Nucleophilic Addition to Fullerenes

The reactivity of fullerenes toward nucleophiles is caused by their electron deficiency. Numerous reactions with nucleophilic reagents leading to useful and interesting derivatives have been described.

The nucleophilic addition to fullerenes corresponds to the common mechanism observed for electron-deficient olefins. A nucleophile A- initially attacks the double bond and a reactive intermediate C-0A- is generated. This can be stabilized in several ways. The product C60AE results from the reaction with an electrophile E+ (Figure 2.54a). These steps may proceed repeatedly to give compounds with a general composition of C60A*Ex- Furthermore, an intramolecular reaction is possible that yields bridging functional groups, and C-0A2 is accessible by oxidative work-up of C60A-.

The alkylation by organolithium- or Grignard-reagents is a basic reaction between a fullerene and a nucleophile. According to the mechanism above, the C60R--anion is generated in a first step. It is then stabilized with H+ in an acidic

Figure 2.54 (a) General mechanism of the nucleophilic addition to a fullerene; (b) reaction of C60 with organo-lithium or Grignard compounds.
C60 Iodine
Figure 2.55 (a) The reaction of C60 with amines yields aminofullerenes; (b) some examples of amino derivatives of C60.

work-up yielding the hydroalkylated fullerene (Figure 2.54b). In analogous ways the reaction may be conducted with aromatic residues R or with acetylides. With a large excess of metal organyl applied, multiple additions of up to five alkyl groups can occur depending on the size of the residues.

Moreover, fullerenes easily enter into nucleophilic additions with primary or secondary amines. Here the first intermediate is an anionic complex with two electrons being transferred from the amine to the C60. Subsequent recombination with Zwitterion generation and ensuing proton transfer yield the hydroaminated product (Figure 2.55a). Still an isolation of individual derivatives usually is impossible because the amines' high nucleophilicity leads to the formation of different multiple adducts. These tend to be inseparable, and just in some cases the selective isolation of the tetraamino-adduct succeeds. What is more, strict exclusion of oxygen is required to prevent the generation of dehydrogenated species and, to some extent, epoxides. Figure 2.55b collects some examples of isolated and characterized amino compounds. With diamines, C60 reacts to give bridged derivatives. The addition takes place on a (6,6)-bond. Here as well, dehydrogenated products are obtained as the amino protons present in the first stage are removed by oxidative elimination. Usually mono- or bisadducts are formed. Tertiary amines cannot react with C-o to yield analogous products. They give charge .transfer complexes instead, with some of them being considerably stable, for example, the C60- complex with the -ewco-form of crystal violet. Apart from that, they may also enter into photochemical or thermal radical processes (Section 2.5.5.5).

In reactions of alkyl cyanides with C60 an intermediate C60CN--anion is formed which may then be saturated by various electrophiles (e.g., H+, Me+, etc.) A special feature of the cyanide addition is the generally exclusive production of the monoad-duct. This turns the reaction valuable to the directed introduction of exactly one functional group.

When treating toluenic solutions of C6 0 with concentrated solutions of potassium hydroxide, a mixture of various hydroxylated products collectively termed fullerenoles is generated. These compounds are rather labile especially toward atmospheric oxygen, which renders their characterization complicated. What is more, these mixed compounds with their various numbers of hydroxyl groups can hardly be separated. Yet the introduction of single hydroxyl groups may be achieved by substituting halogen atoms in halofullerenes, for instance C60F35OH or C70F37OH can be obtained this way.

The Bingel-Hirsch Reaction One ofthe most valuable preparative methods applicable to fullerenes is the Bingel-Hirsch reaction. This is, in detail, the nucleophilic attack of a bromomalonate on the double bond of a fullerene in the course of which a cyclopropane ring is generated. The reaction exclusively yields the meth-anofullerene with a bridged (6,6)-bond. It has first been described by C. Bingel in 1993, and A. Hirsch subsequently optimized the conditions, so today it is one of the best controllable reactions of fullerenes and can be performed with a multitude of reagents and substrates.

The classical approach to this method employs the C-H-acidic diethyl bromoma-lonate that is reacted with sodium hydride, generating the actual reagent by deprotonation. The resulting nucleophile attacks a double bond of the fullerene to give the anionic intermediate. The negative charge in the latter is localized in aposition to the malonate, so this nucleophilic center in the C60-skeleton can perform an intramolecular attack on the brominated carbon atom (SNi-reaction). Finally, the methanofullerene is formed by cleaving Br- (Figure 2.56). The choice of a specific base is an important aspect in conducting the Bingel-Hirsch reaction. Sodium hydride is quite suitable as it does not enter into nucleophilic reactions. Primary and secondary amines on the other hand do not lead to the desired products because they are nucleophiles themselves and can attack C60 as such. Further examples of suitable bases are DBU (1,8-diazabicyclo[5.4.0]undec-7-ene), LDA,

Fullerene Amine

Figure 2.56 From a preparative point of view, the Bingel-Hirsch reaction counts among the most valuable transformations because it tolerates a wide variety of functional groups. Moreover, it provides access to interesting products of multiple additions taking place at defined positions.

Figure 2.56 From a preparative point of view, the Bingel-Hirsch reaction counts among the most valuable transformations because it tolerates a wide variety of functional groups. Moreover, it provides access to interesting products of multiple additions taking place at defined positions.

pyridine, or triethylamine. A mechanochemical (solvent-free) variant employing a vibration mill and sodium carbonate as a base has also been reported. Saponification of the ethyl ester groups yields the methanofullerene dicarbonic acid.

Figure 2.56 collects some exemplary reactions of C60 with different bromoma-lonates and other applicable keto compounds. This collection shows that there is virtually no limit to the choice of side chains, which renders the Bingel-Hirsch reaction an attractive and flexible starting point for the synthesis of fullerene -containing materials. For example, the base -mediated conversion of a malonate and C60 into the respective methanofullerene can also be achieved. With the semiester of malonic acid instead of a malonate, the monosubstituted methanofuller-ene is obtained because the primary product is instantaneously decarboxylated (Figure 2.56). P-Ketoesters may also be reacted under Bingel-Hirsch conditions to give methanofullerenes.

In some cases the preparation of the bromomalonate may be difficult or even impossible. The reactive species may then be generated in situ by treating the malonate with CBr4. The reaction of a malonate with iodine and DBU as a base also yields the respective methanofullerene. Today the in situ generation of a-haloesters and a-ketones find widespread application as it spares the efforts of a purification step before reacting them with the fullerene.

o , one enantiomer of D2-C

2. poten tiostatic electrolysis one enantiomer of D2-C

2. poten tiostatic electrolysis

Figure 2.57 The enantiomeric resolution of D2-C76 is achieved by chromatographic separation of the Bingel-Hirsch adducts and subsequent cleavage of the auxiliary group.

Due to the high reactivity of malonates toward C60, an excess of the reagent will usually lead to multiply functionalized products. Now, as discussed in Section 2.5.1.3, there are several potential positions for a second or third reaction on the fullerene's surface, and so a strategy of regiochemical control is required to realize a certain addition pattern. One method uses interconnected reaction centers. The length of the respective linker then determines the possible sites for the second attack. For instance, with two malonates linked via a polyether chain, a crown-ether derivative, a substituted porphyrine or the like, the reaction with CBr4 (or I2) and a base will regio- and diastereoselectively yield the most favorable isomer depending on the length of the template linker.

It goes without saying that the Bingel-Hirsch reaction also takes place with larger fullerenes, but contrasting C6 0, there are different double bonds, and so several regioisomers can arise. For the addition of diethyl malonate to C70 only the 1,2-adduct is observed experimentally. The reactivity of this 1,2 -double bond by and large corresponds to that in C60 while the double bonds in the belt region of the C70-molecule are less reactive, so here again the position most alike to C60 is attacked preferably. Similar results are found for even larger fullerenes (C7 6 and higher): a major product with the functionality attached to a strongly bent position of the carbon cage is obtained.

The inverse Bingel-Hirsch reaction is of interest, too. It serves to remove Bingel addends from a functionalized fullerene while re-generating the respective double bond. The reduction may be performed electrochemically as well as by reaction with magnesium amalgam or zinc/copper. Now, what is the benefit of removing a substituent once introduced with considerable effort? A first application of the retro - Bingel reaction has been reported for the separation of enantiomers of C76: a pair of diastereomers is generated by functionalization with a suitable malonate. These can easily be separated (Figure 2.57- , and the subsequent cleavage of the Bingel addend from both fractions yields the pure enantiomers of the smallest chiral fullerene. The Bingel addends may also act as protecting (and even directing) groups in further syntheses by occupying certain positions on the fullerene's surface and possibly by exerting directing effects on following additions. In an overall strategy employing protective groups, the Bingel addends are orthogonal to the pyrrolidines accessible by [3+2]-cycloaddition (Section 2.5.5.3) . These will not be cleaved under the conditions presented above.

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