Traceless Linkers Based on Silyl Functionalization

Sihcon-based hnkers can be apphed to the immobilization of aromatic and heteroaromatic entities on a sohd support Protodesilylation procedures used to cleave off the combinatorial compounds leave no functional groups on the final products [90-92]. One limitation of this protocol may be the relatively complicated and multistep synthesis of the actual linker unit. Usually, the starting material has to be bound to the hnker unit first, after which the resulting construct is attached to the support material. In addition, the conditions for the protodesilylation depend on the substitution on the arene ring. 

Recently, two entities (80 and 81) for the construction of silyl-based traceless hnkers have been synthesized, which represent analogues of 79 (Fig. 8). They were reported to be useful for the traceless synthesis of indoles, phenothiazines, and benzodiazepines [95], 

Method of cleavage Cleavage is generally performed by protodesilylation. The conditions depend very much on the nature of the aromatic system, as well as on the substitution. Either neat TFA, TFA vapor or TFA/CH2CI2 can be used. Electron-poor aromatic systems require treatment with CsF in DMF/ water (4 1) at 110 °C. 

For loading onto the resin, (hydroxymethyl)polystyrene (6.00 g, 6 mmol) and imidazole (2.45 g, 36 mmol) were taken up in DMF (40 mL). The arylchlor-osilane (6.92 g, 24.1 mmol) was added to the suspension and the mixture was kept at rt with shaking for 45 h. The resin was then filtered off, washed with DMF (three times), THF (three times), and CH2CI2 (three times), and then dried. Repetition of the above procedure enhanced the loading. 

Linker 88 has been successfully employed in the synthesis of a small hbrary of benzopyranones, of which the individual compounds were obtained in high yields and purities [101]. A further application of the linker has been in the synthesis of oligo(3-aryl-thiophenes) [102]. 

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Newly developed silicon hnkers such as 79 (Scheme 37) have been synthesized in fewer steps as compared with the earlier reported traceless linkers based on silyl functionalization. They allow for an easy binding to the support before performing the combinatorial synthesis [93, 94],... 

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