Methanofullerenes

The most important classes of functionalized [60]fullerene derivatives, e.g. methanofullerenes [341, pyrrolidinofullerenes [35], Diels-Alder adducts [34i] and aziridinofullerene [36], all give rise to a cancellation of the fivefold degeneration of their HOMO and tlireefold degeneration of their LUMO levels (figure Cl.2.5). This stems in a first order approximation from a perturbation of the fullerene s 7i-electron system in combination with a partial loss of the delocalization. 

Arias F, Echegoyen L, WIson S R, Lu Q Y and Lu Q 1995 Methanofullerenes and methanofulleroids have different electrochemical behavior at negative potentials J. Am. Chem. Soc. 117 1422-7... 

Methanofullerene 20 with phenylacetylene dendrimer addends has also been reported [45] (Fig. 10). The UV absorption of fullerodendrimer 20 is particularly strong and is mainly attributed to transitions located on the two dendritic branches of the molecule. The photophysical investigations revealed that the large poly(aryl)acetylene branches act as photon antennae [46]. 

A methanofullerene derivative possessing an ammonium subunit has been prepared and subsequently shown to form a supramolecular complex with a porphyrin-crown ether conjugate <06T1979>. The synthesis and study of these fullerene-containing supramolecular photoactive devices have also been reported <06CRC1022>. 

Another example has been provided by Ito et al., who described the use of methanofullerene derivatives as powerful and stable precursors for glycofullerenes.217 Their study was based on the use of [60]fullerenoacetyl chloride (227), obtained from the ferf-butyl [60]fullerenoacetate derivative 226, which had been prepared in 56% yield by treatment of corresponding stabilized sulfonium ylides 225 with C6o-218 Subsequent transformation with p-TsOH in toluene gave [60]full-erenoacetic acid, which was directly converted into the corresponding acyl chloride 227 by using thionyl chloride. Standard ester formation with methyl 2,3,4-tetra-O-benzyI -/<-d-gl ucopyranoside (228) and 4-(dimethylamino)pyridine (DMAP) afforded the desired hybrid derivative 229 in 66% yield. 

An alternative synthetic approach, first developed by Bingel225 allowed the efficient nucleophilic cyclopropanation of fullerenes via their reaction with bromomalonate derivatives in the presence of base. This approach, the most reliable method for the synthesis of functionalized methanofullerenes, combined the advantages of mild... 

Isaacs, L., and Diederich, F. (1993) Structures and chemistry of methanofullerenes a versatile route into N-[(methanofullerene)carbonyl]-substituted amino acids. Helv. Chim. Acta 76, 2454-2464. 

Fig. 1.3 Fullerene bearing 7 [3-alanine, Baa, and nitroxide malonate methanofullerene... 

Novel nitroxide malonate methanofullerenes (Fig. 1.3), thanks to the presence of nitroxide radicals and fullerene moiety, are able to protect cells from toxic side effects of cyclophosphamide (Gubskaya et al., 2007). Experiments were carried out on mice, in which leukemia P-388 was transplanted. Cyclophosphamide or fullerene individually injected did not increase the average life span of the animals, while the combination of the anticancer drug and nitroxide fullerene derivative resulted in the survival of 70% animals, classifying these compounds as promising modifiers of biological reaction for tumor therapy. 

Gubskaya VP, Berezhnaya LS, Gubaidullin AT, Faingold II, Kotelnikova RA, Konovalova NP, Morozov VI, Litvinov IA, Nuretdinov IA (2007) Synthesis, structure and biological activity of nitroxide malonate methanofullerenes. Org. Biomol. Chem. 5 976-981. 

The first carbon nanostructure that was covalently modified to alter surface properties was the C60 fullerene. After its discovery in the mid-1980s, numerous functionalization methods were developed for obtaining two important classes of derivatives, methanofullerenes and fullerene Diels-Alder adducts. 

F. Diederich, L. Isaacs, D. Philp, Syntheses, structures, and properties of methanofullerenes, Chemical Society Reviews, vol. 23, pp. 243-255,1994. 

C67H7N02 PMFFHA (A-Phenyl-(1,2-methanofullerene C60)61-formohydroxamic acid) Extraction Ce, La, U, V 146-148... 

The 1,3-dipolar addition reaction of fullerene with diazo compounds is one of the most studied reactions in the early stage of the research on fullerene chemistry [7]. The reaction in solution first affords rather labile fulleropyrazoline derivative 26, which is readily converted to the so-called 5,6-open (a bond originally shared by five- and six-membered rings cleaved) fulleroid (27) or 6,6-closed (a bond shared by two six-membered rings remaining closed) methanofullerene derivatives (28) by heat (e.g., refluxing in toluene) or photoirradiation (UV light), respectively (Scheme 11) [7a]. 

As well as the Bingel reaction and its modifications some more reactions that involve the addition-elimination mechanism have been discovered. 1,2-Methano-[60]fullerenes are obtainable in good yields by reaction with phosphorus- [44] or sulfur-ylides [45,46] or by fluorine-ion-mediated reaction with silylated nucleophiles [47]. The reaction with ylides requires stabilized sulfur or phosphorus ylides (Scheme 3.9). As well as representing a new route to l,2-methano[60]fullerenes, the synthesis of methanofullerenes with a formyl group at the bridgehead-carbon is possible. This formyl-group can be easily transformed into imines with various aromatic amines. 

The reaction of Cjq with silylated nucleophiles [47] requires compounds such as silyl ketene acetals, silylketene thioacetals or silyl enol ethers. It proceeds smoothly and in good yields in the presence of fluoride ions (KF/18-crown-6) (Scheme 3.10). The advantage of the latter synthesis is the realization of the cyclopropanation under nearly neutral conditions, which complements the basic conditions that are mandatory for Bingel reactions. Reaction with similar silyl ketene acetals under photochemical conditions and without the use of F does not lead to methanofullerenes but to dihydrofullerene acetate [48]. 

An unusual reaction of electron-deficient acetylenes (usually DMAD is used) and triarylphosphines or -phosphites with Cjq leads to methanofullerenes that bear an a-ylidic ester (Scheme 3.11). Selective hydrolysis of the phosphite ylides yields phosphonate esters, phosphine oxides or phosphonic acids [49-51]. 

Methoxy[(trimethylsilyl)ethoxy]carbene - obtained by thermolysis of the corresponding oxadiazoline 337 - reacts with Cgo in an unprecedented reaction pathway [383,384]. The expected methanofullerene-[2-i-l]-cycloadduct could not be observed. Instead the two dihydrofullerene adducts 338 and 339 were isolated (Scheme 4.69). They are formed by an unusual addition-rearrangement mechanism that includes the migration of the trimethylsilyl group. 

Diazo compounds also undergo cycloaddition with fullerenes [for reviews, see (104),(105)]. These reactions are HOMO(dipole)-LUMO(fullerene) controlled. The initial A -pyrazoline 42 can only be isolated from the reaction of diazomethane with [60]fullerene (106) (Scheme 8.12) or higher substituted derivatives of Ceo (107). Loss of N2 from the thermally labile 42 resulted in the formation of the 6,5-open 1,2-methanofullerene (43) (106). On the other hand, photolysis produced a 4 3 mixture of 43 and the 6,6-closed methanofullerene (44) (108). The three isomeric pyrazolines obtained from the reaction of [70]fullerene and diazomethane behaved analogously (109). With all other diazo compounds so far explored, no pyrazoline ring was isolated and instead the methanofullerenes were obtained directly. As a typical example, the reaction of Cgo with ethyl diazoacetate yielded a mixture of two 6,5-open diastereoisomers 45 and 46 as well as the 6,6-closed adduct 47 (110). In contrast to the parent compound 43, the ester-substituted structures 45 and 46, which are formed under kinetic control, could be thermally isomerized into 47. The fomation of multiple CPh2 adducts from the reaction of Ceo and diazodiphenylmethane was also observed (111). The mechanistic pathway that involves the extrusion of N2 from pyrazolino-fused [60]fullerenes has been investigated using theoretical methods (112). 

Previously Frechet et al. had prepared a dendritic methanofullerene, but its redox properties were not reported. ... 

An important difference between methanofullerenes and fulleroids is that... 

---