Introduction

Just about two decades after the discovery of C60 Buckminster fullerene, carbon allotropes – fullerenes, nanotubes and graphene – have become increasingly important in material sciences1,2,3,4,5,6,7,8,9. Fullerenes are widely known and used as electron acceptors. Beside their electro-chemical properties, several fullerene adducts also possess optical activity, which is often beneficial and sometimes essential for applications in asymmetric synthesis or racemic resolution10,11,12,13,14.

Over the years, different methods for the functionalization of the fullerene core have appeared15,16,17,18,19,20,21,22. Chiral fullerene adducts are either generated through an inherent chiral addition pattern, through chiral addends or a combination of both10c. Hirsch was the first to prepare enantiomerically pure bis- and tris[bis(4-phenyl-2-oxazoline)methano]fullerenes with inherent chiral addition arrangements23,24. Later, his group extended this strategy to bis(4-phenyl-2-oxazoline) derivatives bearing an inherently chiral [3:3] hexaaddition pattern and used these structures as auxiliaries in stereoselective cyclopropanation reactions25. Related systems have also been published by Echegoyen26 and Rubin27.

Results

Herein, we report the syntheses of the first enantiomerically pure [6:0]hexakis[(bisoxazolinyl)methano]fullerenes 2 and the generation of several six-fold metal-complexes based on these compounds. These fullerene structures are not only aesthetically appealing, but also the first purely organic structures offering six metal-chelating sites disposed on a completely rigid scaffold and aligned according to the three orthogonal space directions there are some other completely rigid organic compounds bearing six metal-chelation sites. These do however possess a lower symmetry than the described fullerene adducts28. Potential applications should be found in asymmetric catalysis and as tectons in enantiomerically pure self-assembled supra-molecular structures.

Discussion

Derivatives 2a–c were obtained via cyclopropanation of C60 with the corresponding C2-symmetrical enantiomerically pure bis(oxazolines) 1a–c29 followed by simple silica column chromatography. The reaction conditions initially used by Hirsch to prepare bis- and tris[bis(oxazolinyl)methano]fullerene derivatives were not suitable for six-fold addition23,25, as they only yielded mixtures of lower oligo adducts. The latter could not be separated on achiral stationary phases. However, using the conditions reported by Sun with a 100-fold excess of CBr4 (Conditions A)30, both enantiomers of the phenyl derivatives all-S-2a and all-R-2a were obtained in 32% and 31% yield respectively (Fig. 3 and Table 1, Entries 1,2).

Table 1 Reagents and yields for the six-fold cyclopropanation reaction
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Figure 1
figure 1

13C NMR spectra of compound 2a.

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Figure 2
figure 2

CD spectra of all-S-2a (red) and all-R-2a (blue).

Concentrations in trifluoroethanol (TFE): all-R-2a: 0.058 mg/mL, all-S-2a: 0.060 mg/mL.

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Figure 3
figure 3

(Relating to Table 1) Reagents for the six-fold cyclopropanation reaction.

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Conditions A proved however to be inadequate for the preparation of compounds 2b–c. In all cases, no hexakis derivatives bearing the desired geometry could be found. One of the major products was a pentakis adduct with an addition pattern not leading to the desired octahedral hexakis adducts (results not shown)31. In order to circumvent this problem, we turned to the 9,10-dimethylanthracene (DMA) template-directed activation developed by Hirsch, which is known to generate exclusively the desired penta- and consequently hexakis-regioisomers with an octahedral addition pattern31.

With this method hexakis adducts 2b–c could be obtained. However, the [5:1] hexakis bis(oxazoline)/DMA adduct was in all cases a major side product in these reactions and could not be completely separated from the [6:0] compound. These [5:1] adducts did not further react under the Hirsch conditions, but yielded the corresponding [6:0] hexakis[bis(oxazolinyl)methano]fullerenes 2b–c when first heated to 60°C for 30 min and then reacted with CBr4 (3 eq.), BOX (3 eq.) and DBU (6 eq.) in o-DCB (Conditions B) (Table 1, Entries 3–5)30. Hence, applying either protocols A or B gave access to a whole series of hexakis[bis(oxazoline)] adducts in good to excellent overall yields.

1H and 13C NMR analyses confirm the octahedral addition pattern of compounds 2. The four observed 13C signals at 142.0, 142.1, 145.5 and 145.9 ppm are in agreement with the chiral tetrahedral (T) point group symmetry (Figure 1). These BOX-fullerene adducts are actually less symmetric than most [6:0] hexakis adducts bearing pyritohedral symmetry (Th)32.

Hirsch proved that a fullerene multi-adduct is obtained as diastereomers if C60 is reacted with enantiomerically pure addends, which arrange in an inherently chiral addition pattern23b. Hexakis adducts with an octahedral [6:0] addition pattern have achiral tetrahedral symmetry. Such adducts can consequently only exhibit axial chirality generated through their chiral addends. Thus, all [6:0] hexakis[(bisoxazolinyl)methano]fullerenes generated from enantiomerically pure BOX 1 were obtained as single enantiomer. Optical rotation and CD spectra show the enantiomeric relationship of (all-S-2a/all-R-2a) and (all-S-2b/all-R-2b) (see Figure 2 and SI).

With compounds 2 in hand, we investigated their capacity to build six-fold metal-complexes. Compounds all-S-2a and all-S-2b were treated with [(PhCN)2PdCl2] (10 eq.) and in a third test all-S-2a was reacted with [CuI] (10 eq.). In all three cases, the recovered precipitate proved to be insoluble in conventional solvents. The six-fold complexes could however be detected by mass spectrometry (see SI). In each case, several fragments containing six metal-ions and (6–n) chloride ions were detected (n = 1 to 6). This strongly indicates the formation of six-fold metal-complexes. Due to the weakly bound chloride ions it was not possible to detect the [2Pd6Cl12] species.

We have presented the first synthetic access to [6:0] hexakis[(bisoxazolinyl)methano]fullerenes. These compounds provide an all organic rigid scaffold bearing six metal-chelation sites, which are orthogonally directed. Preliminary experiments indicate that the generation of six-fold metal-complexes is possible. We are currently working to improve the solubility of such metal-complexes in order to purify and completely characterize them.

Methods

Synthesis of all-(R)-2a

BOX derivative (R,R)-1a (1.28 g, 4.16 mmol, 10.0 eq.), CBr4 (13.8 g, 41.6 mmol, 100 eq.), C60 (300 mg, 416 μmol, 1.00 eq.) and DBU (1.25 g, 8.32 mmol, 20.0 eq.) were reacted in dry o-DCB (90.0 mL) as described above. After 72 h of stirring at ambient temperature, the reaction mixture was poured into 300 mL of cyclohexane to remove the o-DCB. The precipitate was filtered off and abundantly washed with cyclohexane. After column chromatography (toluene/ethyl acetate (9:1) + 5% EtOH + 0.2% NEt3) the hexakis fullerene adduct all-(R)-2a was obtained as a brown solid in 31% yield. – Mp: decomposition at T > 286°C. – IR (KBr): = 2896 (vw), 2161 (vw), 2043 (vw), 1657 (vw), 1493 (vw), 1452 (vw), 1355 (vw), 1188 (vw), 1082 (vw), 980 (vw), 928(vw), 749 (vw), 698 (w), 594 (vw), 526 (vw), 420 (vw) cm−1. − UV/VIS (CHCl3): λmax (log ε) = 181 (7.7), 186 (7.7), 211 (7.4), 272 (6.9) nm. – (c = 0.038, THF): −101°·mL·dm−1·g−1. –1H-NMR (500 MHz, CDCl3): δ = 4.29 (dd, 3J = 8.3 Hz, 12 H, 5-H), 4.80 (dd, 2J = 10.0 Hz, 3J = 8.7 Hz, 12 H, 5-H), 5.44 (dd, 2J = 10.0 Hz, 3J = 8.3 Hz, 12 H, 4-H), 7.32−7.35 (m, 60 H, Ph-H) ppm. – 13C-NMR (125 MHz, CDCl3): δ = 34.9 (Cp-Cap), 69.8 (C-5), 70.2 (C60-Csp3), 75.1 (C-4), 127.0 (Ph-Cm), 127.6 (Ph-Cp), 128.7 (Ph-Co), 141.7 (Ph-Ci), 142.0 (C60-Csp2), 142.1 (C60-Csp2), 145.6 (C60-Csp2), 145.8 (C60-Csp2), 161.1 (C = N) ppm. – MS (FAB, 3-NBA) m/z (%): 2544 (55) [M]+, 2412 (9), 2240 (4), 769 (28), 719 (100).

Synthesis of all-R-2b

C60 (360 mg, 500 μmol, 1.00 eq.) and DMA (1.03 g, 5.00 mmol, 10.0 eq.) were stirred for 1 h in dry toluene (210 mL). Then bisoxazoline (R,R)-1b (911 mg, 5.00 mmol, 10.0 eq.) and CBr4 (1.66 g, 5.00 mmol, 10.0 eq.) were added and during 20 min DBU (1.52 g, 10.0 mmol, 20.0 eq.) was dropped into the solution. After 72 h of stirring under argon, the solvent was evaporated and the crude product was subjected to column chromatography (toluene/ethyl acetate (9:1) + 20% EtOH + 0.2% NEt3). The product obtained that way was dissolved in dichloromethane (3 mL) and precipitated by dropping the solution into diethyl ether (100 mL) to remove the silica that was dissolved by the EtOH. That way, besides the pure product, a mixture consisting of the hexakis derivative and some lower adducts was isolated. In a further reaction under conditions c), the latter was converted into the hexakis adduct vide supra. The purification of the crude product was carried out as for the first product batch by chromatography and precipitation. Finally the hexakis BOX methanofullerene all-(R)-2b was isolated in 19% (168 mg, 90.0 μmol) overall yield. – Mp: decomposition at T > 235°C.– IR (KBr): = 3272 (br, vw), 2965 (w), 2895 (vw), 1657 (w), 1447 (vw), 1354 (w), 1288 (w), 1195 (w), 1103 (w), 1064 (w), 1022 (w), 976 (w), 942 (w), 844 (vw), 709 (w), 665 (vw), 539 (w), 523 (w) cm−1. – UV/VIS (CHCl3): λmax (log ε) = 213 (7.0) nm. –1H-NMR (400 MHz, CDCl3): δ = 1.29 (d, 3J = 6.5 Hz, 36 H, CH3), 3.94 (dd, 3J = 7.4 Hz, 12 H, 5-H), 4.32−4.37 (m, 12 H, 4-H), 4.43 (dd, 2J = 9.2 Hz, 3J = 8.0 Hz, 12 H, 5-H) ppm. – 13C-NMR (100 MHz, CDCl3): δ = 21.3 (CH3), 34.4 (Cp-Cap), 62.0 (C-5), 69.7 (C60-Csp3), 74.7 (C-4), 141.9 (C60-Csp2), 142.1 (C60-Csp2), 145.1 (C60-Csp2), 145.3 (C60-Csp2), 160.0 (C60-Csp2) ppm. − MS (FAB, 3-NBA) m/z (%): 1801 (13) [M]+, 1621 (8) [M−C9H12N2O2]+, 745 (13), 720 (29), 154 (100) [3-NBA].