Reactions Bingel

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.

Following the discovery of a bulk fullerene preparation process in 1990, the covalent chemistry of these carbon allotropes has developed at a phenomenal pace. Frontier orbital (LUMO) and tether-directed functionalization concepts have been successfully applied to the regio- and stereoselective preparation of multiple covalent adducts of C60. These have found increasing applications in the construction of functional supramol-ecules. More recently, the sequence of Bingel reaction - retro-Bingel reaction has provided an elegant access to isomerically pure higher fullerenes and, in particular, to pure carbon enantiomers. 

One of the most convenient of these tether-directed functionalization strategies exploits the macrocyclization of C60 with bismalonate derivatives in a double Bingel reaction.156,571 With the exception of the cis-1 bisaddition product, all possible bisaddition patterns have been obtained by this macrocyclization reaction (Figure 13). As a general... 

Scheme 7. Optical resolution of ( )-C76 by the Bingel/ retro-Bingel reaction sequence.

Scheme 20 Solid-state Bingel reaction of under the HSVM conditions...

The electrochemistry of derivatized Cjq has also been widely investigated [8, 23-28], As observed by electrochemical reduction, derivatization usually decreases the electron affinity of the CgQ-sphere. Typically, cathodicaUy (more negative) shifted waves have been observed by cyclovoltammetry and other methods. Depending on the addend, the shifts range from 30 to 350 mV per adduct with respect to those of pure Cgfl. Reduction of some derivatives resulted in the loss of the addend. In some cases, like the retro-Bingel-reaction (Section 3.2.2), this can also be advantageous. 

The Bingel reaction is not restricted to C-H-acidic carbonyl compounds such as malonates. Various other substrates have also been used. Some C-H-acidic compounds, which were successfully subjected to the Bingel reaction, are shown in Table 3.1. 

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]. 

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... 

One modification of the Bingel reaction involves DBU as a base. Initial experiments showed that exposure of CgQpjg to DBU leads to a complete loss of fluorine [71]. Fortunately this defluorination does not take place in the presence of diethyl bromomalonate. Reaction of CgQpjg with DBU and diethylbromomalonate in toluene at room temperature yields three products and unreacted CgQpjg [67, 71]. The three products are the result of mono-, bis- and tris-substitution their relative yield depends on how fast the base is added. The reaction does not - as in the usual Bingel reaction - proceed via a nucleophilic addition reaction to one double bond but as a nucleophilic substitution with a Sj.j2 -mechanism. The bromomalonate anion attacks a double bond in 5-position to one of the least sterically hindered fluorine atoms, which leads to the loss of this fluorine. The bromine atom is not replaced (Scheme 9.6). 

Scheme 9.6 Mechanism of the Bingel reaction with QqFi8 (only a fragment of QoF,g is shown).

The all-trans annulenes can also be obtained by performing the Bingel reaction with malonates such as XCH(C02Et)2 (X= NO2 or S02CH2Ph) [72]. 

The cyclic voltammograms show three reduction waves in the potential window between 0 and —1.3 V versus SCE (Fig. 6.20). The first process is fully reversible, while the second one is chemically irreversible since the dianion is subject to a bond breaking of the cyclopropane ring, known as the retro-Bingel reaction.75 The third... 

Preparation of mono-adducts of fullerene - for studies on electrostatic interactions - was undertaken by cyclopropanation of fullerene with appropriately functionalised malonic esters 1 (Bingel reaction) to form 2. Coupling with the tert-butyl protected oligoamide-amino-dendron 3 and subsequent hydrolysis lead to the water-soluble fullerene dendron 5, which can carry up to nine negative charges after depro to nation. After association with the zinc complex of cytochrome C, photoinduced electron transfer (PET) from the redox protein to the fullerene can be accomplished, which was studied by fluorescence spectroscopy. 

The electrochemical properties of all these bis-adducts have been studied in reasonable detail, using either cyclic voltammetry (CV) or controlled potential electrolysis (CPE) [8], Reductive electrolysis of ester-containing methanofullerenes results in the removal of the adducts in a versatile and useful reaction, initially called the retro-Bingel reaction (Figure 1). Additional work resulted in the discovery of an intramolecular electrochemically induced isomerization of C6o-bis-adducts. Exhaustive reduction with one electron per molecule resulted in seven regio-isomers regardless of which pure bis-adduct regioisomer was electrolyzed. Recently, it has been observed that, in addition to the malonates, electrochemical reduction of other methano-adducts can also lead to removal of the addends,... 

Figure 1 Bingel and retro-Bingel reactions on C60. Position notation for bis-adducts...

Possibly the simplest and most versatile method for the preparation of covalent bis-adducts of C(,o with high regio- and diastereoselectivity is the macrocyclization between C(,o and bismalonate derivatives in a double Bingel reaction [7,8,26,27], In theory, each macrocyclic regio-isomer could form as a mixture of diastereomers, depending on how the EtOCO residues at the two methano bridge C-atoms are oriented with respect to each other (in-in, in-out,... 

At the beginning of this chapter, we mentioned how the removal of di(alkoxycar-bonyljmethano addends on a C6o core can be achieved by electrolytic reduction to yield the parent [60]fullerene. This so-called retro-Bingel reaction was initially conducted on diethyl l,2-methano[60]fullerene-61,61-dicarboxylate (see Figure 1) leading to > 80 % yield of recovered C60 after controlled potential... 

Figure 22 Selective removal of bis(ethoxycarbonyl)methano addends in mixed C60-bis-adducts by the retro-Bingel reaction.

Figure 30 Preparation of the pure enantiomers of D2-C84 by a retro-Bingel reaction of the fourth and fifth fractions of the bis-adducts, and CD spectra of the diastereo-isomeric bis-adduct (top right) as well as of the fullerene enantiomers (bottom right) in CH2C12. The absolute configurations of the fullerene spheroids reflect the structural drawings, but have not been assigned experimentally. Reprinted from ref. [71] with permission from Wiley-VCH.

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