Removal of the tether

Transesterification of the fullerene crown ether conjugate (+)-89 allowed for the removal of the tether, leading to the D2fj-symmetrical bisadduct 94 (34%) [93], which is a very useful building block for further addition chemistry. 

The use of complex radical donors and radical acceptors, such as carbohydrates tethered by an acetal-containing linkage, has been reported by Sinay [98]. Here, the radical addition of an anomeric radical to a 4-exo-methylene sugar derivative (compound 69) proceeds in the 8-endo mode, with formation of a eight-membered acetal ring. The end product of this reaction, after removal of the tether and acetylation, is the C-disaccharide 70 (Scheme 27). 

The addition pattern of ( )-37 was confirmed by transesterification with removal of the tether (Figure 13). Thus the reaction of ( )-37 with CS2CO3 in anhydrous hexanol/THF 1 1 provided the >2h symmetric bis-adduct 45 at 34% yield. Its 13C-NMR spectrum displayed only nine resonances for the fullerene C-atoms, and the expected peaks for four equivalent hexyl residues. Of all possible regio-isomeric bis(dihexyl malonate) adducts of C6o, only the trans-1 compound displays this high symmetry [2],... 

This strategy was mostly exploited by Sinay and his coworkers, enabling them to prepare various C-linked disaccharides in an expeditious fashion, via radical cyclization of temporarily tethered monosaccharidic precursors [111]. Medium-sized ring intermediates are obtained in reasonable yields, leading to the desired compounds after removal of the tether. The prototype of this approach is described below [112a] (O Scheme 52). 

In a full paper describing this and other functionalizations of steroids tethered to benzophenones [34], it was revealed that the 3a-cholestanol ester 8 of benzophenone-4-acetic acid afforded, after hydrolytic removal of the tether, A " -3a-cholestenol 4 as the product along with the diphenylcarbinol from reduction of the benzophenone. The short tether did not permit insertion into the C-14-H bond, so after the oxygen atom of excit-... 

Dialkylvinylsilyl halides are readily prepared, for example, by hydrosilylation of acetylenes indeed, the most simple dimethyl- and diphenylvinylsilyl chlorides are now commercially available. Substitution of the halide with the appropriate hydroxydiene then generates the desired triene precursor. Vinyl silyl ethers are also much more stable than silyl acetals, especially towards hydrolysis nevertheless, a number of mild methods are still available for subsequent removal of the tether. 

Removal of the tether was realized in two ways. Oxidative cleavage of an activated C-Si bond has been shown to proceed with retention of configuration [11]. Thus treating 19 and 20 with 1 equiv of TBAF and a 30% solution of H2O2 in DMF at 55 °C for 2 h afforded the diastereoisomeric diols 21 and 22, respectively, both in 80% yield. Alternatively hydrodesilylation could be achieved using 2 equiv of TBAF in DMF at 60 °C for 4 h. In the case of the cis-fused, bicyclic Diels-Alder adduct 19, the basic conditions of... 

Completion of the synthesis was readily achieved. Diastereoselective reduction of the ketone was accomplished with (S)-BINOL/LiAlH4. Then, removal of the tether by acidic hydrolysis, which also effected silyl ether deprotection, afforded dihydroxy lactol 223 allowing introduction of the final side chain using a Wittig reaction (Scheme 10-71). 

Mixtures of regioisomers were obtained (2-5 1). However, high diastereoselectivities were observed (d.r. 7 1 - 20 1). Enantiomerically pure cyclohexanes and decalins were isolated by separation of the diastereomers and removal of the tether. 

Detailed analysis of the NMR spectra of these two compounds showed that one was the anticipated dimer 26c from the C-2 symmetric substrate and that the second was the exo cycloadduct 27 from the meso substrate. Removal of the tether from dimer 26c gave diol 28, which we considered a key intermediate on the route to kingianin A. 

---