Tether-directed Remote Functionalization of

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. 

Prior to the development of tether-directed functionalization methods, regioisomerically pure higher adducts of C50 usually were obtained by additions of transition metal complexes [31-33] or radical halogenations [34, 35]. These reactions either occur under thermodynamic control or lead to the precipitation of the least soluble derivative. Iso-merically pure higher adducts of C o sometimes are also readily isolated out of more complex product mixtures [36]. Tether-directed remote functionalization of CgQ allows the construction of fullerene derivatives with addition patterns that are difficult to obtain by thermodynamically or kinetically controlled reactions with free untethered reagents. Since the description of the first such reaction in 1994 [7], which is the subject of Section 7.3.1, an increasing variety of such regioselective functionalization protocols have... 

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... 

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. 

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]. 

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. 

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. 

Scheme 7-4 Preparation of bis-adducts 24 (7,47] and 26 [41,47] and tris-adduct 28 [7, 47] by tether-directed remote functionalization. A sequence of e attacks starting from 28 gives hexakis-adduct 30 with a pseudo-octahedral addition pattern [7, 47]. DCC=A(,A("-dicyclohexylcarbodi-imide, HOBT = 1-hydroxy-IW-benzotriazole, DMAP=4-(dimethylamino)pyridine.

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