Solid-phase synthesis of aryl-substituted thienoindolizines: sequential Pictet-Spengler, bromination and Suzuki cross-coupling reactions of thiophenes.
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.
Le Quement
Sebastian T
ST
Carlsberg Laboratory, SPOCC Centre, Gamle Carlsberg Vej 10, DK-2500 Valby, Denmark.
Nielsen
Thomas E
TE
Meldal
Morten
M
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
D007212:Indolizines; D013876:Thiophenes; D001966:Bromine