Bingel cyclopropanation

Dendrimers 5-8 were obtained by taking advantage of the versatile regiose-lective reaction developed in the group of Diederich [24], which led to macro-cyclic bis-adducts of Cgg by a cyclization reaction at the C sphere with bis-mal-onate derivatives in a double Bingel cyclopropanation [25]. Reaction of the dendritic malonates with Cgg, I2, and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in toluene at room temperature afforded the corresponding cyclization products 5-8 (Fig. 2). The relative position of the two cyclopropane rings in 5-8 on the Cgo core was determined based on the molecular symmetry deduced from the and NMR spectra (Cs) as well as on their UV/Vis spectra. It is well estabhshed... 

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... 

Figure 17 Mono (50) and regio-isomeric bis-adducts (51, ( )-52 and ( )-53) formed by Bingel cyclopropanation of [70]fullerene. Also shown are Newman-type projections looking down the C s-symmetry axis of the C70 core on to the two polar pentagons, which show the relative orientations of the addends.

With the bis-malonate 56 containing a vra-disubstituted DB18C6 tether, the regioselectivity of the macrocyclization of C70 via double Bingel cyclopropanation... 

Beyond the widely used synthetic methodologies of 1,3-dipolar cycloadditions, Bingel cyclopropanations, and various other cycloadditions on fullerene skeletons, several novel organofullerene materials have been produced utilizing reactions that do not fall into any of the above-mentioned categories. Nevertheless, due to their unique formation, that could not otherwise be reached via those established synthetic methodologies, a few such chemical transformations of fullerenes are presented in this section. 

Several organofullerene donor-acceptor molecular material hybrid systems have been synthesized via 1,3-dipolar cycloaddition reactions of azomethine ylides, via Bingel cyclopropanation and methanofullerene formation intermediates as well as via cycloaddition reactions, that have already been discussed in previous sections. The majority of such hybrid systems possess always as acceptor unit the fullerene core and as donor moieties porphyrins, tetrathiafulvalenes, ferrocenes, quinones, or electron-rich aromatic compounds that absorb visible light [190-193]. The most active research topic in this particularly technological field relies (i) on the arrangement of several redox-active building blocks in... 

Following our protocol to separate fullerene isomers by the intermediacy of defined covalent adducts, the fraction of fullerene soot was subjected to Bingel cyclopropanation with bis (.S )-l -phenyl butyl malonate (cf. Section III.C).60 Among the products two chiral mono-adducts and four chiral bis-adducts were isolated in pure state and characterized. An analysis taking into consideration the symmetries of the compounds as deduced from H- or 13 C NMR spectroscopy, the magnitudes of their Cotton effects (these are relatively large, between ca. 10 and 200 M 1 cm-1 in the case of chiral fullerene... 

A well-defined C,so-anchored two-arm poly(t-butyl acrylate) has been synthesized by a Bingel cyclopropanation between a two-arm poly(t-butyl acrylate) with a... 

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 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. 

The addition of a particularly useful reagent, bearing two ester functionalities, is obtained by means of the Bingel-Hirsch cyclopropanation [29]. Although the mechanism may not be of carbene-type, the result is formally equivalent to a carbene addition. The presence of the ester groups renders this derivative susceptible for further modifications. 

The stabilization of reaction intermediates RCjq and RC q to form dihydrofullerene derivatives can also be achieved by intramolecular nucleophilic substitutions (SjJ), if R contains a leaving group. As shown by Bingel [31], the generation of a carbon nucleophile by deprotonation of a-halo esters or a-halo ketones leads to a clean cyclopropanation of Cjq. 

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 only electrochemical study on derivatives of Cg4 describes the use of the Bingel-retro-Bingel protocol, now known as the retro-cyclopropanation reaction (see Sect. 6.1.5.2), to isolate the two major isomers of pure Cg4 by removing bis(phenylbutyl)malonate addends from mono and bis-adducts of Cg4 (see (56) in Fig. 22) [54]. CV profiles in DCM (+0.12 M TBAPFg) of two different monoadducts and four different... 

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. 

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. 

Figure 21 Isomerization and retro-cyclopropanation reactions of bis-Bingel adducts of [60]fullerene induced electrolytically.

Finally, the wide applicability and the experimental simplicity of the retro-Bingel reaction was evidenced in the isolation of pure enantiomers of C76, in the formation of methanofullerene compounds not accessible otherwise, such as ( )-75, and in the separation of constitutional isomers as well as of enantiomers of Cg4. The retro-cyclopropanation reaction seems to be generally selective, and still needs to be exploited in the preparation of unusual derivatives with controlled regiochemistry. 

Figure 1.29. Valence isomerization of a primary C2-symmetric Bingel type hexakis-adduct of C70 with two 6-5 closed bonds (leftside), initially formed in the cyclopropanation of bis-adduct ( )-103 (Figure 1.26), to the more stable C2-symmetric structure ( )-112, containing two 6-5 open bonds. The molecules are viewed along the C2-axis.

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