Propylene carbonate in Suzuki-Miyaura reaction

Title : Propylene carbonate in Suzuki-Miyaura reaction

Abstract:

Several efforts were taken to carry out cross-coupling reaction under green and sustainable conditions. The Pd-catalysed cross-coupling of three iodo-heterocyclic compounds with different boronic acids will be discussed under Suzuki-Miyaura reaction conditions, in a green solvent. The propylene carbonate (PC) is a polar, aprotic solvent synthesized by addition of propylene oxide to carbon dioxide. It has a high boiling point and is more or less stable at elevated temperatures. This property of PC allows the Suzuki-Miyaura reaction to be carried out at higher temperatures, but under a shorter reaction time.

In the presence of base, PC suffers ring-opening and the formed propylene-glycol is able to alkylate the nucleophilic N-heteroatom giving byproducts with 2-hydroxypropyl side-chain besides the expected coupled products. We compared the yield of products obtained by traditional oil-heating with those obtained under similar reaction conditions under microwave irradiation as well. In some cases, the reactions were performed under flow conditions too.  Based on the results, we assume that there are two possibilities: alkylation takes place first and then cross coupling happens or vice-versa. The first option was verified according to our investigation.

In sum, a green procedure was developed not only for the Suzuki-Miyaura cross-coupling reaction, but N-alkylation was carried out under sustainable conditions providing compounds not known in the literature, which possess a free OH-group and which may lead to the synthesis of drug candidates after further transformations.  

Biography:

Dr. A. Czompa studied Chemistry at the Babes-Bolyai University, Romania and graduated as chemistry-physics teacher in 1993. She joined the research group of Prof. S. Antus at the Department of Organic Chemistry, University of Debrecen. She received her PhD degree in 2000 at the same institution, in the field of flavonoid derivatives, enzymatic reaction and SAR. After moving to Budapest, at Semmelweis University she continued to deal with organic chemistry and synthesized pyridazinone ethers, glycine transporter-1 inhibitors, optical BAPTA-derivatives, antiarrythmic compounds, SSAO/VAP-1 inhibitors, TRPA1 and V1 receptor antagonists, SzV-1287 and metabolites, respectively new N-, O-, S-heterocyclic compounds.