A Robust Linker for Solid Phase Diversity-Oriented Synthesis
![TBDAS Linker](/sites/default/files/node/2707/images/251096.jpg)
The t-butyldiarylsilyl (TBDAS) linker was developed by Drs. Christine DiBlasi and Daniel Macks in our group for solid phase organic synthesis. This robust linker is stable to a variety of reaction conditions, but can be cleaved with relatively mild, chemoselective fluoride reagents to yield alcohol products.
![Linker Stability](/sites/default/files/node/2707/images/251097.jpg)
As depicted graphically here, the TBDAS linker (blue) is stable to a range of acidic and basic reaction conditions commonly used in organic synthesis. In contrast, previously reported aryldiisopropylsilyl (ArDIPS, red) and alkyldiisopropylsilyl (AlkylDIPS) linkers are generally less stable to these conditions.
![TBDAS Synthesis](/sites/default/files/node/2707/images/251098.jpg)
The TBDAS linker is activated by chlorination with dichorodimethylhydantoin, followed by loading of the desired alcohol-containing substrate. After synthetic transformation, the product is cleaved from the solid support by treatment with TBAF, TAS-F, or HF·pyr. The product can be conveniently separated from the cleavage reagents by passage through a short plug of reverse phase over normal phase silica gel.
For full details on the synthesis and use of this linker, see:
DiBlasi, C. M.; Macks, D. E.; Tan, D. S.* “An acid-stable tert-butyldiarylsilyl (TBDAS) linker for solid-phase organic synthesis.” Org. Lett. 2005, 7, 1777-1780.
[ Abstract | PDF | Supporting Info ]
Highlighted in Letters in Organic Chemistry [PDF]