Solid-phase linkers indole linker

Ruhland reported a novel solid-phase C2-lithiation of the indole ring [279] using a linker that resembled the MOM-protecting group (Scheme 16). Lithiation of resin-bound indole 73 was accomplished by treatment with tert-butyllithium in toluene followed by quenching with benzonitrile. Reductive cleavage of 74 then gave amine 75 in an overall yield of 2%, proof of principle that this type of transformation is possible. 

Larock indole synthesis was applied in a solid-phase synthesis of trisubstituted inodles 113 using an amide group as a linker starting from 114. ... 

PS-TsCl was used in the solid-phase synthesis of indoles. Loading of anilines 8 onto PS-TsCI was followed by Sonogashira coupling (eq 9). The coupled products cyclized under the reaction condihons to provide the corresponding indoles this cycliza-tion was promoted by the electron-withdrawing sulfonyl linker. Traceless cleavage of the sulfonyl linker with TBAF provided the indoles in 85-100% yield. 

The application of transition metal-mediated reactions on solid support is an area of supreme interest for both peptide chemistry and the synthesis of nonpeptidic drug-like molecules. Although many metal-catalyzed reactions have been carried out on resin-bound scaffolds, there are scarce examples of metal-mediated solid-phase reactions promoted by a complexing agent that is covalently bound with the resin in close proximity of the scaffold. Dai and Sun have recently proposed an ingenious route toward the microwave-assisted solid-phase synthesis of a small library of 2-(hetero)aryl indoles. The authors demonstrated the strategic use of a tailor-made linker that features the dual function of a normal linker for scaffold attachment as well as of a promoter for the Cu(II)-mediated hetero-annulation of the intermediates (Scheme 8.17). 

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