Synthesis of diverse indole libraries on polystyrene resin – Scope and limitations of an organometallic reaction on solid supports

Abstract

SummaryThe synthesis of diverse substituted indole structures on solid supports is described. The immobilization of nitrobenzoic acid onto Merrifield resin and the subsequent treatment with alkenyl Grignard reagents delivered indole carboxylates bound to solid supports. In contrast to results in the liquid phase, ortho,ortho-unsubstituted nitroarenes also delivered indole moieties in good yields. Subsequent palladium-catalyzed reactions (Suzuki, Heck, Sonogashira, Stille) delivered, after cleavage, the desired molecules in moderate to good yields over four steps. The scope and limitations are presented.

Applications of Bartoli indole synthesis

“…58 More recently, Braese's group presented the scope and limitation of this procedure, finding the best yields and purities at À40 1C. 73 However, they observed the failure of the reaction with 2-hydroxynitrobenzenes and 2-methoxynitrobenzenes that led to very complex mixtures.…”

Solid phase synthesis of functionalized indazoles using triazenes – scope and limitations

“…23 While almost all literature-known reactions on solid phases using the triazene linkers have been performed with a benzylaminomethylpolystyrene backbone, 6 we switched to the given isopropyl-derivative (2) in order to reflect the conditions of the successful reaction in solution as good as possible. Their subsequent coupling with isopropylaminomethylpolystyrene 2 yielded triazene resins 3a-h according to described procedures.…”

“…[1][2][3][4][5][6][7] In particular, some indazole-containing compounds have a substantial impact when used as therapeutic agents (Figure 1). [1][2][3][4][5][6][7] In particular, some indazole-containing compounds have a substantial impact when used as therapeutic agents (Figure 1).…”

Synthesis, Biological Evaluation and In silico Studies of Compounds Based on Tryptophan‐Naproxen‐Triazole Hybrids

“…Compounds having amino acid moieties are also known to possess favorable biological and pharmacological properties. [30][31][32][33][34][35] Notably, the small peptides are being considered as potential alternatives to the presently available antibiotics and/or possible entities in other medical field. [14-15,36À 38] Considering all these observations and due to our ongoing efforts in the synthesis of library of new chemical entities (NCEs) we designed a template A (Figure 1) that contains a dipeptide along with the structural features of naproxen and tryptophan and a 1,4-disubstituted 1,2,3-triazole ring.…”

“…It is also present in proteins in the form of amino acid i. e. tryptophan. Compounds having amino acid moieties are also known to possess favorable biological and pharmacological properties [30–35] . Notably, the small peptides are being considered as potential alternatives to the presently available antibiotics and/or possible entities in other medical field [14–15,36−38] .…”