Traceless silicon-based linkers

Plunkett MJ, Ellman JA. A silicon-based linker for traceless solid-phase synthesis. J Org Chem 1995 60 6006-6007. 

Chemistry similar to this was used in Ellman s paper to promote application of a silicon-based traceless linker.62 The full report on this work63 shows that both aliphatic and aromatic acid chlorides may be used in the coupling step. The same,approach is also shown to be successful with a germanium-based linker in place of the silicon. The couplings were typically performed for 1 h only, with equilibration time of a few minutes... 

Plunkett, M. J. Ellman, J. A. A Silicon-Based Linker for Traceless Solid-Phase Synthesis, J. Org. Chem. 1995, 60, 6006-6007. 

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],... 

Ellman s group also developed a traceless linker sequence of a different type based on HF release of an aiyl silicon link to the resin (Fig. 1.17) (122). 

F. X. Woolard, J. Paetsch, J. A. Ellman, A Silicon Linker for Direct Loading of Aromatic Compounds to Supports. Traceless Synthesis of Pyridine-Based Tricyclics , J. Org Chem. 1997, 62, 6102-6103. 

Woolard FX, Paetsch J, Ellman JA, A silicon linker for direct loading of aromatic compounds to supports. Traceless synthesis of pyridine-based tricyclics, J. Org. Chem., 62 6102-6103, 1997. 

The traceless anchors based on silicon just described are limited by the need to synthesize a preformed handle consisting of the first building block and the silicon linker. Moreover, traceless release from conventional aryldialkylsilanes is complicated by their low hydrolytic stability and loss of silicon from the resin in the cleavage process. The silyl chloride resin 8h can be used to anchor aryl rings by reaction with aryllithium reagents. The anchor is stable to concentrated TFA and bases, but treatment with TBAF cleaves the final products [353]. 

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