Synthesis and Use of a 2-(Trimethylsilyl)ethoxymethyl-Based Linker in Solid-Phase Organic Chemistry

The synthesis of a linker derived from the 2-(trimethylsilylethoxy)methyl (SEM) protection group is described. This linker is particularly useful for the immobilization of steroids on solid phases, because the linker is robust but allows the substrates to be cleaved from the solid phase by fluoridolysis. The use of the linker is demonstrated by the coupling and cleavage of eight different steroids. Furthermore, two palladium coupling reactions are shown, whereby the steroidal vinyl triflates are attached to the solid phase via this linker.