Fullerenes, cyclopropanation

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... 

Figure 15.8 The Bingel reaction for the modification of fullerenes involves the in situ formation of a reactive halogen species in the presence of the strong base DBU. The cyclopropanation product can be used to create many bioconjugates.

Figure 15.9 The reaction of the amine-blocked derivative of 3-hydroxypropylamine with ethylmalonyl chloride gives an ethylmalonate-protected-amine compound, which can be used in the Bingel reaction to create an amine group on a fullerene surface. Reaction with Cfl in the presence of I2 and DBU gives the cyclopropanation product that can be deprotected with TFA to yield the free amine.

Figure 15.10 Fullerene-PCBM derivatives can be prepared using reactive diazo intermediates, which yield a cyclopropanation product similar to the Bingel reaction derivatives.

The demonstration that the 1,3-dipolar cycloaddition process with azomethine ylides works with nanotubes implies that similar reactions developed for use with fullerenes also may be successful with carbon nanotubes. In particular, the cyclopropanation reactions discussed previously for the modification of Cg0, likely will work for derivatization of SWNTs and MWNTs (Zakharian et al., 2005). 

Treatment of isoxazoline-fiised [60]fullerene 48 with NaOMe in the presence of MeOH gave the p-hydroxy nitrile derivative 49 in good yield <00SL361>. The synthesis of the enantiomerically pure cyclopropane amino acid 51 covalently attached to a fulleroisoxazoline has been achieved . 

The two most commonly used derivatization methods for exohedral functionalization are the nucleophilic cyclopropanation with malonates (Bingel, 1993) and the formation of fulleropyrrolidines (Maggini et al., 1993). Both of these protocols have been used extensively to produce water-soluble fullerenes for biomedical applications. Other stable water-soluble fullerene adducts have also been reported (Hirsch and Brettreich, 2005). Sections 3.2.2-3.2.5 will give a short overview on the state-of-the-art of water-soluble fullerene derivatives and outline some general trends for designing such molecular structures. 

Herrmann A, Ruettimann M, Thilgen C, Diederich F (1995) Multiple cyclopropanations of C70. Synthesis and characterization of bis-, tris-, and tetrakis-adducts and chiroptical properties of bis-adducts with chiral addends, including a recommendation for the configurational description of fullerene derivatives with a chiral addition pattern. Helv. Chim. Acta 78 1673-1704. 

A wide range of olefins can be cyclopropanated with acceptor-substituted carbene complexes. These include acyclic or cyclic alkenes, styrenes [1015], 1,3-dienes [1002], vinyl iodides [1347,1348], arenes [1349], fullerenes [1350], heteroare-nes, enol ethers or esters [1351-1354], ketene acetals, and A-alkoxycarbonyl-[1355,1356] or A-silyl enamines [1357], Electron-rich alkenes are usually cyclopropanated faster than electron-poor alkenes [626,1015],... 

Ethynylated dihydrofullerenes serve as precursors for buckydumbbells (Scheme 3.3). Coupling of the desilylated compound 10 with CuCl leads to the dimer 11 [24]. Reaction of Cjq with the acetylide Li-C=C-Li leads to the dimer with a bridge consisting of one acetylene unit only. Electronic interaction between the fullerene-units in these two buckydumbbells is negligible. Further examples of CgQ-acetylene-hybrids synthesized by using cyclopropanation reactions are shown in Chapter 4. 

Cyclopropanation of Cjq with diethyl bromomalonate in toluene with NaH as auxiliary base proceeds smoothly at room temperature (Scheme 3.5). By-products are unreacted Cjq and higher adducts. The formahon of higher adducts is discussed in detail in Chapter 10. The monoadduct can be isolated easily from the reach on mixture by column chromatography. Saponificahon of such di(efhoxycarbonyl)-methylene adducts of Cgg is achieved by treatment with NaH in toluene at elevated temperatures and subsequent quenching with methanol (Scheme 3.6) [32], This method provides easy access to defined water-soluble fullerenes and can also be applied to higher adducts. These malonic acid derivatives of are very soluble in polar solvents, for example acetone, THF or basic water, but insoluble in aqueous acids. 

The reverse reaction to the Bingel cyclopropanation - the so-called retro-Bingel reaction - was developed by Diederich, Echegoyen and coworkers [70] and opens up the possibility to remove the Bingel-addend completely. This removal was successfully done with Cjq malonates [70, 71], dialkoxyphosphorylmethano[60]-fullerene [72], methano[60]fullerenyl amino acid derivatives [73] and also with... 

Even an oligopeptide has been attached to (Table 4.3, compound 130) [111]. This was achieved by a coupling reaction of the carboxylic group in the side chain of the cyclopropane ring as well. First, the tert-butylcarboxylate 129 was synthesized by the reaction of the corresponding diazomethylbenzoate with Cgg. After hydrolysis with trifluoromethanesulfonic acid, the acyl chloride was generated by treatment with oxalyl chloride. Finally, in a one-step procedure the fullerene peptide 130 was obtained by the reaction with the N-deprotected pentapeptide H-(L-Ala-Aib)2-L-Ala-OMe. 

Cycloadditions to [6,6]-double bonds of Cjq are among the most important reactions in fullerene chemistry. For a second attack to a [6,6]-bond of a C q monoadduct nine different sites are available (Figure 10.1). For bisadducts with different but symmetrical addends nine regioisomeric bisadducts are, in principle, possible. If only one type of symmetrical addends is allowed, eight different regioisomers can be considered, since attack to both e - and e"-positions leads to the same product. Two successive cycloadditions mostly represent the fundamental case and form the basis for the regioselectivity of multiple additions. In a comprehensive study of bisadduct formations with two identical as well as with two different addends, nucleophilic cyclopropanations, Bamford-Stevens reactions with dimethoxybenzo-phenone-tosylhydrazone and nitrene additions have been analyzed in detail (Scheme 10.1) [3, 9, 10]. 

Determination of the absolute configurations of these optically active fullerene derivatives was possible by comparison of their experimental and calculated circular dichroism (CD) spectra [96]. Tether controlled bis-cyclopropanation reactions have been extensively used to synthesize extended fimctional architectures such as dyads. 

Mono-functionalization of Cyg affords, preferrably, C(l)-C(2) adducts (type a) (Figure 13.3). In some cases, for example, upon nucleophilic cyclopropanations they even represent the exclusively formed monoadducts [1-3,17]. Typical examples of addition reactions that afford monoadducts are epoxidations [18,19], osmylation [9], transition metal complex formations [20, 21], hydrogenation [13, 22], many cycloadditions [1, 2] and additions of nucleophiles [23]. For the formation and the chemical transformation of azahomo[70]fullerenes see also Chapter 12 (Schemes 12.4 and 12.5). 

Ortiz AL, Echegoyen L (2010) Unexpected and selective formation of an (e, e, e, e)-tetrakis-[60]fullerene derivative via electrolytic retro-cyclopropanation of a D2h-hexakis-[60]fuller-ene adduct. J Mater Chem 21 1362-1364... 

This chapter presents an up-to-date account of the redox properties of the pristine fullerenes and a large number of their derivatives as revealed by electrochemical studies in solution. The description here is as exhaustive as possible, although not completely comprehensive due to the large number of reports on the subject that have appeared over the years. A section on electrosynthesis of fullerene derivatives is included, with special emphasis on the retro-cyclopropanation reaction, a reaction that has led to the formation of novel derivatives as well as... 

At this point, it is important to indicate that a very large number of C-bridged cyclopropanated fullerene derivatives undergo irreversible reduction processes leading to the removal of the addend and recovery of the pristine parent fullerene. The process has been advantageously used in electrosynthetic procedures, and thus a separate section covering the electrochemically induced retro-cyclopropanation reaction is presented later in this chapter (see Sect. 6.1.5.2). A number of other C-bridged cyclopropanated derivatives will be discussed there. 

A large number of cyclopropanated derivatives of Cgo in which the bridging atom is an electron rich transition metal (see Fig. 16) such as Pt, Pd, Ni, Ir, W, Mo, and Rh has been reported. Their electrochemical properties have been reviewed [83, 141, 142] and, in general, reductions are Cgo centered and negatively shifted with respect to those of pure Cgo, while oxidations are metal centered. In most cases, however, the first reduction is accompanied by breakage of the carbon-metal bonds and recovery of the pristine [60] fullerene. In multiadduct derivatives, the breakage occurs in a stepwise manner. 

Two of the three pairs of diastereomers reduce at potentials more positive than those of the parent [76] fullerene, while the other pair is actually more difficult to reduce. Interestingly, in contrast with similar Ceo and C70 derivatives, the di-and trianions of these C76 monoadducts are much more chemically stable. In fact, the retro-cyclopropanation reaction (see Sect. 6.1.5.2 below), which removes the malonate addend, occurs in very low yields... 

The usefulness of the retro-cyclopropanation reaction is even more remarkable than previously anticipated. It was questioned whether this reaction allowed the selective removal of a Bingel-type addend while leaving addends of a different type unaffected. A variety of mixed bis-adducts such as those shown in Fig. 29, were prepared, all of which contained a bis(ethoxycarbonyl)methano group [182]. In all cases, CPE led to the selective removal of the Bingel addend in over 60% yield, while the other one was retained, confirming that the reaction may be used in a synthetic protection-deprotection protocol to prepare novel fullerene derivatives. 

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