Traceless Linker Based on Aryl Hydrazides

The amino-modified support was reacted with adipic acid dichloride and, after hydrolysis, was coupled with 4-iodophenylhydrazine 128 to yield the immobihzed iodobenzene 129. Intermediate 129 was then employed in Pd-mediated C-C couplings (Stille, Heck, Suzuki, Sonogashira) to yield, for example, compounds 130 and 131. The final products 132 and 133 were obtained in good to excellent yields by oxidation of 130 and 131, respectively. 

Recently, the traceless phenylhydrazide hnker has been apphed in multi-step 

After removal of the protecting group (PG) from 134, the system was amenable to the oxidation/nucleophilic substitution process. Since this hnker represents a reversal of the original phenylhydrazide hnker, the traceless part stayed on the sohd support and the desired compound 135 was released. The utility of the linker was demonstrated in the synthesis of mono-ketopiperazines resulting from a cyclative cleavage. 

Solid-phase-bound phenylhydrazones can also be reduced to the corresponding phenylhydrazines, which can then be used for a traceless Fischer indole synthesis on the solid support [150]. 

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