title: Solid-phase synthesis of aryl-substituted thienoindolizines: sequential Pictet-Spengler, bromination and Suzuki cross-coupling reactions of thiophenes.
abstract: The solid-phase synthesis of a range of novel heterocyclic scaffolds based on the thiophene ring system, including thienoindolizines and aryl-substituted thiophenes, is presented. Specifically, a sequential methodology for the decoration of thienoindolizine scaffolds has been developed. This method involves a highly efficient and diastereoselective intramolecular Pictet-Spengler reaction, a quantitative and regioselective bromination of the thiophene ring, and a final Suzuki cross-coupling with an arylboronic acid. Crude products were generally obtained in high purities (>90%). In addition, an investigation on the acidic and electronic effects governing the rate of the Pictet-Spengler reactions was performed. Finally, a range of substituted thiophenes was attached to solid supports and subjected to the regioselective bromination and Suzuki cross-coupling reactions, thus providing substituted thiophenes with high purities of crude products.
authors.affiliation: Carlsberg Laboratory, SPOCC Centre, Gamle Carlsberg Vej 10, DK-2500 Valby, Denmark.
authors.forename: Sebastian T
authors.initials: ST
authors.lastname: Le Quement
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Nielsen
authors.forename: Morten
authors.initials: M
authors.lastname: Meldal
mesh_terms: D001966:Bromine / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D054879:Halogenation; D007212:Indolizines / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism; D013876:Thiophenes / Q000737:chemistry*; D013997:Time Factors
chemical_list: D007212:Indolizines; D013876:Thiophenes; D001966:Bromine