Tether-directed

Thilgen C., Cardullo F., Haldimann R., Isaacs L., Seiler P., Diederich F., Boudon C., Gisselbrecht J. P., Gross M. Synthesis of Multiple Adducts of C60 With Specific Addition Patterns by Simple and Reversible (Templated) Tether-Directed Remote Functionalization Proc. - Electrochem. Soc. 1996 96-10 1260-1271 Keywords fullerene C60, regiochemistry... 

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 6. Enantioselect-ive synthesis of both enantiomers (fA)-27 and (fC)-27 by diastereoselective tether-directed biscyclopropanation of CgOr followed by transesterification.

L. Isaacs, R. E Haldimann, F. Diederich, Tether-directed Remote Functionalization of Buckminsterfullerene Regiospecific Hexaadduct Formation , Angew. Chem. Int. Ed. Engl. 1994,33, 2339-2342. 

L. Isaacs, E Diederich, R. F. Haldimann, Multiple Adducts of C6o by Tether-Directed Remote Functionalization and Synthesis of Soluble Derivatives of New Carbon Allotropes Cn(60+5) , Helv. Chim Acta 1997, 80, 317-342. 

Diazabishomofullerenes with another addition pattern can only be obtained in good yields if a tether directed synthesis is applied. If the tether between two azide groups is sufficiently rigid a second addition is forced to occur at specific regions of the fullerene cage [36, 37]. 

In 1994, Diederich and co-workers reported a very important approach for the regioselective formation of multiple adducts of Cjq by tether-directed remote functionalization [75]. This technique allows for the synthesis offullerene derivatives with addition patterns that are difficult to obtain by thermodynamically or kinetically controlled reactions with free untethered addends. This important subject has been extensively reviewed [26, 76, 77]. 

Scheme 10.16 Tether-directed remote functionalization leading to the tetraethynylated [2 4] hexakisadduct 76. (i) O2, hv, PhCI (ii) PPhj, PhCI ...

The tether directed cyclopropanations of Cjq discussed so far take advantage of specifically designed open-chain malonates with quite rigid spacers. This is a particularly suitable method for the synthesis of bisadducts. However, for an entry to tris- and higher adducts the design of a suitable steric arrangement becomes more and more difficult... 

Prior to the development of tether-directed functionalization methods, Krautler and co-workers developed a very elegant topochemically controlled, solid-state group-transfer synthesis [12,13] to obtain the trans-1 bisanthracene adduct 9 (Figure 2). 

The tether-directed remote-functionalization methodology has proved to be a very powerful synthetic tool, due to its high regio- and stereoselectivity. Since the first description of such a reaction in 1980 [6] a variety of regioselective protocols have been developed for fullerene derivatization, and these were recently reviewed [7], so this section constitutes a selective overview mainly focused on the pertinent features relevant to this chapter. 

Tethers (which are usually removable) are used to provide spatial separation between addends in tether-directed remote functionalization. The addends can be identical or different, like the ones represented in Figure 3 as A and RG, where A is the anchor addend that is connected initially and RG is a secondary reactive group that is subsequently added to the fullerene. The tether structure and rigidity controls the regio- and, in the occurrence, stereochemistry of the addition pattern between A and RG. 

Figure 3 Tether-directed remote functionalization (A = anchoring point, T = connecting tether, RG = reactive group).

Figure 4 Tether-directed remote functionalization and e addition pattern.

Figure 7 Enantioselective synthesis of (fA)-22 and (fC)-22 by diastereoselective tether-directed bis-cyclopropanation of C60, followed by transesterification.

Figure 8 Tether-directed additions of azomethine ylides to fullerene C60, assisted by a removable anchor.

Tris-adduct Formation by Tether-directed Binge Addition... 

In contrast to the large number of bis-adducts generated through a tether-directed methodology, only a few examples of tris-adducts have been described [19,45,46],... 

Hirsch and co-workers last year introduced a new concept for the tether-directed multifunctionalization of Cgo> with the use of cyclo-[n]-octylmalonates such as 34 (Figure 11) [50], As a result of the identical spacer lengths in these macrocycles, only bis- and tris-adducts with rotational symmetry are formed. The reaction of cyclo-[3]-octylmalonate (34) with Cgo leads to the e,e,e isomer 35 with high regioselectivity and excellent yield (94%). Additionally, 6% of... 

The application of the tether-directed remote functionalization allowed the preparation of stereo-isomeric C70 bis-adducts ( )-55a and ( )-55b with complete regioselectivity, featuring the kinetically disfavored five o clock addition pattern [63], see Figure 18. 

The scope of the tether-directed remote functionalization has been expanded from Cgo to the higher fullerene C70, and the described reactions are completely regioselective, featuring, in the case of C70, the kinetically disfavored addition pattern. The crown ether is a real template, since it can be readily removed by transesterification, giving a much-improved access to certain bis-adducts that are not accessible by the direct route. Cation-binding studies by CV reveal that cyclophane-type crown ethers derived from C60 and C70 form stable complexes with metal cations, and a perturbation of the fullerene reduction potentials occurs because the cation is tightly held close to the fullerene surface. This conclusion is of great importance for future developments of fullerene-based electrochemical ion sensors. 

Figure 1.15. Bis-adducts of C6o obtained by tether-directed Bingel macrocyclization.

Even tris- and tetrakis-adducts of C6o were accessible in a regioselective way by sequential tether-directed macrocyclization steps. A clipping reaction starting from mono-adduct 40 with two tether-linked malonate residues thus yielded tris-adduct ( )-41 (Scheme 1.5).125 Under the assumption that both m-xylylene tethers enforce the expected cis-2 addition, the C2-symmetry of... 

Scheme 1.5. Synthesis of a chiral tris-adduct of Cuo by double tether-directed Bingel macrocy-clization.

Figure 1.19. Chiral bis-adducts of Cgo obtained by tether-directed cycloaddition reactions.

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