Bingel addends

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... 

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. 

However, the chemical reduction reaction does not work efficiently for the removal of two Bingel addends, whereas the electrochemical reduction process works very efficiently. One of the most interesting examples that illustrates the difference between the chemical and electrochemical methodologies involves the cyclophane type trans-1 ( -37) conjugate [76], The chemical reductive protocol fails completely with this compound, presumably due to ion complexation by the crown ether group and consequent stabilization. When the electroreductive method was used, a clean retrocyclopropanation reaction was observed (Figure 25). 

A hint for a removal of a Bingel addend at high temperature is found in ref. 95... 

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 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... 

Clearly, depending on the number of electrons per molecule added during CPE, either removal of the addends [170] or an isomerization reaction was attained. The former reaction was initially called the rctro-Bingd reaction [64], since it was the reverse of the Bingel addition of methano addends to Ceo [171]. The generality of the retro-Bingel and isomerization reactions has since been tested using other multiple-malonate adducts of Ceo [172,173]. In fact, the reaction has made it possible to isolate the Civ isomer of Cyg, a new Cyg bis-adduct, and new isomers of Cg4 [44, 54]. 

Further investigation has proved that addend removal is not limited to Bingel-type... 

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 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.

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.

A Ci-symmetric hexakis-adduct of C6o including an azahomofullerene substructure (addition pattern analogue of homo[60]fullerene derivative ( )-26, Scheme 1.2) was obtained as a side product upon nitrogen extrusion from a fullerene derivative bearing five Bingel type addends and a fused triazoline arranged in a pseudo-octahedral manner.120... 

Hirsch and co-workers subsequently discovered that the yield of hexakis-adducts such as 8 or 9 can be greatly increased and their separation from side products substantially facilitated, if 9,10-dimethylanthracene (DMA) is used as a template (Scheme 7-2) [14, 15]. Anthracene derivatives such as DMA are well known to undergo reversible Diels-Alder additions with fullerenes at ambient temperamre [16-18]. After addition to the fullerene, the template directs diethyl malonate addends in the Bingel addition tegio-selectively into e positions, ultimately yielding the hexakis-adducts with a pseudo-octahedral, all-e addition pattern. The templated activation of e 6-6 bonds (bonds between two six-membered rings) is also efficient starting from C o mono-adducts, and several examples are shown in Scheme 7-2. Thus, bis(alkynyl)methanofullerene 10 [19] reacted with diethyl 2-bromomalonate/DBU (8 equiv) and DMA (12 equiv) to provide hexakis-... 

Since cis-3, trans-3, and trans-2 bis-adducts of 50 with identical addends are chiral as a result of inherently chiral functionalization patterns [10, 44-46], it was of interest to explore whether Bingel macrocyclizations with bismalonates bridged by non-racemic tethers would provide an enantioselective synthesis of these compounds. An overall enantioselective synthesis of optically active Cgg bis-adducts had been achieved previously by asymmetric Sharpless bis-osmylation [77] however, this sequential bis-func-tionalization lacks the regioselectivity of the Bingel macrocyclization, and therefore requires tedious regioisomer separations. 

The two major Bingel bis-adducts with achiral malonate addends,45 and ( )-46 (Fig. 7), were further reacted with diethyl bromomalonate to explore the regioselectivity in the formation of higher adducts. Whereas an achiral tetra-kis-adduct (C2v-symmetrical 60) was obtained from C2v-symmetrical bis-adduct 45, the chiral, C2-symmetrical bis-adduct ( )-46 afforded the C2-symmetrical ( )-61 with an inherently chiral functionalization pattern [54] (Fig. 10). Once C70 bis-adducts are formed, further addition must take place in a hemisphere... 

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