a pair of enantiomers, and they are in equal amounts, which is encountered in other fullerene crystals. 6f,7c The structure of 5 reveals clearly that a heterocycle is bonded to C 60 through a C aryl atom and a N atom at C2 and C3 sites, respectively, and that a carbocycle is bonded to C 60 through two benzyl groups at the C9 and C10 sites, respectively. Two hydrogen atoms are attached to C1 and C4, neighboring the heterocycle. The six-functionalized carbon atoms of the fullerene cage are uplied from the spherical surface notably because of their sp 3 characters. The bond lengths for C1-C2, C2-C3, C3-C4, C1-C9, C9-C10 and C10-C11 are 1.580(2)Å, 1.642(2)Å, 1.557(2)Å, 1.622(3)Å, 1.596(2)Å, and 1.522(2)Å, respectively, and are within the range of typical C-C single bond lengths. In comparison, C5-C6 has a bond length of 1.351(2)Å, thus possessing double bond character. 7b The single-crystal structure of 5 clearly demonstrates that it has a unique "S"shaped conguration.

Conclusions
In summary, we have achieved the efficient and regioselective synthesis of the tetra-functionalized 1,2,4,17-adduct and the hexa-functionalized 1,2,3,4,9,10-adduct of C 60 . The 1,2,4,17adduct has an unprecedented cis-3 0 addition pattern, meanwhile the 1,2,3,4,9,10-adduct exhibits a unique "S"-shaped addition pattern. Both of them bear a carbocycle fused to a [6,6]junction and a heterocycle xed to a [5,6]-junction. The reaction of the electrochemically generated dianonic [60]fulleroindoline with 1,2-bis(bromomethyl)benzene for a short time and subsequent acid quenching afford the expected 1,2,3,16-adduct, proving our assumed addition site in the rst step. Further reaction without acid quenching provides products with different addition patterns depending critically on the reaction temperature. The product obtained at 0 C for 5 h is the desired unprecedented cis-3 0 adduct. In contrast, the same reaction at 25 C for 5 h selectively affords the more stable cis-1 isomer, which turns out to be generated by the rearrangement of the cis-3 0 isomer induced by the negatively charged system. Intriguingly, the obtained cis-3 0 adduct can be further regioselectively transformed into the "S"-shaped hexa-functionalized product. The observed high regioselectivities are controlled by charge distribution, steric effect and reaction temperature. It is anticipated that further chemical or electrochemical manipulations of the tetra-and hexa-functionalized [60]fullerene derivatives would provide new fullerene derivatives with novel addition patterns and physical properties.

Conflicts of interest
The authors declare no conict of interest.