Solution-Phase Parallel Synthesis of a Multi-substituted Benzo[b]thiophene Library

Abstract

Synthesis of a Benzo[b]thiophene Library-Generation of a library using parallel syntheses of multi-substituted benzo[b]thiophenes is described. The requisite 3-iodobenzo [b]thiophenes are readily prepared in excellent yields from various alkynes bearing electron-rich aromatic rings by electrophilic cyclization using I 2 in CH 2 Cl 2 . The heteroaromatic carbon-iodine bonds allow further diversification by palladium-catalyzed Suzuki-Miyaura, Sonogashira, Heck and carboalkoxylation chemistry to give multi-substituted benzo[b]thiophene derivatives.

Palladium(II) Catalyzed Cyclization-Carbonylation-Cyclization Coupling Reaction of (ortho-Alkynyl Phenyl) (Methoxymethyl) Sulfides Using Molecular Oxygen as the Terminal Oxidant

“…We are currently investigating further biological studies of the synthesized compounds 2. Benzo [b]thiophene skeletons are an important class of S-heterocycles [15][16][17][18] and are found in a variety of drugs, pesticides, and biologically active compounds that exhibit various interesting biological properties [19][20][21][22][23][24]. Diaryl ketone scaffolds are also important motifs in natural products and pharmaceuticals [25][26][27][28][29][30] (Figure 1).…”

New protein farnesyltransferase inhibitors in the 3-arylthiophene 2-carboxylic acid series: diversification of the aryl moiety by solid-phase synthesis

“…Such phenylboronic acids bearing electron withdrawing or amino groups have already been coupled on thiophene or benzothiophene rings following this methodology. However, these aromatics were seldom tetrasubstituted or the thiophene ring was not as electrodeficient as our substrate [27][28][29][30][31] . Interestingly, there is no report on palladium-catalyzed thiophene arylation with 4-vinyl phenylboronic acid.…”

A new approach to desketoraloxifene analogs from oxygen-bearing 3-iodobenzo[b]thiophenes prepared via iodocyclization

“…These 3-iodobenzo[ b ]thiophenes 1 are easily further elaborated using a two-step approach involving Suzuki-Miyaura and Mitsunobu coupling reactions to give desketoraloxifene analogs 3 . The first step, the palladium-catalyzed Suzuki-Miyaura coupling of the 3-iodobenzo[ b ]thiophenes 1 with a tetrahydropyranyl (THP) ether-protected boronic acid, e.g.p -THPOC 6 H 4 B(OH) 2 , for 6–8 h, followed by aqueous HCl deprotection, afforded the desired phenolic oxygen products 2 15 in high yield (Scheme 2). …”

“…14 Very recently, a simple and efficient method for the parallel synthesis of multi-substituted benzo[ b ]thiophenes has also been described via known palladium-catalyzed couplings for generation of a diverse set of building blocks starting from 3-iodobenzo[ b ]thiophenes 15,16…”